Clinical trial NCT03259555: A Trial to Assess Brexpiprazole Versus Placebo for the Treatment of Acute Manic Episodes Associated With Bipolar I Disorder
Official title: A Multicenter, Randomized, Double-blind Trial of Brexpiprazole Versus Placebo for the Acute Treatment of Manic Episodes, With or Without Mixed Features, Associated With Bipolar I Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bipolar I Disorder
Manic Episode
Keywords: Brexpiprazole
Bipolar
Manic episode
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
Collaborators: name: H. Lundbeck A/S
First posted: 2017-08-23
Enrollment: 322
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants received a dose of brexpiprazole or placebo for a maximum of 21 days and were evaluated throughout the duration of the study.
Primary purpose: TREATMENT

Brief summary: To demonstrate the efficacy of brexpiprazole for the acute treatment of manic episodes, with or without mixed features, in participants with a diagnosis of bipolar I disorder.

Detailed description: A multicenter, randomized, double-blind trial of brexpiprazole versus placebo for the acute treatment of manic episodes, with or without mixed features, associated with bipolar I disorder. This study also demonstrated the safety and tolerability of brexpiprazole in the study population of males and females aged 18 to 65 years (inclusive, at time of consent).

Eligibility criteria: Inclusion Criteria:

* Male or female participants, ages 18 to 65 years, inclusive, at the time of informed consent.
* Participants willing to discontinue all prohibited medications to meet protocol-required washouts prior to and during the trial period.
* Participants with a Diagnostic \& Statistical Manual on Mental Disorders, 5th Edition (DSM-5) diagnosis of bipolar I disorder displaying an acute manic episode with or without mixed features requiring hospitalization. Diagnosis confirmed by the MINI International Neuropsychiatric Interview and a history of at least 1 previous manic episode with or without mixed features with manic symptoms of sufficient severity to require one of the following interventions: hospitalization or treatment with a mood stabilizer, or treatment with an antipsychotic agent. "Require" was defined as an intervention that occurred rather than one that was recommended.
* Young-mania rating scale (YMRS) score of ≥24 at screening and baseline.

Exclusion Criteria:

* Sexually active male or women of childbearing potential who did not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of investigational medicinal product.
* Females who were breastfeeding and/or who had a positive pregnancy test result prior to receiving trial medication.
* Participants considered unresponsive to clozapine or who were only responsive to clozapine.
* Participants with a history of DSM-5 diagnosis other than bipolar I disorder, including schizophrenia, schizoaffective disorder, major depressive disorder, attention-deficit/hyperactivity disorder, delirium, dementia, amnestic, or other cognitive disorders. Also, participants with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder. All other current diagnoses must have been discussed with the medical monitor.
* Participants whose current manic episode had lasted for more than 4 weeks overall, or who had required hospitalization \>21 days for the current acute episode at the time of the screening visit, excluding hospitalization for psychosocial reasons.
* Participant with manic symptoms better accounted for by another general medical condition or direct physiological effect of substance (for example, medication).
* Participants who have had electroconvulsive treatment within the past 2 months.
* Participants with a positive drug screen for cocaine or other illicit drugs.
* Abnormal laboratory test results, vital signs or electrocardiogram findings, unless based on investigator's judgment the findings are not medically significant or would not impact the safety of the participant or the interpretation of the trial results.
* Rapid cyclers with more than 6 episodes in the previous year.
* Participants with hypothyroidism or hyperthyroidism (unless condition has been stabilized with medications for at least the past 90 days) or an abnormal result for free thyroxine at screening.
* Participants with uncontrolled hypertension or symptomatic hypotension or orthostatic hypotension.
* Participant with epilepsy or history of seizures.
* Participants who participated in a clinical trial within the last 60 days or who participated in more than 2 clinical trials within the past year.
* Use of psychotropic medications (other than benzodiazepines) within 7 days of the baseline YMRS.
* Participants who currently had clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders.
* Participants who received brexpiprazole in any prior clinical trial or currently taking commercially available brexpiprazole (Rexulti).

