Ignite Creation Date:
2025-12-25 @ 12:02 AM
Ignite Modification Date:
2025-12-25 @ 10:00 PM
Study NCT ID:
NCT01922258
Status:
COMPLETED
Last Update Posted:
2020-11-20
First Post:
2013-08-12
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Safety and Tolerability Study of Flexible Dosing of Brexpiprazole in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000544', 'term': 'Alzheimer Disease'}, {'id': 'D001523', 'term': 'Mental Disorders'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D003704', 'term': 'Dementia'}, {'id': 'D060825', 'term': 'Cognitive Dysfunction'}, {'id': 'D011595', 'term': 'Psychomotor Agitation'}], 'ancestors': [{'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': 'D003072', 'term': 'Cognition Disorders'}, {'id': 'D020820', 'term': 'Dyskinesias'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D011596', 'term': 'Psychomotor Disorders'}, {'id': 'D019954', 'term': 'Neurobehavioral Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D000096762', 'term': 'Aberrant Motor Behavior in Dementia'}, {'id': 'D001526', 'term': 'Behavioral Symptoms'}, {'id': 'D001519', 'term': 'Behavior'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000591922', 'term': 'brexpiprazole'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'DT-inquiry@otsuka.jp', 'title': 'Global Clinical Development', 'organization': 'Otsuka Pharmaceutical Development & Commercialization, Inc.'}, 'certainAgreement': {'otherDetails': "Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.", 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Through the trial: From screening to Week 12 and 30 (+2) days follow-up period.', 'description': 'Only participants who received at least 1 dose of investigational medical product were analyzed for safety (Brexpiprazole N=132).', 'eventGroups': [{'id': 'EG000', 'title': 'Brexpiprazole (Flexible Dose Range 0.5 to 2 mg/Day)', 'description': 'Titrate up from 0.25 mg/day brexpiprazole to 1 mg/day brexpiprazole. After achieving 1 mg/day target, dose may be increased or decreased based on efficacy and tolerability. Allowable flexible doses will be 0.5 mg/day, 1 mg/day, or 2 mg/day.', 'otherNumAtRisk': 132, 'deathsNumAtRisk': 132, 'otherNumAffected': 24, 'seriousNumAtRisk': 132, 'deathsNumAffected': 0, 'seriousNumAffected': 7}, {'id': 'EG001', 'title': 'Placebo (Flexible Dose Range 0.5 to 2 mg/Day)', 'description': 'Titrate up from 0.25 mg/day placebo to 1 mg/day placebo. After achieving 1 mg/day target, dose may be increased or decreased based on efficacy and tolerability. Allowable flexible doses will be 0.5 mg/day, 1 mg/day, or 2 mg/day.', 'otherNumAtRisk': 137, 'deathsNumAtRisk': 137, 'otherNumAffected': 29, 'seriousNumAtRisk': 137, 'deathsNumAffected': 1, 'seriousNumAffected': 6}], 'otherEvents': [{'term': 'Somnolence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 5}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 7}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 10}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 17}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}], 'seriousEvents': [{'term': 'Gastrointestinal haemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}, {'term': 'Non-Cardiac Chest Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}, {'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}, {'term': 'Femur Fracture', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}, {'term': 'Hip Fracture', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}, {'term': 'Subdural haematoma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 0}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}, {'term': 'Dehydration', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}, {'term': 'Failure to thrive', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}, {'term': 'Loss of consciousness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}, {'term': 'Presyncope', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}, {'term': 'Seizure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}, {'term': 'Syncope', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}, {'term': 'Dyspnoea Exertional', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}, {'term': 'Hypertensive crisis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 137, 'numAffected': 0}], 'organSystem': 'Vascular disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDra 19.0'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change From Baseline to Week 12/Early Termination in the Cohen-Mansfield Agitation Inventory (CMAI) Total Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '131', 'groupId': 'OG000'}, {'value': '135', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Brexpiprazole (Flexible Dose Range 0.5 to 2 mg/Day)', 'description': 'Titrate up from 0.25 mg/day brexpiprazole to 1 mg/day brexpiprazole. After achieving 1 mg/day target, dose may be increased or decreased based on efficacy and tolerability. Allowable flexible doses will be 0.5 mg/day, 1 mg/day, or 2 mg/day.'