{ "LSD dementia": { "studies": [ { "protocolSection": { "identificationModule": { "nctId": "NCT03633253", "orgStudyIdInfo": { "id": "CODIM-FLP-16 288" }, "organization": { "fullName": "Jewish General Hospital", "class": "OTHER" }, "briefTitle": "The \"Motoric Cognitive Risk\" Syndrome in the Quebec Population", "officialTitle": "The \"Motoric Cognitive Risk\" Syndrome in the Quebec Population: Results From the NuAge Study" }, "statusModule": { "statusVerifiedDate": "2024-02", "overallStatus": "UNKNOWN", "lastKnownStatus": "ACTIVE_NOT_RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2016-12-07", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2020-12-07", "type": "ACTUAL" }, "completionDateStruct": { "date": "2025-12-07", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2018-08-10", "studyFirstSubmitQcDate": "2018-08-13", "studyFirstPostDateStruct": { "date": "2018-08-16", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2024-02-22", "lastUpdatePostDateStruct": { "date": "2024-02-23", "type": "ACTUAL" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "PRINCIPAL_INVESTIGATOR", "investigatorFullName": "Olivier Beauchet", "investigatorTitle": "Professor of Geriatrics", "investigatorAffiliation": "Jewish General Hospital" }, "leadSponsor": { "name": "Jewish General Hospital", "class": "OTHER" } }, "oversightModule": { "oversightHasDmc": false, "isFdaRegulatedDrug": false, "isFdaRegulatedDevice": false }, "descriptionModule": { "briefSummary": "The overall objective of the proposal is to examine the epidemiology of the newly reported \"motoric cognitive risk\" (MCR) syndrome, which is a pre-dementia syndrome combining subjective cognitive complaint (i.e.; memory complaint) with objective slow gait speed, in the Quebec elderly population.\n\nCognition and locomotion are two human abilities controlled by the brain. Their decline is highly prevalent with physiological and pathological aging, and is greater than the simple sum of their respective prevalence, suggesting a complex age-related interplay between cognition and locomotion. Both declines in cognition and locomotion are associated, furthermore the temporal nature of their association has been unclear for a long time. Recently, a systematic review and meta-analysis has provided evidence that poor gait performance predicts dementia and, in particular, has demonstrated that MCR syndrome is a pre-dementia syndrome, suggesting that low gait performance is the first symptom of dementia. The uniqueness of MCR syndrome is that it does not rely on a complex evaluation or laboratory investigations. Indeed, this syndrome combined subjective cognitive complaint and objective slow gait speed, and is easy to apply in population-based settings.\n\nPrevalence and incidence of MCR syndrome, as well as its association with incidence of cognitive decline and impairment, have never been reported in Canada. Nutrition as a determinant of successful aging: The Quebec longitudinal Study (the NuAge study) is a Quebec population-based observational cohort study performed in healthy older community-dwellers adults which provides a unique opportunity to: 1) obtain reliable estimates of MCR syndrome prevalence and incidence, 2) determine the distribution of clinical characteristics associated with MCR syndrome, 3) examine the association of MCR syndrome with cognitive decline and incidence of cognitive impairment in the Quebec elderly population." }, "conditionsModule": { "conditions": [ "Cognition Disorders in Old Age", "Dementia" ] }, "designModule": { "studyType": "OBSERVATIONAL", "patientRegistry": false, "designInfo": { "observationalModel": "COHORT", "timePerspective": "RETROSPECTIVE" }, "enrollmentInfo": { "count": 1741, "type": "ESTIMATED" } }, "armsInterventionsModule": { "armGroups": [ { "label": "MCR syndroms", "interventionNames": [ "Other: Summarize of participants' characteristics using means and standard deviations or frequencies and percentages" ] }, { "label": "Non MCR syndroms", "interventionNames": [ "Other: Summarize of participants' characteristics using means and standard deviations or frequencies and percentages" ] } ], "interventions": [ { "type": "OTHER", "name": "Summarize of participants' characteristics using means and standard deviations or frequencies and percentages", "description": "First, prevalence of MCR syndrome will be determined by classifying participants into MCR and non-MCR syndrome groups. Second, between-group comparisons of participants' characteristics will be performed using unpaired t-test, Mann-Whitney, analysis of variance with LSD correction or Chi-square test, as appropriate. Third, multiple regressions will be performed to examine the association between MCR syndrome (dependent variable) and cardio-vascular risk factors and/or diseases (independent variables) adjusted on participants' characteristics. Fourth, the incidence of MCR syndrome during the follow-up period of NuAge study will be reported. Fifth, regression will be performed to examine the association between MCR syndrome (dependent variable) and cognitive decline as well cognitive impairment (independent variables, separated model) adjusted on participants' characteristics.", "armGroupLabels": [ "MCR syndroms", "Non MCR syndroms" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "MCR syndrome criteria", "description": "Diagnosis of MCR syndrome following Verghese et al. criteria", "timeFrame": "1 day" } ], "secondaryOutcomes": [ { "measure": "Cognitive decline and impairment", "description": "Modified Mini-Mental State (3MS) in the NuAge study.", "timeFrame": "1 day" }, { "measure": "Covariates", "description": "Cardio-vascular risk factors and diseases assessed using reported health condition", "timeFrame": "1 day" }, { "measure": "Covariates", "description": "Cardio-vascular risk factors and diseases assessed using physical examination: body mass index", "timeFrame": "1 day" }, { "measure": "Covariates", "description": "Cardio-vascular risk factors and diseases assessed using physical examination: hip waist ratio from hip and waist circumference", "timeFrame": "1 day" }, { "measure": "Covariates", "description": "Cardio-vascular risk factors and diseases assessed using physical examination: blood pressure (value of systolic, diastolic when participants are seated in an upright position in a chair)", "timeFrame": "1 day" } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria:\n\nIndividuals eligible for this study will be participants of the NuAge study\n\nExclusion Criteria:\n\nIndividuals not eligible for the NuAge study, No information about cognitive complaint, No measure of walking speed, No follow-up completed", "healthyVolunteers": true, "sex": "ALL", "stdAges": [ "CHILD", "ADULT", "OLDER_ADULT" ], "studyPopulation": "Individuals eligible for this study will be participants of the NuAge study (n=1,793). All included participants of NuAge Study were healthy and, in particular, they were cognitively intact at baseline and had no mobility disability.", "samplingMethod": "NON_PROBABILITY_SAMPLE" }, "contactsLocationsModule": { "locations": [ { "facility": "Jewish General Hospital", "city": "Montreal", "state": "Quebec", "zip": "H3T 1E2", "country": "Canada", "geoPoint": { "lat": 45.50884, "lon": -73.58781 } } ] }, "ipdSharingStatementModule": { "ipdSharing": "NO" } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2026-07-09" }, "conditionBrowseModule": { "meshes": [ { "id": "D003704", "term": "Dementia" } ], "ancestors": [ { "id": "D001927", "term": "Brain Diseases" }, { "id": "D002493", "term": "Central Nervous System Diseases" }, { "id": "D009422", "term": "Nervous System Diseases" }, { "id": "D019965", "term": "Neurocognitive Disorders" }, { "id": "D001523", "term": "Mental Disorders" } ] } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT05046275", "orgStudyIdInfo": { "id": "2021-245" }, "organization": { "fullName": "Centre integre universitaire de sante et de services sociaux du Centre-Sud-de-l'\u00cele-de-Montr\u00e9al", "class": "OTHER_GOV" }, "briefTitle": "MCR Syndrome in Quebec : Results From NuAge Study", "officialTitle": "The \"Motoric Cognitive Risk\" Syndrome in the Quebec Population: Results From the NuAge Study - Sub-study: The Biological Underpinnings of Motoric Cognitive Risk Syndrome: a Multicenter Study" }, "statusModule": { "statusVerifiedDate": "2024-02", "overallStatus": "UNKNOWN", "lastKnownStatus": "ACTIVE_NOT_RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2020-11-03", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2025-11-02", "type": "ESTIMATED" }, "completionDateStruct": { "date": "2025-12-01", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2021-09-08", "studyFirstSubmitQcDate": "2021-09-08", "studyFirstPostDateStruct": { "date": "2021-09-16", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2024-02-22", "lastUpdatePostDateStruct": { "date": "2024-02-23", "type": "ACTUAL" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "PRINCIPAL_INVESTIGATOR", "investigatorFullName": "Olivier Beauchet", "investigatorTitle": "MD, PhD, Senior researcher, Director of laboratory", "investigatorAffiliation": "Centre integre universitaire de sante et de services sociaux du Centre-Sud-de-l'\u00cele-de-Montr\u00e9al" }, "leadSponsor": { "name": "Centre integre universitaire de sante et de services sociaux du Centre-Sud-de-l'\u00cele-de-Montr\u00e9al", "class": "OTHER_GOV" } }, "oversightModule": { "oversightHasDmc": false, "isFdaRegulatedDrug": false, "isFdaRegulatedDevice": false }, "descriptionModule": { "briefSummary": "The overall objective of the proposal is to examine the epidemiology of the newly reported \"motoric cognitive risk\" (MCR) syndrome, which is a pre-dementia syndrome combining subjective cognitive complaint (i.e.; memory complaint) with objective slow gait speed, in the Quebec elderly population.\n\nCognition and locomotion are two human abilities controlled by the brain. Their decline is highly prevalent with physiological and pathological aging, and is greater than the simple sum of their respective prevalence, suggesting a complex age-related interplay between cognition and locomotion. Both declines in cognition and locomotion are associated, furthermore the temporal nature of their association has been unclear for a long time. Recently, a systematic review and meta-analysis has provided evidence that poor gait performance predicts dementia and, in particular, has demonstrated that MCR syndrome is a pre-dementia syndrome, suggesting that low gait performance is the first symptom of dementia. The uniqueness of MCR syndrome is that it does not rely on a complex evaluation or laboratory investigations. Indeed, this syndrome combined subjective cognitive complaint and objective slow gait speed, and is easy to apply in population-based settings.\n\nPrevalence and incidence of MCR syndrome, as well as its association with incidence of cognitive decline and impairment, have never been reported in Canada. Nutrition as a determinant of successful aging: The Quebec longitudinal Study (the NuAge study) is a Quebec population-based observational cohort study performed in healthy older community-dwellers adults which provides a unique opportunity to: 1) obtain reliable estimates of MCR syndrome prevalence and incidence, 2) determine the distribution of clinical and biological (blood biomarkers and genetic) characteristics associated with MCR syndrome, 3) examine the association of MCR syndrome and its biological characteristics with cognitive decline and incidence of cognitive impairment in the Quebec elderly population." }, "conditionsModule": { "conditions": [ "Motoric Cognitive Risk Syndrome", "Aging Disorder" ] }, "designModule": { "studyType": "OBSERVATIONAL", "patientRegistry": false, "designInfo": { "observationalModel": "COHORT", "timePerspective": "RETROSPECTIVE" }, "enrollmentInfo": { "count": 1741, "type": "ACTUAL" } }, "armsInterventionsModule": { "armGroups": [ { "label": "MCR syndroms", "description": "Summarize of participants' characteristics using means and standard deviations or frequencies and percentages First, prevalence of MCR syndrome will be determined by classifying participants into MCR and non-MCR syndrome groups. Second, between-group comparisons of participants' characteristics will be performed using unpaired t-test, Mann-Whitney, analysis of variance with LSD correction or Chi-square test, as appropriate. Third, multiple regressions will be performed to examine the association between MCR syndrome (dependent variable) and cardio-vascular risk factors and/or diseases (independent variables) adjusted on participants' characteristics. Fourth, the incidence of MCR syndrome during the follow-up period of NuAge study will be reported. Fifth, regression will be performed to examine the association between MCR syndrome (dependent variable) and cognitive decline as well cognitive impairment (independent variables, separated model) adjusted on participants' characteristics.", "interventionNames": [ "Other: Data analysis" ] }, { "label": "Non MCR syndroms", "description": "Summarize of participants' characteristics using means and standard deviations or frequencies and percentages First, prevalence of MCR syndrome will be determined by classifying participants into MCR and non-MCR syndrome groups. Second, between-group comparisons of participants' characteristics will be performed using unpaired t-test, Mann-Whitney, analysis of variance with LSD correction or Chi-square test, as appropriate. Third, multiple regressions will be performed to examine the association between MCR syndrome (dependent variable) and cardio-vascular risk factors and/or diseases (independent variables) adjusted on participants' characteristics. Fourth, the incidence of MCR syndrome during the follow-up period of NuAge study will be reported. Fifth, regression will be performed to examine the association between MCR syndrome (dependent variable) and cognitive decline as well cognitive impairment (independent variables, separated model) adjusted on participants' characteristics.", "interventionNames": [ "Other: Data analysis" ] } ], "interventions": [ { "type": "OTHER", "name": "Data analysis", "description": "No intervention, data analysis only", "armGroupLabels": [ "MCR syndroms", "Non MCR syndroms" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "prevalence of MCR syndrome", "description": "Diagnosis of MCR syndrome following Verghese et al. criteria", "timeFrame": "3 years" } ], "secondaryOutcomes": [ { "measure": "Cognitive decline and impairment", "description": "Modified Mini-Mental State (3MS) in the NuAge study.", "timeFrame": "3 years" }, { "measure": "Covariates", "description": "Cardio-vascular risk factors and diseases assessed using reported health condition", "timeFrame": "3 years" }, { "measure": "Covariates", "description": "Cardio-vascular risk factors and diseases assessed using physical examination: body mass index", "timeFrame": "3 years" }, { "measure": "Covariates", "description": "Cardio-vascular risk factors and diseases assessed using physical examination: hip waist ratio from hip and waist circumference", "timeFrame": "3 years" }, { "measure": "Covariates", "description": "Cardio-vascular risk factors and diseases assessed using physical examination: blood pressure (value of systolic, diastolic when participants are seated in an upright position in a chair)", "timeFrame": "3 years" }, { "measure": "Biological characteristics", "description": "we selected biomarkers that consistently show associations with clinical risk factors for MCR : IL-6, high-sensitivity CRP and Malondialdehyde (MDA). These biomarkers are associated with individual MCR components. CRP was associated with plaques. Inflammation is hypothesized to be a precursor to neurofibrillary tangles and amyloid plaques; hallmarks of AD. Oxidative stress damage is elevated in vulnerable brain regions in early AD and MCI.\n\nWe propose a multi-level examination of vascular pathways in MCR including biomarkers (CRP and homocysteine).\n\nWe include homocysteine, a vascular biomarker, linked to gait and cognitive deficits in other studies.", "timeFrame": "3 years" }, { "measure": "Genetic approach", "description": "we propose to derive polygenic risk scores for cognitive and obesity phenotypes in NuAge, and to examine its predictive validity for MCR syndrome and incident cognitive impairment", "timeFrame": "3 years" } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria:\n\n* All included participants of NuAge Study\n\nExclusion Criteria:\n\n* no information about cognitive complaint in NuAge database\n* no measure of walking speed in NuAge database\n* no follow-up completed in NuAge database", "sex": "ALL", "minimumAge": "65 Years", "stdAges": [ "OLDER_ADULT" ], "studyPopulation": "All included participants of NuAge Study were healthy and, in particular, they were cognitively intact at baseline and had no mobility disability.", "samplingMethod": "NON_PROBABILITY_SAMPLE" }, "contactsLocationsModule": { "locations": [ { "facility": "CRIUGM", "city": "Montreal", "state": "Quebec", "zip": "H3W 1W5", "country": "Canada", "geoPoint": { "lat": 45.50884, "lon": -73.58781 } } ] }, "ipdSharingStatementModule": { "ipdSharing": "NO" } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2026-07-09" } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT00975481", "orgStudyIdInfo": { "id": "B1451037" }, "organization": { "fullName": "Pfizer", "class": "INDUSTRY" }, "briefTitle": "A Study To Evaluate The Abuse Potential Of Single Oral Doses Of Dimebon (Latrepirdine) In Healthy Recreational Polydrug Users", "officialTitle": "A Randomized, Double-Blind, Placebo- And Active-Controlled Single-Dose, Crossover Study To Evaluate The Abuse Potential Of Single Doses Of Dimebon (Latrepirdine) In Healthy Recreational Polydrug Users" }, "statusModule": { "statusVerifiedDate": "2013-02", "overallStatus": "COMPLETED", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2009-10" }, "primaryCompletionDateStruct": { "date": "2010-02", "type": "ACTUAL" }, "completionDateStruct": { "date": "2010-02", "type": "ACTUAL" }, "studyFirstSubmitDate": "2009-09-10", "studyFirstSubmitQcDate": "2009-09-10", "studyFirstPostDateStruct": { "date": "2009-09-11", "type": "ESTIMATED" }, "resultsFirstSubmitDate": "2012-12-03", "resultsFirstSubmitQcDate": "2013-02-20", "resultsFirstPostDateStruct": { "date": "2013-04-02", "type": "ESTIMATED" }, "lastUpdateSubmitDate": "2013-02-20", "lastUpdatePostDateStruct": { "date": "2013-04-02", "type": "ESTIMATED" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR" }, "leadSponsor": { "name": "Pfizer", "class": "INDUSTRY" }, "collaborators": [ { "name": "Medivation, Inc.", "class": "INDUSTRY" } ] }, "oversightModule": { "oversightHasDmc": false }, "descriptionModule": { "briefSummary": "Dimebon will not exhibit abuse potential when compared to placebo or a positive control (alprazolam).", "detailedDescription": "The main purpose for this study is to determine whether dimebon exhibits abuse potential." }, "conditionsModule": { "conditions": [ "Alzheimer's Disease", "Huntington's Disease" ], "keywords": [ "oral single-dose 6-way crossover recreational drug users abuse potential pharmacodynamics safety" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "PHASE1" ], "designInfo": { "allocation": "RANDOMIZED", "interventionModel": "CROSSOVER", "maskingInfo": { "masking": "DOUBLE", "whoMasked": [ "PARTICIPANT", "INVESTIGATOR" ] } }, "enrollmentInfo": { "count": 36, "type": "ACTUAL" } }, "armsInterventionsModule": { "armGroups": [ { "label": "dimebon 20 mg", "type": "EXPERIMENTAL", "interventionNames": [ "Drug: dimebon" ] }, { "label": "dimebon 40 mg", "type": "EXPERIMENTAL", "interventionNames": [ "Drug: dimebon" ] }, { "label": "dimebon 60 mg", "type": "EXPERIMENTAL", "interventionNames": [ "Drug: dimebon" ] }, { "label": "placebo", "type": "PLACEBO_COMPARATOR", "interventionNames": [ "Drug: placebo" ] }, { "label": "alprazolam 1 mg", "type": "ACTIVE_COMPARATOR", "interventionNames": [ "Drug: alprazolam" ] }, { "label": "alprazolam 3 mg", "type": "ACTIVE_COMPARATOR", "interventionNames": [ "Drug: alprazolam" ] } ], "interventions": [ { "type": "DRUG", "name": "dimebon", "description": "Oral tablet; 20 mg dimebon, single dose", "armGroupLabels": [ "dimebon 20 mg" ] }, { "type": "DRUG", "name": "dimebon", "description": "Oral tablet; 40 mg dimebon, single dose", "armGroupLabels": [ "dimebon 40 mg" ] }, { "type": "DRUG", "name": "dimebon", "description": "Oral tablet; 60 mg dimebon, single dose", "armGroupLabels": [ "dimebon 60 mg" ] }, { "type": "DRUG", "name": "placebo", "description": "Oral tablet or capsule; placebo, single dose", "armGroupLabels": [ "placebo" ] }, { "type": "DRUG", "name": "alprazolam", "description": "Oral capsule; 1 mg alprazolam, single dose", "armGroupLabels": [ "alprazolam 1 mg" ] }, { "type": "DRUG", "name": "alprazolam", "description": "Oral capsule; 3 mg alprazolam, single dose", "armGroupLabels": [ "alprazolam 3 mg" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)", "description": "Drug liking VAS is one of the measures of balance of effects that assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar visual analogue scale (VAS) anchored in the center with a neutral anchor of \"neither like nor dislike\" (score of 50 mm), on the left with \"strong disliking\" (score of 0 mm) and on the right with \"strong liking\" (score of 100 mm).\n\nEmax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose.", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)", "description": "Overall drug liking VAS is one of the measures of balance of effects that assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carryover effects). A 100 mm bipolar VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = \"strong disliking\", 50 mm= \"neither like nor dislike\", and 100 mm= \"strong liking\").\n\nEmax is the largest effect score between 6 to 24 hours post-dose. Emin is the smallest effect score between 6 to 24 hours post-dose.", "timeFrame": "6, 12, 24 hours post-dose" }, { "measure": "Balance of Effects- Take Drug Again VAS: Peak Effect (Maximum Effect [Emax])", "description": "Take drug again VAS is one of the measures of balance of effects. It is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm bipolar VAS with score ranging from 0 mm to 100 mm (score of 0 mm = \"definitely not\", 50 mm = \"do not care\", and 100 mm = \"definitely so\").\n\nEmax is largest effect score between 6 hours to 24 hours.", "timeFrame": "6, 12, 24 hours post-dose" }, { "measure": "Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)", "description": "Good and Bad effects VAS is one of the measures of balance of effects that assesses the effect experienced by the participant on a 100 mm bipolar VAS, anchored in the center with a neutral anchor of neither good nor bad effects (score of 50 mm), on the left with bad effects(score of 0 mm) and on the right with good effects (score of 100 mm).\n\nEmax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose.", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Balance of Effects- Subjective Drug Value (SDV): Maximum Effect (Emax)", "description": "SDV is one of measures of balance of effects. It is a proxy measure of reinforcing efficacy that involves a series of independent, theoretical forced choices between drug administered and different monetary values. Participants were asked to choose between receiving another dose of same drug or an envelope containing specified amount of money, but they did not receive drug or money as described. Possible score range from 0.25 to 50. Higher score range indicates higher SDV. Emax: largest effect score between 6-24 hours post-dose.", "timeFrame": "6, 12, 24 hrs post-dose" }, { "measure": "Positive Effects- Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG): Maximum Effect (Emax)", "description": "ARCI (MBG) is one of the measures of positive effects. It is a set of 16 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to the scoring direction. Score range: 0 to 16, higher score indicated positive effects. Emax: largest effect score between 0 to 24 hours post-dose.", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 12, 24 hours post-dose" }, { "measure": "Positive Effects- Good Drug Effects: Peak Effect (Maximum Effect [Emax])", "description": "Good drug effects VAS is one of the measures of positive effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so).\n\nEmax is the largest effect score between 0.5 to 24 hours post-dose.", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Positive Effects- High VAS: Peak Effect (Maximum Effect [Emax])", "description": "High VAS is one of the measures of positive effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so).\n\nEmax is largest effect score between 0 to 24 hours.", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Negative Effects- Bad Drug Effects: Peak Effect (Maximum Effect [Emax])", "description": "Bad effects VAS is one of the measures of negative effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so).\n\nEmax is largest effect score between 0.5 to 24 hrs.", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Negative Effects- Addiction Research Center Inventory (ARCI) Lysergic Acid Diethylamide (LSD): Maximum Effect (Emax)", "description": "ARCI (LSD) is one of the measures of negative effects. It is a set of 14 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to scoring direction. Score range: 0 to 14, higher score indicated higher negative effects. Emax: largest effect score between 0 to 24 hours post-dose.", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Sedative Effects- Addiction Research Center Inventory (ARCI) Pentobarbital Chlorpromazine Group (PCAG): Maximum Effect (Emax)", "description": "ARCI (PCAG) is one of the measures of sedative effects. It is a set of 15 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when answer is opposite to scoring direction. Score range: 0 to 15, higher score indicated higher sedative effects. Emax: largest effect score between 0 to 24 hours post-dose.", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Sedative Effects- Alertness/Drowsiness: Minimum Effect (Emin)", "description": "Alertness/Drowsiness VAS is one of the measures of sedative effects. It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of \"neither drowsy nor alert\" (score of 50 mm), on the left with \"very drowsy\" (score of 0 mm) and on the right with \"very alert\" (score of 100 mm). Emin is the smallest effect score between 0 to 24 hours post-dose.", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Other Subjective Effects- Any Drug Effects: Peak Effect (Maximum Effect [Emax])", "description": "Any drug effects VAS is one of the measures of other subjective effects. It assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is the largest effect score between 0.5 to 24 hours post-dose.", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Other Subjective Effects- Drug Similarity", "description": "Drug similarity VAS is one of the measures of other subjective effects. It assesses the similarity of the drug recently received by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= not at all similar) to 'extremely' (score of 100 mm= very similar). Recently received drugs were compared with placebo, benzodiazepines, codeine/morphine, Tetrahydrocannabinol (THC), pseudoephedrine.", "timeFrame": "12 hours post-dose" }, { "measure": "Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin)", "description": "ARCI (BG) is measure of other subjective effects. It is a set of 13 questions in which each question contributes to total score. Participants select 'False' / 'True' for response. One point given for each response that agrees with scoring direction, true items receive score of 1 if answer 'True', false items receive score of 1 if answer 'False'. No points if answer is opposite to scoring direction. Score range: 0 to 13, higher score indicated higher other subjective effects. Emax: largest effect score between 0 - 24 hours post-dose. Emin: smallest effect score between 0 - 24 hours post-dose.", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria:\n\n* Healthy male and/or female subjects between the ages of 18 and 55 years.\n* Recreational polydrug user with a history of CNS depressant use.\n\nExclusion Criteria:\n\n* History of clinically significant neurologic condition(s), such as seizures, convulsions, epilepsy, or significant head injury, as judged by the investigator or designee.\n* A known history of hypersensitivity or previous intolerance to dimebon or other antihistamines.\n* Self-reported history of drug or alcohol dependence (except nicotine or caffeine) in the 2 years prior to screening, or drug or alcohol dependence as defined by the (DSM-IV-TR) in 12 months prior to screening, including subjects who have ever been in a substance rehabilitation program (other than treatment for smoking cessation).\n* History of clinically significant psychiatric disorder(s), as judged by the investigator or qualified designee.", "healthyVolunteers": false, "sex": "ALL", "minimumAge": "18 Years", "maximumAge": "55 Years", "stdAges": [ "ADULT" ] }, "contactsLocationsModule": { "overallOfficials": [ { "name": "Pfizer CT.gov Call Center", "affiliation": "Pfizer", "role": "STUDY_DIRECTOR" } ] }, "referencesModule": { "seeAlsoLinks": [ { "label": "To obtain contact information for a study center near you, click here.", "url": "https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1451037&StudyName=A%20Study%20To%20Evaluate%20The%20Abuse%20Potential%20Of%20Single%20Oral%20Doses%20Of%20Dimebon%20%28Latrepirdine%29%20In%20Healthy%20Recreational%20Polydrug%20Users" } ] } }, "resultsSection": { "participantFlowModule": { "groups": [ { "id": "FG000", "title": "PBO, ALP 1mg, DIM 60 mg, ALP 3 mg, DIM 40 mg, DIM 20 mg", "description": "Placebo (PBO) matched to 3 alprazolam (ALP) capsules and placebo matched to 3 dimebon (DIM) tablets on Day 1 in the first intervention period; followed by alprazolam 1 milligram (mg) capsule, placebo matched to 2 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the second intervention period; then dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the third intervention period; then alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in fourth intervention period; then dimebon 40 mg tablets and placebo matched to dimebon tablet and placebo matched to 3 alprazolam capsules on Day 1 in the fifth intervention period; and dimebon 20 mg tablet, placebo matched to 2 dimebon tablets and placebo matched to 3 alprazolam capsules on Day 1 in the sixth intervention period. A washout period of at least 7 days was maintained between each dose." }, { "id": "FG001", "title": "ALP 1 mg, ALP 3 mg, PBO, DIM 20 mg, DIM 60 mg, DIM 40 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the first intervention period; followed by alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in the second intervention period; then placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the third intervention period; then dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 in the fourth intervention period; then dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the fifth intervention period; and dimebon 40 mg tablets, placebo matched to dimebon tablet and placebo matched to 3 alprazolam capsules on Day 1 in the sixth intervention period. A washout period of at least 7 days was maintained between each dose." }, { "id": "FG002", "title": "ALP 3 mg, DIM 20 mg, ALP 1 mg, DIM 40 mg, PBO, DIM 60 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in the first intervention period; followed by dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 in the second intervention period; then alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the third intervention period; then dimebon 40 mg tablets, placebo matched to dimebon tablet and placebo matched to 3 alprazolam capsules on Day 1 in the fourth interventional period; then placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the fifth intervention period; and dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the sixth intervention period. A washout period of 7 days was maintained between each dose." }, { "id": "FG003", "title": "DIM 20 mg, DIM 40 mg, ALP 3 mg, DIM 60 mg, ALP 1 mg, PBO", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets and placebo matched to 3 alprazolam capsules on Day 1 in the first intervention period; followed by dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 in the second intervention period; then alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in the third intervention period; then dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the fourth intervention period; then alprazolam 1mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 in the fifth intervention period; and placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the sixth intervention period. A washout period of at least 7 days was maintained between each dose." }, { "id": "FG004", "title": "DIM 40 mg, DIM 60 mg, DIM 20 mg, PBO, ALP 3 mg, ALP 1 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 in the first intervention period; followed by dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the second intervention period; then dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 in the third intervention period; then placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the fourth intervention period; then alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in the fifth intervention period; and alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 in the sixth intervention period. A washout period of at least 7 days was maintained between each dose." }, { "id": "FG005", "title": "DIM 60 mg, PBO, DIM 40 mg, ALP 1mg, DIM 20 mg, ALP 3 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the first intervention period; followed by placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the second intervention period; then dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 in the third intervention period; then alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 in the fourth intervention group; then dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 in the fifth intervention period; and alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in the sixth intervention period. A washout period of at least 7 days was maintained between each dose." } ], "periods": [ { "title": "First Intervention Period", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "6" }, { "groupId": "FG001", "numSubjects": "6" }, { "groupId": "FG002", "numSubjects": "6" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "6" }, { "groupId": "FG001", "numSubjects": "6" }, { "groupId": "FG002", "numSubjects": "6" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Washout Period (at Least 7 Days)", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "6" }, { "groupId": "FG001", "numSubjects": "6" }, { "groupId": "FG002", "numSubjects": "6" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "6" }, { "groupId": "FG001", "numSubjects": "6" }, { "groupId": "FG002", "numSubjects": "6" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Second Intervention Period", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "6" }, { "groupId": "FG001", "numSubjects": "6" }, { "groupId": "FG002", "numSubjects": "6" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "2" }, { "groupId": "FG001", "numSubjects": "1" }, { "groupId": "FG002", "numSubjects": "1" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ], "dropWithdraws": [ { "type": "Adverse Event", "reasons": [ { "groupId": "FG000", "numSubjects": "2" }, { "groupId": "FG001", "numSubjects": "1" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] }, { "type": "Withdrawal by Subject", "reasons": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "1" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Washout Period (at Least 7 Days)", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Third Intervention Period", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Washout Period (at Least 7 Days)", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Fourth Intervention Period", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "1" }, { "groupId": "FG003", "numSubjects": "1" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ], "dropWithdraws": [ { "type": "Withdrawal by Subject", "reasons": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "1" }, { "groupId": "FG003", "numSubjects": "1" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Washout Period (at Least 7 Days)", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Fifth Intervention Period", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "5" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "1" }, { "groupId": "FG005", "numSubjects": "0" } ] } ], "dropWithdraws": [ { "type": "Withdrawal by Subject", "reasons": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "1" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Washout Period (at Least 7 Days)", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "5" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "5" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Sixth Intervention Period", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "5" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "5" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] } ] }, "baselineCharacteristicsModule": { "groups": [ { "id": "BG000", "title": "Entire Study Population", "description": "Includes participants randomized to receive placebo first, alprazolam 1 mg first, alprazolam 3 mg first, dimebon 20 mg first, dimebon 40 mg first and dimebon 60 mg first." