Clinical trial NCT01862640: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Agitation Associated With
Alzheimer's Disease
Alzheimer's Type
Mental Disorder
Nervous System Diseases
Keywords: OPC-34712
brexpiprazole
Dementia
Alzheimer's Disease
Cognitive Disorders
Agitation
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
Collaborators: name: H. Lundbeck A/S
First posted: 2013-05-24
Enrollment: 433
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline In The Cohen-Mansfield Agitation Inventory (CMAI) Total Score After 12 Weeks Of Brexpiprazole Treatment
timeFrame: Baseline, Week 12/Early Termination (ET)
Secondary outcomes:
measure: 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
timeFrame: Baseline, Week 12/ET
Other outcomes:
Locations:
city: Tuscaloosa
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Bellflower
country: United States
state: California
city: Costa Mesa
country: United States
state: California
city: Downey
country: United States
state: California
city: Orange
country: United States
state: California
city: Redlands
country: United States
state: California
city: Yorba Linda
country: United States
state: California
city: Norwalk
country: United States
state: Connecticut
city: Coconut Creek
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Lauderhill
country: United States
state: Florida
city: Miami Springs
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Decatur
country: United States
state: Georgia
city: Suwanee
country: United States
state: Georgia
city: Weymouth
country: United States
state: Massachusetts
city: Saint Louis
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Manchester
country: United States
state: New Jersey
city: Mount Arlington
country: United States
state: New Jersey
city: Toms River
country: United States
state: New Jersey
city: Hickory
country: United States
state: North Carolina
city: Oklahoma City
country: United States
state: Oklahoma
city: Franklin
country: United States
state: Tennessee
city: Bedford
country: United States
state: Texas
city: Waukesha
country: United States
state: Wisconsin
city: Rijeka
country: Croatia
city: Zadar
country: Croatia
city: Zagreb
country: Croatia
city: Zagreb
country: Croatia
city: Mittweida
country: Germany
state: Saxony
city: Achim
country: Germany
city: Berlin
country: Germany
city: Bielefeld
country: Germany
city: Bochum
country: Germany
city: Hamburg
country: Germany
city: Koln
country: Germany
city: Ostfildern
country: Germany
city: Westerstede
country: Germany
city: Ekaterinburg
country: Russian Federation
city: Samara
country: Russian Federation
city: Saratov
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Tonnel'nyy
country: Russian Federation
city: Belgrade
country: Serbia
city: Kovin
country: Serbia
city: Kragujevac
country: Serbia
city: Nis
country: Serbia
city: Novi Knezevac
country: Serbia
city: Novi Sad
country: Serbia
city: Vrsac
country: Serbia
city: Barcelona
country: Spain
city: Getafe
country: Spain
city: Girona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Pamplona
country: Spain
city: Salamanca
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Zamora
country: Spain
city: Kharkiv
country: Ukraine
city: Kherson
country: Ukraine
city: Kiev
country: Ukraine
city: Lviv
country: Ukraine
city: Odessa
country: Ukraine
city: Odessa
country: Ukraine
city: Poltava
country: Ukraine
Study officials:
affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.
name: Eva Kohegyi, MD
role: STUDY_DIRECTOR
References:
citation: 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.