}, {'id': 'OG001', 'title': 'Placebo (Flexible Dose Range 0.5 to 2 mg/Day)', 'description': 'Titrate up from 0.25 mg/day placebo to 1 mg/day placebo. After achieving 1 mg/day target, dose may be increased or decreased based on efficacy and tolerability. Allowable flexible doses will be 0.5 mg/day, 1 mg/day, or 2 mg/day.'}], 'classes': [{'categories': [{'measurements': [{'value': '-18.9', 'spread': '1.17', 'groupId': 'OG000'}, {'value': '-16.5', 'spread': '1.13', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '=0.1454', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Treatment Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-2.34', 'ciLowerLimit': '-5.49', 'ciUpperLimit': '0.82', 'statisticalMethod': 'Mixed-effect model repeated measure', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'From screening to week 12/early termination', 'description': 'The CMAI is widely used in clinical research for evaluation of agitation associated with Alzheimer\'s dementia, with reliability and validity in both institutionalized and noninstitutionalized participants. It consists of 29 items, all rated on a 1 to 7 scale (1=Never and 7=Several times in an hour), with 1 being the "best" rating and 7 being the "worst" rating. The total score is the sum of ratings for all 29 items. The possible total scores range from 29 to 203. The total score will be unevaluable if less than 24 of the 29 items are recorded. If 24 to 28 of the 29 items are recorded, the total score will be the mean of the recorded items multiplied by 29 and rounded to the first decimal place. The mean change from baseline (Day 0) to week 12 in the CMAI total score is reported. Statistical comparison of interest was brexpiprazole flexible dose versus placebo, analyzed using a mixed-effect model repeated measure approach. A decrease in score indicates improvement in symptoms.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'The intent-to-treat (ITT) population consisted of all participants in the randomized sample, who took at least 1 dose of the investigational medicinal product (IMP) and had a baseline and at least one postbaseline evaluation for the CMAI total score.'}, {'type': 'SECONDARY', 'title': 'Change in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Symptoms of Agitation', 'denoms': [{'units': 'Participants', 'counts': [{'value': '131', 'groupId': 'OG000'}, {'value': '135', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Brexpiprazole (Flexible Dose Range 0.5 to 2 mg/Day)', 'description': 'Titrate up from 0.25 mg/day brexpiprazole to 1 mg/day brexpiprazole. After achieving 1 mg/day target, dose may be increased or decreased based on efficacy and tolerability. Allowable flexible doses will be 0.5 mg/day, 1 mg/day, or 2 mg/day.'}, {'id': 'OG001', 'title': 'Placebo (Flexible Dose Range 0.5 to 2 mg/Day)', 'description': 'Titrate up from 0.25 mg/day placebo to 1 mg/day placebo. After achieving 1 mg/day target, dose may be increased or decreased based on efficacy and tolerability. Allowable flexible doses will be 0.5 mg/day, 1 mg/day, or 2 mg/day.'}], 'classes': [{'categories': [{'measurements': [{'value': '4.54', 'spread': '0.77', 'groupId': 'OG000'}, {'value': '4.51', 'spread': '0.74', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'From screening to week 12/early termination', 'description': 'The severity of agitation for each participant was rated using the CGI-S. The investigator (or designee) answered the following question: "Considering your total clinical experience with this particular population, how mentally ill (as related to agitation) was the participant at the observation period?" Response choices were 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. The score 0 (= not assessed) was set to missing. The CGI-S was therefore a 7-point scale (1-7). The primary analysis used a mixed-effect model repeated measure approach.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'The intent-to-treat (ITT) population consisted of all participants in the randomized sample, who took at least 1 dose of the IMP and had a baseline and at least one postbaseline evaluation for the CMAI total score.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Brexpiprazole (Flexible Dose Range 0.5 to 2 mg/Day)', 'description': 'Titrate up from 0.25 mg/day brexpiprazole to 1 mg/day brexpiprazole. After achieving 1 mg/day target, dose may be increased or decreased based on efficacy and tolerability. Allowable flexible doses will be 0.5 mg/day, 1 mg/day, or 2 mg/day.'