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "BG000", "value": "36" } ] } ], "measures": [ { "title": "Age Continuous", "paramType": "MEAN", "dispersionType": "STANDARD_DEVIATION", "unitOfMeasure": "Years", "classes": [ { "categories": [ { "measurements": [ { "groupId": "BG000", "value": "35.4", "spread": "9.7" } ] } ] } ] }, { "title": "Sex: Female, Male", "paramType": "COUNT_OF_PARTICIPANTS", "unitOfMeasure": "Participants", "classes": [ { "categories": [ { "title": "Female", "measurements": [ { "groupId": "BG000", "value": "8" } ] }, { "title": "Male", "measurements": [ { "groupId": "BG000", "value": "28" } ] } ] } ] }, { "title": "Body Mass Index", "paramType": "MEAN", "dispersionType": "STANDARD_DEVIATION", "unitOfMeasure": "kilogram/square meter (kg/m^2)", "classes": [ { "categories": [ { "measurements": [ { "groupId": "BG000", "value": "24.6", "spread": "3.4" } ] } ] } ] } ] }, "outcomeMeasuresModule": { "outcomeMeasures": [ { "type": "PRIMARY", "title": "Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)", "description": "Drug liking VAS is one of the measures of balance of effects that assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar visual analogue scale (VAS) anchored in the center with a neutral anchor of \"neither like nor dislike\" (score of 50 mm), on the left with \"strong disliking\" (score of 0 mm) and on the right with \"strong liking\" (score of 100 mm).\n\nEmax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis population included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "title": "Emax", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "57.8", "spread": "10.03" }, { "groupId": "OG001", "value": "78.6", "spread": "17.53" }, { "groupId": "OG002", "value": "82.2", "spread": "14.55" }, { "groupId": "OG003", "value": "57.2", "spread": "11.76" }, { "groupId": "OG004", "value": "55.8", "spread": "9.41" }, { "groupId": "OG005", "value": "58.5", "spread": "12.54" } ] } ] }, { "title": "Emin", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "47.0", "spread": "9.38" }, { "groupId": "OG001", "value": "45.4", "spread": "11.21" }, { "groupId": "OG002", "value": "37.4", "spread": "17.32" }, { "groupId": "OG003", "value": "48.4", "spread": "8.89" }, { "groupId": "OG004", "value": "49.0", "spread": "3.59" }, { "groupId": "OG005", "value": "46.5", "spread": "10.44" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95 percent (%) Confidence Interval (CI) were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with Restricted Maximum Likelihood (REML) estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "20.8096", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "15.0866", "ciUpperLimit": "26.5327" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "24.4625", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "18.7321", "ciUpperLimit": "30.1929" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8428", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.5792", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-6.3385", "ciUpperLimit": "5.1800" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4957", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.9993", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-7.7832", "ciUpperLimit": "3.7845" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.7431", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.9683", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.8567", "ciUpperLimit": "6.7932" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-21.3889", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-27.1044", "ciUpperLimit": "-15.6734" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-22.8090", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-28.5584", "ciUpperLimit": "-17.0596" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Median Difference (Final Values)", "paramValue": "-19.8414", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-25.6435", "ciUpperLimit": "-14.0393" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-25.0418", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-30.6705", "ciUpperLimit": "-19.4130" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-26.4618", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-32.1455", "ciUpperLimit": "-20.7782" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-23.4943", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-29.2440", "ciUpperLimit": "-17.7445" }, { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5720", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.4538", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-6.5274", "ciUpperLimit": "3.6198" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0006", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-8.9938", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-14.0695", "ciUpperLimit": "-3.9180" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4704", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "1.8686", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-3.2342", "ciUpperLimit": "6.9713" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4255", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "2.0725", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-3.0533", "ciUpperLimit": "7.1984" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8959", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.3425", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-5.5053", "ciUpperLimit": "4.8204" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.1967", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "3.3224", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.7402", "ciUpperLimit": "8.3850" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.1733", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "3.5264", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.5676", "ciUpperLimit": "8.6203" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6697", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "1.1113", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.0285", "ciUpperLimit": "6.2512" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "10.8623", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "5.8712", "ciUpperLimit": "15.8535" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "11.0663", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "6.0281", "ciUpperLimit": "16.1045" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0010", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "8.6513", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "3.5552", "ciUpperLimit": "13.7474" } ] }, { "type": "PRIMARY", "title": "Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)", "description": "Overall drug liking VAS is one of the measures of balance of effects that assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carryover effects). A 100 mm bipolar VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = \"strong disliking\", 50 mm= \"neither like nor dislike\", and 100 mm= \"strong liking\").\n\nEmax is the largest effect score between 6 to 24 hours post-dose. Emin is the smallest effect score between 6 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "6, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to 1 dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "title": "Emax", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "57.8", "spread": "14.31" }, { "groupId": "OG001", "value": "74.6", "spread": "18.99" }, { "groupId": "OG002", "value": "78.0", "spread": "15.50" }, { "groupId": "OG003", "value": "56.5", "spread": "11.44" }, { "groupId": "OG004", "value": "55.4", "spread": "11.29" }, { "groupId": "OG005", "value": "58.1", "spread": "12.52" } ] } ] }, { "title": "Emin", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "52.5", "spread": "9.13" }, { "groupId": "OG001", "value": "64.5", "spread": "20.17" }, { "groupId": "OG002", "value": "62.6", "spread": "18.13" }, { "groupId": "OG003", "value": "48.2", "spread": "15.96" }, { "groupId": "OG004", "value": "52.0", "spread": "8.75" }, { "groupId": "OG005", "value": "51.1", "spread": "8.94" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "16.6388", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "10.5727", "ciUpperLimit": "22.7049" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "19.8432", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "13.7627", "ciUpperLimit": "25.9238" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6029", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.6121", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-7.7209", "ciUpperLimit": "4.4967" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.3477", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-2.9241", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-9.0571", "ciUpperLimit": "3.2089" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.9769", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.0908", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-6.0850", "ciUpperLimit": "6.2667" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-18.2509", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-24.3155", "ciUpperLimit": "-12.1864" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-19.5629", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-25.6616", "ciUpperLimit": "-13.4642" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-16.5480", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-22.7036", "ciUpperLimit": "-10.3923" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-21.4554", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-27.4199", "ciUpperLimit": "-15.4908" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "pValueComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "statisticalMethod": "Mixed Models Analysis", "paramType": "Mean Difference (Final Values)", "paramValue": "-22.7673", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-28.7925", "ciUpperLimit": "-16.7422" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-19.7524", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-25.8485", "ciUpperLimit": "-13.6563" }, { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0006", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "12.0888", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "5.3225", "ciUpperLimit": "18.8551" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0038", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "10.0768", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "3.3132", "ciUpperLimit": "16.8403" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.2257", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.1875", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-10.9890", "ciUpperLimit": "2.6139" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8042", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.8589", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-7.6927", "ciUpperLimit": "5.9750" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6399", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.6335", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-8.5177", "ciUpperLimit": "5.2506" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-16.2763", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-23.0228", "ciUpperLimit": "-9.5229" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0002", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-12.9477", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-19.7374", "ciUpperLimit": "-6.1580" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-13.7223", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-20.5720", "ciUpperLimit": "-6.8727" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-14.2643", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-20.9226", "ciUpperLimit": "-7.6060" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0016", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-10.9356", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-17.6548", "ciUpperLimit": "-4.2165" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0008", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-11.7103", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-18.5055", "ciUpperLimit": "-4.9151" } ] }, { "type": "PRIMARY", "title": "Balance of Effects- Take Drug Again VAS: Peak Effect (Maximum Effect [Emax])", "description": "Take drug again VAS is one of the measures of balance of effects. It is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm bipolar VAS with score ranging from 0 mm to 100 mm (score of 0 mm = \"definitely not\", 50 mm = \"do not care\", and 100 mm = \"definitely so\").\n\nEmax is largest effect score between 6 hours to 24 hours.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "6, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam tablets, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "53.9", "spread": "22.30" }, { "groupId": "OG001", "value": "77.5", "spread": "22.26" }, { "groupId": "OG002", "value": "83.2", "spread": "15.99" }, { "groupId": "OG003", "value": "47.6", "spread": "28.66" }, { "groupId": "OG004", "value": "50.4", "spread": "26.23" }, { "groupId": "OG005", "value": "52.5", "spread": "25.66" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "24.0090", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "13.7265", "ciUpperLimit": "34.2916" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "29.4156", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "19.1160", "ciUpperLimit": "39.7151" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.2239", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-6.3979", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-16.7479", "ciUpperLimit": "3.9521" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4326", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.1396", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-14.5328", "ciUpperLimit": "6.2526" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.7447", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.7283", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-12.1950", "ciUpperLimit": "8.7383" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-30.4069", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-40.6795", "ciUpperLimit": "-20.1343" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-28.1487", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-38.4812", "ciUpperLimit": "-17.8161" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-25.7374", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-36.1651", "ciUpperLimit": "-15.3096" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-35.8134", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-45.9257", "ciUpperLimit": "-25.7012" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-33.5552", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-43.7675", "ciUpperLimit": "-23.3429" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-31.1439", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-41.4754", "ciUpperLimit": "-20.8124" } ] }, { "type": "PRIMARY", "title": "Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)", "description": "Good and Bad effects VAS is one of the measures of balance of effects that assesses the effect experienced by the participant on a 100 mm bipolar VAS, anchored in the center with a neutral anchor of neither good nor bad effects (score of 50 mm), on the left with bad effects(score of 0 mm) and on the right with good effects (score of 100 mm).\n\nEmax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsule, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "title": "Emax", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "56.2", "spread": "7.15" }, { "groupId": "OG001", "value": "80.9", "spread": "15.93" }, { "groupId": "OG002", "value": "81.9", "spread": "14.40" }, { "groupId": "OG003", "value": "57.9", "spread": "13.53" }, { "groupId": "OG004", "value": "56.6", "spread": "11.21" }, { "groupId": "OG005", "value": "57.6", "spread": "8.92" } ] } ] }, { "title": "Emin", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "48.0", "spread": "8.83" }, { "groupId": "OG001", "value": "46.7", "spread": "10.70" }, { "groupId": "OG002", "value": "38.6", "spread": "15.76" }, { "groupId": "OG003", "value": "49.3", "spread": "2.79" }, { "groupId": "OG004", "value": "48.3", "spread": "8.82" }, { "groupId": "OG005", "value": "48.9", "spread": "3.03" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "24.8779", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "19.5658", "ciUpperLimit": "30.1899" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "25.9857", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "20.6670", "ciUpperLimit": "31.3043" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4489", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "2.0544", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-3.2911", "ciUpperLimit": "7.3998" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8329", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.5743", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.7941", "ciUpperLimit": "5.9427" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5387", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "1.6863", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-3.7203", "ciUpperLimit": "7.0929" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-22.8235", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-28.1283", "ciUpperLimit": "-17.5187" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-24.3036", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-29.6400", "ciUpperLimit": "-18.9672" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-23.1916", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-28.5768", "ciUpperLimit": "-17.8064" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-23.9313", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-29.1559", "ciUpperLimit": "-18.7066" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-25.4114", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-30.6869", "ciUpperLimit": "-20.1358" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-24.2994", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-29.6361", "ciUpperLimit": "-18.9626" }, { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5349", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.4301", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-5.9725", "ciUpperLimit": "3.1123" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-9.1367", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-13.6684", "ciUpperLimit": "-4.6050" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5637", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "1.3357", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-3.2244", "ciUpperLimit": "5.8958" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8612", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.4065", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.1779", "ciUpperLimit": "4.9909" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6954", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.9175", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-3.7022", "ciUpperLimit": "5.5373" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.2287", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "2.7658", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.7552", "ciUpperLimit": "7.2868" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4267", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "1.8366", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-2.7158", "ciUpperLimit": "6.3890" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.3140", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "2.3476", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-2.2429", "ciUpperLimit": "6.9381" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "10.4724", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "5.9992", "ciUpperLimit": "14.9456" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "9.5432", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "5.0320", "ciUpperLimit": "14.0544" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "10.0542", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "5.4940", "ciUpperLimit": "14.6144" } ] }, { "type": "PRIMARY", "title": "Balance of Effects- Subjective Drug Value (SDV): Maximum Effect (Emax)", "description": "SDV is one of measures of balance of effects. It is a proxy measure of reinforcing efficacy that involves a series of independent, theoretical forced choices between drug administered and different monetary values. Participants were asked to choose between receiving another dose of same drug or an envelope containing specified amount of money, but they did not receive drug or money as described. Possible score range from 0.25 to 50. Higher score range indicates higher SDV. Emax: largest effect score between 6-24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "Dollar", "timeFrame": "6, 12, 24 hrs post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsule, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "4.805", "spread": "9.7833" }, { "groupId": "OG001", "value": "19.621", "spread": "16.2519" }, { "groupId": "OG002", "value": "25.551", "spread": "17.0192" }, { "groupId": "OG003", "value": "6.098", "spread": "12.3269" }, { "groupId": "OG004", "value": "3.836", "spread": "6.5345" }, { "groupId": "OG005", "value": "4.573", "spread": "9.8211" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "14.4728", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "9.4718", "ciUpperLimit": "19.4737" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.9348", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.2088", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.8289", "ciUpperLimit": "5.2466" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5009", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.7271", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-6.7841", "ciUpperLimit": "3.3299" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8975", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.3325", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-5.4245", "ciUpperLimit": "4.7595" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-14.2640", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-19.2660", "ciUpperLimit": "-9.2619" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-16.1999", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-21.2294", "ciUpperLimit": "-11.1704" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-14.8053", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-19.8822", "ciUpperLimit": "-9.7283" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-19.5195", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-24.4361", "ciUpperLimit": "-14.6030" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-21.4555", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-26.4230", "ciUpperLimit": "-16.4880" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-20.0609", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-25.0872", "ciUpperLimit": "-15.0345" } ] }, { "type": "PRIMARY", "title": "Positive Effects- Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG): Maximum Effect (Emax)", "description": "ARCI (MBG) is one of the measures of positive effects. It is a set of 16 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to the scoring direction. Score range: 0 to 16, higher score indicated positive effects. Emax: largest effect score between 0 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "Units on scale", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "3.2", "spread": "2.51" }, { "groupId": "OG001", "value": "6.2", "spread": "4.16" }, { "groupId": "OG002", "value": "8.1", "spread": "4.37" }, { "groupId": "OG003", "value": "3.5", "spread": "3.10" }, { "groupId": "OG004", "value": "3.6", "spread": "3.22" }, { "groupId": "OG005", "value": "3.5", "spread": "2.87" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "3.1634", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "1.9014", "ciUpperLimit": "4.4254" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "4.6706", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "3.4066", "ciUpperLimit": "5.9346" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8184", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.1478", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.1217", "ciUpperLimit": "1.4173" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.7324", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.2211", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.0540", "ciUpperLimit": "1.4963" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8844", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.0946", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.1898", "ciUpperLimit": "1.3791" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.0156", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.2754", "ciUpperLimit": "-1.7558" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-2.9423", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.2101", "ciUpperLimit": "-1.6745" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.0688", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.3484", "ciUpperLimit": "-1.7891" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.5228", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-5.7651", "ciUpperLimit": "-3.2805" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.4495", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-5.7031", "ciUpperLimit": "-3.1959" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.5760", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-5.8438", "ciUpperLimit": "-3.3081" } ] }, { "type": "PRIMARY", "title": "Positive Effects- Good Drug Effects: Peak Effect (Maximum Effect [Emax])", "description": "Good drug effects VAS is one of the measures of positive effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so).\n\nEmax is the largest effect score between 0.5 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "35.2", "spread": "31.94" }, { "groupId": "OG001", "value": "81.2", "spread": "18.16" }, { "groupId": "OG002", "value": "84.7", "spread": "14.32" }, { "groupId": "OG003", "value": "34.4", "spread": "32.87" }, { "groupId": "OG004", "value": "32.0", "spread": "32.33" }, { "groupId": "OG005", "value": "39.7", "spread": "31.34" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "46.0798", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "34.0453", "ciUpperLimit": "58.1142" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "49.8771", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "37.8247", "ciUpperLimit": "61.9295" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.9248", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.5797", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-12.6918", "ciUpperLimit": "11.5325" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5857", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.3632", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-15.5264", "ciUpperLimit": "8.8000" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4768", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "4.4225", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-7.8270", "ciUpperLimit": "16.6719" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-46.6594", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-58.6804", "ciUpperLimit": "-34.6385" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-49.4430", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-61.5346", "ciUpperLimit": "-37.3514" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-41.6573", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-53.8600", "ciUpperLimit": "-29.4546" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-50.4567", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-62.2925", "ciUpperLimit": "-38.6210" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-53.2403", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-65.1923", "ciUpperLimit": "-41.2882" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-45.4546", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-57.5459", "ciUpperLimit": "-33.3633" } ] }, { "type": "PRIMARY", "title": "Positive Effects- High VAS: Peak Effect (Maximum Effect [Emax])", "description": "High VAS is one of the measures of positive effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so).\n\nEmax is largest effect score between 0 to 24 hours.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "30.4", "spread": "30.22" }, { "groupId": "OG001", "value": "77.1", "spread": "24.93" }, { "groupId": "OG002", "value": "88.0", "spread": "13.13" }, { "groupId": "OG003", "value": "25.9", "spread": "28.39" }, { "groupId": "OG004", "value": "29.9", "spread": "33.07" }, { "groupId": "OG005", "value": "35.8", "spread": "32.44" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-62.5926", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-74.5881", "ciUpperLimit": "-50.5971" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-58.6906", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-70.7965", "ciUpperLimit": "-46.5847" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-52.3018", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-64.5427", "ciUpperLimit": "-40.0609" } ] }, { "type": "PRIMARY", "title": "Negative Effects- Bad Drug Effects: Peak Effect (Maximum Effect [Emax])", "description": "Bad effects VAS is one of the measures of negative effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so).\n\nEmax is largest effect score between 0.5 to 24 hrs.