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Agitation Associated WithPhase 3NCT01862640

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

A Phase 3 study testing Brexpiprazole, OPC-34712 in people with Agitation Associated With and Alzheimer's Disease, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 85 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 55 to 90 years
What is being tested?
Brexpiprazole, OPC-34712
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
433 participants
Where
85 sitesin 7 countries
Study dates
11 Jul 2013to 15 Mar 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

85 sites in 7 countries.

85 sites in 7 countries

United States37 sites

  • Study site

    Bedford, Texas, 76022

  • Study site

    Bellflower, California, 90706

  • Study site

    Coconut Creek, Florida, 33024

  • Study site

    Costa Mesa, California, 92627

  • Study site

    Decatur, Georgia, 30033

  • Study site

    Downey, California, 90706

  • Study site

    Franklin, Tennessee, 37064

  • Study site

    Hialeah, Florida, 33012

  • Study site

    Hialeah, Florida, 33013

  • Study site

    Hialeah, Florida, 33018

  • Study site

    Hickory, North Carolina, 28601

  • Study site

    Las Vegas, Nevada, 89148

  • Study site

    Lauderhill, Florida, 33319

  • Study site

    Miami, Florida, 33122

  • Study site

    Miami, Florida, 33126

  • Study site

    Miami, Florida, 33136

  • Study site

    Miami, Florida, 33137

  • Study site

    Miami, Florida, 33145

  • Study site

    Miami, Florida, 33161

  • Study site

    Miami, Florida, 33174

  • Study site

    Miami Springs, Florida, 33166

  • Study site

    Mount Arlington, New Jersey, 07856

  • Study site

    Norwalk, Connecticut, 06851

  • Study site

    Oklahoma City, Oklahoma, 73118

  • Study site

    Orange, California, 92868

  • Study site

    Paterson, New Jersey, 08759

  • Study site

    Phoenix, Arizona, 85013

  • Study site

    Redlands, California, 92373

  • Study site

    Sarasota, Florida, 34239

  • Study site

    St Louis, Missouri, 63128

  • Study site

    St Louis, Missouri, 63141

  • Study site

    Suwanee, Georgia, 30024

  • Study site

    Toms River, New Jersey, 08755

  • Study site

    Tuscaloosa, Alabama, 35404

  • Study site

    Waukesha, Wisconsin, 53188

  • Study site

    Weymouth, Massachusetts, 02190

  • Study site

    Yorba Linda, California, 92886

Other trials in United States

Spain11 sites

  • Study site

    Barcelona, 08028

  • Study site

    Getafe, 28905

  • Study site

    Girona, 17190

  • Study site

    Madrid, 28034

  • Study site

    Madrid, 28040

  • Study site

    Madrid, 28049

  • Study site

    Pamplona, 31014

  • Study site

    Salamanca, 37003

  • Study site

    Valencia, 46010

  • Study site

    Valencia, 46026

  • Study site

    Zamora, 49021

Other trials in Spain

Russia10 sites

  • Study site

    Saint Petersburg, 190000

  • Study site

    Saint Petersburg, 190005

  • Study site

    Saint Petersburg, 191119

  • Study site

    Saint Petersburg, 192019

  • Study site

    Saint Petersburg, 197341

  • Study site

    Saint Petersburg, 198510

  • Study site

    Samara, 443016

  • Study site

    Saratov, 410060

  • Study site

    Tonnel'nyy, 357034

  • Study site

    Yekaterinburg, 620030

Other trials in Russia

Germany9 sites

  • Study site

    Achim, 28832

  • Study site

    Berlin, 12209

  • Study site

    Bielefeld, 33647

  • Study site

    Bochum, 44791

  • Study site

    Cologne, 50935

  • Study site

    Hamburg, 22083

  • Study site

    Mittweida, Saxony, 09648

  • Study site

    Ostfildern, 73760

  • Study site

    Westerstede, 26655

Other trials in Germany

Serbia7 sites

  • Study site

    Belgrade, 11000

  • Study site

    Kovin, 26220

  • Study site

    Kragujevac, 34000

  • Study site

    Niš, 18000

  • Study site

    Novi Kneževac, 23330

  • Study site

    Novi Sad, 21000

  • Study site

    Vršac, 26300

Other trials in Serbia

Ukraine7 sites

  • Study site

    Kharkiv, 61068

  • Study site

    Kherson, 73488

  • Study site

    Kiev, 04080

  • Study site

    Lviv, 79021

  • Study site

    Odesa, 65006

  • Study site

    Odesa, 67513

  • Study site

    Poltava, 36013

Other trials in Ukraine

Croatia4 sites

  • Study site

    Rijeka, 57000

  • Study site

    Zadar, 23000

  • Study site

    Zagreb, 10000

  • Study site

    Zagreb, 10090

Other trials in Croatia

About this study

Official title: 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 (OPC-34712) in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type

To compare the efficacy of 2 fixed doses of brexpiprazole with placebo in participants with agitation associated with dementia of the Alzheimer's type.

Read the detailed description

Behavioral symptoms, such as agitation, are core features in participants with Alzheimer's disease and related dementias and develop in the majority of dementia participants. The presence of agitation in participants with Alzheimer's disease places a significant burden not only on participants and their caregivers but also on the healthcare system.

This is a trial designed to assess the safety and efficacy of brexpiprazole in the treatment of participants with agitation associated with dementia of the Alzheimer's Type. The trial consists of a continuous 12-week double-blind treatment period with a 30-day follow-up. The trial population will include male and female participants 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 participant is not living alone.

Being tested
Brexpiprazole, OPC-34712, Placebo Oral Tablet
Keywords
OPC-34712, brexpiprazole, Dementia, Alzheimer's Disease, Cognitive Disorders, Agitation
Medical subject headings
Alzheimer Disease, Mental Disorders, Nervous System Diseases, Dementia, Cognitive Dysfunction, Psychomotor Agitation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Brexpiprazole, OPC-34712Drug

    Once-daily, tablets

  • Placebo Oral TabletDrug

    Once-daily, tablets

Study groups in NCT01862640
Study groupRoleWhat they receive
PlaceboPlacebo comparatorMatching placebo once daily
Receives: Drug: Placebo Oral Tablet
Brexpiprazole 1 mgExperimentalTitrate up from 0.25 milligrams (mg)/day brexpiprazole to 1 mg/day brexpiprazole
Receives: Drug: Brexpiprazole, OPC-34712
Brexpiprazole 2 mgExperimentalTitrate up from 0.25 mg/day brexpiprazole to 2 mg/day brexpiprazole
Receives: Drug: Brexpiprazole, OPC-34712

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline, Week 12/Early Termination (ET)

Secondary outcomes (1)

  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

    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 Alzheimer's dementia, by the assessment of CGI-S score after 12 weeks of treatment. The CGI-S was used to rate the severity of agitation. Scores 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. A decrease in score indicates improvement in symptoms.

    Measured: Baseline, Week 12/ET

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 May 2013 (estimated)
  2. Study start11 Jul 2013
  3. Primary completion15 Mar 2017
  4. Study completion15 Mar 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
433 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01862640
Sponsor's protocol ID
331-12-283
Status last verified
Dec 2020
First submitted
22 May 2013
Last updated
31 Dec 2020
Data monitoring committee
Yes
Individual data sharing
Yes: 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.

Publications

  • Porsteinsson AP, Chumki SR, Palma AM, Zhang Z, Wang D, Such P, Montano CB. Brexpiprazole for Individual Agitation Symptoms in Alzheimer's Dementia: A Caregiver-Centered Post Hoc Analysis. Neurol Ther. 2026 Oct 16. doi: 10.1007/s40120-026-01037-4. Online ahead of print.

    PubMed 42888370

  • Montano CB, Chumki SR, Wang D, Palma AM, Zhang Z, Porsteinsson AP. Brexpiprazole With Antidepressants for Agitation in Alzheimer's Dementia: Post Hoc Analysis. Am J Geriatr Psychiatry. 2026 Jun 30:S1064-7481(26)00450-1. doi: 10.1016/j.jagp.2026.06.015. Online ahead of print.

    PubMed 42502037

  • Tariot PN, Chumki SR, Wang D, Such P, Palma AM, Zhang Z, Montano CB. Brexpiprazole for Agitation in Patients with Alzheimer's Dementia with and without Co-Occurring Psychosis: Post Hoc Analysis of Short- and Long-Term Trials. Neuropsychiatr Dis Treat. 2026 Apr 21;22:586701. doi: 10.2147/NDT.S586701. eCollection 2026.

    PubMed 42052145

  • Porsteinsson AP, Chumki SR, Wang D, Such P, Palma AM, Zhang Z, Shah A, Kalu U, Montano CB. Short-Term and Long-Term Safety Analyses of Brexpiprazole for Agitation Associated with Dementia due to Alzheimer's Disease: Timing and Duration of Adverse Events. Drug Saf. 2026 Aug;49(8):969-983. doi: 10.1007/s40264-026-01670-w. Epub 2026 Apr 10.

    PubMed 41961243

  • Stroud J, Cummings JL, Chumki SR, Such P, Wang D, Palma AM, Zhang Z, Grossberg GT. Brexpiprazole for treating agitation in different groups of people with Alzheimer's dementia: a plain language summary. Neurodegener Dis Manag. 2026 Apr;16(2):113-121. doi: 10.1080/17582024.2026.2623968. Epub 2026 Feb 14.

    PubMed 41689409

  • 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 Mar;46(3):281-292. doi: 10.1007/s40261-025-01517-9. Epub 2026 Jan 27.

    PubMed 41591746

  • Shah 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. 2025 Dec;41(12):2369-2377. doi: 10.1080/03007995.2025.2608578. Epub 2026 Jan 14.

    PubMed 41533472

  • Grossberg 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. 2026 Sep;39(5):589-601. doi: 10.1177/08919887251407124. Epub 2025 Dec 24.

    PubMed 41439450

  • Stroud 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.

    PubMed 40847656

  • 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.

    PubMed 40681915

  • 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.

    PubMed 39108660

  • 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.

    PubMed 31708380

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Brexpiprazole, OPC-34712 in people with Agitation Associated With and Alzheimer's Disease, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 85 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 85 sites in United States, Spain, Russia, Germany, Serbia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline In The Cohen-Mansfield Agitation Inventory (CMAI) Total Score After 12 Weeks Of Brexpiprazole Treatment (time frame: Baseline, Week 12/Early Termination (ET)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01862640, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2020.

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