}, {'id': 'FG001', 'title': 'Placebo (Flexible Dose Range 0.5 to 2 mg/Day)', 'description': 'Titrate up from 0.25 mg/day placebo to 1 mg/day placebo. After achieving 1 mg/day target, dose may be increased or decreased based on efficacy and tolerability. Allowable flexible doses will be 0.5 mg/day, 1 mg/day, or 2 mg/day.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '133'}, {'groupId': 'FG001', 'numSubjects': '137'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '117'}, {'groupId': 'FG001', 'numSubjects': '121'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '16'}, {'groupId': 'FG001', 'numSubjects': '16'}]}], 'dropWithdraws': [{'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '2'}]}, {'type': 'Met Withdrawal Criteria', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '4'}]}, {'type': 'Withdrawn by the Investigator', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '4'}]}, {'type': 'Withdrawal by participant', 'reasons': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '5'}]}]}], 'recruitmentDetails': 'The trial was conducted at 62 sites in 9 countries: Bulgaria, Canada, Finland, France, Russia, Slovenia, Ukraine, the United Kingdom (UK), and the United States (US) and 270 participants were randomized. The date of the first ICF signed by a participant in this trial was 28 October 2013 and the date of the last trial observation was 30 March 2017.', 'preAssignmentDetails': "The screening period ranged from 2 to 42 days (with an option to extend with approval of the medical monitor). The screening period was to determine the participant's eligibility and to washout prohibited concomitant pharmacotherapy prior to randomization."}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '133', 'groupId': 'BG000'}, {'value': '137', 'groupId': 'BG001'}, {'value': '270', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Brexpiprazole (Flexible Dose Range 0.5 to 2 mg/Day)', 'description': 'Titrate up from 0.25 mg/day brexpiprazole to 1 mg/day brexpiprazole. After achieving 1 mg/day target, dose may be increased or decreased based on efficacy and tolerability. Allowable flexible doses will be 0.5 mg/day, 1 mg/day, or 2 mg/day.'}, {'id': 'BG001', 'title': 'Placebo (Flexible Dose Range 0.5 to 2 mg/Day)', 'description': 'Titrate up from 0.25 mg/day placebo to 1 mg/day placebo. After achieving 1 mg/day target, dose may be increased or decreased based on efficacy and tolerability. Allowable flexible doses will be 0.5 mg/day, 1 mg/day, or 2 mg/day.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Customized', 'classes': [{'categories': [{'title': '<65 years', 'measurements': [{'value': '24', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '43', 'groupId': 'BG002'}]}, {'title': '>=65 <75 years', 'measurements': [{'value': '46', 'groupId': 'BG000'}, {'value': '49', 'groupId': 'BG001'}, {'value': '95', 'groupId': 'BG002'}]}, {'title': '>=75 years', 'measurements': [{'value': '63', 'groupId': 'BG000'}, {'value': '69', 'groupId': 'BG001'}, {'value': '132', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '82', 'groupId': 'BG000'}, {'value': '88', 'groupId': 'BG001'}, {'value': '170', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '51', 'groupId': 'BG000'}, {'value': '49', 'groupId': 'BG001'}, {'value': '100', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '128', 'groupId': 'BG000'}, {'value': '129', 'groupId': 'BG001'}, {'value': '257', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'All participants who were randomized into this trial. Participants were considered randomized when they were assigned a treatment number by interactive voice response system (IVRS) at the end of screening period. A participant who received trial treatment outside of the IVRS was not considered randomized, but safety was reported.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2015-09-10', 'size': 13480967, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2020-05-12T14:11', 'hasProtocol': True}, {'date': '2017-03-22', 'size': 2019391, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2020-05-12T14:11', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 270}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-09', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-11', 'dispFirstSubmitDate': '2018-05-15', 'completionDateStruct': {'date': '2017-03', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-11-04', 'studyFirstSubmitDate': '2013-08-12', 'dispFirstSubmitQcDate': '2018-05-15', 'resultsFirstSubmitDate': '2020-05-15', 'studyFirstSubmitQcDate': '2013-08-12', 'dispFirstPostDateStruct': {'date': '2018-05-17', 'type': 'ACTUAL'}, 