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "17.2", "spread": "24.38" }, { "groupId": "OG001", "value": "33.9", "spread": "29.88" }, { "groupId": "OG002", "value": "44.6", "spread": "23.58" }, { "groupId": "OG003", "value": "15.9", "spread": "25.38" }, { "groupId": "OG004", "value": "16.8", "spread": "24.27" }, { "groupId": "OG005", "value": "19.7", "spread": "25.47" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8254", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.1425", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-11.3591", "ciUpperLimit": "9.0742" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0028", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-15.7134", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-25.9136", "ciUpperLimit": "-5.5132" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0135", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-13.0325", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-23.3295", "ciUpperLimit": "-2.7355" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-29.1396", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-39.1071", "ciUpperLimit": "-19.1721" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-27.2502", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-37.3224", "ciUpperLimit": "-17.1780" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-24.5693", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-34.7614", "ciUpperLimit": "-14.3772" } ] }, { "type": "PRIMARY", "title": "Negative Effects- Addiction Research Center Inventory (ARCI) Lysergic Acid Diethylamide (LSD): Maximum Effect (Emax)", "description": "ARCI (LSD) is one of the measures of negative effects. It is a set of 14 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to scoring direction. Score range: 0 to 14, higher score indicated higher negative effects. Emax: largest effect score between 0 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "Units on Scale", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "3.8", "spread": "1.83" }, { "groupId": "OG001", "value": "4.9", "spread": "1.76" }, { "groupId": "OG002", "value": "7.0", "spread": "2.57" }, { "groupId": "OG003", "value": "3.8", "spread": "1.42" }, { "groupId": "OG004", "value": "3.8", "spread": "1.50" }, { "groupId": "OG005", "value": "3.6", "spread": "1.58" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.3347", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.3418", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-0.3559", "ciUpperLimit": "1.0396" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.3678", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.3208", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-0.3808", "ciUpperLimit": "1.0225" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.9197", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.0360", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-0.6686", "ciUpperLimit": "0.7406" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0099", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.9117", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.6013", "ciUpperLimit": "-0.2220" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0008", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.2175", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.9171", "ciUpperLimit": "-0.5178" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.1802", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-3.8656", "ciUpperLimit": "-2.4947" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.4650", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.1583", "ciUpperLimit": "-2.7717" } ] }, { "type": "PRIMARY", "title": "Sedative Effects- Addiction Research Center Inventory (ARCI) Pentobarbital Chlorpromazine Group (PCAG): Maximum Effect (Emax)", "description": "ARCI (PCAG) is one of the measures of sedative effects. It is a set of 15 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when answer is opposite to scoring direction. Score range: 0 to 15, higher score indicated higher sedative effects. Emax: largest effect score between 0 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "Units on Scale", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "4.7", "spread": "2.57" }, { "groupId": "OG001", "value": "9.9", "spread": "3.51" }, { "groupId": "OG002", "value": "11.5", "spread": "2.48" }, { "groupId": "OG003", "value": "5.3", "spread": "3.26" }, { "groupId": "OG004", "value": "5.5", "spread": "2.75" }, { "groupId": "OG005", "value": "5.5", "spread": "2.75" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.3571", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-5.5887", "ciUpperLimit": "-3.1255" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-6.2437", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-7.4397", "ciUpperLimit": "-5.0477" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-5.9611", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-7.1812", "ciUpperLimit": "-4.7410" } ] }, { "type": "PRIMARY", "title": "Sedative Effects- Alertness/Drowsiness: Minimum Effect (Emin)", "description": "Alertness/Drowsiness VAS is one of the measures of sedative effects. It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of \"neither drowsy nor alert\" (score of 50 mm), on the left with \"very drowsy\" (score of 0 mm) and on the right with \"very alert\" (score of 100 mm). Emin is the smallest effect score between 0 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "42.1", "spread": "18.77" }, { "groupId": "OG001", "value": "14.4", "spread": "17.83" }, { "groupId": "OG002", "value": "8.6", "spread": "9.36" }, { "groupId": "OG003", "value": "42.9", "spread": "21.32" }, { "groupId": "OG004", "value": "37.7", "spread": "21.32" }, { "groupId": "OG005", "value": "38.5", "spread": "16.10" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-26.6205", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-33.1192", "ciUpperLimit": "-20.1219" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-32.5724", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-39.1073", "ciUpperLimit": "-26.0375" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5685", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "1.8966", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.6607", "ciUpperLimit": "8.4540" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.2848", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.5761", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-10.1590", "ciUpperLimit": "3.0068" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.3440", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.1754", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-9.7855", "ciUpperLimit": "3.4347" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "28.5172", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "22.0454", "ciUpperLimit": "34.9890" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "23.0445", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "16.5383", "ciUpperLimit": "29.5506" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "23.4452", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "16.8772", "ciUpperLimit": "30.0131" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "34.4690", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "28.1136", "ciUpperLimit": "40.8244" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "28.9963", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "22.5734", "ciUpperLimit": "35.4192" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "29.3970", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "22.8946", "ciUpperLimit": "35.8994" } ] }, { "type": "PRIMARY", "title": "Other Subjective Effects- Any Drug Effects: Peak Effect (Maximum Effect [Emax])", "description": "Any drug effects VAS is one of the measures of other subjective effects. It assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is the largest effect score between 0.5 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "37.2", "spread": "35.30" }, { "groupId": "OG001", "value": "84.0", "spread": "23.27" }, { "groupId": "OG002", "value": "88.7", "spread": "11.12" }, { "groupId": "OG003", "value": "37.5", "spread": "35.91" }, { "groupId": "OG004", "value": "33.4", "spread": "34.54" }, { "groupId": "OG005", "value": "44.4", "spread": "34.44" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "46.6044", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "33.4091", "ciUpperLimit": "59.7996" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "50.7222", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "37.5038", "ciUpperLimit": "63.9407" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.9174", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.6987", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-13.9815", "ciUpperLimit": "12.5840" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5002", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.5629", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-17.9006", "ciUpperLimit": "8.7749" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.3482", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "6.3982", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-7.0337", "ciUpperLimit": "19.8301" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-47.3031", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-60.4869", "ciUpperLimit": "-34.1193" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-51.1672", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-64.4276", "ciUpperLimit": "-37.9069" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-40.2062", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-53.5890", "ciUpperLimit": "-26.8234" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-51.4210", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-64.3974", "ciUpperLimit": "-38.4445" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-55.2851", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-68.3904", "ciUpperLimit": "-42.1798" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-44.3241", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-57.5825", "ciUpperLimit": "-31.0656" } ] }, { "type": "PRIMARY", "title": "Other Subjective Effects- Drug Similarity", "description": "Drug similarity VAS is one of the measures of other subjective effects. It assesses the similarity of the drug recently received by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= not at all similar) to 'extremely' (score of 100 mm= very similar). Recently received drugs were compared with placebo, benzodiazepines, codeine/morphine, Tetrahydrocannabinol (THC), pseudoephedrine.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. 'n' is signifying those participants who were evaluated for this measure for various drugs for similarity in each treatment group.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "12 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "title": "Placebo (n=32, 33, 34, 33, 32, 31)", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "56.3", "spread": "42.65" }, { "groupId": "OG001", "value": "10.2", "spread": "22.20" }, { "groupId": "OG002", "value": "4.0", "spread": "12.27" }, { "groupId": "OG003", "value": "61.4", "spread": "36.34" }, { "groupId": "OG004", "value": "57.8", "spread": "43.15" }, { "groupId": "OG005", "value": "55.7", "spread": "42.15" } ] } ] }, { "title": "Benzodiazepines (n=23, 23, 25, 24, 22, 22)", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "51.0", "spread": "38.99" }, { "groupId": "OG001", "value": "88.6", "spread": "21.87" }, { "groupId": "OG002", "value": "92.7", "spread": "20.66" }, { "groupId": "OG003", "value": "33.0", "spread": "40.56" }, { "groupId": "OG004", "value": "42.6", "spread": "40.81" }, { "groupId": "OG005", "value": "53.0", "spread": "40.45" } ] } ] }, { "title": "Codeine/Morphine (n=20, 20, 23, 22, 20, 20)", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "18.5", "spread": "28.02" }, { "groupId": "OG001", "value": "42.7", "spread": "38.43" }, { "groupId": "OG002", "value": "46.3", "spread": "33.82" }, { "groupId": "OG003", "value": "14.7", "spread": "28.49" }, { "groupId": "OG004", "value": "24.5", "spread": "29.55" }, { "groupId": "OG005", "value": "28.2", "spread": "29.66" } ] } ] }, { "title": "THC (n=32, 33, 34, 33, 32, 31)", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "21.2", "spread": "27.97" }, { "groupId": "OG001", "value": "45.6", "spread": "37.08" }, { "groupId": "OG002", "value": "48.9", "spread": "32.96" }, { "groupId": "OG003", "value": "21.9", "spread": "30.44" }, { "groupId": "OG004", "value": "16.2", "spread": "25.88" }, { "groupId": "OG005", "value": "25.3", "spread": "31.56" } ] } ] }, { "title": "Pseudoephedrine (n=6, 6, 6, 6, 7, 5)", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "21.8", "spread": "33.42" }, { "groupId": "OG001", "value": "21.5", "spread": "27.70" }, { "groupId": "OG002", "value": "66.5", "spread": "12.14" }, { "groupId": "OG003", "value": "31.7", "spread": "35.35" }, { "groupId": "OG004", "value": "30.7", "spread": "28.89" }, { "groupId": "OG005", "value": "33.4", "spread": "26.32" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI was obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-46.3823", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-62.1244", "ciUpperLimit": "-30.6401" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-51.5199", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-67.2633", "ciUpperLimit": "-35.7765" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4524", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "6.0366", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-9.7924", "ciUpperLimit": "21.8657" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.7620", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "2.4423", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-13.4599", "ciUpperLimit": "18.3446" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.9846", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.1573", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-15.8609", "ciUpperLimit": "16.1754" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "52.4189", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "36.7157", "ciUpperLimit": "68.1221" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "48.8246", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "33.0228", "ciUpperLimit": "64.6264" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "46.5395", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "30.5968", "ciUpperLimit": "62.4823" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "57.5565", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "42.0679", "ciUpperLimit": "73.0451" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "53.9622", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "38.3293", "ciUpperLimit": "69.5952" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "51.6772", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "35.8660", "ciUpperLimit": "67.4884" }, { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0003", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "37.4454", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "17.7051", "ciUpperLimit": "57.1857" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "41.6714", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "22.2888", "ciUpperLimit": "61.0540" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0744", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-17.7583", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-37.2956", "ciUpperLimit": "1.7789" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.3458", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-9.5551", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-29.5573", "ciUpperLimit": "10.4471" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.9375", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.7920", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-19.1777", "ciUpperLimit": "20.7616" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-55.2037", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-74.8113", "ciUpperLimit": "-35.5961" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-47.0005", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-67.0020", "ciUpperLimit": "-26.9989" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0004", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-36.6534", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-56.7246", "ciUpperLimit": "-16.5822" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-59.4297", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-78.5162", "ciUpperLimit": "-40.3433" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-51.2265", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-70.8131", "ciUpperLimit": "-31.6399" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-40.8794", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-60.4726", "ciUpperLimit": "-21.2862" }, { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0102", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "23.5197", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "5.7096", "ciUpperLimit": "41.3298" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0021", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "27.7321", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "10.3632", "ciUpperLimit": "45.1011" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5935", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.7334", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-22.2807", "ciUpperLimit": "12.8140" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6945", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "3.5486", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-14.3397", "ciUpperLimit": "21.4370" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4177", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "7.2936", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-10.4975", "ciUpperLimit": "25.0847" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0019", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-28.2531", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-45.8020", "ciUpperLimit": "-10.7042" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0299", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-19.9711", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-37.9541", "ciUpperLimit": "-1.9880" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0759", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-16.2261", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-34.1785", "ciUpperLimit": "1.7264" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0002", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-32.4655", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-49.2278", "ciUpperLimit": "-15.7032" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0069", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-24.1835", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-41.5832", "ciUpperLimit": "-6.7838" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0222", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-20.4385", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-37.8861", "ciUpperLimit": "-2.9910" }, { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0002", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "24.5890", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "12.0126", "ciUpperLimit": "37.1654" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "29.1100", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "16.4903", "ciUpperLimit": "41.7298" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6809", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "2.6428", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-10.0309", "ciUpperLimit": "15.3165" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6067", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.3215", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-16.0415", "ciUpperLimit": "9.3985" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.3999", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "5.4722", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-7.3350", "ciUpperLimit": "18.2795" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0007", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-21.9461", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-34.5327", "ciUpperLimit": "-9.3596" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-27.9105", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-40.5640", "ciUpperLimit": "-15.2570" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0036", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-19.1168", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-31.8907", "ciUpperLimit": "-6.3428" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-26.4672", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-38.8298", "ciUpperLimit": "-14.1046" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-32.4315", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-44.9250", "ciUpperLimit": "-19.9380" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0003", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-23.6378", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-36.2802", "ciUpperLimit": "-10.9954" }, { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.9728", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.6675", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-39.7080", "ciUpperLimit": "41.0430" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0246", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "42.7977", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "6.1059", "ciUpperLimit": "79.4894" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.7068", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "7.5411", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-33.7850", "ciUpperLimit": "48.8672" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5492", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "10.7069", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-26.0358", "ciUpperLimit": "47.4496" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5899", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "11.1248", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-31.3098", "ciUpperLimit": "53.5595" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6998", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "6.8736", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-29.8691", "ciUpperLimit": "43.6163" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6187", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "10.0394", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-31.4818", "ciUpperLimit": "51.5606" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5863", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "10.4573", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-29.0355", "ciUpperLimit": "49.9502" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0832", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-35.2566", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-75.6080", "ciUpperLimit": "5.0948" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0827", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-32.0907", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-68.7519", "ciUpperLimit": "4.5704" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.1386", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-31.6728", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-74.5352", "ciUpperLimit": "11.1895" } ] }, { "type": "PRIMARY", "title": "Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin)", "description": "ARCI (BG) is measure of other subjective effects. It is a set of 13 questions in which each question contributes to total score. Participants select 'False' / 'True' for response. One point given for each response that agrees with scoring direction, true items receive score of 1 if answer 'True', false items receive score of 1 if answer 'False'. No points if answer is opposite to scoring direction. Score range: 0 to 13, higher score indicated higher other subjective effects. Emax: largest effect score between 0 - 24 hours post-dose. Emin: smallest effect score between 0 - 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "Units on Scale", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "title": "Emax", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "6.3", "spread": "1.14" }, { "groupId": "OG001", "value": "6.6", "spread": "1.34" }, { "groupId": "OG002", "value": "7.2", "spread": "2.01" }, { "groupId": "OG003", "value": "6.5", "spread": "1.72" }, { "groupId": "OG004", "value": "6.3", "spread": "1.66" }, { "groupId": "OG005", "value": "6.4", "spread": "1.38" } ] } ] }, { "title": "Emin", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "4.8", "spread": "1.90" }, { "groupId": "OG001", "value": "2.5", "spread": "2.05" }, { "groupId": "OG002", "value": "1.7", "spread": "1.31" }, { "groupId": "OG003", "value": "4.4", "spread": "2.08" }, { "groupId": "OG004", "value": "4.7", "spread": "1.72" }, { "groupId": "OG005", "value": "4.3", "spread": "1.85" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.1691", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.3637", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-0.1566", "ciUpperLimit": "0.8840" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0017", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.8444", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "0.3238", "ciUpperLimit": "1.3650" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4305", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.2093", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-0.3141", "ciUpperLimit": "0.7327" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6517", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.1206", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-0.4064", "ciUpperLimit": "0.6476" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8892", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.0374", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-0.5666", "ciUpperLimit": "0.4919" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5576", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.1544", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-0.6737", "ciUpperLimit": "0.3649" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.3594", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.2431", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-0.7658", "ciUpperLimit": "0.2796" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.1355", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.4011", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-0.9291", "ciUpperLimit": "0.1270" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0153", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.6351", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.1466", "ciUpperLimit": "-0.1236" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0065", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.7238", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.2418", "ciUpperLimit": "-0.2059" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0011", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.8818", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.4042", "ciUpperLimit": "-0.3594" }, { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-2.1614", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-2.9373", "ciUpperLimit": "-1.3856" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.0336", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-3.8085", "ciUpperLimit": "-2.2587" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.", "eventGroups": [ { "id": "EG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods.", "seriousNumAffected": 0, "seriousNumAtRisk": 32, "otherNumAffected": 11, "otherNumAtRisk": 32 }, { "id": "EG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods.", "seriousNumAffected": 0, "seriousNumAtRisk": 33, "otherNumAffected": 30, "otherNumAtRisk": 33 }, { "id": "EG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods.", "seriousNumAffected": 0, "seriousNumAtRisk": 34, "otherNumAffected": 34, "otherNumAtRisk": 34 }, { "id": "EG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods.", "seriousNumAffected": 0, "seriousNumAtRisk": 33, "otherNumAffected": 18, "otherNumAtRisk": 33 }, { "id": "EG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods.", "seriousNumAffected": 0, "seriousNumAtRisk": 32, "otherNumAffected": 20, "otherNumAtRisk": 32 }, { "id": "EG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods.", "seriousNumAffected": 0, "seriousNumAtRisk": 31, "otherNumAffected": 17, "otherNumAtRisk": 31 } ], "otherEvents": [ { 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"numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Diarrhoea", "organSystem": "Gastrointestinal disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Nausea", "organSystem": "Gastrointestinal disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, 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"numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 1, "numAtRisk": 31 } ] }, { "term": "Influenza like illness", "organSystem": "General disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Pyrexia", "organSystem": "General disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { 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"EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Nasopharyngitis", "organSystem": "Infections and infestations", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Upper respiratory tract infection", "organSystem": "Infections and infestations", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Excoriation", "organSystem": "Injury, poisoning and procedural complications", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Fall", "organSystem": "Injury, poisoning and procedural complications", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Mouth injury", "organSystem": "Injury, poisoning and procedural complications", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Soft tissue injury", "organSystem": "Injury, 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"numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Back pain", "organSystem": "Musculoskeletal and connective tissue disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Musculoskeletal stiffness", "organSystem": "Musculoskeletal and connective tissue disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Myalgia", "organSystem": "Musculoskeletal and connective tissue disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Neck pain", "organSystem": "Musculoskeletal and connective tissue disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 2, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Disturbance in attention", "organSystem": "Nervous system disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Dizziness", "organSystem": "Nervous system disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 1, "numAtRisk": 31 } ] }, { "term": "Dysarthria", "organSystem": "Nervous system disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 2, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Head discomfort", "organSystem": "Nervous system disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 2, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Headache", "organSystem": "Nervous system disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 2, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 3, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 2, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 2, "numAtRisk": 31 } ] }, { "term": "Hypoaesthesia", "organSystem": "Nervous system disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Somnolence", "organSystem": "Nervous system disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 9, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 26, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 34, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 7, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 12, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 13, "numAtRisk": 31 } ] }, { "term": "Speech disorder", "organSystem": "Nervous system disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Syncope", "organSystem": "Nervous system disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Anxiety", "organSystem": "Psychiatric disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Euphoric mood", "organSystem": "Psychiatric disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 2, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 3, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Hypervigilance", "organSystem": "Psychiatric disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Tension", "organSystem": "Psychiatric disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Oropharyngeal pain", "organSystem": "Respiratory, thoracic and mediastinal disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 1, "numAtRisk": 31 } ] }, { "term": "Rhinorrhoea", "organSystem": "Respiratory, thoracic and mediastinal disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Dermatitis contact", "organSystem": "Skin and subcutaneous tissue disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Erythema", "organSystem": "Skin and subcutaneous tissue disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Pruritus", "organSystem": "Skin and subcutaneous tissue disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Rash", "organSystem": "Skin and subcutaneous tissue disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Hypotension", "organSystem": "Vascular disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] } ] }, "moreInfoModule": { "certainAgreement": { "piSponsorEmployee": false, "restrictionType": "OTHER", "restrictiveAgreement": true, "otherDetails": "Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results." }, "pointOfContact": { "title": "Pfizer ClinicalTrials.gov Call Center", "organization": "Pfizer, Inc.", "email": "ClinicalTrials.gov_Inquiries@pfizer.com", "phone": "1-800-718-1021" } } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2026-07-09", "removedCountries": [ "Canada" ] }, "conditionBrowseModule": { "meshes": [ { "id": "D000544", "term": "Alzheimer Disease" }, { "id": "D006816", "term": "Huntington Disease" } ], "ancestors": [ { "id": "D003704", "term": "Dementia" }, { "id": "D001927", "term": "Brain Diseases" }, { "id": "D002493", "term": "Central Nervous System Diseases" }, { "id": "D009422", "term": "Nervous System Diseases" }, { "id": "D024801", "term": "Tauopathies" }, { "id": "D019636", "term": "Neurodegenerative Diseases" }, { "id": "D019965", "term": "Neurocognitive Disorders" }, { "id": "D001523", "term": "Mental Disorders" }, { "id": "D001480", "term": "Basal Ganglia Diseases" }, { "id": "D002819", "term": "Chorea" }, { "id": "D020820", "term": "Dyskinesias" }, { "id": "D009069", "term": "Movement Disorders" }, { "id": "D020271", "term": "Heredodegenerative Disorders, Nervous System" }, { "id": "D030342", "term": "Genetic Diseases, Inborn" }, { "id": "D009358", "term": "Congenital, Hereditary, and Neonatal Diseases and Abnormalities" }, { "id": "D003072", "term": "Cognition Disorders" } ] }, "interventionBrowseModule": { "meshes": [ { "id": "C010119", "term": "latrepirdine" }, { "id": "D000525", "term": "Alprazolam" } ], "ancestors": [ { "id": "D001569", "term": "Benzodiazepines" }, { "id": "D001552", "term": "Benzazepines" }, { "id": "D006574", "term": "Heterocyclic Compounds, 2-Ring" }, { "id": "D000072471", "term": "Heterocyclic Compounds, Fused-Ring" }, { "id": "D006571", "term": "Heterocyclic Compounds" } ] } }, "hasResults": true } ] }, "lysergic acid diethylamide Alzheimer": { "studies": [ { "protocolSection": { "identificationModule": { "nctId": "NCT00975481", "orgStudyIdInfo": { "id": "B1451037" }, "organization": { "fullName": "Pfizer", "class": "INDUSTRY" }, "briefTitle": "A Study To Evaluate The Abuse Potential Of Single Oral Doses Of Dimebon (Latrepirdine) In Healthy Recreational Polydrug Users", "officialTitle": "A Randomized, Double-Blind, Placebo- And Active-Controlled Single-Dose, Crossover Study To Evaluate The Abuse Potential Of Single Doses Of Dimebon (Latrepirdine) In Healthy Recreational Polydrug Users" }, "statusModule": { "statusVerifiedDate": "2013-02", "overallStatus": "COMPLETED", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2009-10" }, "primaryCompletionDateStruct": { "date": "2010-02", "type": "ACTUAL" }, "completionDateStruct": { "date": "2010-02", "type": "ACTUAL" }, "studyFirstSubmitDate": "2009-09-10", "studyFirstSubmitQcDate": "2009-09-10", "studyFirstPostDateStruct": { "date": "2009-09-11", "type": "ESTIMATED" }, "resultsFirstSubmitDate": "2012-12-03", "resultsFirstSubmitQcDate": "2013-02-20", "resultsFirstPostDateStruct": { "date": "2013-04-02", "type": "ESTIMATED" }, "lastUpdateSubmitDate": "2013-02-20", "lastUpdatePostDateStruct": { "date": "2013-04-02", "type": "ESTIMATED" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR" }, "leadSponsor": { "name": "Pfizer", "class": "INDUSTRY" }, "collaborators": [ { "name": "Medivation, Inc.", "class": "INDUSTRY" } ] }, "oversightModule": { "oversightHasDmc": false }, "descriptionModule": { "briefSummary": "Dimebon will not exhibit abuse potential when compared to placebo or a positive control (alprazolam).", "detailedDescription": "The main purpose for this study is to determine whether dimebon exhibits abuse potential." }, "conditionsModule": { "conditions": [ "Alzheimer's Disease", "Huntington's Disease" ], "keywords": [ "oral single-dose 6-way crossover recreational drug users abuse potential pharmacodynamics safety" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "PHASE1" ], "designInfo": { "allocation": "RANDOMIZED", "interventionModel": "CROSSOVER", "maskingInfo": { "masking": "DOUBLE", "whoMasked": [ "PARTICIPANT", "INVESTIGATOR" ] } }, "enrollmentInfo": { "count": 36, "type": "ACTUAL" } }, "armsInterventionsModule": { "armGroups": [ { "label": "dimebon 20 mg", "type": "EXPERIMENTAL", "interventionNames": [ "Drug: dimebon" ] }, { "label": "dimebon 40 mg", "type": "EXPERIMENTAL", "interventionNames": [ "Drug: dimebon" ] }, { "label": "dimebon 60 mg", "type": "EXPERIMENTAL", "interventionNames": [ "Drug: dimebon" ] }, { "label": "placebo", "type": "PLACEBO_COMPARATOR", "interventionNames": [ "Drug: placebo" ] }, { "label": "alprazolam 1 mg", "type": "ACTIVE_COMPARATOR", "interventionNames": [ "Drug: alprazolam" ] }, { "label": "alprazolam 3 mg", "type": "ACTIVE_COMPARATOR", "interventionNames": [ "Drug: alprazolam" ] } ], "interventions": [ { "type": "DRUG", "name": "dimebon", "description": "Oral tablet; 20 mg dimebon, single dose", "armGroupLabels": [ "dimebon 20 mg" ] }, { "type": "DRUG", "name": "dimebon", "description": "Oral tablet; 40 mg dimebon, single dose", "armGroupLabels": [ "dimebon 40 mg" ] }, { "type": "DRUG", "name": "dimebon", "description": "Oral tablet; 60 mg dimebon, single dose", "armGroupLabels": [ "dimebon 60 mg" ] }, { "type": "DRUG", "name": "placebo", "description": "Oral tablet or capsule; placebo, single dose", "armGroupLabels": [ "placebo" ] }, { "type": "DRUG", "name": "alprazolam", "description": "Oral capsule; 1 mg alprazolam, single dose", "armGroupLabels": [ "alprazolam 1 mg" ] }, { "type": "DRUG", "name": "alprazolam", "description": "Oral capsule; 3 mg alprazolam, single dose", "armGroupLabels": [ "alprazolam 3 mg" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)", "description": "Drug liking VAS is one of the measures of balance of effects that assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar visual analogue scale (VAS) anchored in the center with a neutral anchor of \"neither like nor dislike\" (score of 50 mm), on the left with \"strong disliking\" (score of 0 mm) and on the right with \"strong liking\" (score of 100 mm).