Clinical trial NCT01922258: Safety and Tolerability Study of Flexible Dosing of Brexpiprazole in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer's Type
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
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: 2013-08-14
Enrollment: 270
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 flexible dosing of brexpiprazole with placebo in subjects with agitation associated with dementia of the Alzheimer's type

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline to Week 12/Early Termination in the Cohen-Mansfield Agitation Inventory (CMAI) Total Score
timeFrame: From screening to week 12/early termination
Secondary outcomes:
measure: Change in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Symptoms of Agitation
timeFrame: From screening to week 12/early termination
Other outcomes:
Locations:
city: Imperial
country: United States
state: California
city: Lakewood
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Panorama City
country: United States
state: California
city: Universal City
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Bradenton
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: Orange City
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Smyrna
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Indianapolis
country: United States
state: Indiana
city: Quincy
country: United States
state: Massachusetts
city: South Dartmouth
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Brooklyn
country: United States
state: New York
city: Buffalo
country: United States
state: New York
city: New Hyde Park
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Woodstock
country: United States
state: Vermont
city: Burgas
country: Bulgaria
city: Kardzhali
country: Bulgaria
city: Pazardzhik
country: Bulgaria
city: Ruse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Veliko Tarnovo
country: Bulgaria
city: Penticton
country: Canada
state: British Columbia
city: Kentville
country: Canada
city: Kuopio
country: Finland
city: Turku
country: Finland
city: Bourg en Bresse
country: France
city: Douai
country: France
city: Elancourt
country: France
city: Limoges
country: France
city: Nice
country: France
city: Toulouse
country: France
city: Tonnel'nyy
country: Russian Federation
state: Stavropol Region
city: Ekaterinburg
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: Ljubljana
country: Slovenia
city: Maribor
country: Slovenia
city: Sempeter pri Gorici
country: Slovenia
city: Donetsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kharkov
country: Ukraine
city: Kherson
country: Ukraine
city: Kiev
country: Ukraine
city: Kiev
country: Ukraine
city: Lviv
country: Ukraine
city: Poltava
country: Ukraine
city: Simferopol
country: Ukraine
city: Vinnytsia
country: Ukraine
city: Crewe
country: United Kingdom
city: Manchester
country: United Kingdom
city: Margate
country: United Kingdom
city: Torpoint
country: United Kingdom
Study officials:
affiliation: Otsuka Pharmaceutical Development and Commercialization, Inc.
name: Eva Koheygi, 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.