'lastUpdatePostDateStruct': {'date': '2020-11-20', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2020-06-30', 'studyFirstPostDateStruct': {'date': '2013-08-14', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2020-07-07', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2017-03', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change From Baseline to Week 12/Early Termination in the Cohen-Mansfield Agitation Inventory (CMAI) Total Score', 'timeFrame': 'From screening to week 12/early termination', 'description': 'The CMAI is widely used in clinical research for evaluation of agitation associated with Alzheimer\'s dementia, with reliability and validity in both institutionalized and noninstitutionalized participants. It consists of 29 items, all rated on a 1 to 7 scale (1=Never and 7=Several times in an hour), with 1 being the "best" rating and 7 being the "worst" rating. The total score is the sum of ratings for all 29 items. The possible total scores range from 29 to 203. The total score will be unevaluable if less than 24 of the 29 items are recorded. If 24 to 28 of the 29 items are recorded, the total score will be the mean of the recorded items multiplied by 29 and rounded to the first decimal place. The mean change from baseline (Day 0) to week 12 in the CMAI total score is reported. Statistical comparison of interest was brexpiprazole flexible dose versus placebo, analyzed using a mixed-effect model repeated measure approach. A decrease in score indicates improvement in symptoms.'}], 'secondaryOutcomes': [{'measure': 'Change in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Symptoms of Agitation', 'timeFrame': 'From screening to week 12/early termination', 'description': 'The severity of agitation for each participant was rated using the CGI-S. The investigator (or designee) answered the following question: "Considering your total clinical experience with this particular population, how mentally ill (as related to agitation) was the participant at the observation period?" Response choices were 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. The score 0 (= not assessed) was set to missing. The CGI-S was therefore a 7-point scale (1-7). The primary analysis used a mixed-effect model repeated measure approach.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['OPC-34712', 'brexpiprazole', 'Dementia', "Alzheimer's Disease", 'Cognitive Disorders', 'Agitation'], 'conditions': ['Agitation Associated With', "Alzheimer's Disease", "Alzheimer's Type", 'Mental Disorder', 'Nervous System Diseases']}, 'referencesModule': {'references': [{'pmid': '40681915', 'type': 'DERIVED', 'citation': "Shah A, Estilo A, Sheridan PL, Kalu U, Chen D, Chang D, Slomkowski M, Lee D, Hefting N, Hobart M, Behl S, Such P, Brubaker M, Grossberg GT. Safety and Tolerability of Brexpiprazole in Participants with Agitation Associated with Dementia due to Alzheimer's Disease: Pooled Analysis of Three Randomized Trials and an Extension Trial. CNS Drugs. 2025 Oct;39(10):1011-1023. doi: 10.1007/s40263-025-01200-9. Epub 2025 Jul 19."}, {'pmid': '39108660', 'type': 'DERIVED', 'citation': "Meunier J, Creel K, Loubert A, Larsen KG, Aggarwal J, Hefting N, Oberdhan D. Defining a clinically meaningful within-patient change threshold for the Cohen-Mansfield Agitation Inventory in Alzheimer's dementia. Front Neurol. 2024 Jul 23;15:1379062. doi: 10.3389/fneur.2024.1379062. eCollection 2024."}, {'pmid': '31708380', 'type': 'DERIVED', 'citation': "Grossberg GT, Kohegyi E, Mergel V, Josiassen MK, Meulien D, Hobart M, Slomkowski M, Baker RA, McQuade RD, Cummings JL. Efficacy and Safety of Brexpiprazole for the Treatment of Agitation in Alzheimer's Dementia: Two 12-Week, Randomized, Double-Blind, Placebo-Controlled Trials. Am J Geriatr Psychiatry. 2020 Apr;28(4):383-400. doi: 10.1016/j.jagp.2019.09.009. Epub 2019 Oct 1."}]}, 'descriptionModule': {'briefSummary': "To compare the efficacy of flexible dosing of brexpiprazole with placebo in subjects with agitation associated with dementia of the Alzheimer's type", 'detailedDescription': "Behavioral symptoms, such as agitation, are core features in subjects with Alzheimer's disease and related dementias and develop in the majority of dementia subjects. The presence of agitation in subjects with Alzheimer's disease places a significant burden not only on subjects and their caregivers but also on the healthcare system.\n\nThis is a trial designed to assess the safety and efficacy of flexible dosing of brexpiprazole in the treatment of subjects with agitation associated with dementia of the Alzheimer's type. The trial consists of a 12-week double-blind treatment period with a 30-day follow-up. The trial population will include male and female subjects between 55 and 90 years of age (inclusive) with a diagnosis of probable Alzheimer's disease, who are residing either in an institutionalized setting or in a non-institutionalized setting where the subject is not living alone."