\n\nEmax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose.", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)", "description": "Overall drug liking VAS is one of the measures of balance of effects that assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carryover effects). A 100 mm bipolar VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = \"strong disliking\", 50 mm= \"neither like nor dislike\", and 100 mm= \"strong liking\").\n\nEmax is the largest effect score between 6 to 24 hours post-dose. Emin is the smallest effect score between 6 to 24 hours post-dose.", "timeFrame": "6, 12, 24 hours post-dose" }, { "measure": "Balance of Effects- Take Drug Again VAS: Peak Effect (Maximum Effect [Emax])", "description": "Take drug again VAS is one of the measures of balance of effects. It is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm bipolar VAS with score ranging from 0 mm to 100 mm (score of 0 mm = \"definitely not\", 50 mm = \"do not care\", and 100 mm = \"definitely so\").\n\nEmax is largest effect score between 6 hours to 24 hours.", "timeFrame": "6, 12, 24 hours post-dose" }, { "measure": "Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)", "description": "Good and Bad effects VAS is one of the measures of balance of effects that assesses the effect experienced by the participant on a 100 mm bipolar VAS, anchored in the center with a neutral anchor of neither good nor bad effects (score of 50 mm), on the left with bad effects(score of 0 mm) and on the right with good effects (score of 100 mm).\n\nEmax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose.", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Balance of Effects- Subjective Drug Value (SDV): Maximum Effect (Emax)", "description": "SDV is one of measures of balance of effects. It is a proxy measure of reinforcing efficacy that involves a series of independent, theoretical forced choices between drug administered and different monetary values. Participants were asked to choose between receiving another dose of same drug or an envelope containing specified amount of money, but they did not receive drug or money as described. Possible score range from 0.25 to 50. Higher score range indicates higher SDV. Emax: largest effect score between 6-24 hours post-dose.", "timeFrame": "6, 12, 24 hrs post-dose" }, { "measure": "Positive Effects- Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG): Maximum Effect (Emax)", "description": "ARCI (MBG) is one of the measures of positive effects. It is a set of 16 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to the scoring direction. Score range: 0 to 16, higher score indicated positive effects. Emax: largest effect score between 0 to 24 hours post-dose.", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 12, 24 hours post-dose" }, { "measure": "Positive Effects- Good Drug Effects: Peak Effect (Maximum Effect [Emax])", "description": "Good drug effects VAS is one of the measures of positive effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so).\n\nEmax is the largest effect score between 0.5 to 24 hours post-dose.", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Positive Effects- High VAS: Peak Effect (Maximum Effect [Emax])", "description": "High VAS is one of the measures of positive effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so).\n\nEmax is largest effect score between 0 to 24 hours.", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Negative Effects- Bad Drug Effects: Peak Effect (Maximum Effect [Emax])", "description": "Bad effects VAS is one of the measures of negative effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so).\n\nEmax is largest effect score between 0.5 to 24 hrs.", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Negative Effects- Addiction Research Center Inventory (ARCI) Lysergic Acid Diethylamide (LSD): Maximum Effect (Emax)", "description": "ARCI (LSD) is one of the measures of negative effects. It is a set of 14 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to scoring direction. Score range: 0 to 14, higher score indicated higher negative effects. Emax: largest effect score between 0 to 24 hours post-dose.", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Sedative Effects- Addiction Research Center Inventory (ARCI) Pentobarbital Chlorpromazine Group (PCAG): Maximum Effect (Emax)", "description": "ARCI (PCAG) is one of the measures of sedative effects. It is a set of 15 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when answer is opposite to scoring direction. Score range: 0 to 15, higher score indicated higher sedative effects. Emax: largest effect score between 0 to 24 hours post-dose.", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Sedative Effects- Alertness/Drowsiness: Minimum Effect (Emin)", "description": "Alertness/Drowsiness VAS is one of the measures of sedative effects. It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of \"neither drowsy nor alert\" (score of 50 mm), on the left with \"very drowsy\" (score of 0 mm) and on the right with \"very alert\" (score of 100 mm). Emin is the smallest effect score between 0 to 24 hours post-dose.", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Other Subjective Effects- Any Drug Effects: Peak Effect (Maximum Effect [Emax])", "description": "Any drug effects VAS is one of the measures of other subjective effects. It assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is the largest effect score between 0.5 to 24 hours post-dose.", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" }, { "measure": "Other Subjective Effects- Drug Similarity", "description": "Drug similarity VAS is one of the measures of other subjective effects. It assesses the similarity of the drug recently received by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= not at all similar) to 'extremely' (score of 100 mm= very similar). Recently received drugs were compared with placebo, benzodiazepines, codeine/morphine, Tetrahydrocannabinol (THC), pseudoephedrine.", "timeFrame": "12 hours post-dose" }, { "measure": "Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin)", "description": "ARCI (BG) is measure of other subjective effects. It is a set of 13 questions in which each question contributes to total score. Participants select 'False' / 'True' for response. One point given for each response that agrees with scoring direction, true items receive score of 1 if answer 'True', false items receive score of 1 if answer 'False'. No points if answer is opposite to scoring direction. Score range: 0 to 13, higher score indicated higher other subjective effects. Emax: largest effect score between 0 - 24 hours post-dose. Emin: smallest effect score between 0 - 24 hours post-dose.", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose" } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria:\n\n* Healthy male and/or female subjects between the ages of 18 and 55 years.\n* Recreational polydrug user with a history of CNS depressant use.\n\nExclusion Criteria:\n\n* History of clinically significant neurologic condition(s), such as seizures, convulsions, epilepsy, or significant head injury, as judged by the investigator or designee.\n* A known history of hypersensitivity or previous intolerance to dimebon or other antihistamines.\n* Self-reported history of drug or alcohol dependence (except nicotine or caffeine) in the 2 years prior to screening, or drug or alcohol dependence as defined by the (DSM-IV-TR) in 12 months prior to screening, including subjects who have ever been in a substance rehabilitation program (other than treatment for smoking cessation).\n* History of clinically significant psychiatric disorder(s), as judged by the investigator or qualified designee.", "healthyVolunteers": false, "sex": "ALL", "minimumAge": "18 Years", "maximumAge": "55 Years", "stdAges": [ "ADULT" ] }, "contactsLocationsModule": { "overallOfficials": [ { "name": "Pfizer CT.gov Call Center", "affiliation": "Pfizer", "role": "STUDY_DIRECTOR" } ] }, "referencesModule": { "seeAlsoLinks": [ { "label": "To obtain contact information for a study center near you, click here.", "url": "https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1451037&StudyName=A%20Study%20To%20Evaluate%20The%20Abuse%20Potential%20Of%20Single%20Oral%20Doses%20Of%20Dimebon%20%28Latrepirdine%29%20In%20Healthy%20Recreational%20Polydrug%20Users" } ] } }, "resultsSection": { "participantFlowModule": { "groups": [ { "id": "FG000", "title": "PBO, ALP 1mg, DIM 60 mg, ALP 3 mg, DIM 40 mg, DIM 20 mg", "description": "Placebo (PBO) matched to 3 alprazolam (ALP) capsules and placebo matched to 3 dimebon (DIM) tablets on Day 1 in the first intervention period; followed by alprazolam 1 milligram (mg) capsule, placebo matched to 2 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the second intervention period; then dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the third intervention period; then alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in fourth intervention period; then dimebon 40 mg tablets and placebo matched to dimebon tablet and placebo matched to 3 alprazolam capsules on Day 1 in the fifth intervention period; and dimebon 20 mg tablet, placebo matched to 2 dimebon tablets and placebo matched to 3 alprazolam capsules on Day 1 in the sixth intervention period. A washout period of at least 7 days was maintained between each dose." }, { "id": "FG001", "title": "ALP 1 mg, ALP 3 mg, PBO, DIM 20 mg, DIM 60 mg, DIM 40 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the first intervention period; followed by alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in the second intervention period; then placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the third intervention period; then dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 in the fourth intervention period; then dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the fifth intervention period; and dimebon 40 mg tablets, placebo matched to dimebon tablet and placebo matched to 3 alprazolam capsules on Day 1 in the sixth intervention period. A washout period of at least 7 days was maintained between each dose." }, { "id": "FG002", "title": "ALP 3 mg, DIM 20 mg, ALP 1 mg, DIM 40 mg, PBO, DIM 60 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in the first intervention period; followed by dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 in the second intervention period; then alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the third intervention period; then dimebon 40 mg tablets, placebo matched to dimebon tablet and placebo matched to 3 alprazolam capsules on Day 1 in the fourth interventional period; then placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the fifth intervention period; and dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the sixth intervention period. A washout period of 7 days was maintained between each dose." }, { "id": "FG003", "title": "DIM 20 mg, DIM 40 mg, ALP 3 mg, DIM 60 mg, ALP 1 mg, PBO", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets and placebo matched to 3 alprazolam capsules on Day 1 in the first intervention period; followed by dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 in the second intervention period; then alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in the third intervention period; then dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the fourth intervention period; then alprazolam 1mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 in the fifth intervention period; and placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the sixth intervention period. A washout period of at least 7 days was maintained between each dose." }, { "id": "FG004", "title": "DIM 40 mg, DIM 60 mg, DIM 20 mg, PBO, ALP 3 mg, ALP 1 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 in the first intervention period; followed by dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the second intervention period; then dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 in the third intervention period; then placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the fourth intervention period; then alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in the fifth intervention period; and alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 in the sixth intervention period. A washout period of at least 7 days was maintained between each dose." }, { "id": "FG005", "title": "DIM 60 mg, PBO, DIM 40 mg, ALP 1mg, DIM 20 mg, ALP 3 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the first intervention period; followed by placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the second intervention period; then dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 in the third intervention period; then alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 in the fourth intervention group; then dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 in the fifth intervention period; and alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in the sixth intervention period. A washout period of at least 7 days was maintained between each dose." } ], "periods": [ { "title": "First Intervention Period", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "6" }, { "groupId": "FG001", "numSubjects": "6" }, { "groupId": "FG002", "numSubjects": "6" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "6" }, { "groupId": "FG001", "numSubjects": "6" }, { "groupId": "FG002", "numSubjects": "6" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Washout Period (at Least 7 Days)", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "6" }, { "groupId": "FG001", "numSubjects": "6" }, { "groupId": "FG002", "numSubjects": "6" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "6" }, { "groupId": "FG001", "numSubjects": "6" }, { "groupId": "FG002", "numSubjects": "6" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Second Intervention Period", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "6" }, { "groupId": "FG001", "numSubjects": "6" }, { "groupId": "FG002", "numSubjects": "6" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "2" }, { "groupId": "FG001", "numSubjects": "1" }, { "groupId": "FG002", "numSubjects": "1" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ], "dropWithdraws": [ { "type": "Adverse Event", "reasons": [ { "groupId": "FG000", "numSubjects": "2" }, { "groupId": "FG001", "numSubjects": "1" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] }, { "type": "Withdrawal by Subject", "reasons": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "1" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Washout Period (at Least 7 Days)", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Third Intervention Period", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Washout Period (at Least 7 Days)", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Fourth Intervention Period", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "5" }, { "groupId": "FG003", "numSubjects": "6" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "1" }, { "groupId": "FG003", "numSubjects": "1" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ], "dropWithdraws": [ { "type": "Withdrawal by Subject", "reasons": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "1" }, { "groupId": "FG003", "numSubjects": "1" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Washout Period (at Least 7 Days)", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Fifth Intervention Period", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "6" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "5" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "1" }, { "groupId": "FG005", "numSubjects": "0" } ] } ], "dropWithdraws": [ { "type": "Withdrawal by Subject", "reasons": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "1" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Washout Period (at Least 7 Days)", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "5" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "5" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] }, { "title": "Sixth Intervention Period", "milestones": [ { "type": "STARTED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "5" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "4" }, { "groupId": "FG001", "numSubjects": "5" }, { "groupId": "FG002", "numSubjects": "4" }, { "groupId": "FG003", "numSubjects": "5" }, { "groupId": "FG004", "numSubjects": "5" }, { "groupId": "FG005", "numSubjects": "6" } ] }, { "type": "NOT COMPLETED", "achievements": [ { "groupId": "FG000", "numSubjects": "0" }, { "groupId": "FG001", "numSubjects": "0" }, { "groupId": "FG002", "numSubjects": "0" }, { "groupId": "FG003", "numSubjects": "0" }, { "groupId": "FG004", "numSubjects": "0" }, { "groupId": "FG005", "numSubjects": "0" } ] } ] } ] }, "baselineCharacteristicsModule": { "groups": [ { "id": "BG000", "title": "Entire Study Population", "description": "Includes participants randomized to receive placebo first, alprazolam 1 mg first, alprazolam 3 mg first, dimebon 20 mg first, dimebon 40 mg first and dimebon 60 mg first." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "BG000", "value": "36" } ] } ], "measures": [ { "title": "Age Continuous", "paramType": "MEAN", "dispersionType": "STANDARD_DEVIATION", "unitOfMeasure": "Years", "classes": [ { "categories": [ { "measurements": [ { "groupId": "BG000", "value": "35.4", "spread": "9.7" } ] } ] } ] }, { "title": "Sex: Female, Male", "paramType": "COUNT_OF_PARTICIPANTS", "unitOfMeasure": "Participants", "classes": [ { "categories": [ { "title": "Female", "measurements": [ { "groupId": "BG000", "value": "8" } ] }, { "title": "Male", "measurements": [ { "groupId": "BG000", "value": "28" } ] } ] } ] }, { "title": "Body Mass Index", "paramType": "MEAN", "dispersionType": "STANDARD_DEVIATION", "unitOfMeasure": "kilogram/square meter (kg/m^2)", "classes": [ { "categories": [ { "measurements": [ { "groupId": "BG000", "value": "24.6", "spread": "3.4" } ] } ] } ] } ] }, "outcomeMeasuresModule": { "outcomeMeasures": [ { "type": "PRIMARY", "title": "Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)", "description": "Drug liking VAS is one of the measures of balance of effects that assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar visual analogue scale (VAS) anchored in the center with a neutral anchor of \"neither like nor dislike\" (score of 50 mm), on the left with \"strong disliking\" (score of 0 mm) and on the right with \"strong liking\" (score of 100 mm).\n\nEmax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis population included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "title": "Emax", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "57.8", "spread": "10.03" }, { "groupId": "OG001", "value": "78.6", "spread": "17.53" }, { "groupId": "OG002", "value": "82.2", "spread": "14.55" }, { "groupId": "OG003", "value": "57.2", "spread": "11.76" }, { "groupId": "OG004", "value": "55.8", "spread": "9.41" }, { "groupId": "OG005", "value": "58.5", "spread": "12.54" } ] } ] }, { "title": "Emin", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "47.0", "spread": "9.38" }, { "groupId": "OG001", "value": "45.4", "spread": "11.21" }, { "groupId": "OG002", "value": "37.4", "spread": "17.32" }, { "groupId": "OG003", "value": "48.4", "spread": "8.89" }, { "groupId": "OG004", "value": "49.0", "spread": "3.59" }, { "groupId": "OG005", "value": "46.5", "spread": "10.44" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95 percent (%) Confidence Interval (CI) were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with Restricted Maximum Likelihood (REML) estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "20.8096", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "15.0866", "ciUpperLimit": "26.5327" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4957", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.9993", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-7.7832", "ciUpperLimit": "3.7845" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.7431", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.9683", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.8567", "ciUpperLimit": "6.7932" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-26.4618", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-32.1455", "ciUpperLimit": "-20.7782" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-23.4943", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-29.2440", "ciUpperLimit": "-17.7445" }, { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5720", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.4538", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-6.5274", "ciUpperLimit": "3.6198" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6697", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "1.1113", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.0285", "ciUpperLimit": "6.2512" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "10.8623", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "5.8712", "ciUpperLimit": "15.8535" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "11.0663", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "6.0281", "ciUpperLimit": "16.1045" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0010", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "8.6513", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "3.5552", "ciUpperLimit": "13.7474" } ] }, { "type": "PRIMARY", "title": "Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)", "description": "Overall drug liking VAS is one of the measures of balance of effects that assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carryover effects). A 100 mm bipolar VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = \"strong disliking\", 50 mm= \"neither like nor dislike\", and 100 mm= \"strong liking\").\n\nEmax is the largest effect score between 6 to 24 hours post-dose. Emin is the smallest effect score between 6 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "6, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to 1 dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "title": "Emax", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "57.8", "spread": "14.31" }, { "groupId": "OG001", "value": "74.6", "spread": "18.99" }, { "groupId": "OG002", "value": "78.0", "spread": "15.50" }, { "groupId": "OG003", "value": "56.5", "spread": "11.44" }, { "groupId": "OG004", "value": "55.4", "spread": "11.29" }, { "groupId": "OG005", "value": "58.1", "spread": "12.52" } ] } ] }, { "title": "Emin", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "52.5", "spread": "9.13" }, { "groupId": "OG001", "value": "64.5", "spread": "20.17" }, { "groupId": "OG002", "value": "62.6", "spread": "18.13" }, { "groupId": "OG003", "value": "48.2", "spread": "15.96" }, { "groupId": "OG004", "value": "52.0", "spread": "8.75" }, { "groupId": "OG005", "value": "51.1", "spread": "8.94" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "16.6388", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "10.5727", "ciUpperLimit": "22.7049" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "19.8432", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "13.7627", "ciUpperLimit": "25.9238" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6029", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.6121", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-7.7209", "ciUpperLimit": "4.4967" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.3477", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-2.9241", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-9.0571", "ciUpperLimit": "3.2089" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.9769", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.0908", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-6.0850", "ciUpperLimit": "6.2667" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-18.2509", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-24.3155", "ciUpperLimit": "-12.1864" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-19.5629", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-25.6616", "ciUpperLimit": "-13.4642" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-16.5480", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-22.7036", "ciUpperLimit": "-10.3923" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-21.4554", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-27.4199", "ciUpperLimit": "-15.4908" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "pValueComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "statisticalMethod": "Mixed Models Analysis", "paramType": "Mean Difference (Final Values)", "paramValue": "-22.7673", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-28.7925", "ciUpperLimit": "-16.7422" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-19.7524", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-25.8485", "ciUpperLimit": "-13.6563" }, { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0006", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "12.0888", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "5.3225", "ciUpperLimit": "18.8551" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0038", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "10.0768", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "3.3132", "ciUpperLimit": "16.8403" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.2257", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.1875", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-10.9890", "ciUpperLimit": "2.6139" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8042", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.8589", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-7.6927", "ciUpperLimit": "5.9750" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6399", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.6335", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-8.5177", "ciUpperLimit": "5.2506" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-16.2763", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-23.0228", "ciUpperLimit": "-9.5229" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0002", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-12.9477", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-19.7374", "ciUpperLimit": "-6.1580" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-13.7223", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-20.5720", "ciUpperLimit": "-6.8727" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-14.2643", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-20.9226", "ciUpperLimit": "-7.6060" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0016", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-10.9356", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-17.6548", "ciUpperLimit": "-4.2165" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0008", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-11.7103", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-18.5055", "ciUpperLimit": "-4.9151" } ] }, { "type": "PRIMARY", "title": "Balance of Effects- Take Drug Again VAS: Peak Effect (Maximum Effect [Emax])", "description": "Take drug again VAS is one of the measures of balance of effects. It is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm bipolar VAS with score ranging from 0 mm to 100 mm (score of 0 mm = \"definitely not\", 50 mm = \"do not care\", and 100 mm = \"definitely so\").\n\nEmax is largest effect score between 6 hours to 24 hours.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "6, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam tablets, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "53.9", "spread": "22.30" }, { "groupId": "OG001", "value": "77.5", "spread": "22.26" }, { "groupId": "OG002", "value": "83.2", "spread": "15.99" }, { "groupId": "OG003", "value": "47.6", "spread": "28.66" }, { "groupId": "OG004", "value": "50.4", "spread": "26.23" }, { "groupId": "OG005", "value": "52.5", "spread": "25.66" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "24.0090", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "13.7265", "ciUpperLimit": "34.2916" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "29.4156", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "19.1160", "ciUpperLimit": "39.7151" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.2239", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-6.3979", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-16.7479", "ciUpperLimit": "3.9521" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4326", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.1396", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-14.5328", "ciUpperLimit": "6.2526" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.7447", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.7283", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-12.1950", "ciUpperLimit": "8.7383" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-30.4069", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-40.6795", "ciUpperLimit": "-20.1343" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-28.1487", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-38.4812", "ciUpperLimit": "-17.8161" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-25.7374", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-36.1651", "ciUpperLimit": "-15.3096" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-35.8134", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-45.9257", "ciUpperLimit": "-25.7012" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-33.5552", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-43.7675", "ciUpperLimit": "-23.3429" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-31.1439", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-41.4754", "ciUpperLimit": "-20.8124" } ] }, { "type": "PRIMARY", "title": "Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin)", "description": "Good and Bad effects VAS is one of the measures of balance of effects that assesses the effect experienced by the participant on a 100 mm bipolar VAS, anchored in the center with a neutral anchor of neither good nor bad effects (score of 50 mm), on the left with bad effects(score of 0 mm) and on the right with good effects (score of 100 mm).