Safety and Tolerability Study of Flexible Dosing of Brexpiprazole in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type
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
1 other identifier
interventional
270
9 countries
70
Brief Summary
To compare the efficacy of flexible dosing of brexpiprazole with placebo in subjects with agitation associated with dementia of the Alzheimer's type
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Sep 2013
Typical duration for phase_3
70 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 12, 2013
CompletedFirst Posted
Study publicly available on registry
August 14, 2013
CompletedStudy Start
First participant enrolled
September 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2017
CompletedResults Posted
Study results publicly available
July 7, 2020
CompletedNovember 20, 2020
November 1, 2020
3.5 years
August 12, 2013
May 15, 2020
November 4, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline to Week 12/Early Termination in the Cohen-Mansfield Agitation Inventory (CMAI) Total Score
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.
From screening to week 12/early termination
Secondary Outcomes (1)
Change in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Symptoms of Agitation
From screening to week 12/early termination
Study Arms (2)
Placebo
PLACEBO COMPARATORMatching Placebo Once-Daily
Brexpiprazole (flexible dose range 0.5 to 2 mg)
EXPERIMENTALTitrate 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.
Interventions
Flexible dose of 0.5 to 2 mg/day or placebo tablets for up to 12 weeks
Eligibility Criteria
You may qualify if:
- Male and female subjects 55 to 90 years of age, inclusive, at the time of informed consent.
- 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.
- Subjects with diagnosis of probable Alzheimer's disease according to NINCDS-ADRDA criteria.
- Subjects with a MMSE score of 5 to 22, inclusive, at screening and baseline visits.
- Subjects with onset of symptoms of agitation at least 2 weeks prior to the screening visit.
- 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.
- 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.
- 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.
You may not qualify if:
- Subjects with dementia or other memory impairment not due to Alzheimer's disease.
- Subjects with history of stroke, well-documented transient ischemic attack, or pulmonary or cerebral embolism.
- Subjects who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, gastrointestinal, or psychiatric disorders.
- Subjects who have been diagnosed with an Axis I disorder (DSM-IV-TR criteria).
- Subjects with uncontrolled hypertension.
- Subjects with uncontrolled insulin-dependent diabetes mellitus (IDDM)
- Subjects with epilepsy or a history of seizures.
- Subjects considered in poor general health based on the investigator's judgment.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (70)
Unknown Facility
Imperial, California, 92251, United States
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Lakewood, California, 08755, United States
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Long Beach, California, 90806, United States
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Long Beach, California, 90822, United States
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Panorama City, California, 91402, United States
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Universal City, California, 91950, United States
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Denver, Colorado, 80209, United States
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Bradenton, Florida, 34205, United States
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Miami, Florida, 33142, United States
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Miami, Florida, 33165, United States
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Miami, Florida, 33176, United States
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Orange City, Florida, 32763, United States
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Atlanta, Georgia, 30331, United States
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Smyrna, Georgia, 30080, United States
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Honolulu, Hawaii, 96817, United States
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Indianapolis, Indiana, 46256, United States
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Quincy, Massachusetts, 02169, United States
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South Dartmouth, Massachusetts, 02747, United States
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Ann Arbor, Michigan, 48105, United States
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Brooklyn, New York, 11214, United States
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Buffalo, New York, 14215, United States
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New Hyde Park, New York, 11040, United States
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Charlotte, North Carolina, 28270, United States
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Raleigh, North Carolina, 27609, United States
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Austin, Texas, 78757, United States
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Dallas, Texas, 75231, United States
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Dallas, Texas, 75243, United States
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Woodstock, Vermont, 05091, United States
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Burgas, 8000, Bulgaria
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Kardzhali, 6600, Bulgaria
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Pazardzhik, 4400, Bulgaria
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Rousse, 7003, Bulgaria
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Sofia, 1113, Bulgaria
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Sofia, 1154, Bulgaria
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Sofia, 1431, Bulgaria
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Varna, 9020, Bulgaria
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Veliko Tarnovo, 5000, Bulgaria
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Penticton, British Columbia, V2A 4M4, Canada
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Kentville, B4N 4K9, Canada
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Kuopio, 70210, Finland
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Turku, 20520, Finland
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Bourg-en-Bresse, 01012, France
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Douai, 59500, France
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Élancourt, 78990, France
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Limoges, 87042, France
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Nice, 06100, France
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Toulouse, 31059, France
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Tonnel’nyy, Stavropol Kray, 357034, Russia
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Saint Petersburg, 188820, Russia
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Saint Petersburg, 190005, Russia
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Saint Petersburg, 195176, Russia
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Saint Petersburg, 197341, Russia
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Saratov, 410060, Russia
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Yekaterinburg, 620030, Russia
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Ljubljana, 1000, Slovenia
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Maribor, 2000, Slovenia
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Šempeter pri Gorici, 5290, Slovenia
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Donetsk, 83037, Ukraine
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Kharkiv, 61068, Ukraine
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Kherson, 73488, Ukraine
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Kiev, 04080, Ukraine
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Kiev, 04114, Ukraine
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Lviv, 79021, Ukraine
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Poltava, 36013, Ukraine
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Simferopol, 95006, Ukraine
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Vinnytsia, 21005, Ukraine
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Crewe, CW1 2ER, United Kingdom
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Manchester, M8 5RB, United Kingdom
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Margate, CT20 1JY, United Kingdom
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Torpoint, PL11 2TB, United Kingdom
Related Publications (5)
Cummings JL, Chumki SR, Chang D, Zhang Z, Brubaker M, Hefting N, Such P, Wang D, Grossberg GT. Efficacy of Brexpiprazole in Participants with Agitation Associated with Dementia Due to Alzheimer's Disease: Pooled Analysis of Randomized Controlled Trials. Clin Drug Investig. 2026 Jan 27. doi: 10.1007/s40261-025-01517-9. Online ahead of print.
PMID: 41591746DERIVEDShah A, Kalu U, Chen D, Slomkowski M, Hobart M, Such P, Grossberg GT. Brexpiprazole side-effect profile in people with agitation in Alzheimer's dementia: a plain language summary. Curr Med Res Opin. 2026 Jan 14:1-3. doi: 10.1080/03007995.2025.2608578. Online ahead of print.
PMID: 41533472DERIVEDShah 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: 40681915DERIVEDMeunier 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: 39108660DERIVEDGrossberg 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.
PMID: 31708380DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Development
- Organization
- Otsuka Pharmaceutical Development & Commercialization, Inc.
Study Officials
- STUDY DIRECTOR
Eva Koheygi, MD
Otsuka Pharmaceutical Development and Commercialization, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 12, 2013
First Posted
August 14, 2013
Study Start
September 1, 2013
Primary Completion
March 1, 2017
Study Completion
March 1, 2017
Last Updated
November 20, 2020
Results First Posted
July 7, 2020
Record last verified: 2020-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- 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.
- Access Criteria
- 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
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.