A Phase 3, 12-week, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of 2 Fixed Doses of Brexpiprazole in the Treatment of Alzheimer's Agitation
1 other identifier
interventional
433
7 countries
85
Brief Summary
To compare the efficacy of 2 fixed doses of brexpiprazole with placebo in participants 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 Jul 2013
Typical duration for phase_3
85 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
May 22, 2013
CompletedFirst Posted
Study publicly available on registry
May 24, 2013
CompletedStudy Start
First participant enrolled
July 11, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 15, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
March 15, 2017
CompletedResults Posted
Study results publicly available
June 16, 2020
CompletedDecember 31, 2020
December 1, 2020
3.7 years
May 22, 2013
April 16, 2020
December 8, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline In The Cohen-Mansfield Agitation Inventory (CMAI) Total Score After 12 Weeks Of Brexpiprazole Treatment
To compare the efficacy of 2 fixed doses (1 mg/day and 2 mg/day) of brexpiprazole with placebo in participants with agitation associated with dementia of the Alzheimer's type, by the assessment of CMAI after 12 weeks of treatment. The CMAI assesses the frequency of agitated behaviors in elderly persons, such as hitting, cursing, and restlessness. It consists of 29 items all rated on a 1 to 7 scale with 1 being the "best" rating and 7 being the "worst" rating. The minimum possible CMAI total score is 29, and the maximum possible CMAI total score is 203. A decrease in score indicates improvement in symptoms. To control the overall type I error at 0.05 level when making 2 comparisons of brexpiprazole doses versus placebo, statistical testing was carried out using a hierarchical testing procedure in the order of: 1) comparison of 2 mg/day brexpiprazole versus placebo, and 2) comparison of 1 mg/day brexpiprazole versus placebo.
Baseline, Week 12/Early Termination (ET)
Secondary Outcomes (1)
Change From Baseline In The Clinical Global Impression-Severity Of Illness (CGI-S) Score, As Related To Symptoms Of Agitation After 12 Weeks Of Brexpiprazole Treatment
Baseline, Week 12/ET
Study Arms (3)
Placebo
PLACEBO COMPARATORMatching placebo once daily
Brexpiprazole 1 mg
EXPERIMENTALTitrate up from 0.25 milligrams (mg)/day brexpiprazole to 1 mg/day brexpiprazole
Brexpiprazole 2 mg
EXPERIMENTALTitrate up from 0.25 mg/day brexpiprazole to 2 mg/day brexpiprazole
Interventions
Eligibility Criteria
You may qualify if:
- Male and female participants 55 to 90 years of age, inclusive, at the time of informed consent.
- Participants 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.
- Participants with a diagnosis of probable Alzheimer's disease according to National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association.
- Participants with a Mini-Mental State Exam score of 5 to 22, inclusive, at screening and baseline visits.
- Participants with onset of symptoms of agitation at least 2 weeks prior to the screening visit.
- Participants with a score of ≥ 4 on the agitation/aggression item of the Neuropsychiatric Inventory-Nursing Home at the screening and baseline visits.
- Participants who require pharmacotherapy for treatment of agitation per the investigator's judgment, after an evaluation for reversible factors (for example, pain, infection, polypharmacy) and a trial of nonpharmacological intervention.
- Participants must have a previous magnetic resonance imaging or computed tomography 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:
- Participants with dementia or other memory impairment not due to Alzheimer's disease
- Participants with a history of stroke, well-documented transient ischemic attack, pulmonary or cerebral embolism.
- Participants who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, gastrointestinal, or psychiatric disorders.