\n\nEmax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsule, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "title": "Emax", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "56.2", "spread": "7.15" }, { "groupId": "OG001", "value": "80.9", "spread": "15.93" }, { "groupId": "OG002", "value": "81.9", "spread": "14.40" }, { "groupId": "OG003", "value": "57.9", "spread": "13.53" }, { "groupId": "OG004", "value": "56.6", "spread": "11.21" }, { "groupId": "OG005", "value": "57.6", "spread": "8.92" } ] } ] }, { "title": "Emin", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "48.0", "spread": "8.83" }, { "groupId": "OG001", "value": "46.7", "spread": "10.70" }, { "groupId": "OG002", "value": "38.6", "spread": "15.76" }, { "groupId": "OG003", "value": "49.3", "spread": "2.79" }, { "groupId": "OG004", "value": "48.3", "spread": "8.82" }, { "groupId": "OG005", "value": "48.9", "spread": "3.03" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "24.8779", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "19.5658", "ciUpperLimit": "30.1899" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "25.9857", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "20.6670", "ciUpperLimit": "31.3043" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4489", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "2.0544", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-3.2911", "ciUpperLimit": "7.3998" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8329", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.5743", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.7941", "ciUpperLimit": "5.9427" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5387", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "1.6863", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-3.7203", "ciUpperLimit": "7.0929" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-22.8235", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-28.1283", "ciUpperLimit": "-17.5187" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-24.3036", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-29.6400", "ciUpperLimit": "-18.9672" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-23.1916", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-28.5768", "ciUpperLimit": "-17.8064" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-23.9313", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-29.1559", "ciUpperLimit": "-18.7066" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-25.4114", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-30.6869", "ciUpperLimit": "-20.1358" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-24.2994", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-29.6361", "ciUpperLimit": "-18.9626" }, { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5349", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.4301", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-5.9725", "ciUpperLimit": "3.1123" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-9.1367", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-13.6684", "ciUpperLimit": "-4.6050" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5637", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "1.3357", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-3.2244", "ciUpperLimit": "5.8958" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8612", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.4065", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.1779", "ciUpperLimit": "4.9909" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6954", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.9175", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-3.7022", "ciUpperLimit": "5.5373" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.2287", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "2.7658", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.7552", "ciUpperLimit": "7.2868" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4267", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "1.8366", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-2.7158", "ciUpperLimit": "6.3890" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.3140", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "2.3476", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-2.2429", "ciUpperLimit": "6.9381" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "10.4724", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "5.9992", "ciUpperLimit": "14.9456" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "9.5432", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "5.0320", "ciUpperLimit": "14.0544" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "10.0542", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "5.4940", "ciUpperLimit": "14.6144" } ] }, { "type": "PRIMARY", "title": "Balance of Effects- Subjective Drug Value (SDV): Maximum Effect (Emax)", "description": "SDV is one of measures of balance of effects. It is a proxy measure of reinforcing efficacy that involves a series of independent, theoretical forced choices between drug administered and different monetary values. Participants were asked to choose between receiving another dose of same drug or an envelope containing specified amount of money, but they did not receive drug or money as described. Possible score range from 0.25 to 50. Higher score range indicates higher SDV. Emax: largest effect score between 6-24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "Dollar", "timeFrame": "6, 12, 24 hrs post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsule, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "4.805", "spread": "9.7833" }, { "groupId": "OG001", "value": "19.621", "spread": "16.2519" }, { "groupId": "OG002", "value": "25.551", "spread": "17.0192" }, { "groupId": "OG003", "value": "6.098", "spread": "12.3269" }, { "groupId": "OG004", "value": "3.836", "spread": "6.5345" }, { "groupId": "OG005", "value": "4.573", "spread": "9.8211" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "14.4728", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "9.4718", "ciUpperLimit": "19.4737" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "19.7284", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "14.7131", "ciUpperLimit": "24.7437" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.9348", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.2088", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.8289", "ciUpperLimit": "5.2466" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5009", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.7271", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-6.7841", "ciUpperLimit": "3.3299" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8975", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.3325", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-5.4245", "ciUpperLimit": "4.7595" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-14.2640", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-19.2660", "ciUpperLimit": "-9.2619" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-16.1999", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-21.2294", "ciUpperLimit": "-11.1704" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-14.8053", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-19.8822", "ciUpperLimit": "-9.7283" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-19.5195", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-24.4361", "ciUpperLimit": "-14.6030" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-21.4555", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-26.4230", "ciUpperLimit": "-16.4880" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-20.0609", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-25.0872", "ciUpperLimit": "-15.0345" } ] }, { "type": "PRIMARY", "title": "Positive Effects- Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG): Maximum Effect (Emax)", "description": "ARCI (MBG) is one of the measures of positive effects. It is a set of 16 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to the scoring direction. Score range: 0 to 16, higher score indicated positive effects. Emax: largest effect score between 0 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "Units on scale", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "3.2", "spread": "2.51" }, { "groupId": "OG001", "value": "6.2", "spread": "4.16" }, { "groupId": "OG002", "value": "8.1", "spread": "4.37" }, { "groupId": "OG003", "value": "3.5", "spread": "3.10" }, { "groupId": "OG004", "value": "3.6", "spread": "3.22" }, { "groupId": "OG005", "value": "3.5", "spread": "2.87" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "3.1634", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "1.9014", "ciUpperLimit": "4.4254" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "4.6706", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "3.4066", "ciUpperLimit": "5.9346" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8184", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.1478", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.1217", "ciUpperLimit": "1.4173" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.7324", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.2211", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.0540", "ciUpperLimit": "1.4963" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.8844", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.0946", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.1898", "ciUpperLimit": "1.3791" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.0156", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.2754", "ciUpperLimit": "-1.7558" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-2.9423", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.2101", "ciUpperLimit": "-1.6745" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.0688", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.3484", "ciUpperLimit": "-1.7891" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.5228", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-5.7651", "ciUpperLimit": "-3.2805" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.4495", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-5.7031", "ciUpperLimit": "-3.1959" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.5760", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-5.8438", "ciUpperLimit": "-3.3081" } ] }, { "type": "PRIMARY", "title": "Positive Effects- Good Drug Effects: Peak Effect (Maximum Effect [Emax])", "description": "Good drug effects VAS is one of the measures of positive effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so).\n\nEmax is the largest effect score between 0.5 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "35.2", "spread": "31.94" }, { "groupId": "OG001", "value": "81.2", "spread": "18.16" }, { "groupId": "OG002", "value": "84.7", "spread": "14.32" }, { "groupId": "OG003", "value": "34.4", "spread": "32.87" }, { "groupId": "OG004", "value": "32.0", "spread": "32.33" }, { "groupId": "OG005", "value": "39.7", "spread": "31.34" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "46.0798", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "34.0453", "ciUpperLimit": "58.1142" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "49.8771", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "37.8247", "ciUpperLimit": "61.9295" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-62.5926", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-74.5881", "ciUpperLimit": "-50.5971" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-58.6906", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-70.7965", "ciUpperLimit": "-46.5847" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-52.3018", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-64.5427", "ciUpperLimit": "-40.0609" } ] }, { "type": "PRIMARY", "title": "Negative Effects- Bad Drug Effects: Peak Effect (Maximum Effect [Emax])", "description": "Bad effects VAS is one of the measures of negative effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so).\n\nEmax is largest effect score between 0.5 to 24 hrs.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "17.2", "spread": "24.38" }, { "groupId": "OG001", "value": "33.9", "spread": "29.88" }, { "groupId": "OG002", "value": "44.6", "spread": "23.58" }, { "groupId": "OG003", "value": "15.9", "spread": "25.38" }, { "groupId": "OG004", "value": "16.8", "spread": "24.27" }, { "groupId": "OG005", "value": "19.7", "spread": "25.47" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0135", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-13.0325", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-23.3295", "ciUpperLimit": "-2.7355" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-29.1396", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-39.1071", "ciUpperLimit": "-19.1721" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-27.2502", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-37.3224", "ciUpperLimit": "-17.1780" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-24.5693", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-34.7614", "ciUpperLimit": "-14.3772" } ] }, { "type": "PRIMARY", "title": "Negative Effects- Addiction Research Center Inventory (ARCI) Lysergic Acid Diethylamide (LSD): Maximum Effect (Emax)", "description": "ARCI (LSD) is one of the measures of negative effects. It is a set of 14 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to scoring direction. Score range: 0 to 14, higher score indicated higher negative effects. Emax: largest effect score between 0 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "Units on Scale", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "3.8", "spread": "1.83" }, { "groupId": "OG001", "value": "4.9", "spread": "1.76" }, { "groupId": "OG002", "value": "7.0", "spread": "2.57" }, { "groupId": "OG003", "value": "3.8", "spread": "1.42" }, { "groupId": "OG004", "value": "3.8", "spread": "1.50" }, { "groupId": "OG005", "value": "3.6", "spread": "1.58" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0008", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-1.2175", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-1.9171", "ciUpperLimit": "-0.5178" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.1802", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-3.8656", "ciUpperLimit": "-2.4947" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.4650", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.1583", "ciUpperLimit": "-2.7717" } ] }, { "type": "PRIMARY", "title": "Sedative Effects- Addiction Research Center Inventory (ARCI) Pentobarbital Chlorpromazine Group (PCAG): Maximum Effect (Emax)", "description": "ARCI (PCAG) is one of the measures of sedative effects. It is a set of 15 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when answer is opposite to scoring direction. Score range: 0 to 15, higher score indicated higher sedative effects. Emax: largest effect score between 0 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "Units on Scale", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "4.7", "spread": "2.57" }, { "groupId": "OG001", "value": "9.9", "spread": "3.51" }, { "groupId": "OG002", "value": "11.5", "spread": "2.48" }, { "groupId": "OG003", "value": "5.3", "spread": "3.26" }, { "groupId": "OG004", "value": "5.5", "spread": "2.75" }, { "groupId": "OG005", "value": "5.5", "spread": "2.75" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.4453", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-5.6662", "ciUpperLimit": "-3.2244" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.3571", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-5.5887", "ciUpperLimit": "-3.1255" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-6.2437", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-7.4397", "ciUpperLimit": "-5.0477" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-6.0493", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-7.2568", "ciUpperLimit": "-4.8419" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-5.9611", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-7.1812", "ciUpperLimit": "-4.7410" } ] }, { "type": "PRIMARY", "title": "Sedative Effects- Alertness/Drowsiness: Minimum Effect (Emin)", "description": "Alertness/Drowsiness VAS is one of the measures of sedative effects. It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of \"neither drowsy nor alert\" (score of 50 mm), on the left with \"very drowsy\" (score of 0 mm) and on the right with \"very alert\" (score of 100 mm). Emin is the smallest effect score between 0 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "42.1", "spread": "18.77" }, { "groupId": "OG001", "value": "14.4", "spread": "17.83" }, { "groupId": "OG002", "value": "8.6", "spread": "9.36" }, { "groupId": "OG003", "value": "42.9", "spread": "21.32" }, { "groupId": "OG004", "value": "37.7", "spread": "21.32" }, { "groupId": "OG005", "value": "38.5", "spread": "16.10" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-26.6205", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-33.1192", "ciUpperLimit": "-20.1219" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-32.5724", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-39.1073", "ciUpperLimit": "-26.0375" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5685", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "1.8966", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-4.6607", "ciUpperLimit": "8.4540" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.2848", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.5761", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-10.1590", "ciUpperLimit": "3.0068" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.3440", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.1754", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-9.7855", "ciUpperLimit": "3.4347" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "28.5172", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "22.0454", "ciUpperLimit": "34.9890" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "23.0445", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "16.5383", "ciUpperLimit": "29.5506" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "23.4452", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "16.8772", "ciUpperLimit": "30.0131" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "34.4690", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "28.1136", "ciUpperLimit": "40.8244" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "28.9963", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "22.5734", "ciUpperLimit": "35.4192" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "29.3970", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "22.8946", "ciUpperLimit": "35.8994" } ] }, { "type": "PRIMARY", "title": "Other Subjective Effects- Any Drug Effects: Peak Effect (Maximum Effect [Emax])", "description": "Any drug effects VAS is one of the measures of other subjective effects. It assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is the largest effect score between 0.5 to 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "categories": [ { "measurements": [ { "groupId": "OG000", "value": "37.2", "spread": "35.30" }, { "groupId": "OG001", "value": "84.0", "spread": "23.27" }, { "groupId": "OG002", "value": "88.7", "spread": "11.12" }, { "groupId": "OG003", "value": "37.5", "spread": "35.91" }, { "groupId": "OG004", "value": "33.4", "spread": "34.54" }, { "groupId": "OG005", "value": "44.4", "spread": "34.44" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "46.6044", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "33.4091", "ciUpperLimit": "59.7996" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "50.7222", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "37.5038", "ciUpperLimit": "63.9407" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.9174", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-0.6987", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-13.9815", "ciUpperLimit": "12.5840" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5002", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.5629", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-17.9006", "ciUpperLimit": "8.7749" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-47.3031", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-60.4869", "ciUpperLimit": "-34.1193" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-51.1672", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-64.4276", "ciUpperLimit": "-37.9069" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-40.2062", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-53.5890", "ciUpperLimit": "-26.8234" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-51.4210", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-64.3974", "ciUpperLimit": "-38.4445" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-55.2851", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-68.3904", "ciUpperLimit": "-42.1798" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-44.3241", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-57.5825", "ciUpperLimit": "-31.0656" } ] }, { "type": "PRIMARY", "title": "Other Subjective Effects- Drug Similarity", "description": "Drug similarity VAS is one of the measures of other subjective effects. It assesses the similarity of the drug recently received by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= not at all similar) to 'extremely' (score of 100 mm= very similar). Recently received drugs were compared with placebo, benzodiazepines, codeine/morphine, Tetrahydrocannabinol (THC), pseudoephedrine.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. 'n' is signifying those participants who were evaluated for this measure for various drugs for similarity in each treatment group.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "mm", "timeFrame": "12 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "title": "Placebo (n=32, 33, 34, 33, 32, 31)", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "56.3", "spread": "42.65" }, { "groupId": "OG001", "value": "10.2", "spread": "22.20" }, { "groupId": "OG002", "value": "4.0", "spread": "12.27" }, { "groupId": "OG003", "value": "61.4", "spread": "36.34" }, { "groupId": "OG004", "value": "57.8", "spread": "43.15" }, { "groupId": "OG005", "value": "55.7", "spread": "42.15" } ] } ] }, { "title": "Benzodiazepines (n=23, 23, 25, 24, 22, 22)", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "51.0", "spread": "38.99" }, { "groupId": "OG001", "value": "88.6", "spread": "21.87" }, { "groupId": "OG002", "value": "92.7", "spread": "20.66" }, { "groupId": "OG003", "value": "33.0", "spread": "40.56" }, { "groupId": "OG004", "value": "42.6", "spread": "40.81" }, { "groupId": "OG005", "value": "53.0", "spread": "40.45" } ] } ] }, { "title": "Codeine/Morphine (n=20, 20, 23, 22, 20, 20)", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "18.5", "spread": "28.02" }, { "groupId": "OG001", "value": "42.7", "spread": "38.43" }, { "groupId": "OG002", "value": "46.3", "spread": "33.82" }, { "groupId": "OG003", "value": "14.7", "spread": "28.49" }, { "groupId": "OG004", "value": "24.5", "spread": "29.55" }, { "groupId": "OG005", "value": "28.2", "spread": "29.66" } ] } ] }, { "title": "THC (n=32, 33, 34, 33, 32, 31)", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "21.2", "spread": "27.97" }, { "groupId": "OG001", "value": "45.6", "spread": "37.08" }, { "groupId": "OG002", "value": "48.9", "spread": "32.96" }, { "groupId": "OG003", "value": "21.9", "spread": "30.44" }, { "groupId": "OG004", "value": "16.2", "spread": "25.88" }, { "groupId": "OG005", "value": "25.3", "spread": "31.56" } ] } ] }, { "title": "Pseudoephedrine (n=6, 6, 6, 6, 7, 5)", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "21.8", "spread": "33.42" }, { "groupId": "OG001", "value": "21.5", "spread": "27.70" }, { "groupId": "OG002", "value": "66.5", "spread": "12.14" }, { "groupId": "OG003", "value": "31.7", "spread": "35.35" }, { "groupId": "OG004", "value": "30.7", "spread": "28.89" }, { "groupId": "OG005", "value": "33.4", "spread": "26.32" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI was obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-46.3823", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-62.1244", "ciUpperLimit": "-30.6401" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-51.5199", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-67.2633", "ciUpperLimit": "-35.7765" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4524", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "6.0366", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-9.7924", "ciUpperLimit": "21.8657" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.7620", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "2.4423", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-13.4599", "ciUpperLimit": "18.3446" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.9846", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.1573", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-15.8609", "ciUpperLimit": "16.1754" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "52.4189", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "36.7157", "ciUpperLimit": "68.1221" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "48.8246", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "33.0228", "ciUpperLimit": "64.6264" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "46.5395", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "30.5968", "ciUpperLimit": "62.4823" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "57.5565", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "42.0679", "ciUpperLimit": "73.0451" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "53.9622", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "38.3293", "ciUpperLimit": "69.5952" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "51.6772", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "35.8660", "ciUpperLimit": "67.4884" }, { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0003", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "37.4454", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "17.7051", "ciUpperLimit": "57.1857" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "41.6714", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "22.2888", "ciUpperLimit": "61.0540" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0744", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-17.7583", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-37.2956", "ciUpperLimit": "1.7789" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.3458", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-9.5551", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-29.5573", "ciUpperLimit": "10.4471" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.9375", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.7920", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-19.1777", "ciUpperLimit": "20.7616" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-55.2037", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-74.8113", "ciUpperLimit": "-35.5961" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-47.0005", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-67.0020", "ciUpperLimit": "-26.9989" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0004", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-36.6534", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-56.7246", "ciUpperLimit": "-16.5822" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-59.4297", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-78.5162", "ciUpperLimit": "-40.3433" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-51.2265", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-70.8131", "ciUpperLimit": "-31.6399" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-40.8794", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-60.4726", "ciUpperLimit": "-21.2862" }, { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0102", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "23.5197", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "5.7096", "ciUpperLimit": "41.3298" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0021", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "27.7321", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "10.3632", "ciUpperLimit": "45.1011" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5935", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-4.7334", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-22.2807", "ciUpperLimit": "12.8140" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6945", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "3.5486", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-14.3397", "ciUpperLimit": "21.4370" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.4177", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "7.2936", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-10.4975", "ciUpperLimit": "25.0847" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0019", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-28.2531", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-45.8020", "ciUpperLimit": "-10.7042" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0299", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-19.9711", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-37.9541", "ciUpperLimit": "-1.9880" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0759", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-16.2261", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-34.1785", "ciUpperLimit": "1.7264" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0002", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-32.4655", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-49.2278", "ciUpperLimit": "-15.7032" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0069", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-24.1835", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-41.5832", "ciUpperLimit": "-6.7838" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0222", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-20.4385", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-37.8861", "ciUpperLimit": "-2.9910" }, { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0002", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "24.5890", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "12.0126", "ciUpperLimit": "37.1654" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "29.1100", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "16.4903", "ciUpperLimit": "41.7298" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6809", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "2.6428", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-10.0309", "ciUpperLimit": "15.3165" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6067", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-3.3215", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-16.0415", "ciUpperLimit": "9.3985" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.3999", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "5.4722", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-7.3350", "ciUpperLimit": "18.2795" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0007", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-21.9461", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-34.5327", "ciUpperLimit": "-9.3596" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-27.9105", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-40.5640", "ciUpperLimit": "-15.2570" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0036", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-19.1168", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-31.8907", "ciUpperLimit": "-6.3428" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-26.4672", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-38.8298", "ciUpperLimit": "-14.1046" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "<0.0001", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-32.4315", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-44.9250", "ciUpperLimit": "-19.9380" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0003", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-23.6378", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-36.2802", "ciUpperLimit": "-10.9954" }, { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.9728", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.6675", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-39.7080", "ciUpperLimit": "41.0430" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0246", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "42.7977", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "6.1059", "ciUpperLimit": "79.4894" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.7068", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "7.5411", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-33.7850", "ciUpperLimit": "48.8672" }, { "groupIds": [ "OG000", "OG004" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5492", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "10.7069", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-26.0358", "ciUpperLimit": "47.4496" }, { "groupIds": [ "OG000", "OG005" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5899", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "11.1248", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-31.3098", "ciUpperLimit": "53.5595" }, { "groupIds": [ "OG001", "OG003" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6998", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "6.8736", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-29.8691", "ciUpperLimit": "43.6163" }, { "groupIds": [ "OG001", "OG004" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.6187", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "10.0394", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-31.4818", "ciUpperLimit": "51.5606" }, { "groupIds": [ "OG001", "OG005" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.5863", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "10.4573", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-29.0355", "ciUpperLimit": "49.9502" }, { "groupIds": [ "OG002", "OG003" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0832", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-35.2566", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-75.6080", "ciUpperLimit": "5.0948" }, { "groupIds": [ "OG002", "OG004" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0827", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-32.0907", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-68.7519", "ciUpperLimit": "4.5704" }, { "groupIds": [ "OG002", "OG005" ], "groupDescription": "For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.1386", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "-31.6728", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-74.5352", "ciUpperLimit": "11.1895" } ] }, { "type": "PRIMARY", "title": "Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin)", "description": "ARCI (BG) is measure of other subjective effects. It is a set of 13 questions in which each question contributes to total score. Participants select 'False' / 'True' for response. One point given for each response that agrees with scoring direction, true items receive score of 1 if answer 'True', false items receive score of 1 if answer 'False'. No points if answer is opposite to scoring direction. Score range: 0 to 13, higher score indicated higher other subjective effects. Emax: largest effect score between 0 - 24 hours post-dose. Emin: smallest effect score between 0 - 24 hours post-dose.", "populationDescription": "The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period.", "reportingStatus": "POSTED", "paramType": "MEAN", "dispersionType": "Standard Deviation", "unitOfMeasure": "Units on Scale", "timeFrame": "0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose", "groups": [ { "id": "OG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods." }, { "id": "OG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods." }, { "id": "OG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods." } ], "denoms": [ { "units": "Participants", "counts": [ { "groupId": "OG000", "value": "32" }, { "groupId": "OG001", "value": "33" }, { "groupId": "OG002", "value": "34" }, { "groupId": "OG003", "value": "33" }, { "groupId": "OG004", "value": "32" }, { "groupId": "OG005", "value": "31" } ] } ], "classes": [ { "title": "Emax", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "6.3", "spread": "1.14" }, { "groupId": "OG001", "value": "6.6", "spread": "1.34" }, { "groupId": "OG002", "value": "7.2", "spread": "2.01" }, { "groupId": "OG003", "value": "6.5", "spread": "1.72" }, { "groupId": "OG004", "value": "6.3", "spread": "1.66" }, { "groupId": "OG005", "value": "6.4", "spread": "1.38" } ] } ] }, { "title": "Emin", "categories": [ { "measurements": [ { "groupId": "OG000", "value": "4.8", "spread": "1.90" }, { "groupId": "OG001", "value": "2.5", "spread": "2.05" }, { "groupId": "OG002", "value": "1.7", "spread": "1.31" }, { "groupId": "OG003", "value": "4.4", "spread": "2.08" }, { "groupId": "OG004", "value": "4.7", "spread": "1.72" }, { "groupId": "OG005", "value": "4.3", "spread": "1.85" } ] } ] } ], "analyses": [ { "groupIds": [ "OG000", "OG001" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.1691", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.3637", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "-0.1566", "ciUpperLimit": "0.8840" }, { "groupIds": [ "OG000", "OG002" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model.", "testedNonInferiority": false, "nonInferiorityType": "SUPERIORITY_OR_OTHER", "pValue": "0.0017", "statisticalMethod": "Mixed Models Analysis", "statisticalComment": "Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm.", "paramType": "Mean Difference (Final Values)", "paramValue": "0.8444", "ciPctValue": "95", "ciNumSides": "TWO_SIDED", "ciLowerLimit": "0.3238", "ciUpperLimit": "1.3650" }, { "groupIds": [ "OG000", "OG003" ], "groupDescription": "For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. 