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '90 Years', 'minimumAge': '55 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Male and female subjects 55 to 90 years of age, inclusive, at the time of informed consent.\n* Subjects who are residing at their current location for at least 14 days before screening and are expected to remain at the same location for the duration of the trial.\n* Subjects with diagnosis of probable Alzheimer's disease according to NINCDS-ADRDA criteria.\n* Subjects with a MMSE score of 5 to 22, inclusive, at screening and baseline visits.\n* Subjects with onset of symptoms of agitation at least 2 weeks prior to the screening visit.\n* Subjects with a total score greater than or equal to 4 on the agitation aggression item of the NPI-NH or NPI/NPI-NH at the screening and baseline visits.\n* Subjects who require pharmacotherapy for the treatment of agitation per the investigator's judgement, after an evaluation of reversible factors (eg, pain, infection, polypharmacy) and a trial of nonpharmacological interventions.\n* Subjects must have a previous MRI or CT scan of the brain, which was performed after the onset of symptoms of dementia, with findings consistent with the diagnosis of Alzheimer's disease.\n\nExclusion Criteria:\n\n* Subjects with dementia or other memory impairment not due to Alzheimer's disease.\n* Subjects with history of stroke, well-documented transient ischemic attack, or pulmonary or cerebral embolism.\n* Subjects who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, gastrointestinal, or psychiatric disorders.\n* Subjects who have been diagnosed with an Axis I disorder (DSM-IV-TR criteria).\n* Subjects with uncontrolled hypertension.\n* Subjects with uncontrolled insulin-dependent diabetes mellitus (IDDM)\n* Subjects with epilepsy or a history of seizures.\n* Subjects considered in poor general health based on the investigator's judgment."}, 'identificationModule': {'nctId': 'NCT01922258', 'briefTitle': "Safety and Tolerability Study of Flexible Dosing of Brexpiprazole in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type", 'organization': {'class': 'INDUSTRY', 'fullName': 'Otsuka Pharmaceutical Development & Commercialization, Inc.'}, 'officialTitle': "A Phase 3, 12-week, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Flexible Dosing of Brexpiprazole (OPC-34712) in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type", 'orgStudyIdInfo': {'id': '331-12-284'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Matching Placebo Once-Daily', 'interventionNames': ['Drug: Brexpiprazole, OPC-34712']}, {'type': 'EXPERIMENTAL', 'label': 'Brexpiprazole (flexible dose range 0.5 to 2 mg)', 'description': 'Titrate up from 0.25 mg/day brexpiprazole to 1 mg/day brexpiprazole. After achieving 1 mg/day target dose may be increased or decreased based on efficacy and tolerability. Allowable flexible doses will be 0.5 mg/day, 1 mg/day, or 2 mg/day.', 'interventionNames': ['Drug: Brexpiprazole, OPC-34712']}], 'interventions': [{'name': 'Brexpiprazole, OPC-34712', 'type': 'DRUG', 'description': 'Flexible dose of 0.5 to 2 mg/day or placebo tablets for up to 12 weeks', 'armGroupLabels': ['Brexpiprazole (flexible dose range 0.5 to 2 mg)', 'Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '92251', 'city': 'Imperial', 'state': 'California', 'country': 'United States', 'geoPoint': {'lat': 32.84755, 'lon': -115.56944}}, {'zip': '08755', 'city': 'Lakewood', 'state': 'California', 'country': 'United States', 'geoPoint': {'lat': 33.85363, 'lon': -118.13396}}, {'zip': '90806', 'city': 'Long Beach', 'state': 'California', 'country': 'United States', 'geoPoint': {'lat': 33.76696, 'lon': -118.18923}}, {'zip': '90822', 'city': 'Long Beach', 'state': 'California', 'country': 'United States', 'geoPoint': {'lat': 33.76696, 'lon': -118.18923}}, {'zip': '91402', 'city': 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'Otsuka Pharmaceutical Development and Commercialization, Inc.'}]}, 'ipdSharingStatementModule': {'url': 'https://clinical-trials.otsuka.com', 'infoTypes': ['STUDY_PROTOCOL', 'SAP', 'ICF', 'CSR'], 'timeFrame': 'Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.', 'ipdSharing': 'YES', 'description': 'Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.', 'accessCriteria': 'Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Otsuka Pharmaceutical Development & Commercialization, Inc.', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'H. Lundbeck A/S', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}