- Participants who have been diagnosed with an Axis I disorder (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision criteria)
- Participants with uncontrolled hypertension
- Participants with uncontrolled insulin-dependent diabetes mellitus
- Participants with epilepsy or a history of seizures
- Participants considered in poor general health based on the investigator's judgment.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (85)
Unknown Facility
Tuscaloosa, Alabama, 35404, United States
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Phoenix, Arizona, 85013, United States
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Bellflower, California, 90706, United States
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Costa Mesa, California, 92627, United States
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Downey, California, 90706, United States
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Orange, California, 92868, United States
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Redlands, California, 92373, United States
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Yorba Linda, California, 92886, United States
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Norwalk, Connecticut, 06851, United States
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Coconut Creek, Florida, 33024, United States
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Hialeah, Florida, 33012, United States
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Hialeah, Florida, 33013, United States
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Hialeah, Florida, 33018, United States
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Lauderhill, Florida, 33319, United States
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Miami, Florida, 33122, United States
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Miami, Florida, 33126, United States
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Miami, Florida, 33136, United States
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Miami, Florida, 33137, United States
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Miami, Florida, 33145, United States
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Miami, Florida, 33161, United States
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Miami, Florida, 33174, United States
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Miami Springs, Florida, 33166, United States
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Sarasota, Florida, 34239, United States
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Decatur, Georgia, 30033, United States
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Suwanee, Georgia, 30024, United States
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Weymouth, Massachusetts, 02190, United States
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St Louis, Missouri, 63128, United States
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St Louis, Missouri, 63141, United States
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Las Vegas, Nevada, 89148, United States
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Mount Arlington, New Jersey, 07856, United States
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Paterson, New Jersey, 08759, United States
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Toms River, New Jersey, 08755, United States
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Hickory, North Carolina, 28601, United States
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Oklahoma City, Oklahoma, 73118, United States
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Franklin, Tennessee, 37064, United States
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Bedford, Texas, 76022, United States
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Waukesha, Wisconsin, 53188, United States
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Rijeka, 57000, Croatia
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Zadar, 23000, Croatia
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Zagreb, 10000, Croatia
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Zagreb, 10090, Croatia
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Mittweida, Saxony, 09648, Germany
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Achim, 28832, Germany
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Berlin, 12209, Germany
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Bielefeld, 33647, Germany
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Bochum, 44791, Germany
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Cologne, 50935, Germany
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Hamburg, 22083, Germany
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Ostfildern, 73760, Germany
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Westerstede, 26655, Germany
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Saint Petersburg, 190000, Russia
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Saint Petersburg, 190005, Russia
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Saint Petersburg, 191119, Russia
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Saint Petersburg, 192019, Russia
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Saint Petersburg, 197341, Russia
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Saint Petersburg, 198510, Russia
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Samara, 443016, Russia
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Saratov, 410060, Russia
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Tonnel’nyy, 357034, Russia
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Yekaterinburg, 620030, Russia
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Belgrade, 11000, Serbia
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Kovin, 26220, Serbia
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Kragujevac, 34000, Serbia
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Niš, 18000, Serbia
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Novi Kneževac, 23330, Serbia
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Novi Sad, 21000, Serbia
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Vršac, 26300, Serbia
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Barcelona, 08028, Spain
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Getafe, 28905, Spain
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Girona, 17190, Spain
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Madrid, 28034, Spain
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Madrid, 28040, Spain
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Madrid, 28049, Spain
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Pamplona, 31014, Spain
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Salamanca, 37003, Spain
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Valencia, 46010, Spain
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Valencia, 46026, Spain
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Zamora, 49021, Spain
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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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Lviv, 79021, Ukraine
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Odesa, 65006, Ukraine
Unknown Facility
Odesa, 67513, Ukraine
Unknown Facility
Poltava, 36013, Ukraine
Related Publications (7)
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: 41533472DERIVEDGrossberg GT, Sabbagh MN, Chumki SR, Wang D, Such P, Zhang Z, Palma AM, Cummings JL. Efficacy of Brexpiprazole on Neuropsychiatric Symptoms and Impact on Caregivers: Pooled Neuropsychiatric Inventory (NPI) Analysis in Patients With Agitation Associated With Dementia due to Alzheimer's Disease. J Geriatr Psychiatry Neurol. 2025 Dec 24:8919887251407124. doi: 10.1177/08919887251407124. Online ahead of print.
PMID: 41439450DERIVEDStroud J, Cummings JL, Chumki SR, Such P, Wang D, Palma AM, Zhang Z, Brubaker M, Grossberg GT. Brexpiprazole for agitation in clinically relevant patient subgroups: a post hoc analysis of efficacy and safety in patients with agitation associated with dementia due to Alzheimer's disease. Curr Med Res Opin. 2025 Aug;41(8):1523-1534. doi: 10.1080/03007995.2025.2552278. Epub 2025 Sep 5.
PMID: 40847656DERIVEDShah 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)
Limitations and Caveats
None reported
Results Point of Contact
- Title
- Global Clinical Development
- Organization
- Otsuka Pharmaceutical Development & Commercialization, Inc.
Study Officials
- STUDY DIRECTOR
Eva Kohegyi, MD
Otsuka Pharmaceutical Development & 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
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 22, 2013
First Posted
May 24, 2013
Study Start
July 11, 2013
Primary Completion
March 15, 2017
Study Completion
March 15, 2017
Last Updated
December 31, 2020
Results First Posted
June 16, 2020
Record last verified: 2020-12
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, 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.