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

NCT ID: NCT01862640

Last Updated: 2020-12-31

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

433 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-07-11

Study Completion Date

2017-03-15

Brief Summary

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

Detailed Description

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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.

Conditions

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Agitation Associated With Alzheimer's Disease Alzheimer's Type Mental Disorder Nervous System Diseases

Keywords

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OPC-34712 brexpiprazole Dementia Alzheimer's Disease Cognitive Disorders Agitation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Placebo

Matching placebo once daily

Group Type PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type DRUG

Once-daily, tablets

Brexpiprazole 1 mg

Titrate up from 0.25 milligrams (mg)/day brexpiprazole to 1 mg/day brexpiprazole

Group Type EXPERIMENTAL

Brexpiprazole, OPC-34712

Intervention Type DRUG

Once-daily, tablets

Brexpiprazole 2 mg

Titrate up from 0.25 mg/day brexpiprazole to 2 mg/day brexpiprazole

Group Type EXPERIMENTAL

Brexpiprazole, OPC-34712

Intervention Type DRUG

Once-daily, tablets

Interventions

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Brexpiprazole, OPC-34712

Once-daily, tablets

Intervention Type DRUG

Placebo Oral Tablet

Once-daily, tablets

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

55 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role lead

H. Lundbeck A/S

INDUSTRY

Sponsor Role collaborator

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eva Kohegyi, MD

Role: STUDY_DIRECTOR

Otsuka Pharmaceutical Development & Commercialization, Inc.

Locations

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Tuscaloosa, Alabama, United States

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Phoenix, Arizona, United States

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Bellflower, California, United States

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Costa Mesa, California, United States

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Downey, California, United States

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Orange, California, United States

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Redlands, California, United States

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Yorba Linda, California, United States

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Norwalk, Connecticut, United States

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Coconut Creek, Florida, United States

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Hialeah, Florida, United States

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Hialeah, Florida, United States

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Hialeah, Florida, United States

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Lauderhill, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami Springs, Florida, United States

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Sarasota, Florida, United States

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Decatur, Georgia, United States

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Suwanee, Georgia, United States

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Weymouth, Massachusetts, United States

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St Louis, Missouri, United States

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St Louis, Missouri, United States

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Las Vegas, Nevada, United States

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Mount Arlington, New Jersey, United States

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Paterson, New Jersey, United States

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Toms River, New Jersey, United States

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Hickory, North Carolina, United States

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Oklahoma City, Oklahoma, United States

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Franklin, Tennessee, United States

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Bedford, Texas, United States

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Waukesha, Wisconsin, United States

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Rijeka, , Croatia

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Zadar, , Croatia

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Zagreb, , Croatia

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Zagreb, , Croatia

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Mittweida, Saxony, Germany

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Achim, , Germany

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Berlin, , Germany

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Bielefeld, , Germany

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Bochum, , Germany

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Cologne, , Germany

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Hamburg, , Germany

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Ostfildern, , Germany

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Westerstede, , Germany

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Samara, , Russia

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Saratov, , Russia

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Tonnel'nyy, , Russia

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Yekaterinburg, , Russia

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Belgrade, , Serbia

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Kovin, , Serbia

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Kragujevac, , Serbia

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Niš, , Serbia

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Novi Kneževac, , Serbia

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Novi Sad, , Serbia

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Vršac, , Serbia

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Barcelona, , Spain

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Getafe, , Spain

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Girona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Pamplona, , Spain

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Salamanca, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Zamora, , Spain

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Kharkiv, , Ukraine

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Kherson, , Ukraine

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Kiev, , Ukraine

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Lviv, , Ukraine

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Odesa, , Ukraine

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Odesa, , Ukraine

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Poltava, , Ukraine

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Countries

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United States Croatia Germany Russia Serbia Spain Ukraine

References

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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 Sep 5:1-12. doi: 10.1080/03007995.2025.2552278. Online ahead of print.

Reference Type DERIVED
PMID: 40847656 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40681915 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39108660 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31708380 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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331-12-283

Identifier Type: -

Identifier Source: org_study_id