Primary outcomes:
measure: Change From Baseline In Young-Mania Rating Scale (YMRS) Score At Week 3
timeFrame: Baseline, Week 3
Secondary outcomes:
measure: Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At Week 3
timeFrame: Baseline, Week 3
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Woodland International Research Group
state: Arkansas
city: Rogers
country: United States
facility: Woodland Research Northwest, LLC
state: Arkansas
city: Culver City
country: United States
facility: ProScience Research Group
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Glendale
country: United States
facility: Behavioral Research Specialists, LLC
state: California
city: Oakland
country: United States
facility: Pacific Research Partners, LLC
state: California
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: Panorama City
country: United States
facility: Asclepes Research Centers
state: California
city: Riverside
country: United States
facility: Ci Trials
state: California
city: San Diego
country: United States
facility: Sharp Vista Hospital
state: California
city: Hialeah
country: United States
facility: Galiz Research
state: Florida
city: Homestead
country: United States
facility: Advanced Research Institute of Miami
state: Florida
city: Largo
country: United States
facility: Florida Behavioral Medicine
state: Florida
city: Miami
country: United States
facility: Optimus U Corporation
state: Florida
city: North Miami
country: United States
facility: Behavioral Clinical Research, Inc.
state: Florida
city: North Miami
country: United States
facility: Segal Trials
state: Florida
city: Atlanta
country: United States
facility: Radiant Research Inc.
state: Georgia
city: Hoffman Estates
country: United States
facility: Alexian Brothers Center for Psychiatric Research
state: Illinois
city: Gaithersburg
country: United States
facility: CBH Health
state: Maryland
city: Saint Louis
country: United States
facility: Advanced Clinical Research Center, LLC
state: Missouri
city: Raleigh
country: United States
facility: Richard H Weisler, MD, PA, and Associates
state: North Carolina
city: Oklahoma City
country: United States
facility: SP Research PLLC
state: Oklahoma
city: Oklahoma City
country: United States
facility: Cutting Edge Research Group
state: Oklahoma
city: Charleston
country: United States
facility: Carolina Clinical Trials, Inc.
state: South Carolina
city: Austin
country: United States
facility: University of Texas at Austin
state: Texas
city: Austin
country: United States
facility: Community Clinical Research, Inc.
state: Texas
city: Garland
country: United States
facility: Pillar Clinical Research, LLC
state: Texas
city: Richardson
country: United States
facility: Pillar Clinical Research, LLC
state: Texas
city: Richland
country: United States
facility: Mid Columbia Research
state: Washington
city: Burgas
country: Bulgaria
facility: Mental Health Center Prof. Dr. Ivan Temkov - Burgas EOOD
city: Kardzhali
country: Bulgaria
facility: State Psychiatry Hospital - Kardzhali
city: Novi Iskar
country: Bulgaria
facility: State Psychiatry Hospital Sv. Ivan Rilski
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
city: Ruse
country: Bulgaria
facility: Mental Health Center - Ruse EOOD
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Alexandrovska EAD
city: Targovishte
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Targovishte AD
city: Veliko Tarnovo
country: Bulgaria
facility: Mental Health Center - Veliko Tarnovo EOOD
city: Vratsa
country: Bulgaria
facility: Mental Health Center - Vratsa EOOD
city: Choroszcz
country: Poland
facility: Samodzielny Publiczny Psychiatryczny Zaklad Opieki Zdrowotnej im. Dr. Stanislawa Deresza w Choroszczy
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne w Gdansku Klinika Psychiatrii Doroslych
city: Poznań
country: Poland
facility: NZOZ Centrum Medyczne HCP Sp. z o. o.
city: Tuszyn
country: Poland
facility: NZOZ Prywatna Klinika Psychiatryczna Inventiva
city: Belgrade
country: Serbia
facility: Clinic for Psychiatric Disorders Dr Laza Lazarevic
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Dr Dragisa Misovic-Dedinje
city: Kovin
country: Serbia
facility: Special Hospital for Psychiatric Diseases Kovin
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: Novi Sad
country: Serbia
facility: Clinical Center of Vojvodina
Study officials:
affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.
name: Matthew Leoni, M.D.
role: STUDY_DIRECTOR
References: