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Agitation Associated WithPhase 3NCT01922258

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 study testing Brexpiprazole, OPC-34712 in people with Agitation Associated With and Alzheimer's Disease, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 70 sites in 9 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 flexible dosing of brexpiprazole with placebo in subjects 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
270 participants
Where
70 sitesin 9 countries
Study dates
Sep 2013to 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 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.

Who cannot join

  • 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.

Trial locations and contacts

70 sites in 9 countries.

70 sites in 9 countries

United States28 sites

  • Study site

    Ann Arbor, Michigan, 48105

  • Study site

    Atlanta, Georgia, 30331

  • Study site

    Austin, Texas, 78757

  • Study site

    Bradenton, Florida, 34205

  • Study site

    Brooklyn, New York, 11214

  • Study site

    Buffalo, New York, 14215

  • Study site

    Charlotte, North Carolina, 28270

  • Study site

    Dallas, Texas, 75231

  • Study site

    Dallas, Texas, 75243

  • Study site

    Denver, Colorado, 80209

  • Study site

    Honolulu, Hawaii, 96817

  • Study site

    Imperial, California, 92251

  • Study site

    Indianapolis, Indiana, 46256

  • Study site

    Lakewood, California, 08755

  • Study site

    Long Beach, California, 90806

  • Study site

    Long Beach, California, 90822

  • Study site

    Miami, Florida, 33142

  • Study site

    Miami, Florida, 33165

  • Study site

    Miami, Florida, 33176

  • Study site

    New Hyde Park, New York, 11040

  • Study site

    Orange City, Florida, 32763

  • Study site

    Panorama City, California, 91402

  • Study site

    Quincy, Massachusetts, 02169

  • Study site

    Raleigh, North Carolina, 27609

  • Study site

    Smyrna, Georgia, 30080

  • Study site

    South Dartmouth, Massachusetts, 02747

  • Study site

    Universal City, California, 91950

  • Study site

    Woodstock, Vermont, 05091

Other trials in United States

Bulgaria9 sites

  • Study site

    Burgas, 8000

  • Study site

    Kardzhali, 6600

  • Study site

    Pazardzhik, 4400

  • Study site

    Rousse, 7003

  • Study site

    Sofia, 1113

  • Study site

    Sofia, 1154

  • Study site

    Sofia, 1431

  • Study site

    Varna, 9020

  • Study site

    Veliko Tarnovo, 5000

Other trials in Bulgaria

Ukraine9 sites

  • Study site

    Donetsk, 83037

  • Study site

    Kharkiv, 61068

  • Study site

    Kherson, 73488

  • Study site

    Kiev, 04080

  • Study site

    Kiev, 04114

  • Study site

    Lviv, 79021

  • Study site

    Poltava, 36013

  • Study site

    Simferopol, 95006

  • Study site

    Vinnytsia, 21005

Other trials in Ukraine

Russia7 sites

  • Study site

    Saint Petersburg, 188820

  • Study site

    Saint Petersburg, 190005

  • Study site

    Saint Petersburg, 195176

  • Study site

    Saint Petersburg, 197341

  • Study site

    Saratov, 410060

  • Study site

    Tonnel’nyy, Stavropol Kray, 357034

  • Study site

    Yekaterinburg, 620030

Other trials in Russia

France6 sites

  • Study site

    Bourg-en-Bresse, 01012

  • Study site

    Douai, 59500

  • Study site

    Élancourt, 78990

  • Study site

    Limoges, 87042

  • Study site

    Nice, 06100

  • Study site

    Toulouse, 31059

Other trials in France

United Kingdom4 sites

  • Study site

    Crewe, CW1 2ER

  • Study site

    Manchester, M8 5RB

  • Study site

    Margate, CT20 1JY

  • Study site

    Torpoint, PL11 2TB

Other trials in United Kingdom

Slovenia3 sites

  • Study site

    Ljubljana, 1000

  • Study site

    Maribor, 2000

  • Study site

    Sempeter pri Gorici, 5290

Other trials in Slovenia

Canada2 sites

  • Study site

    Kentville, B4N 4K9

  • Study site

    Penticton, British Columbia, V2A 4M4

Other trials in Canada

Finland2 sites

  • Study site

    Kuopio, 70210

  • Study site

    Turku, 20520

Other trials in Finland

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 Flexible Dosing of Brexpiprazole (OPC-34712) in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type

To compare the efficacy of flexible dosing of brexpiprazole with placebo in subjects with agitation associated with dementia of the Alzheimer's type

Read the detailed description

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.

This 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.

Being tested
Brexpiprazole, OPC-34712
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

    Flexible dose of 0.5 to 2 mg/day or placebo tablets for up to 12 weeks

Study groups in NCT01922258
Study groupRoleWhat they receive
PlaceboPlacebo comparatorMatching Placebo Once-Daily
Receives: Drug: Brexpiprazole, OPC-34712
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.
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 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.

    Measured: From screening to week 12/early termination

Secondary outcomes (1)

  1. Change in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Symptoms of Agitation

    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.

    Measured: From screening to week 12/early termination

Timeline

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

  1. First posted14 Aug 2013 (estimated)
  2. Study startSep 2013
  3. Primary completionMar 2017
  4. Study completionMar 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
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
270 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01922258
Sponsor's protocol ID
331-12-284
Status last verified
Nov 2020
First submitted
12 Aug 2013
Last updated
20 Nov 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, 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

  • 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

  • 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 70 sites in 9 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 20 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 70 sites in United States, Bulgaria, Ukraine, Russia, France and 4 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 7 Jul 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 to Week 12/Early Termination in the Cohen-Mansfield Agitation Inventory (CMAI) Total Score (time frame: From screening to week 12/early termination). 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 NCT01922258, which also lists 6 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 20 Nov 2020.

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