Safety and Tolerability Study of Flexible Dosing of Brexpiprazole in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type

NCT ID: NCT01922258

Last Updated: 2020-11-20

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

270 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-30

Study Completion Date

2017-03-31

Brief Summary

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To compare the efficacy of flexible dosing of brexpiprazole with placebo in subjects 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 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.

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

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Matching Placebo Once-Daily

Group Type PLACEBO_COMPARATOR

Brexpiprazole, OPC-34712

Intervention Type DRUG

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

Brexpiprazole (flexible dose range 0.5 to 2 mg)

Titrate 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.

Group Type EXPERIMENTAL

Brexpiprazole, OPC-34712

Intervention Type DRUG

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

Interventions

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Brexpiprazole, OPC-34712

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

55 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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H. Lundbeck A/S

INDUSTRY

Sponsor Role collaborator

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eva Koheygi, MD

Role: STUDY_DIRECTOR

Otsuka Pharmaceutical Development and Commercialization, Inc.

Locations

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Imperial, California, United States

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Lakewood, California, United States

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Long Beach, California, United States

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Long Beach, California, United States

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Panorama City, California, United States

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Universal City, California, United States

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Denver, Colorado, United States

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Bradenton, 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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Orange City, Florida, United States

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Atlanta, Georgia, United States

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Smyrna, Georgia, United States

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Honolulu, Hawaii, United States

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Indianapolis, Indiana, United States

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Quincy, Massachusetts, United States

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South Dartmouth, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Brooklyn, New York, United States

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Buffalo, New York, United States

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New Hyde Park, New York, United States

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Charlotte, North Carolina, United States

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Raleigh, North Carolina, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Woodstock, Vermont, United States

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Burgas, , Bulgaria

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Kardzhali, , Bulgaria

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Pazardzhik, , Bulgaria

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Rousse, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Veliko Tarnovo, , Bulgaria

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Penticton, British Columbia, Canada

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Kentville, , Canada

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Kuopio, , Finland

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Turku, , Finland

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Bourg-en-Bresse, , France

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Douai, , France

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Élancourt, , France

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Limoges, , France

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Nice, , France

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Toulouse, , France

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Tonnel’nyy, Stavropol Kray, 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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Saratov, , Russia

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Yekaterinburg, , Russia

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Ljubljana, , Slovenia

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Maribor, , Slovenia

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Šempeter pri Gorici, , Slovenia

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Donetsk, , Ukraine

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Kharkiv, , Ukraine

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Kherson, , Ukraine

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Kiev, , Ukraine

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Kiev, , Ukraine

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Lviv, , Ukraine

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Poltava, , Ukraine

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Simferopol, , Ukraine

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Vinnytsia, , Ukraine

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Crewe, , United Kingdom

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Manchester, , United Kingdom

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Margate, , United Kingdom

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Torpoint, , United Kingdom

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Countries

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United States Bulgaria Canada Finland France Russia Slovenia Ukraine United Kingdom

References

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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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331-12-284

Identifier Type: -

Identifier Source: org_study_id