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An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.", "eventGroups": [ { "id": "EG000", "title": "Placebo", "description": "Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods.", "seriousNumAffected": 0, "seriousNumAtRisk": 32, "otherNumAffected": 11, "otherNumAtRisk": 32 }, { "id": "EG001", "title": "Alprazolam 1 mg", "description": "Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods.", "seriousNumAffected": 0, "seriousNumAtRisk": 33, "otherNumAffected": 30, "otherNumAtRisk": 33 }, { "id": "EG002", "title": "Alprazolam 3 mg", "description": "Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods.", "seriousNumAffected": 0, "seriousNumAtRisk": 34, "otherNumAffected": 34, "otherNumAtRisk": 34 }, { "id": "EG003", "title": "Dimebon 20 mg", "description": "Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods.", "seriousNumAffected": 0, "seriousNumAtRisk": 33, "otherNumAffected": 18, "otherNumAtRisk": 33 }, { "id": "EG004", "title": "Dimebon 40 mg", "description": "Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods.", "seriousNumAffected": 0, "seriousNumAtRisk": 32, "otherNumAffected": 20, "otherNumAtRisk": 32 }, { "id": "EG005", "title": "Dimebon 60 mg", "description": "Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods.", "seriousNumAffected": 0, "seriousNumAtRisk": 31, "otherNumAffected": 17, "otherNumAtRisk": 31 } ], "otherEvents": [ { "term": "Dry eye", "organSystem": "Eye disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Abdominal discomfort", "organSystem": "Gastrointestinal disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Diarrhoea", "organSystem": "Gastrointestinal disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Nausea", "organSystem": "Gastrointestinal disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Vomiting", "organSystem": "Gastrointestinal disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 1, "numAtRisk": 31 } ] }, { "term": "Chills", "organSystem": "General disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 1, "numAtRisk": 31 } ] }, { "term": "Fatigue", "organSystem": "General disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 2, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 4, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 5, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 2, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 3, "numAtRisk": 31 } ] }, { "term": "Feeling of relaxation", "organSystem": "General disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 1, "numAtRisk": 31 } ] }, { "term": "Influenza like illness", "organSystem": "General disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Pyrexia", "organSystem": "General disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { 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"groupId": "EG000", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Somnolence", "organSystem": "Nervous system disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 9, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 26, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 34, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 7, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 12, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 13, "numAtRisk": 31 } ] }, { "term": "Speech disorder", "organSystem": "Nervous system disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Syncope", "organSystem": "Nervous system disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Anxiety", "organSystem": "Psychiatric disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Euphoric mood", "organSystem": "Psychiatric disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 2, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 3, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Hypervigilance", "organSystem": "Psychiatric disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Tension", "organSystem": "Psychiatric disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Oropharyngeal pain", "organSystem": "Respiratory, thoracic and mediastinal disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 1, "numAtRisk": 31 } ] }, { "term": "Rhinorrhoea", "organSystem": "Respiratory, thoracic and mediastinal disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Dermatitis contact", "organSystem": "Skin and subcutaneous tissue disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Erythema", "organSystem": "Skin and subcutaneous tissue disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { 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"groupId": "EG002", "numAffected": 1, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 1, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] }, { "term": "Hypotension", "organSystem": "Vascular disorders", "sourceVocabulary": "MedDRA 13.0", "assessmentType": "NON_SYSTEMATIC_ASSESSMENT", "stats": [ { "groupId": "EG000", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG001", "numAffected": 1, "numAtRisk": 33 }, { "groupId": "EG002", "numAffected": 0, "numAtRisk": 34 }, { "groupId": "EG003", "numAffected": 0, "numAtRisk": 33 }, { "groupId": "EG004", "numAffected": 0, "numAtRisk": 32 }, { "groupId": "EG005", "numAffected": 0, "numAtRisk": 31 } ] } ] }, "moreInfoModule": { "certainAgreement": { "piSponsorEmployee": false, "restrictionType": "OTHER", "restrictiveAgreement": true, "otherDetails": "Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results." }, "pointOfContact": { "title": "Pfizer ClinicalTrials.gov Call Center", "organization": "Pfizer, Inc.", "email": "ClinicalTrials.gov_Inquiries@pfizer.com", "phone": "1-800-718-1021" } } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2026-07-09", "removedCountries": [ "Canada" ] }, "conditionBrowseModule": { "meshes": [ { "id": "D000544", "term": "Alzheimer Disease" }, { "id": "D006816", "term": "Huntington Disease" } ], "ancestors": [ { "id": "D003704", "term": "Dementia" }, { "id": "D001927", "term": "Brain Diseases" }, { "id": "D002493", "term": "Central Nervous System Diseases" }, { "id": "D009422", "term": "Nervous System Diseases" }, { "id": "D024801", "term": "Tauopathies" }, { "id": "D019636", "term": "Neurodegenerative Diseases" }, { "id": "D019965", "term": "Neurocognitive Disorders" }, { "id": "D001523", "term": "Mental Disorders" }, { "id": "D001480", "term": "Basal Ganglia Diseases" }, { "id": "D002819", "term": "Chorea" }, { "id": "D020820", "term": "Dyskinesias" }, { "id": "D009069", "term": "Movement Disorders" }, { "id": "D020271", "term": "Heredodegenerative Disorders, Nervous System" }, { "id": "D030342", "term": "Genetic Diseases, Inborn" }, { "id": "D009358", "term": "Congenital, Hereditary, and Neonatal Diseases and Abnormalities" }, { "id": "D003072", "term": "Cognition Disorders" } ] }, "interventionBrowseModule": { "meshes": [ { "id": "C010119", "term": "latrepirdine" }, { "id": "D000525", "term": "Alprazolam" } ], "ancestors": [ { "id": "D001569", "term": "Benzodiazepines" }, { "id": "D001552", "term": "Benzazepines" }, { "id": "D006574", "term": "Heterocyclic Compounds, 2-Ring" }, { "id": "D000072471", "term": "Heterocyclic Compounds, Fused-Ring" }, { "id": "D006571", "term": "Heterocyclic Compounds" } ] } }, "hasResults": true } ] }, "psychedelic dementia": { "studies": [ { "protocolSection": { "identificationModule": { "nctId": "NCT01740960", "orgStudyIdInfo": { "id": "GER001-02-03" }, "secondaryIdInfos": [ { "id": "2012-001841-42", "type": "EUDRACT_NUMBER" } ], "organization": { "fullName": "Radboud University Medical Center", "class": "OTHER" }, "briefTitle": "Safety and Tolerability of Namisol in the Elderly", "officialTitle": "Safety and Tolerability of Oral Namisol\u00ae, a Tablet Containing Delta-9-Tetrahydrocannabinol, in Elderly Subjects: A Randomized Controlled Trial", "acronym": "THC" }, "statusModule": { "statusVerifiedDate": "2012-07", "overallStatus": "COMPLETED", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2012-08" }, "primaryCompletionDateStruct": { "date": "2012-12", "type": "ACTUAL" }, "completionDateStruct": { "date": "2012-12", "type": "ACTUAL" }, "studyFirstSubmitDate": "2012-11-15", "studyFirstSubmitQcDate": "2012-11-30", "studyFirstPostDateStruct": { "date": "2012-12-04", "type": "ESTIMATED" }, "lastUpdateSubmitDate": "2014-01-06", "lastUpdatePostDateStruct": { "date": "2014-01-07", "type": "ESTIMATED" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR" }, "leadSponsor": { "name": "Radboud University Medical Center", "class": "OTHER" } }, "oversightModule": { "oversightHasDmc": false }, "descriptionModule": { "briefSummary": "The results of phase I Namisol\u00ae study (Klumpers et al. Br J Clin Pharmacol, 2012), implicate that Namisol\u00ae may have a favorable PK and PD characteristics and is safe to use in people. However, the study included only young adults with a mean age of 21.4 years. In a previous THC study, subjects age has been associated with treatment response and tolerance of adverse reactions. This association was not supported by Lane et al. and Volicer et al.\n\nThere is concern about the safety and tolerability of THC in the elderly population. This is because, elderly persons in general have higher risk of adverse drug reactions due to a combination of physiological factors such as decreasing in lean body mass, the reduction of renal and hepatic clearance, and medical comorbidity which can lead to polypharmacy and drug-drug interactions. Therefore, data from the phase I trial cannot be translated directly to an elderly (and likely more vulnerable) population. This makes it important to evaluate the safety and tolerability profiles of different Namisol\u00ae doses in the elderly. In our study in progress \"Delta-THC in Behavioral Disturbances in Dementia\", the Namisol\u00ae doses of 0,75 mg and 1,5 mg are, until now, well tolerated by elderly subjects. These doses are, however, very low in comparison with the doses used in phase I study with young adults (5 mg, 6,5 mg and 8 mg). The current study on the safety and tolerability of relatively high doses of Namisol\u00ae will help us in the future to provide broad advice on the therapeutic index and safety profile of Namisol\u00ae in the elderly population.", "detailedDescription": "Subjects will visit the site 5 times. The first visit, is a 2 hour screening visit for eligibility in which volunteers after signing informed consent will have a medical history, physical examination, ECG, hematological and biochemical blood tests, Mini Mental State Examination (MMSE), Geriatric Depression scale (GDS-30) and body sway test.\n\nEligible subjects will be randomly allocated to receive three doses Namisol\u00ae (3 mg or 5 mg or 6,5 mg) and placebo in double-blind crossover design (visit 1 to 4). The wash-out period between visits will be at least 2 weeks to a maximum of 4 weeks. Each visit will be preceded by baseline assessment measures. The safety and tolerability profiles of Namisol\u00ae will be evaluated on each intervention visit by using a standardized THC adverse effects checklist and self-reporting, vital signs, 12-lead ECG, body sway, Visual Analogue Scales (subtest feeling high), and Test for Attentional Performance (TAP, subtest alertness) and a follow up phone call the following day. Four blood samples will be collected on each visit to determine the relationship between the pharmacodynamic effects (VAS-feeling high, TAP-alertness and body sway) and the plasma concentrations of THC and its active metabolites 11-OH-THC and THC-COOH. In addition, a blood sample will be only collected on the first intervention day for genotyping of cytochrome P450 enzymes CYP2C9 CYP2C19 and CYP3A4." }, "conditionsModule": { "conditions": [ "Drug Safety" ], "keywords": [ "delta-9-tetrahydrocannabinol", "THC", "Cannabis" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "PHASE1" ], "designInfo": { "allocation": "RANDOMIZED", "interventionModel": "CROSSOVER", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "QUADRUPLE", "whoMasked": [ "PARTICIPANT", "CARE_PROVIDER", "INVESTIGATOR", "OUTCOMES_ASSESSOR" ] } }, "enrollmentInfo": { "count": 12, "type": "ACTUAL" } }, "armsInterventionsModule": { "armGroups": [ { "label": "delta-9-tetrahydrocannabinol", "type": "ACTIVE_COMPARATOR", "description": "Subjects will be randomized to receive 3 doses Namisol\u00ae (3 mg, 5 mg, 6,5 mg)", "interventionNames": [ "Drug: delta-9-tetrahydrocannabinol" ] }, { "label": "Placebo", "type": "PLACEBO_COMPARATOR", "description": "The control product is placebo, consisting of a tablet with similar appearance and taste of the test product.", "interventionNames": [ "Drug: Placebo" ] } ], "interventions": [ { "type": "DRUG", "name": "delta-9-tetrahydrocannabinol", "description": "During the intervention phases, subjects will be randomly allocated to receive 1 of 3 doses Namisol\u00ae: 3 mg, 5 mg, 6,5 mg (or placebo) The washout period between the intervention periods will be at least 2 weeks.", "armGroupLabels": [ "delta-9-tetrahydrocannabinol" ], "otherNames": [ "Namisol", "Cannabis", "ECP002A" ] }, { "type": "DRUG", "name": "Placebo", "description": "On each intervention day the subjects will receive the same amount of drugs in order to insure the blinding of the study", "armGroupLabels": [ "Placebo" ], "otherNames": [ "The control product is placebo" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "THC adverse effects checklist and self-reporting by the subjects", "description": "Safety and tolerability of Namisol\u00ae will be evaluated by assessing the incidence and severity of adverse events on each intervention visit by using a standardized THC adverse effects checklist and self-reporting by the subjects.", "timeFrame": "Pre dose, 0h30m, 1h30m and at 2h30m post ingestion" } ], "secondaryOutcomes": [ { "measure": "Body Sway Test (SwayStar\u2122)", "description": "On each intervention visit the body sway will be assessed by using the SwayStar\u00ae.The SwayStar\u00ae device consists of 2 digitally-based angular velocity transducers and is worn on the lower back (at the level of the lumbar spine, lumbar 2-3). It is a wireless device, which makes it possible to examine subjects\" balance while walking. The transducers can accurately assess angular movement and angular velocities in 2 directions: anterior-posterior (pitch plane) and mediolateral (roll plane)", "timeFrame": "Pre dose, 0h40m, 0h55m and at 2 hour post ingestion" }, { "measure": "Visual analogue scales, subtest \"feeling high\"", "description": "The Bowdle visual analogue scales (VAS) of psychedelic effects will be performed on each intervention visit in order to measure subjective feeling high", "timeFrame": "Pre dose, 0h40m, 0h55m and at 2 hour post ingestion" }, { "measure": "Test for Attentional Performance (TAP), subtest alertness", "description": "On each intervention visit the alertness of subjects will be measured by using the TAP. The TAP subtest \"Alertness\" measures the subject's ability to respond to a visual stimulus and to increase the attentional level in expectance of a stimulus of high priority. The computer-assisted test is given under 2 conditions: (1) Simple reaction time to a visual stimulus (Greek cross) appearing at randomly varying intervals on the monitor screen is measured. (2) In the second condition, the visual stimulus (= critical stimulus) is preceded by a cue sound presented as warning tone.", "timeFrame": "Pre dose, 0h40m, 0h55m and at 2 hour post ingestion" }, { "measure": "Plasma concentrations of THC and its active metabolites 11-OH-THC and THC-COOH", "description": "Four blood samples will be collected on each visit to determine the relationship between the pharmacodynamic effects ( using VAS-feeling high, TAP-alertness and body sway) and the plasma concentrations of THC and its active metabolite 11-OH-THC and THC-COOH.", "timeFrame": "Pre dose, 0h40m, 0h55m and at 2 hour post ingestion" } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria:\n\n* Subject is a healthy old person as established by medical history, physical examination, electrocardiography, results of hematological and biochemical blood tests on screening.\n* Age 65 years\n* Body mass index between 18.0 and 30 kg m-2\n* Subject is able and willing to sign the Informed Consent Form prior to screening evaluations\n\nExclusion Criteria:\n\n* Regular cannabis user, defined as: smoking one or more joints per week\n* Documented history of sensitivity/idiosyncrasy to cannabis\n* Relevant history or presence of severe pulmonary disorders \\[e.g. COPD GOLD III or IV\\], serious cardiovascular disorders \\[e.g. myocardial infarction \\< 6 months ago; atrial fibrillation; heart failure NYHA III or IV; severe heart valve disease, orthostatic hypotension defined as systolic drop of 20 mm Hg Safety and Tolerability of Namisol in the Elderly Page 8 Version 2, 10 07 2012 or diastolic drop of 10 mm Hg\\], seizures, migraine, psychiatric disorders \\[e.g. depression (based on documented history or GDS-30 on screening \u2265 10); mania; psychosis; dementia\\], cognitive impairment \\[based on documented history or MMSE on screening \\< 28, significant renal (GFR \\< 30 ml/min) or hepatic disorders \\[e.g. cancer, cirrhosis. ALT or AST \u2265 twice the upper limit of normal\\], diabetes mellitus, coagulation disorders\n* Inability to understand the nature and extent of the trial and the procedures required\n* Current alcohol abuse or use of more than 2 alcoholic consumptions daily\n* History of, or current drug abuse\n* Using drugs that are inhibitors of CYP2C9, CYP2C19 and CYP3A4 (see appendix 13.3)\n* Participation in a drug trial within 60 days prior to the first intervention day\n* Donation of blood within 60 days prior to the first intervention day\n* Known lactose intolerance\n* Using more than six units of (methyl)xanthine products per day (e.g. coffee, tea, cola, chocolate)\n* Smoking more than ten cigarettes per day\n* High fall-risk (based on body sway test)", "healthyVolunteers": true, "sex": "ALL", "minimumAge": "65 Years", "stdAges": [ "OLDER_ADULT" ] }, "contactsLocationsModule": { "overallOfficials": [ { "name": "Marcel Olde Rikkert, prof. dr.", "affiliation": "Radboud University Medical Center Nijmegen", "role": "PRINCIPAL_INVESTIGATOR" } ], "locations": [ { "facility": "Radboud University Medical Centre, department of Geriatrics", "city": "Nijmegen", "state": "Gelderland", "country": "Netherlands", "geoPoint": { "lat": 51.8425, "lon": 5.85278 } } ] } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2026-07-09" }, "conditionBrowseModule": { "meshes": [ { "id": "D002189", "term": "Marijuana Abuse" } ], "ancestors": [ { "id": "D019966", "term": "Substance-Related Disorders" }, { "id": "D064419", "term": "Chemically-Induced Disorders" }, { "id": "D001523", "term": "Mental Disorders" } ] }, "interventionBrowseModule": { "meshes": [ { "id": "D013759", "term": "Dronabinol" }, { "id": "C587251", "term": "nabiximols" } ], "ancestors": [ { "id": "D002186", "term": "Cannabinoids" }, { "id": "D013729", "term": "Terpenes" }, { "id": "D006838", "term": "Hydrocarbons" }, { "id": "D009930", "term": "Organic Chemicals" } ] } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT07091747", "orgStudyIdInfo": { "id": "DAZACANN Open-Label Phase" }, "secondaryIdInfos": [ { "id": "CAAE: 86640925.4.0000.8527", "type": "REGISTRY", "domain": "BRAZIL PLATFORM" } ], "organization": { "fullName": "Federal University of Latin American Integration", "class": "OTHER" }, "briefTitle": "Use of a Product Containing the Cannabinoids CBD and THC as a Treatment Strategy for Alzheimer's Disease - Alzheimer's Disease and Cannabis Clinical Trial (DAZACANN) Open-Label Phase", "officialTitle": "Use of a Product Containing the Cannabinoids CBD and THC as a Treatment Strategy for Alzheimer's Disease - Alzheimer's Disease and Cannabis Clinical Trial (DAZACANN) Open-Label Phase", "acronym": "DAZA OPEN" }, "statusModule": { "statusVerifiedDate": "2025-08", "overallStatus": "ACTIVE_NOT_RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2025-04-07", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2025-12-12", "type": "ESTIMATED" }, "completionDateStruct": { "date": "2025-12-12", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2025-07-21", "studyFirstSubmitQcDate": "2025-07-21", "studyFirstPostDateStruct": { "date": "2025-07-29", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2025-08-07", "lastUpdatePostDateStruct": { "date": "2025-08-12", "type": "ACTUAL" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "PRINCIPAL_INVESTIGATOR", "investigatorFullName": "FRANCISNEY PINTO DO NASCIMENTO", "investigatorTitle": "University Professor", "investigatorAffiliation": "Federal University of Latin American Integration" }, "leadSponsor": { "name": "Federal University of Latin American Integration", "class": "OTHER" }, "collaborators": [ { "name": "Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico", "class": "OTHER_GOV" } ] }, "oversightModule": { "oversightHasDmc": true, "isFdaRegulatedDrug": false, "isFdaRegulatedDevice": false }, "descriptionModule": { "briefSummary": "Alzheimer's Disease (AD) has become a significant public health issue due to the increase in its incidence from 2.0 to 16.8 cases per thousand people in a year, based on 2022 data. As many countries experience population aging, there is an increase in the prevalence of AD cases, which is the main form of dementia in the elderly. It commonly begins around the age of 60, with aging being the primary risk factor. AD is a neurodegenerative disorder characterized by the presence of extracellular beta-amyloid plaques and intracellular neurofibrillary tangles of Tau protein. Among the main symptoms of AD is progressive memory loss, with varying degrees of cognitive impairment. These symptoms share common clinical features such as a progressive decline in cognitive functions, including abstract thinking, judgment, language, personality changes, and behavioral symptoms, as well as the emergence of certain comorbidities.\n\nAs there are currently no curative treatments for this disease, pharmacotherapy aims to control the progressive symptoms, improving cognitive and functional aspects in patients, and consequently their quality of life. In this context, there is a need for further research to identify effective drugs that can delay or alleviate symptoms.\n\nThis study is part of the second phase of the project entitled: Use of a Product Containing the Cannabinoids CBD and THC as a Treatment Strategy for Alzheimer's Disease - Alzheimer's Disease and Cannabis Clinical Trial (DAZACANN): A randomized, double-blind, placebo-controlled clinical trial previously approved by the Human Ethics Committee - CEP (CAAE 60167722.6.0000.0107). The trial is being finalized at the Laboratory of Medicinal Cannabis and Psychedelic Science, located in the city of Foz do Igua\u00e7u, Paran\u00e1, and will continue with a new experimental design, now as an open-label trial (all participants will receive the extract and will be informed about the formulation they are receiving).\n\nThe objective of this study remains to evaluate the clinical and biochemical effects of using cannabinoid-based products with low doses of purified CBD and THC, both individually and in combination, in patients with AD." }, "conditionsModule": { "conditions": [ "Alzheimer Disease (AD)" ], "keywords": [ "Alzheimer's Disease", "Cannabidiol (CBD)", "Tetrahydrocannabinol (THC)", "Open Label" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "PHASE1", "PHASE2" ], "designInfo": { "allocation": "NA", "interventionModel": "SINGLE_GROUP", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "NONE" } }, "enrollmentInfo": { "count": 61, "type": "ACTUAL" } }, "armsInterventionsModule": { "armGroups": [ { "label": "Open label group", "type": "EXPERIMENTAL", "description": "They will use the extract at a daily dose of 50 mg of CBD and 5 mg of THC from a product with a CBD:THC concentration of 50 mg/ml:5 mg/ml for a period of 24 months.", "interventionNames": [ "Other: Cannabis 50 mg of CBD and 5 mg of THC" ] } ], "interventions": [ { "type": "OTHER", "name": "Cannabis 50 mg of CBD and 5 mg of THC", "description": "Cannabis 50 mg of CBD and 5 mg of THC", "armGroupLabels": [ "Open label group" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "Mini Mental State Examination", "description": "Assess cognitive function and disease progression. Cognitive function preserved (27 to 30 points), Mild cognitive impairment (21 to 26 points), Moderate cognitive impairment (10 to 20 points), Severe cognitive impairment (0 to 9 points).", "timeFrame": "24 months" } ], "secondaryOutcomes": [ { "measure": "Neuropsychiatric Inventory", "description": "Identify neuropsychiatric symptoms across different domains using the Neuropsychiatric Inventory. Score Range: 0-20 Mild symptoms or no significant impairment, 21-50 Moderate symptoms, 51-120 Severe symptoms with major impact", "timeFrame": "24 months" }, { "measure": "Quality of Life in Alzheimer's Disease scale (QoL-AD)", "description": "The scale has 3 versions, one of which is applied to the patient, another to the caregiver to answer about the patient's life, and one for the caregiver to answer about their own life. The score may vary, the one the investigators will use is the sum of the questionnaires about the patient, caregiver version and patient version, with the patient version having a weight of 2. Its score varies from 13, indicating the worst possible quality of life, up to 52, and the higher the score, the higher the quality of life.", "timeFrame": "24 month" }, { "measure": "Epworth Sleepiness Scale (ESS )", "description": "Evaluates 8 items with scores ranging from 0 to 24, in which scores higher than 10 indicate sleep disturbances.", "timeFrame": "24 month" }, { "measure": "Specific markers of Alzheimer's disease", "description": "The following proteins will be quantified in the cerebrospinal fluid: beta-amyloid 40, beta-amyloid 42, tau protein (fraction 181), and phosphorylated tau protein.", "timeFrame": "24 month" }, { "measure": "Brain Derived Neurotrophic Factor", "description": "It will be measured in serum or plasma", "timeFrame": "24 month" }, { "measure": "Inflammatory markers", "description": "TNF\u03b1 (Tumor Necrosis Factor alpha), IL-6 (Interleukin-6), IL-1\u03b2 (Interleukin-1 beta), and IL-10 (Interleukin-10), it will be measured in serum or plasma.", "timeFrame": "24 month" }, { "measure": "Safety Endpoints - UKU Side Effect Rating Scale", "description": "Will be conducted on patients and caregivers during all planned visits to ascertain the frequency and severity of adverse events. There will be neurological and physical examinations as well as laboratory testing. Total Score Sum of all 48 item scores (minimum 0; maximum 144), indicates greater overall severity of psychotropic side effects.", "timeFrame": "24 month" } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria:\n\n* Have participated in and completed all assessments conducted in the first phase of the project.\n* Agree to and sign a new informed consent form.\n\nExclusion Criteria:\n\n* Patients who did not participate in the first stage.\n* Patients who began participating in the first stage but withdrew at any time.\n* Patients who do not agree and/or fail to sign the new informed consent form", "healthyVolunteers": false, "sex": "ALL", "minimumAge": "60 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ] }, "contactsLocationsModule": { "locations": [ { "facility": "Universidade Federal da Integra\u00e7\u00e3o Latino-Americana", "city": "Foz do Igua\u00e7u", "state": "Paran\u00e1", "zip": "85870-650", "country": "Brazil", "geoPoint": { "lat": -25.54778, "lon": -54.58806 } } ] }, "ipdSharingStatementModule": { "ipdSharing": "NO" } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2026-07-09" }, "conditionBrowseModule": { "meshes": [ { "id": "D000544", "term": "Alzheimer Disease" } ], "ancestors": [ { "id": "D003704", "term": "Dementia" }, { "id": "D001927", "term": "Brain Diseases" }, { "id": "D002493", "term": "Central Nervous System Diseases" }, { "id": "D009422", "term": "Nervous System Diseases" }, { "id": "D024801", "term": "Tauopathies" }, { "id": "D019636", "term": "Neurodegenerative Diseases" }, { "id": "D019965", "term": "Neurocognitive Disorders" }, { "id": "D001523", "term": "Mental Disorders" } ] }, "interventionBrowseModule": { "meshes": [ { "id": "C587251", "term": "nabiximols" }, { "id": "D013759", "term": "Dronabinol" } ], "ancestors": [ { "id": "D002186", "term": "Cannabinoids" }, { "id": "D013729", "term": "Terpenes" }, { "id": "D006838", "term": "Hydrocarbons" }, { "id": "D009930", "term": "Organic Chemicals" } ] } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT06570928", "orgStudyIdInfo": { "id": "DAZACANN" }, "organization": { "fullName": "Federal University of Latin American Integration", "class": "OTHER" }, "briefTitle": "Use of a Cannabinoids as a Treatment Strategy for Alzheimer's Disease", "officialTitle": "Use of a Product Containing the Cannabinoids CBD and THC as a Treatment Strategy for Alzheimer's Disease - Clinical Trial Alzheimer's Disease and Cannabis (DAZACANN)", "acronym": "DAZACANN" }, "statusModule": { "statusVerifiedDate": "2025-05", "overallStatus": "COMPLETED", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2024-08-13", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2024-08-27", "type": "ACTUAL" }, "completionDateStruct": { "date": "2025-03-27", "type": "ACTUAL" }, "studyFirstSubmitDate": "2024-08-19", "studyFirstSubmitQcDate": "2024-08-22", "studyFirstPostDateStruct": { "date": "2024-08-26", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2025-05-20", "lastUpdatePostDateStruct": { "date": "2025-05-25", "type": "ACTUAL" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "PRINCIPAL_INVESTIGATOR", "investigatorFullName": "FRANCISNEY PINTO DO NASCIMENTO", "investigatorTitle": "Professor and Coordinator of the Laboratory of Medicinal Cannabis and Psychedelic Science", "investigatorAffiliation": "Federal University of Latin American Integration" }, "leadSponsor": { "name": "Federal University of Latin American Integration", "class": "OTHER" } }, "oversightModule": { "oversightHasDmc": true, "isFdaRegulatedDrug": false, "isFdaRegulatedDevice": false }, "descriptionModule": { "briefSummary": "Brief Summary:\n\nThe objective of the study is to evaluate the effect of cannabinoids on Alzheimer's Disease. This is a double-blind, randomized, placebo-controlled clinical trial. The study aims to recruit patients of both sexes diagnosed with Alzheimer's Disease who are in the mild and moderate stages for treatment with cannabinoids.\n\nThe specific objectives of the study are:\n\nPrimary Outcome\n\n* To evaluate the effect of Cannabis sativa at low doses according to the Mini-Mental State Examination (MMSE) scale - Memory and Cognition test - in patients with Alzheimer's Disease.\n\nSecondary Outcomes\n\n* To evaluate the effect of Cannabis sativa at low doses according to the Cornell scale - Depression in dementia test.\n* To evaluate the effect of Cannabis sativa at low doses according to the GDS scale - Depression in elderly people test.\n* To evaluate the effect of Cannabis sativa at low doses according to the QoL scale - Quality of Life test.\n* To evaluate the effect of Cannabis sativa at low doses according to the Epworth scale - Drowsiness test.\n* To evaluate the adverse effects of Cannabis sativa at low doses given daily for 26 weeks in patients with Alzheimer's Disease.\n\nParticipants will use a compound containing CBD/THC 50/5 mg/mL, administered as 0.2 mL once a day. The placebo group will use a compound identical to the treatment but containing only vehicle. To address the questions above, the treated group will be compared with the placebo group over a period of 6 months. Participants will be assessed every 2 months. Additionally, blood and cerebrospinal fluid tests will be conducted to measure specific proteins related to Alzheimer's Disease and inflammatory markers.", "detailedDescription": "Alzheimer's disease (AD) is closely linked to the accumulation of neurotoxins derived from A\u03b2 and tau, leading to cognitive impairment. This project posits that an imbalance in the endocannabinoid system occurs in an AD-dependent manner. Reported connections between dementia, inflammation, A\u03b2, and alterations in the cannabinoid system in experimental models of AD support this hypothesis. Cannabinoids may restore baseline brain function while avoiding major side effects. Despite extensive research into new AD therapies, no significant improvement has been achieved recently, and there is little consensus on how scientists will innovate to develop a new treatment. Cannabinoid-based therapy has emerged as crucial for the treatment of many diseases considered incurable. The expected results of this project will provide important insights into the ability of cannabinoids to counteract neurochemical imbalance during AD progression, thereby improving memory performance and affecting inflammation as well as A\u03b2 and tau levels.\n\nThe key point is to provide evidence that cannabinoids can serve as an efficient treatment for AD while avoiding major side effects. The aim of this project is to determine the effect of cannabinoids in AD patients, evaluating memory and cognition. It is expected that the results will establish that cannabinoids are critical for restoring the baseline function of the endocannabinoid system in AD brains and their beneficial effects. This project may be instrumental in validating new therapeutic approaches for AD.\n\nTo evaluate the pharmacological activity of low doses of CBD, a double-blind, randomized, placebo-controlled clinical trial will be conducted for a duration of 6 months. A baseline assessment will be performed, and patients will be evaluated every 60 days for a period of 6 months, totaling 4 evaluation sessions. For this purpose, the following questionnaires will be applied: Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS), Alzheimer's Disease Quality of Life version patient, version caregiver and caregiver-patient version, Cornell Depression in Dementia Scale, and Epworth Sleepiness Scale. All questionnaires are references in their assessment domains and are validated for Portuguese/Brazil. In addition to the evaluation scales, biological material will be collected with blood and cerebrospinal fluid samples at baseline and at the end (after 6 months). The following analytes will be measured in the CSF: BDNF, beta-amyloid, Tau protein, TNF\u03b1, IL-6, IL-1\u03b2, and IL-10. During the research and data collection, patients' conventional treatments will not be altered.\n\nStatistical Analysis Plan SPSS software, version 29.0 will be used for the analyses. For quantitative data, the Shapiro-Wilk distribution test will be performed. Potential associations between qualitative variables will be analyzed using the Chi-Square test with adjusted residual analysis (\u03c7\u00b2). The means (\u00b1SD) will be analyzed using the Student's t test for independent samples. Medians \\[IQR\\] will be calculated using the Mann-Whitney U test. Paired quantitative data will be compared individually by group across the analyzed time points using Friedman's ANOVA test.\n\nA generalized estimating equations (GEE) model, linear or with log-gamma link, and Bonferroni correction will be used to simultaneously evaluate quantitative parameters over time and between groups. For these descriptive analyses, data will be presented as means \u00b1 standard errors (\u00b1SEM). Pearson or Spearman correlations can be performed between variables of interest. For all analyses, the significance level will be set at 5%." }, "conditionsModule": { "conditions": [ "Alzheimer Disease" ], "keywords": [ "Alzheimer Disease", "Cannabinoids", "Cannabidiol", "Tetrahydrocannabinol (THC)", "Nervous System Diseases" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "PHASE2" ], "designInfo": { "allocation": "RANDOMIZED", "interventionModel": "PARALLEL", "interventionModelDescription": "72 patients will be randomized into 2 groups. One group will receive a product containing CBD/THC and the other group will receive a placebo, a compound with the same characteristics, without an active ingredient.", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "TRIPLE", "maskingDescription": "Participants and caregivers will not know what they are using. The investigators evaluating it won't know either. Only a team member who is not part of the investigative team will know.", "whoMasked": [ "PARTICIPANT", "CARE_PROVIDER", "INVESTIGATOR" ] } }, "enrollmentInfo": { "count": 72, "type": "ACTUAL" } }, "armsInterventionsModule": { "armGroups": [ { "label": "Placebo arm", "type": "PLACEBO_COMPARATOR", "description": "Patients will receive a liquid solution only with vehicle and no cannabinoid.", "interventionNames": [ "Other: Placebo" ] }, { "label": "Experimental arm", "type": "EXPERIMENTAL", "description": "Patients will receive the dose of 0,2 ml of a compound contain CBD:THC (50 mg:5 mg).", "interventionNames": [ "Other: Cannabis" ] } ], "interventions": [ { "type": "OTHER", "name": "Cannabis", "description": "0,2 ml of CBD:THC (50 mg:5 mg)", "armGroupLabels": [ "Experimental arm" ], "otherNames": [ "CBD:THC (50 mg:5 mg)" ] }, { "type": "OTHER", "name": "Placebo", "description": "Product vehicle, medium chain triglycerides (MCT)", "armGroupLabels": [ "Placebo arm" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "Mini Mental State Exam (MMSE)", "description": "scores range from 0 to 30, with higher scores indicating cognitive improvement.", "timeFrame": "The participants will be evaluated before starting treatment, and then every 60 days until 180 days are complete, resulting in 4 evaluations." } ], "secondaryOutcomes": [ { "measure": "Neuropsychiatric Inventory-Questionnaire (NPI-Q)", "description": "Assesses neuropsychiatric symptoms in patients with dementia. Evaluates 12 symptoms in the following domains: delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor behaviors, nocturnal behavioral disorders, and appetite disorders. The score ranges from 0 to 144.", "timeFrame": "The participants will be evaluated before starting treatment, and then every 60 days until 180 days are complete, resulting in 4 evaluations." }, { "measure": "Geriatric Depression Scale (GDS)", "description": "Assesses depressive symptoms in the elderly. The investigators will use the short version, which has a score from 0 to 15. The higher the score, the greater the depressive symptoms.", "timeFrame": "The participants will be evaluated before starting treatment, and then every 60 days until 180 days are complete, resulting in 4 evaluations." }, { "measure": "Quality of Life in Alzheimer's Disease scale (QoL-AD)", "description": "The scale has 3 versions, one of which is applied to the patient, another to the caregiver to answer about the patient's life, and one for the caregiver to answer about their own life. The score may vary, the one the investigators will use is the sum of the questionnaires about the patient, caregiver version and patient version, with the patient version having a weight of 2. Its score varies from 13, indicating the worst possible quality of life, up to 52, and the higher the score, the higher the quality of life.", "timeFrame": "The participants will be evaluated before starting treatment, and then every 60 days until 180 days are complete, resulting in 4 evaluations." }, { "measure": "Cornell Scale for Depression in Dementia (CSDD)", "description": "Assess symptoms of depression in patients with dementia. Has 19 questions applied to caregiver and patient. The maximum score is 38 points, with scores higher than 10 indicating probable major depression and greater than 18 as major depression.", "timeFrame": "The participants will be evaluated before starting treatment, and then every 60 days until 180 days are complete, resulting in 4 evaluations." }, { "measure": "Epworth Sleepiness Scale (ESS )", "description": "Evaluates 8 items with scores ranging from 0 to 24, in which scores higher than 10 indicate sleep disturbances.", "timeFrame": "The participants will be evaluated before starting treatment, and then every 60 days until 180 days are complete, resulting in 4 evaluations." }, { "measure": "Specific markers of Alzheimer's disease: Beta-amyloid 40, beta-amyloid 42, tau protein (fraction 181), and phosphorylated tau protein", "description": "The following proteins will be quantified in the cerebrospinal fluid: beta-amyloid 40, beta-amyloid 42, tau protein (fraction 181), and phosphorylated tau protein.", "timeFrame": "Collections will be made at the initial time, before the start of treatment and at the end time, after 180 days." }, { "measure": "BDNF (Brain Derived Neurotrophic Factor)", "description": "It will be measured in serum or plasma", "timeFrame": "Collections will be made at the initial time, before the start of treatment and at the end time, after 180 days." }, { "measure": "Inflammatory markers: TNF\u03b1 (Tumor Necrosis Factor alpha), IL-6 (Interleukin-6), IL-1\u03b2 (Interleukin-1 beta), and IL-10 (Interleukin-10)", "description": "It will be measured in serum or plasma", "timeFrame": "Collections will be made at the initial time, before the start of treatment and at the end time, after 180 days." } ], "otherOutcomes": [ { "measure": "Safety Endpoints - UKU Side Effect Rating Scale", "description": "Will be conducted on patients and caregivers during all planned visits to ascertain the frequency and severity of adverse events. There will be neurological and physical examinations as well as laboratory testing.", "timeFrame": "The participants will be evaluated before starting treatment, and then every 60 days until 180 days are complete, resulting in 4 evaluations." } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria:\n\n* Be over 60 years old;\n* Have been diagnosed with AD at least 1 year ago;\n* Present mild to moderate symptoms of AD.\n\nExclusion Criteria:\n\n* Have a diagnosis of other dementias or factors correlated;\n* Present psychosis or first-degree relatives with a history from psychosis, schizophrenia, epilepsy;\n* Individuals with a history of psychoactive substance abuse will be included in the study;\n* Present severe symptoms of AD.", "healthyVolunteers": true, "sex": "ALL", "minimumAge": "60 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ] }, "contactsLocationsModule": { "overallOfficials": [ { "name": "Taynara Silva, 1", "affiliation": "Universidade Federal de Santa Catarina", "role": "PRINCIPAL_INVESTIGATOR" } ], "locations": [ { "facility": "Federal University of Latin American Integration", "city": "Foz do Igua\u00e7u", "state": "Paran\u00e1", "zip": "85870-650", "country": "Brazil", "geoPoint": { "lat": -25.54778, "lon": -54.58806 } } ] }, "ipdSharingStatementModule": { "ipdSharing": "NO" } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2026-07-09" }, "conditionBrowseModule": { "meshes": [ { "id": "D000544", "term": "Alzheimer Disease" }, { "id": "D009422", "term": "Nervous System Diseases" } ], "ancestors": [ { "id": "D003704", "term": "Dementia" }, { "id": "D001927", "term": "Brain Diseases" }, { "id": "D002493", "term": "Central Nervous System Diseases" }, { "id": "D024801", "term": "Tauopathies" }, { "id": "D019636", "term": "Neurodegenerative Diseases" }, { "id": "D019965", "term": "Neurocognitive Disorders" }, { "id": "D001523", "term": "Mental Disorders" } ] }, "interventionBrowseModule": { "meshes": [ { "id": "C587251", "term": "nabiximols" } ] } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT04123314", "orgStudyIdInfo": { "id": "IRB00175915" }, "organization": { "fullName": "Johns Hopkins University", "class": "OTHER" }, "briefTitle": "Psilocybin for Depression in People With Mild Cognitive Impairment or Early Alzheimer's Disease", "officialTitle": "Pilot Study of Serotonin 2A Receptor (5-HT2A) Agonist Psilocybin for Depression in Patients With Mild Cognitive Impairment or Early Alzheimer's Disease" }, "statusModule": { "statusVerifiedDate": "2026-03", "overallStatus": "RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2021-03-24", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2026-09-30", "type": "ESTIMATED" }, "completionDateStruct": { "date": "2026-12-31", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2019-10-09", "studyFirstSubmitQcDate": "2019-10-09", "studyFirstPostDateStruct": { "date": "2019-10-10", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2026-03-12", "lastUpdatePostDateStruct": { "date": "2026-03-16", "type": "ACTUAL" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR" }, "leadSponsor": { "name": "Johns Hopkins University", "class": "OTHER" }, "collaborators": [ { "name": "Council On Spiritual Practices", "class": "UNKNOWN" }, { "name": "Heffter Research Institute", "class": "OTHER" } ] }, "oversightModule": { "oversightHasDmc": false, "isFdaRegulatedDrug": true, "isFdaRegulatedDevice": false }, "descriptionModule": { "briefSummary": "This open-label pilot study examines whether the hallucinogenic drug, psilocybin, given under supportive conditions, is safe and effective for depression in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD). This study will also assess whether psilocybin may improve quality of life in those individuals.", "detailedDescription": "This is a pilot study evaluating the potential efficacy of psilocybin to produce improvement in depression compared to pre-treatment in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD) and clinically significant symptoms of depression. The study will be an open-label trial in a sample of up to 20 treatment-seeking participants with a diagnosis of MCI or early AD. Participants will complete an 8-week course of study treatment including two psilocybin sessions (15 mg/70 kg in week 4 and 15 or 25 mg/70 kg in week 6), with follow-up assessments up to 6 months after the final psilocybin session. The study will assess changes in depressed mood at 1 week after the second psilocybin session compared to pre-treatment, and quality of life in participants from pre- to post-treatment." }, "conditionsModule": { "conditions": [ "Depressive Symptoms", "Depression", "Alzheimer Disease", "Mild Cognitive Impairment" ], "keywords": [ "Psilocybin", "Hallucinogen", "Psychedelic" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "EARLY_PHASE1" ], "designInfo": { "allocation": "NA", "interventionModel": "SINGLE_GROUP", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "NONE" } }, "enrollmentInfo": { "count": 20, "type": "ESTIMATED" } }, "armsInterventionsModule": { "armGroups": [ { "label": "Psilocybin", "type": "EXPERIMENTAL", "description": "Participants will complete an 8-week course of study treatment including weekly psychological support and two moderate to high dose psilocybin administrations in weeks 4 and 6.", "interventionNames": [ "Drug: Psilocybin" ] } ], "interventions": [ { "type": "DRUG", "name": "Psilocybin", "description": "Dosing at the first session will be 15 mg/70 kg. For the second session participants will either remain at the initial dose, or increase to 25 mg/70 kg at the discretion of the study team.", "armGroupLabels": [ "Psilocybin" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "Change in Cornell Scale for Depression in Dementia (CSDD) score", "description": "The Cornell Scale for Depression in Dementia (CSDD) is administered via patient and informant interviews to assess the presence and severity of depressive mood and behavioral symptoms during the past week. Has 19 items, each scored from 0 to 2 with higher scores indicating severe symptom.Total score range from 0 to 38.", "timeFrame": "Baseline and 1 week after second psilocybin session" } ], "secondaryOutcomes": [ { "measure": "Change in Quality of Life Alzheimer's Disease (QOL-AD) scale score", "description": "The Quality of Life Alzheimer's Disease (QOL-AD) scale is a 13-item measure administered via patient and informant interviews to assess overall mood, physical and cognitive function, and quality of relationships in people with Alzheimer's Disease. Each item is scored 1 to 4, with higher score indicating better quality of life. Total score range from 13 to 52.", "timeFrame": "Baseline and 2 weeks after second psilocybin session" } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria:\n\n* Must meet either A) Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) criteria for Mild Neurocognitive Disorder due to AD or Major Neurocognitive Disorder due to AD with Mild severity (including probable), or B) meet criteria for MCI including a subjective memory complaint relative to previous functioning and confirmed by Clinical Dementia Rating (CDR) Memory score at screening of \\>0.5\n* Have Mini-Mental State Examination scores \\>18\n* Have a Montreal Cognitive Assessment score \\<26.\n* Have Cornell Scale for Depression in Dementia (CSDD) patient score \\>/= 6, or Geriatric Depression Scale-Short Form score \u2265 5, indicating at minimum a mild to moderate degree of distress.\n* Acetylcholinesterase inhibitors are allowed so long as the dose has been stable for \\> 6 weeks.\n* Concurrent pharmacotherapy with selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), and/or bupropion is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening. Allowable bupropion doses for participants will be \u2264300mg/day.\n* Have a close friend or family member willing and able to serve the role of community observer / informant for data collection procedures\n\nExclusion Criteria:\n\n* Individuals 86 years of age or older will be excluded.\n* Currently taking antipsychotics, monoamine oxidase (MAO) inhibitors, or antidepressant medications other than SSRIs, SNRIs, or bupropion. Allowable bupropion doses for participants will be \u2264300mg/day.\n* Long-acting opioid pain medications (e.g. oxycodone sustained release, morphine sustained release - which are usually taken at 12 hour intervals) will be allowed if the last dose occurred at least 2 hours before psilocybin administration and the next dose was not scheduled until at least 8 hours after psilocybin administration.\n* Participants must agree not to take sildenafil, tadalafil, or similar medications within 72 hours of each psilocybin administration, as these medications may potentiate hypotensive reactions to psilocybin\n* Cardiovascular conditions: angina, a clinically significant ECG abnormality (e.g. atrial fibrillation or heart-rate corrected QT interval (QTc) \\>450msec), Transient Ischemic Attack (TIA) in the last 6 months, stroke, artificial heart valves, or uncontrolled hypertension with resting blood pressure systolic \\>150 or diastolic \\>95\n* Minimum acceptable heartrate at screening is 50 bpm unless the individual is cleared for participation by a cardiologist, in accord with the American College of Cardiology's 2018 guidelines for bradycardia\n* Seizure disorder\n* Insulin dependent diabetes mellitus\n* Renal disease (creatinine clearance \\< 40 ml/min using the Cockcroft and Gault equation)\n* Baseline liver enzyme elevation \\>2x the upper limit of normal\n* Current or past history of meeting DSM-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder\n* Family (i.e., 1st degree relative) history of Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder\n* Past-year hallucinogen use.", "healthyVolunteers": false, "sex": "ALL", "minimumAge": "18 Years", "maximumAge": "85 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ] }, "contactsLocationsModule": { "centralContacts": [ { "name": "Ian Geithner, MPS", "role": "CONTACT", "phone": "4105505466", "email": "igeithn1@jhmi.edu" }, { "name": "Albert Garcia-Romeu, PhD", "role": "CONTACT", "phone": "4105501972", "email": "agarci33@jhmi.edu" } ], "overallOfficials": [ { "name": "Albert Garcia-Romeu, PhD", "affiliation": "Johns Hopkins University", "role": "PRINCIPAL_INVESTIGATOR" } ], "locations": [ { "facility": "Johns Hopkins Center for Psychedelic and Consciousness Research", "status": "RECRUITING", "city": "Baltimore", "state": "Maryland", "zip": "21224", "country": "United States", "contacts": [ { "name": "Ian Geithner, MPS", "role": "CONTACT", "phone": "410-550-5466", "email": "igeithn1@jhmi.edu" }, { "name": "Albert Garcia-Romeu, PhD", "role": "CONTACT", "phone": "410-550-1972", "email": "agarci33@jhmi.edu" }, { "name": "Albert Garcia-Romeu, PhD", "role": "PRINCIPAL_INVESTIGATOR" }, { "name": "Paul B Rosenberg, MD", "role": "PRINCIPAL_INVESTIGATOR" } ], "geoPoint": { "lat": 39.29038, "lon": -76.61219 } } ] }, "referencesModule": { "seeAlsoLinks": [ { "label": "Study information and application form", "url": "https://www.hopkinspsychedelic.org/alzheimers-study" } ] }, "ipdSharingStatementModule": { "ipdSharing": "NO" } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2026-07-09" }, "conditionBrowseModule": { "meshes": [ { "id": "D003863", "term": "Depression" }, { "id": "D000544", "term": "Alzheimer Disease" }, { "id": "D060825", "term": "Cognitive Dysfunction" } ], "ancestors": [ { "id": "D001526", "term": "Behavioral Symptoms" }, { "id": "D001519", "term": "Behavior" }, { "id": "D003704", "term": "Dementia" }, { "id": "D001927", "term": "Brain Diseases" }, { "id": "D002493", "term": "Central Nervous System Diseases" }, { "id": "D009422", "term": "Nervous System Diseases" }, { "id": "D024801", "term": "Tauopathies" }, { "id": "D019636", "term": "Neurodegenerative Diseases" }, { "id": "D019965", "term": "Neurocognitive Disorders" }, { "id": "D001523", "term": "Mental Disorders" }, { "id": "D003072", "term": "Cognition Disorders" } ] }, "interventionBrowseModule": { "meshes": [ { "id": "D011562", "term": "Psilocybin" } ], "ancestors": [ { "id": "D026121", "term": "Indole Alkaloids" }, { "id": "D000470", "term": "Alkaloids" }, { "id": "D006571", "term": "Heterocyclic Compounds" }, { "id": "D007211", "term": "Indoles" }, { "id": "D006574", "term": "Heterocyclic Compounds, 2-Ring" }, { "id": "D000072471", "term": "Heterocyclic Compounds, Fused-Ring" }, { "id": "D014363", "term": "Tryptamines" }, { "id": "D054836", "term": "Indolizidines" }, { "id": "D007212", "term": "Indolizines" } ] } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT06812221", "orgStudyIdInfo": { "id": "BMND08-03" }, "organization": { "fullName": "Biomind Labs Inc.", "class": "INDUSTRY" }, "briefTitle": "Efficacy of Sublingual 5-MeO-DMT for Reducing Anxiety and Depression in MCI", "officialTitle": "A Phase 1/2 Randomized, Double-Blind, Placebo-Controlled Trial of Multiple Sublingual 5-MeO-DMT Microdoses for Reducing Anxiety and/or Depression in Patients With Mild Cognitive Impairment.", "acronym": "5-MeO-DMT" }, "statusModule": { "statusVerifiedDate": "2024-11", "overallStatus": "COMPLETED", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2024-12-15", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2025-02-15", "type": "ACTUAL" }, "completionDateStruct": { "date": "2025-03-15", "type": "ACTUAL" }, "studyFirstSubmitDate": "2024-12-10", "studyFirstSubmitQcDate": "2025-01-31", "studyFirstPostDateStruct": { "date": "2025-02-06", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2025-04-08", "lastUpdatePostDateStruct": { "date": "2025-04-09", "type": "ACTUAL" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR" }, "leadSponsor": { "name": "Biomind Labs Inc.", "class": "INDUSTRY" }, "collaborators": [ { "name": "Hospital Descentralizado Dr. Marcial V. Quiroga", "class": "UNKNOWN" }, { "name": "Universidad Cat\u00f3lica de Cuyo", "class": "UNKNOWN" } ] }, "oversightModule": { "oversightHasDmc": false, "isFdaRegulatedDrug": false, "isFdaRegulatedDevice": false }, "descriptionModule": { "briefSummary": "This Phase I/II clinical trial aims to test the effectiveness of a new sublingual formulation of 5-MeO-DMT in reducing symptoms of anxiety, depression, and cognitive decline in individuals with mild to moderate Alzheimer's disease. The study will include participants who have a Clinical Dementia Rating (CDR) score between 0.5 and 1, indicating mild to moderate cognitive impairment, and who meet specific educational and cognitive criteria. Participants must have an ACE-III score of \u226486 for individuals with a high level of education (\u226512 years) or \\<62 for those with a low educational level (\u226412 years). Additionally, participants must show moderate to high levels of anxiety, as indicated by the State-Trait Anxiety Inventory (STAI), with STAI-S (State) scores \u226520 for men and \u226523 for women, and STAI-T (Trait) scores \u226520 for men and \u226526 for women. Participants also need to exhibit moderate to severe depressive symptoms, as indicated by a Beck Depression Inventory (BDI) score of \u226521.\n\nTo ensure that participants are cognitively functional but showing signs of impairment, they are assessed with the CDR and ADLQ scales to confirm they can maintain independence in daily activities. All participants must have scores above the threshold on cognitive screening tests like the ACE III and IFS, ensuring no significant cognitive impairment at the baseline.\n\nThe study will measure the effects of 5-MeO-DMT through a range of cognitive and psychiatric assessments:\n\nCognitive Assessments: These include the Rey Auditory Verbal Learning Test (RAVLT) for episodic memory, the Trail Making Test (TMT) for attention and cognitive flexibility, the Semantic and Phonological Fluency Test (SFT-FAS) for verbal fluency, the Paced Auditory Serial Addition Test (PASAT) for processing speed, and the Digit Span Subtests (DSS) for attention and working memory. These tests will provide valuable insights into how 5-MeO-DMT affects cognitive functions.\n\nPsychiatric Assessments: These will assess symptoms of suicidal ideation (SSI), mood (BDI II), anxiety (STAI), and mindfulness (FFMQ), as well as self-reported cognitive complaints (CQC). These evaluations will help determine the psychological and emotional impact of 5-MeO-DMT on participants.\n\nIn addition, the study will include biochemical assessments such as microalbuminuria, blood glucose levels, liver and kidney function, cholesterol, and several biomarkers of inflammation. Cardiovascular evaluations will also be conducted during the trial, ensuring comprehensive monitoring of potential side effects.\n\nThis structured approach will help researchers assess the cognitive and psychological effects of 5-MeO-DMT in individuals with mild to moderate Alzheimer's disease. By focusing on participants with elevated anxiety, depression, and early cognitive decline, this trial aims to provide insights into the therapeutic potential of 5-MeO-DMT for neurodegenerative conditions.", "detailedDescription": "This Phase I/II clinical trial is designed to rigorously evaluate the efficacy of a novel sublingual formulation of 5-MeO-DMT in reducing symptoms of anxiety, depression, and cognitive decline in individuals diagnosed with mild to moderate Alzheimer's disease. The trial will employ a randomized, double-blind, placebo-controlled design, considered the gold standard in clinical research, to ensure unbiased and reliable results. By blinding both participants and investigators to treatment allocations, the study aims to generate robust data on the therapeutic potential of 5-MeO-DMT in this specific patient population.\n\nParticipants will be randomly assigned to one the placebo group or to the groups receiving 6 mg 5-MeO-DMT. Each dose group will include 10 participants, with a total of 20 volunteers enrolled. The dosing regimen consists of one sublingual administration per week over four consecutive weeks, allowing the study to assess both immediate and cumulative effects of 5-MeO-DMT on cognitive, mood, and anxiety symptoms.\n\nOutcome Measures and Assessments: The primary outcome measure will focus on evaluating changes in cognitive function, mood, and anxiety symptoms, using a comprehensive set of neuropsychological and psychiatric assessments at multiple time points throughout the trial. Key cognitive assessments will include the Clinical Dementia Rating (CDR), Activities of Daily Living Questionnaire (ADLQ), and the Addenbrooke's Cognitive Examination III (ACE-III). These scales will provide a detailed overview of cognitive decline and the ability of 5-MeO-DMT to potentially mitigate these effects. Additionally, the Ineco Frontal Screening (IFS) will be administered to assess frontal lobe functioning.\n\nKey psychiatric assessments will include the State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Suicidal Ideation Scale (SSI), which are validated tools for measuring anxiety, depression, and suicidal thoughts. These assessments will help evaluate the emotional and psychological impact of 5-MeO-DMT on participants with Alzheimer's-related cognitive impairment.\n\nNeurocognitive Assessments: To further evaluate the impact of 5-MeO-DMT on cognitive function, a battery of neurocognitive tests will be conducted. These will include the Rey Auditory Verbal Learning Test (RAVLT) to assess episodic memory, the Trail Making Test (TMT) for attention and cognitive flexibility, and the Digit Span Subtests (DSS) to measure working memory and attention. These tests will be administered at baseline, during dosing, and at the conclusion of the study (week 5) to monitor changes in cognitive function across time.\n\nStudy Design and Safety Measures: Safety will be closely monitored throughout the study. Regular assessments will be conducted to track vital signs, including heart rate, blood pressure, and temperature. Electrocardiograms (ECGs) will be taken to monitor any potential cardiovascular effects. Biochemical markers will be measured to assess any systemic effects, and psychological evaluations will be conducted to identify any changes in emotional or cognitive states that may signal adverse reactions or therapeutic benefits of the drug.\n\nThe findings from this study will offer valuable insights into the potential efficacy of sublingual 5-MeO-DMT in improving cognitive function and reducing symptoms of anxiety and depression in individuals with mild to moderate Alzheimer's disease. By focusing on participants with cognitive impairment and comorbid emotional symptoms, this trial aims to determine whether 5-MeO-DMT could be a beneficial treatment option for individuals suffering from both neurodegeneration and mental health disorders. The results will contribute to the growing body of evidence supporting the use of psychedelic compounds in treating cognitive decline, anxiety, and depression, providing new possibilities for managing Alzheimer's disease." }, "conditionsModule": { "conditions": [ "Mild Cognitive Impairment", "Anxiety State", "Depression Anxiety Disorder" ], "keywords": [ "double blind placebo-controlled", "Phase I/II clinical trial", "ramdomized", "sublingual administration", "5-MeO.DMT", "anxiety", "Depression", "Mild Cognitive Impairment" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "PHASE1", "PHASE2" ], "designInfo": { "allocation": "RANDOMIZED", "interventionModel": "PARALLEL", "interventionModelDescription": "This Phase I/II clinical trial uses a randomized, double-blind, placebo-controlled design to evaluate the effects of 6 mg sublingual 5-MeO-DMT on individuals with Mild Cognitive Impairment (MCI). Participants will be randomly assigned to either the active treatment group or the placebo group, each consisting of 10 participants. The trial will last 4 weeks, with weekly doses administered under supervision. Primary outcomes include assessments of cognitive function (via ACE III and IFS) and mood (via BDI II and STAI). Safety will be closely monitored through regular checks on vital signs, ECGs, biochemical markers, and psychological evaluations. The goal is to assess the cognitive and psychological effects of 5-MeO-DMT, contributing to the understanding of its potential as a treatment for MCI-related symptoms.", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "TRIPLE", "whoMasked": [ "PARTICIPANT", "CARE_PROVIDER", "INVESTIGATOR" ] } }, "enrollmentInfo": { "count": 20, "type": "ACTUAL" } }, "armsInterventionsModule": { "armGroups": [ { "label": "Experimental: Arm 1: 6 mg 5-MeO-DMT Sublingual Administration", "type": "EXPERIMENTAL", "description": "In this arm, participants will receive a single sublingual dose of 6 mg of 5-MeO-DMT once a week for four consecutive weeks. This dosage aims to assess the potential therapeutic effects of 5-MeO-DMT in reducing anxiety and depression symptoms in individuals with Mild Cognitive Impairment (MCI). The 6 mg dose is selected to avoid inducing strong psychedelic effects, focusing on emotional well-being improvement. Participants will undergo standardized psychiatric assessments, such as STAI and BDI II, to measure changes in mood and anxiety levels. Additionally, neurocognitive assessments, including the Phonological Verbal Fluency Test (FAS), Paced Auditory Serial Addition Test (PASAT), and Digit Span Scale (DSS), will evaluate cognitive effects on executive function, processing speed, and working memory. Participants will be monitored closely for any adverse effects, changes in vital signs, and alterations in emotional or cognitive states throughout the study.", "interventionNames": [ "Drug: Sublingual administration", "Procedure: Electroencephalography", "Diagnostic Test: Biochemical mesurements", "Diagnostic Test: Acute Subjective Ratings of Psychedelic Effects", "Diagnostic Test: Vital signs", "Diagnostic Test: Cognitive Assessments", "Diagnostic Test: Psychiatric Assessments" ] }, { "label": ": Arm 2: Placebo Sublingual Administration", "type": "EXPERIMENTAL", "description": "Participants will receive a placebo formulation that mirrors the appearance, taste, and administration method of the 5-MeO-DMT doses but contains no active ingredient. This group will serve as the comparator, allowing the effects of the active 5-MeO-DMT treatment to be evaluated. Participants will undergo the same psychiatric and neurocognitive assessments as those in the experimental arm, including the STAI, BDI II, DASS-21, and cognitive tests. The placebo group will provide essential baseline data on mood, anxiety, and cognitive function, helping to determine whether observed changes in the experimental arms are due to the active drug. Monitoring for adverse events and changes in emotional or cognitive states will also be conducted in this group. The differences between this group and the 5-MeO-DMT arms will help establish the efficacy of 5-MeO-DMT for improving mood and cognitive function in individuals with MCI.", "interventionNames": [ "Drug: Sublingual administration", "Procedure: Electroencephalography", "Diagnostic Test: Biochemical mesurements", "Diagnostic Test: Acute Subjective Ratings of Psychedelic Effects", "Diagnostic Test: Vital signs", "Diagnostic Test: Cognitive Assessments", "Diagnostic Test: Psychiatric Assessments" ] } ], "interventions": [ { "type": "DRUG", "name": "Sublingual administration", "description": "Participants will receive a sublingual dose of 5-MeO-DMT or placebo, once a week for four consecutive weeks.", "armGroupLabels": [ ": Arm 2: Placebo Sublingual Administration", "Experimental: Arm 1: 6 mg 5-MeO-DMT Sublingual Administration" ] }, { "type": "PROCEDURE", "name": "Electroencephalography", "description": "Conducting baseline electroencephalography and during the consumption of the corresponding dose.", "armGroupLabels": [ ": Arm 2: Placebo Sublingual Administration", "Experimental: Arm 1: 6 mg 5-MeO-DMT Sublingual Administration" ] }, { "type": "DIAGNOSTIC_TEST", "name": "Biochemical mesurements", "description": "Biochemical determinations will be performed to assess hematological, renal, hepatic, cardiac, and cellular lysis functions. The biochemical markers that will be measured include red blood cells, hematocrit, hemoglobin, glycated hemoglobin, white blood cells, microalbuminuria (urine albumin/creatinine ratio), and various serum markers such as cortisol, glucose, urea, serum creatinine, total cholesterol, HDL, LDL, triglycerides, AST, ALT, lactate dehydrogenase (LDH), creatine kinase (CK), CK-MB, and C-reactive protein.", "armGroupLabels": [ ": Arm 2: Placebo Sublingual Administration", "Experimental: Arm 1: 6 mg 5-MeO-DMT Sublingual Administration" ] }, { "type": "DIAGNOSTIC_TEST", "name": "Acute Subjective Ratings of Psychedelic Effects", "description": "To determine the intensity of the acute effects experienced by subjects, retrospective ratings will be collected 1 hour after 5-MeO-DMT or placebo exposure. Subjective ratings will include the Peak Experience Scale (PES), the Ego Dissolution Inventory (EDI), and the Mystical Experiences Questionnaire (MEQ).", "armGroupLabels": [ ": Arm 2: Placebo Sublingual Administration", "Experimental: Arm 1: 6 mg 5-MeO-DMT Sublingual Administration" ] }, { "type": "DIAGNOSTIC_TEST", "name": "Vital signs", "description": "Vital signs, including blood pressure, heart rate, oxygen saturation, respiration rate, body temperature, and electrocardiograms (ECGs), will be monitored over the six weeks of the treatment.", "armGroupLabels": [ ": Arm 2: Placebo Sublingual Administration", "Experimental: Arm 1: 6 mg 5-MeO-DMT Sublingual Administration" ] }, { "type": "DIAGNOSTIC_TEST", "name": "Cognitive Assessments", "description": "Cognitive assessments will evaluate the effects of sublingual 5-MeO-DMT on cognitive functions. Participants will complete the Phonological Verbal Fluency Test (FAS) to assess executive function, the Paced Auditory Serial Addition Test (PASAT) to evaluate processing speed, and the Digit Span Scale (DSS) to measure attention span and working memory. These tests will be administered at baseline, during treatment, and post-treatment to monitor any cognitive changes in response to either a 6 mg dose of 5-MeO-DMT or placebo. This will help determine how the intervention may affect cognitive processing, memory, and attention.", "armGroupLabels": [ ": Arm 2: Placebo Sublingual Administration", "Experimental: Arm 1: 6 mg 5-MeO-DMT Sublingual Administration" ] }, { "type": "DIAGNOSTIC_TEST", "name": "Psychiatric Assessments", "description": "Psychiatric evaluations will be conducted to assess the emotional and psychological effects of sublingual 5-MeO-DMT. Participants will complete the Beck Depression Inventory II (BDI II) to measure mood and depressive symptoms, the State-Trait Anxiety Inventory (STAI) to evaluate state anxiety, and the Depression, Anxiety, and Stress Scale (DASS-21) to assess stress levels. Additionally, the Suicidal Ideation Scale (SSI) will be used to monitor any changes in suicidal ideation throughout the study. These psychiatric assessments will be administered at multiple time points during the study to evaluate the potential therapeutic effects of 5-MeO-DMT in improving mood, anxiety, and overall psychological well-being.", "armGroupLabels": [ ": Arm 2: Placebo Sublingual Administration", "Experimental: Arm 1: 6 mg 5-MeO-DMT Sublingual Administration" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "Change in Phonological Verbal Fluency Test (FAS) from Baseline to Week 5", "description": "The Phonological Verbal Fluency Test (FAS) measures executive function by assessing a participant's ability to generate words within a specific time limit, categorized by a starting letter. The task is designed to evaluate verbal memory, cognitive flexibility, and processing speed. A higher score indicates better performance.", "timeFrame": "The FAS will be administered at baseline (Week 0), during treatment (Weeks 1-4), and at follow-up (Week 5) to assess changes in executive function during and after sublingual 5-MeO-DMT administration." }, { "measure": "Change in Paced Auditory Serial Addition Test (PASAT) from Baseline to Week 5", "description": "The Paced Auditory Serial Addition Test (PASAT) is a cognitive test used to measure processing speed and attention. Participants are presented with a sequence of numbers and must add each new number to the previous one as quickly as possible. Performance is scored based on the number of correct responses within a given time. A higher score reflects better cognitive processing and attention.", "timeFrame": "The PASAT will be administered at baseline (Week 0), during treatment (Weeks 1-4), and at follow-up (Week 5) to evaluate the effects of 5-MeO-DMT on cognitive processing speed and attention." }, { "measure": "Change in Digit Span Scale (DSS) from Baseline to Week 5", "description": "The Digit Span Scale (DSS) is used to assess attention span and working memory. In this test, participants must repeat a series of numbers either in the same order (forward) or in reverse (backward). The DSS measures short-term memory and cognitive flexibility. A higher score indicates better working memory and attention capacity.", "timeFrame": "The DSS will be administered at baseline (Week 0), during treatment (Weeks 1-4), and at follow-up (Week 5) to assess changes in attention and working memory following 5-MeO-DMT administration." }, { "measure": "Mystical Experience Questionnaire (MEQ) Assessment at 40 Minutes Post-Administration", "description": "The Mystical Experience Questionnaire (MEQ) is used to assess the subjective mystical experiences following psychedelic administration. It evaluates aspects such as feelings of unity, transcendence, and the sense of the sacred. The MEQ includes questions about altered perceptions of time, space, and self, as well as emotional and cognitive shifts. Higher scores indicate a stronger experience of mystical qualities.", "timeFrame": "The MEQ will be completed at 40 minutes post-administration during each dosing week (Weeks 1-4) to assess the subjective mystical experiences induced by sublingual 5-MeO-DMT." }, { "measure": "Peak Experience Scale (PES) Assessment at 40 Minutes Post-Administration", "description": "The Peak Experience Scale (PES) is a tool for measuring the intensity and quality of peak experiences following psychedelic use. It includes items related to emotional intensity, personal insight, and transcendence. Participants rate the emotional and psychological impact of their experiences, with higher scores reflecting more intense peak experiences.", "timeFrame": "The PES will be completed at 40 minutes post-administration during each dosing week (Weeks 1-4) to capture the intensity and emotional impact of the 5-MeO-DMT experience." }, { "measure": "Ego Dissolution Inventory (EDI) Assessment at 40 Minutes Post-Administration", "description": "The Ego Dissolution Inventory (EDI) assesses the extent to which participants experience a loss of ego boundaries or self-identity following psychedelic administration. It includes questions that explore the feeling of oneness with the environment, other people, or the universe, as well as the dissolution of self-related thoughts and ego. Higher scores indicate stronger experiences of ego dissolution.", "timeFrame": "The EDI will be completed at 40 minutes post-administration during each dosing week (Weeks 1-4) to evaluate the degree of ego dissolution experienced after 5-MeO-DMT consumption." } ], "secondaryOutcomes": [ { "measure": "Mean change in Beck Depression Inventory II (BDI-II) from Baseline to Week 5", "description": "The Beck Depression Inventory II (BDI-II) is a 21-item self-report questionnaire designed to assess the severity of depressive symptoms. Each item is scored from 0 to 3, with the total score ranging from 0 to 63. Higher scores indicate more severe depression.", "timeFrame": "The BDI-II will be conducted at baseline (Week 0), during treatment (Weeks 1-4), and at follow-up (Week 5) to assess the impact of 5-MeO-DMT on the severity of depression." }, { "measure": "Mean change in State-Trait Anxiety Inventory (STAI) from Baseline to Week 5", "description": "The State-Trait Anxiety Inventory (STAI) is a 40-item scale that measures both state anxiety (current feelings of anxiety) and trait anxiety (general tendency to experience anxiety). Each item is scored from 1 to 4, with the overall score ranging from 20 to 80. Higher scores indicate higher levels of anxiety.", "timeFrame": "STAI evaluations will be conducted at baseline (Week 0), during treatment (Weeks 1-4), and at follow-up (Week 5) to assess the impact of 5-MeO-DMT on anxiety levels." }, { "measure": "Mean change in Depression, Anxiety, and Stress Scale (DASS-21) from Baseline to Week 5", "description": "The Depression, Anxiety, and Stress Scale (DASS-21) is a 21-item questionnaire that measures the severity of depression, anxiety, and stress symptoms. Each item is scored from 0 to 3, with higher scores indicating more severe symptoms. The total score ranges from 0 to 63.", "timeFrame": "DASS-21 will be conducted at baseline (Week 0), during treatment (Weeks 1-4), and at follow-up (Week 5) to evaluate the impact of 5-MeO-DMT on mood and stress." } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria:\n\n* Adults aged 40 to 80 years\n* Diagnosis of mild to moderate Alzheimer's disease\n* Clinical Dementia Rating (CDR) score between 0.5 and 1\n* ACE-III score \u2264 86 for individuals with high educational levels (\u226512 years of schooling)\n* ACE-III score \\< 62 for individuals with low educational levels (\u226412 years of schooling)\n* Moderate to high levels of anxiety, as defined by:\n* State-Trait Anxiety Inventory (STAI-S) State score \u226520 for men, \u226523 for women\n* STAI-Trait score \u226520 for men, \u226526 for women\n* Mild to moderate depressive symptoms, as indicated by a Beck Depression Inventory (BDI) score \u226521\n* Must provide written informed consent to participate in the study\n\nExclusion Criteria:\n\n* Liver dysfunction\n* Cardiovascular conditions (e.g., uncontrolled hypertension, angina, significant ECG abnormalities, recent transient ischemic attack or stroke, peripheral/pulmonary vascular disease without active claudication).\n* Blood pressure \\>140 mmHg systolic or \\>90 mmHg diastolic\n* Epilepsy or history of seizures\n* Kidney failure\n* Insulin-dependent diabetes\n* Chronic obstructive pulmonary disease (COPD)\n* Increased intracranial or cerebrospinal pressure\n* Hyperthyroidism\n* Psychotic symptoms or family history of psychotic disorders\n* Prodromal symptoms of schizophrenia or dissociative identity disorder\n* Severe depression or anxiety requiring immediate treatment with antidepressants or daily anxiolytics, particularly in cases with suicidal ideation\n* Medications: Regular use of psychoactive medications, including benzodiazepines, serotonin-active medications (e.g., ondansetron), or monoamine oxidase inhibitors (MAOIs)\n* Drug Interactions: Use of potent metabolic inducers or inhibitors, such as: Inducers: rifampicin, anticonvulsants (e.g., carbamazepine, phenytoin), nevirapine, efavirenz, taxol, dexamethasone. Inhibitors: HIV protease inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, troleandomycin.", "healthyVolunteers": true, "sex": "ALL", "minimumAge": "40 Years", "maximumAge": "80 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ] }, "contactsLocationsModule": { "overallOfficials": [ { "name": "Martin A. Bruno, PhD", "affiliation": "Biomind Labs Inc.", "role": "STUDY_CHAIR" } ], "locations": [ { "facility": "Hospital Descentralizado Dr. Marcial V. Quiroga.", "city": "San Juan", "state": "Rivadavia", "zip": "5400", "country": "Argentina", "geoPoint": { "lat": -31.53726, "lon": -68.52568 } } ] }, "referencesModule": { "seeAlsoLinks": [ { "label": "Biomind Labs is developing the next generation of pharmaceuticals to treat patients suffering from neurological disorders. This unique approach targets the original and initial drivers of the diseases.", "url": "https://www.biomindlabs.com/" } ] }, "ipdSharingStatementModule": { "ipdSharing": "YES", "description": "The study is committed to advancing scientific research by planning to share individual participant data (IPD) to contribute valuable insights to the research community. We will provide a detailed data dictionary alongside the IPD, outlining the variables and types of data collected for each participant, facilitating comprehensive analysis by researchers.\n\nSpecifically, we plan to share all IPD collected throughout the trial, including data that underlie published results. Importantly, all personal information and identifying details of participants will remain strictly confidential and will not be disclosed. This commitment ensures the privacy of individuals involved while enabling meaningful contributions to scientific knowledge.", "infoTypes": [ "STUDY_PROTOCOL", "ICF" ], "timeFrame": "The individual participant data (IPD) and any supporting information will be made available starting 6 months after the publication of the study results. This will allow sufficient time for data analysis and the dissemination of primary findings. The data will remain available for at least 5 years following the publication, ensuring ample time for other researchers to access and utilize the data for further analysis or related studies. In case of any modifications to the availability period, these will be communicated clearly along with the reasons. This time frame is subject to ethical and regulatory requirements and may be adjusted if necessary.", "accessCriteria": "Researchers seeking access to the individual participant data (IPD) and supporting information must submit a formal request outlining their proposed analyses. This proposal should detail the types of analyses, including the statistical methods to be used, which will be reviewed for scientific merit and methodological rigor. A signed data sharing agreement will be required, and the request must be submitted through the designated data sharing platform or by email to the study's data management team. Access to IPD will be granted based on ethical review and approval, ensuring that the proposed research aligns with the study's objectives and respects participant confidentiality. All requests will be reviewed by an independent committee responsible for overseeing data sharing, ensuring transparency, and safeguarding participant privacy." } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2026-07-09" }, "conditionBrowseModule": { "meshes": [ { "id": "D060825", "term": "Cognitive Dysfunction" }, { "id": "D001008", "term": "Anxiety Disorders" }, { "id": "D003863", "term": "Depression" } ], "ancestors": [ { "id": "D003072", "term": "Cognition Disorders" }, { "id": "D019965", "term": "Neurocognitive Disorders" }, { "id": "D001523", "term": "Mental Disorders" }, { "id": "D001526", "term": "Behavioral Symptoms" }, { "id": "D001519", "term": "Behavior" } ] }, "interventionBrowseModule": { "meshes": [ { "id": "D000286", "term": "Administration, Sublingual" }, { "id": "D055986", "term": "Vital Signs" } ], "ancestors": [ { "id": "D000284", "term": "Administration, Oral" }, { "id": "D004333", "term": "Drug Administration Routes" }, { "id": "D004358", "term": "Drug Therapy" }, { "id": "D013812", "term": "Therapeutics" }, { "id": "D010808", "term": "Physical Examination" }, { "id": "D019937", "term": "Diagnostic Techniques and Procedures" }, { "id": "D003933", "term": "Diagnosis" } ] } }, "hasResults": false } ] }, "psilocybin Alzheimer dementia": { "studies": [ { "protocolSection": { "identificationModule": { "nctId": "NCT07386730", "orgStudyIdInfo": { "id": "25-45261" }, "secondaryIdInfos": [ { "id": "A146672", "type": "OTHER_GRANT", "domain": "Brain & Behavior Research Foundation" } ], "organization": { "fullName": "University of California, San Francisco", "class": "OTHER" }, "briefTitle": "A Study of Psychedelics in Healthy Older Adults With Low Well-being", "officialTitle": "A Double Blind, Randomized Trial Investigating the Safety, Feasibility, and Mechanisms of Psychedelics in Healthy Older Adults With Low Well-being as Moderated by Biomarkers for Preclinical Alzheimer's Disease", "acronym": "OAD1" }, "statusModule": { "statusVerifiedDate": "2025-12", "overallStatus": "RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2026-06-01", "type": "ESTIMATED" }, "primaryCompletionDateStruct": { "date": "2030-02", "type": "ESTIMATED" }, "completionDateStruct": { "date": "2030-02", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2026-01-20", "studyFirstSubmitQcDate": "2026-01-29", "studyFirstPostDateStruct": { "date": "2026-02-04", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2026-06-04", "lastUpdatePostDateStruct": { "date": "2026-06-08", "type": "ACTUAL" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR_INVESTIGATOR", "investigatorFullName": "Jennifer Mitchell", "investigatorTitle": "Professor", "investigatorAffiliation": "University of California, San Francisco" }, "leadSponsor": { "name": "Jennifer Mitchell", "class": "OTHER" } }, "oversightModule": { "oversightHasDmc": false, "isFdaRegulatedDrug": true, "isFdaRegulatedDevice": false }, "descriptionModule": { "briefSummary": "This study is being conducted to understand changes in brain activity following administration of two different drugs (Psilocybin and Dextromethorphan) in older adults with low well-being.\n\nThe main questions it aims to answer are, does psilocybin:\n\n1. Acutely increase complexity of EEG activity in older adults with low well-being, as modulated by the presence of biomarkers of Alzheimer's disease (AD) pathology.\n2. Longitudinally decrease plasma markers of neuroinflammation, as modulated by the presence of biomarkers of AD pathology.\n3. Explore longitudinal changes in autonomic physiology via wearable recording devices as well as longitudinal structural and functional brain changes measured in the MRI\n\nParticipants will be in the study for up to 3 months, which will include 3 to 4 in person visits and 3 to 4 remote visits. Most visits will be between 1 to 3 hours, but the dosing visit will last a minimum of 8 hours and could be as long as 12 hours. During the dosing visit, all participants will receive a single dose of the study drugs and dosages listed below.\n\nResearchers will compare participants who receive the following drug options:\n\n* A low-to-moderate dose of Psilocybin (5-10 mg)\n* A moderate-to-high dose of Psilocybin (25-30 mg)\n* A low-to-moderate dose of Dextromethorphan (30-60 mg)\n* A moderate-to-high dose of Dextromethorphan (80-90 mg)" }, "conditionsModule": { "conditions": [ "Anhedonia in Healthy Volunteers", "Older Adults (50-90 Years)" ], "keywords": [ "Psilocybin", "Dextromethorphan", "older adults", "well-being", "EEG", "MRI", "neuroinflammation", "Alzheimer's disease plasma markers", "wearables" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "PHASE1" ], "designInfo": { "allocation": "RANDOMIZED", "interventionModel": "PARALLEL", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "TRIPLE", "whoMasked": [ "PARTICIPANT", "CARE_PROVIDER", "OUTCOMES_ASSESSOR" ] } }, "enrollmentInfo": { "count": 80, "type": "ESTIMATED" } }, "armsInterventionsModule": { "armGroups": [ { "label": "A low-to-moderate dose of Psilocybin (5-10 mg)", "type": "EXPERIMENTAL", "description": "A single low-to-moderate dose of Psilocybin (5-10 mg)", "interventionNames": [ "Drug: Psilocybin (drug)" ] }, { "label": "A moderate-to-high dose of Psilocybin (25-30 mg)", "type": "EXPERIMENTAL", "description": "A single moderate-to-high dose of Psilocybin (25-30 mg)", "interventionNames": [ "Drug: Psilocybin (drug)" ] }, { "label": "A low-to-moderate dose of Dextromethorphan (30-60 mg)", "type": "EXPERIMENTAL", "description": "A single low-to-moderate dose of Dextromethorphan (30-60 mg)", "interventionNames": [ "Drug: Dextromethorphan (DXM)" ] }, { "label": "A moderate-to-high dose of Dextromethorphan (80-90 mg)", "type": "EXPERIMENTAL", "description": "A single moderate-to-high dose of Dextromethorphan (80-90 mg)", "interventionNames": [ "Drug: Dextromethorphan (DXM)" ] } ], "interventions": [ { "type": "DRUG", "name": "Psilocybin (drug)", "description": "Participants will receive either Psilocybin or Dextromethorphan in this clinical trial", "armGroupLabels": [ "A low-to-moderate dose of Psilocybin (5-10 mg)", "A moderate-to-high dose of Psilocybin (25-30 mg)" ] }, { "type": "DRUG", "name": "Dextromethorphan (DXM)", "description": "Participants will receive either Psilocybin or Dextromethorphan in this clinical trial", "armGroupLabels": [ "A low-to-moderate dose of Dextromethorphan (30-60 mg)", "A moderate-to-high dose of Dextromethorphan (80-90 mg)" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "Acute changes in EEG-based ESBA", "description": "Compare acute changes in EEG-based Lempel Ziv complexity (pre- to post-dose, arbitrary unit) between the four study arms, with the presence of biomarkers of AD pathology used in the statistical analyses as a moderator. Lempel-Ziv complexity in EEG is a non-linear analysis tool that quantifies the amount of entropy of spontaneous brain activity (ESBA).", "timeFrame": "Pre- to post-dose two hours later" } ], "secondaryOutcomes": [ { "measure": "Changes in TNF-alpha", "description": "Compare changes in a biomarkers of neuroinflammation (TNF-alpha) psilocybin across the four study arms, with the presence of biomarkers of AD pathology used in the statistical analyses as a moderator. Reference Range 0.56-1.40 pg/mL", "timeFrame": "Screening to three weeks post dosing" } ] }, "eligibilityModule": { "eligibilityCriteria": "The eligibility criteria are deliberately incomplete to preserve the scientific integrity of the study.\n\nInclusion Criteria:\n\n* Are between 50-85 years inclusive at time of consent signing\n* Have below-average well-being, defined by the World Health Organization Well-Being Index (WHO-5)\n* Have no cognitive impairments, indicated by a Mini-Mental State Examination (MMSE) score \\>24\n* Have an identified willing contact person with at least weekly contact with the participant to be able to provide meaningful information about the participant's daily function and able to pick up the study participant at the end of the Dosing Visit\n* Participants assigned female sex at birth must be non-lactating, and post-menopausal, defined as a period of over 12 months since the last menstrual period, or otherwise physically unable to become pregnant\n* Participants assigned male sex at birth must 1) refrain from sperm donation for 3 months after the Dosing Visit, and 2) if engaging in sexual activities that may result in pregnancy, must use a condom, plus their partner of childbearing potential must use a second, highly effective form of contraception for 3 months after the Dosing Visit\n* Be proficient in English\n* Are able and willing to provide consent as assessed by comprehension questions in informed consent process\n* Stated willingness to comply with all study procedures and availability for the duration of the study\n* Ability to swallow oral medications (capsules)\n\nExclusion Criteria:\n\nGeneral:\n\n* Have a known allergic or severe reaction to Psilocybin, Dextromethorphan, or any of the non-active components of the IMP capsules\n* Insufficient ability to report on symptoms to make a valid assessment on any required instrument\n* Have a condition or presence of clinical feature which, in the opinion of the investigators might interfere with or prevent appropriate study participation or interfere with data interpretation\n\nMRI Exclusions:\n\n* Any implanted object or device that poses a safety risk or could interfere with MRI scanning (e.g. aneurysm clips, cardiac pacemakers, defibrillators, neurostimulators, cochlear implants, spinal cord stimulators, insulin or infusion pumps, metallic prostheses or fragments, heart valves, vascular stents, or shunts. surgical staples, clips, or joint replacements, radiation seeds, medication patches containing metal, or any other metallic or electronic implants)\n* History of metallic injury to the eyes or body, or those with tattoos containing metallic ink, permanent makeup, or body piercings that cannot be removed.\n* Any condition that poses a safety risk or could interfere with MRI scanning (e.g. severe claustrophobia or motion disorders or breathing problems, etc)\n\nPsychiatric:\n\n\u2022History of hallucinogen persisting perception disorder (HPPD) (as per DSM-5 criteria)\n\nCardiovascular:\n\n* Clinically significant cardiovascular conditions e.g., clinically significant EKG abnormalities, transient ischemic attack in the last 6 months, history of hemorrhagic stroke, history of myocardial infarction within 1 year of signing informed consent form (ICF)\n* Baseline (heart rate \\< 60 bpm or \\> 90 bpm at screening or pre-dose\n* Baseline hypertension (\u2265140 SBP or \u226590 DBP), after repeated measurements\n* QTc Interval \\> 450msec on 12-lead EKG. Note: If QT-prolonging medications are started or increased in dose after enrollment and prior to dosing visit, a repeat EKG must be done \\>12-hours after this change to assure continued safe enrollment in the trial\n* Clinically significant arrhythmia (e.g., uncontrolled atrial fibrillation, or untreated supraventricular tachycardia)\n* Any current condition where physical activity is associated with palpitations, anginal pain or syncope\n\nGeneral health:\n\n* Major systemic disorders, including seizure, insulin dependent diabetes mellitus, recent history (last 12 months) of advanced cancer or its treatment (radiation therapy or chemotherapy), had major surgery within 6 months from screening or plans to have surgery while enrolled in the study\n* Inadequate hepatic function as determined by total bilirubin or alkaline phosphatase \\>3x institutional upper limit of normal; or aspartate aminotransferase (AST) or alanine transaminase (ALT) \\>3x institutional upper limit of normal. However, participants with Gilbert syndrome are allowed to enroll\n* Inadequate renal function as determined by estimated glomerular filtration rate (eGFR) \\< 60 mL/min/1.73 m2 (based on the MDRD equation)\n* Participant is at increased risk of falls", "healthyVolunteers": true, "sex": "ALL", "minimumAge": "50 Years", "maximumAge": "85 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ] }, "contactsLocationsModule": { "centralContacts": [ { "name": "Gabriella Mace", "role": "CONTACT", "phone": "415-707-5399", "email": "agingandpsychedelics@ucsf.edu" } ], "overallOfficials": [ { "name": "Lorenzo Pasquini, PhD", "affiliation": "University of California, San Francisco", "role": "PRINCIPAL_INVESTIGATOR" }, { "name": "Jennifer Mitchell, PhD", "affiliation": "University of California, San Francisco", "role": "PRINCIPAL_INVESTIGATOR" } ], "locations": [ { "facility": "University of California San Francisco, Sandler Neuroscience Building", "status": "RECRUITING", "city": "San Francisco", "state": "California", "zip": "94158", "country": "United States", "contacts": [ { "name": "Gabriella Mace", "role": "CONTACT", "phone": "415-707-5399", "email": "agingandpsychedelics@ucsf.edu" }, { "name": "Lorenzo Pasquini, PhD", "role": "SUB_INVESTIGATOR" }, { "name": "Jennifer Mitchell, PhD", "role": "PRINCIPAL_INVESTIGATOR" } ], "geoPoint": { "lat": 37.77493, "lon": -122.41942 } } ] }, "ipdSharingStatementModule": { "ipdSharing": "NO" } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2026-07-09" }, "conditionBrowseModule": { "meshes": [ { "id": "D000090862", "term": "Neuroinflammatory Diseases" } ], "ancestors": [ { "id": "D009422", "term": "Nervous System Diseases" }, { "id": "D007249", "term": "Inflammation" }, { "id": "D010335", "term": "Pathologic Processes" }, { "id": "D013568", "term": "Pathological Conditions, Signs and Symptoms" } ] }, "interventionBrowseModule": { "meshes": [ { "id": "D011562", "term": "Psilocybin" }, { "id": "D004364", "term": "Pharmaceutical Preparations" }, { "id": "D003915", "term": "Dextromethorphan" } ], "ancestors": [ { "id": "D026121", "term": "Indole Alkaloids" }, { "id": "D000470", "term": "Alkaloids" }, { "id": "D006571", "term": "Heterocyclic Compounds" }, { "id": "D007211", "term": "Indoles" }, { "id": "D006574", "term": "Heterocyclic Compounds, 2-Ring" }, { "id": "D000072471", "term": "Heterocyclic Compounds, Fused-Ring" }, { "id": "D014363", "term": "Tryptamines" }, { "id": "D054836", "term": "Indolizidines" }, { "id": "D007212", "term": "Indolizines" }, { "id": "D009019", "term": "Morphinans" }, { "id": "D053610", "term": "Opiate Alkaloids" }, { "id": "D006572", "term": "Heterocyclic Compounds, Bridged-Ring" }, { "id": "D006576", "term": "Heterocyclic Compounds, 4 or More Rings" }, { "id": "D010616", "term": "Phenanthrenes" }, { "id": "D011084", "term": "Polycyclic Aromatic Hydrocarbons" }, { "id": "D011083", "term": "Polycyclic Compounds" } ] } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT04123314", "orgStudyIdInfo": { "id": "IRB00175915" }, "organization": { "fullName": "Johns Hopkins University", "class": "OTHER" }, "briefTitle": "Psilocybin for Depression in People With Mild Cognitive Impairment or Early Alzheimer's Disease", "officialTitle": "Pilot Study of Serotonin 2A Receptor (5-HT2A) Agonist Psilocybin for Depression in Patients With Mild Cognitive Impairment or Early Alzheimer's Disease" }, "statusModule": { "statusVerifiedDate": "2026-03", "overallStatus": "RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2021-03-24", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2026-09-30", "type": "ESTIMATED" }, "completionDateStruct": { "date": "2026-12-31", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2019-10-09", "studyFirstSubmitQcDate": "2019-10-09", "studyFirstPostDateStruct": { "date": "2019-10-10", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2026-03-12", "lastUpdatePostDateStruct": { "date": "2026-03-16", "type": "ACTUAL" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR" }, "leadSponsor": { "name": "Johns Hopkins University", "class": "OTHER" }, "collaborators": [ { "name": "Council On Spiritual Practices", "class": "UNKNOWN" }, { "name": "Heffter Research Institute", "class": "OTHER" } ] }, "oversightModule": { "oversightHasDmc": false, "isFdaRegulatedDrug": true, "isFdaRegulatedDevice": false }, "descriptionModule": { "briefSummary": "This open-label pilot study examines whether the hallucinogenic drug, psilocybin, given under supportive conditions, is safe and effective for depression in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD). This study will also assess whether psilocybin may improve quality of life in those individuals.", "detailedDescription": "This is a pilot study evaluating the potential efficacy of psilocybin to produce improvement in depression compared to pre-treatment in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD) and clinically significant symptoms of depression. The study will be an open-label trial in a sample of up to 20 treatment-seeking participants with a diagnosis of MCI or early AD. Participants will complete an 8-week course of study treatment including two psilocybin sessions (15 mg/70 kg in week 4 and 15 or 25 mg/70 kg in week 6), with follow-up assessments up to 6 months after the final psilocybin session. The study will assess changes in depressed mood at 1 week after the second psilocybin session compared to pre-treatment, and quality of life in participants from pre- to post-treatment." }, "conditionsModule": { "conditions": [ "Depressive Symptoms", "Depression", "Alzheimer Disease", "Mild Cognitive Impairment" ], "keywords": [ "Psilocybin", "Hallucinogen", "Psychedelic" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "EARLY_PHASE1" ], "designInfo": { "allocation": "NA", "interventionModel": "SINGLE_GROUP", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "NONE" } }, "enrollmentInfo": { "count": 20, "type": "ESTIMATED" } }, "armsInterventionsModule": { "armGroups": [ { "label": "Psilocybin", "type": "EXPERIMENTAL", "description": "Participants will complete an 8-week course of study treatment including weekly psychological support and two moderate to high dose psilocybin administrations in weeks 4 and 6.", "interventionNames": [ "Drug: Psilocybin" ] } ], "interventions": [ { "type": "DRUG", "name": "Psilocybin", "description": "Dosing at the first session will be 15 mg/70 kg. For the second session participants will either remain at the initial dose, or increase to 25 mg/70 kg at the discretion of the study team.", "armGroupLabels": [ "Psilocybin" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "Change in Cornell Scale for Depression in Dementia (CSDD) score", "description": "The Cornell Scale for Depression in Dementia (CSDD) is administered via patient and informant interviews to assess the presence and severity of depressive mood and behavioral symptoms during the past week. Has 19 items, each scored from 0 to 2 with higher scores indicating severe symptom.Total score range from 0 to 38.", "timeFrame": "Baseline and 1 week after second psilocybin session" } ], "secondaryOutcomes": [ { "measure": "Change in Quality of Life Alzheimer's Disease (QOL-AD) scale score", "description": "The Quality of Life Alzheimer's Disease (QOL-AD) scale is a 13-item measure administered via patient and informant interviews to assess overall mood, physical and cognitive function, and quality of relationships in people with Alzheimer's Disease. Each item is scored 1 to 4, with higher score indicating better quality of life. Total score range from 13 to 52.", "timeFrame": "Baseline and 2 weeks after second psilocybin session" } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria:\n\n* Must meet either A) Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) criteria for Mild Neurocognitive Disorder due to AD or Major Neurocognitive Disorder due to AD with Mild severity (including probable), or B) meet criteria for MCI including a subjective memory complaint relative to previous functioning and confirmed by Clinical Dementia Rating (CDR) Memory score at screening of \\>0.5\n* Have Mini-Mental State Examination scores \\>18\n* Have a Montreal Cognitive Assessment score \\<26.\n* Have Cornell Scale for Depression in Dementia (CSDD) patient score \\>/= 6, or Geriatric Depression Scale-Short Form score \u2265 5, indicating at minimum a mild to moderate degree of distress.\n* Acetylcholinesterase inhibitors are allowed so long as the dose has been stable for \\> 6 weeks.\n* Concurrent pharmacotherapy with selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), and/or bupropion is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening. Allowable bupropion doses for participants will be \u2264300mg/day.\n* Have a close friend or family member willing and able to serve the role of community observer / informant for data collection procedures\n\nExclusion Criteria:\n\n* Individuals 86 years of age or older will be excluded.\n* Currently taking antipsychotics, monoamine oxidase (MAO) inhibitors, or antidepressant medications other than SSRIs, SNRIs, or bupropion. Allowable bupropion doses for participants will be \u2264300mg/day.\n* Long-acting opioid pain medications (e.g. oxycodone sustained release, morphine sustained release - which are usually taken at 12 hour intervals) will be allowed if the last dose occurred at least 2 hours before psilocybin administration and the next dose was not scheduled until at least 8 hours after psilocybin administration.\n* Participants must agree not to take sildenafil, tadalafil, or similar medications within 72 hours of each psilocybin administration, as these medications may potentiate hypotensive reactions to psilocybin\n* Cardiovascular conditions: angina, a clinically significant ECG abnormality (e.g. atrial fibrillation or heart-rate corrected QT interval (QTc) \\>450msec), Transient Ischemic Attack (TIA) in the last 6 months, stroke, artificial heart valves, or uncontrolled hypertension with resting blood pressure systolic \\>150 or diastolic \\>95\n* Minimum acceptable heartrate at screening is 50 bpm unless the individual is cleared for participation by a cardiologist, in accord with the American College of Cardiology's 2018 guidelines for bradycardia\n* Seizure disorder\n* Insulin dependent diabetes mellitus\n* Renal disease (creatinine clearance \\< 40 ml/min using the Cockcroft and Gault equation)\n* Baseline liver enzyme elevation \\>2x the upper limit of normal\n* Current or past history of meeting DSM-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder\n* Family (i.e., 1st degree relative) history of Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder\n* Past-year hallucinogen use.", "healthyVolunteers": false, "sex": "ALL", "minimumAge": "18 Years", "maximumAge": "85 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ] }, "contactsLocationsModule": { "centralContacts": [ { "name": "Ian Geithner, MPS", "role": "CONTACT", "phone": "4105505466", "email": "igeithn1@jhmi.edu" }, { "name": "Albert Garcia-Romeu, PhD", "role": "CONTACT", "phone": "4105501972", "email": "agarci33@jhmi.edu" } ], "overallOfficials": [ { "name": "Albert Garcia-Romeu, PhD", "affiliation": "Johns Hopkins University", "role": "PRINCIPAL_INVESTIGATOR" } ], "locations": [ { "facility": "Johns Hopkins Center for Psychedelic and Consciousness Research", "status": "RECRUITING", "city": "Baltimore", "state": "Maryland", "zip": "21224", "country": "United States", "contacts": [ { "name": "Ian Geithner, MPS", "role": "CONTACT", "phone": "410-550-5466", "email": "igeithn1@jhmi.edu" }, { "name": "Albert Garcia-Romeu, PhD", "role": "CONTACT", "phone": "410-550-1972", "email": "agarci33@jhmi.edu" }, { "name": "Albert Garcia-Romeu, PhD", "role": "PRINCIPAL_INVESTIGATOR" }, { "name": "Paul B Rosenberg, MD", "role": "PRINCIPAL_INVESTIGATOR" } ], "geoPoint": { "lat": 39.29038, "lon": -76.61219 } } ] }, "referencesModule": { "seeAlsoLinks": [ { "label": "Study information and application form", "url": "https://www.hopkinspsychedelic.org/alzheimers-study" } ] }, "ipdSharingStatementModule": { "ipdSharing": "NO" } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2026-07-09" }, "conditionBrowseModule": { "meshes": [ { "id": "D003863", "term": "Depression" }, { "id": "D000544", "term": "Alzheimer Disease" }, { "id": "D060825", "term": "Cognitive Dysfunction" } ], "ancestors": [ { "id": "D001526", "term": "Behavioral Symptoms" }, { "id": "D001519", "term": "Behavior" }, { "id": "D003704", "term": "Dementia" }, { "id": "D001927", "term": "Brain Diseases" }, { "id": "D002493", "term": "Central Nervous System Diseases" }, { "id": "D009422", "term": "Nervous System Diseases" }, { "id": "D024801", "term": "Tauopathies" }, { "id": "D019636", "term": "Neurodegenerative Diseases" }, { "id": "D019965", "term": "Neurocognitive Disorders" }, { "id": "D001523", "term": "Mental Disorders" }, { "id": "D003072", "term": "Cognition Disorders" } ] }, "interventionBrowseModule": { "meshes": [ { "id": "D011562", "term": "Psilocybin" } ], "ancestors": [ { "id": "D026121", "term": "Indole Alkaloids" }, { "id": "D000470", "term": "Alkaloids" }, { "id": "D006571", "term": "Heterocyclic Compounds" }, { "id": "D007211", "term": "Indoles" }, { "id": "D006574", "term": "Heterocyclic Compounds, 2-Ring" }, { "id": "D000072471", "term": "Heterocyclic Compounds, Fused-Ring" }, { "id": "D014363", "term": "Tryptamines" }, { "id": "D054836", "term": "Indolizidines" }, { "id": "D007212", "term": "Indolizines" } ] } }, "hasResults": false } ] } }