Clinical trial NCT03257865: 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 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: 2017-08-22
Enrollment: 333
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 (MINI) and a history of at least one 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 (WOCBP) 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 (IMP).
* 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, medications).
* 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 and 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.
* Participants 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: Atria Clinical Research
state: Arkansas
city: Little Rock
country: United States
facility: Woodland International Research Group, LLC
state: Arkansas
city: Bellflower
country: United States
facility: CiTrials
state: California
city: Cerritos
country: United States
facility: CNS Research Science Inc.
state: California
city: Long Beach
country: United States
facility: Apostle Clinical Trials
state: California
city: San Diego
country: United States
facility: CNRI-San Diego
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Santa Ana
country: United States
facility: CiTrials
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Yorba Linda
country: United States
facility: Shreenath Clinical Service
state: California
city: Hialeah
country: United States
facility: Galiz Research
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America LLC
state: Florida
city: Miami Springs
country: United States
facility: South Florida Research Phase I-IV
state: Florida
city: Miami
country: United States
facility: Optimus U Corporation
state: Florida
city: Orlando
country: United States
facility: Meridien Research
state: Florida
city: Decatur
country: United States
facility: iResearch Atlanta, LLC
state: Georgia
city: Chicago
country: United States
facility: Uptown Research Institute LLC
state: Illinois
city: Winfield
country: United States
facility: Neuropsychiatric Research & Associates, LTD
state: Illinois
city: Shreveport
country: United States
facility: Louisiana Clinical Research
state: Louisiana
city: Saint Louis
country: United States
facility: Arch Clinical Trials, LLC
state: Missouri
city: Saint Louis
country: United States
facility: St Louis Clinical Trials LLC
state: Missouri
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Jamaica
country: United States
facility: CNS Research Science, Inc.
state: New York
city: Charlotte
country: United States
facility: New Hope Clinical Research
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Department of Psychiatry and Behavorial Science
state: Ohio
city: DeSoto
country: United States
facility: InSite Clinical Research LLC
state: Texas
city: Richardson
country: United States
facility: Pillar Clinical Research, LLC
state: Texas
city: Rijeka
country: Croatia
facility: Clinical Hospital Centre Rijeka
city: Dnipro
country: Ukraine
facility: Communal Institution "Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikov
city: Kharkiv
country: Ukraine
facility: SI ""Institute of Neurology, Psychiatry and Narcology of National Academy of Medical Sciences of Ukraine
city: Kherson
country: Ukraine
facility: Communal Establishment "Kherson Regional Psychiatric Hospital" of Kherson Regional Council
city: Kyiv
country: Ukraine
facility: Kyiv Regional Medical Incorporation "Psychiatry", Center for Novel Treatment and Rehabilitation of Psychotic disorders
city: Lviv
country: Ukraine
facility: Communal Institution of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital", Department #20
city: Lviv
country: Ukraine
facility: Communal Institution of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital", Department #25
city: Oleksandrivka
country: Ukraine
facility: Communal Establishment "Odesa Regional Psychiatric Hospital #2
city: Poltava
country: Ukraine
facility: O.F. Maltsev Poltava Regional Psychiatric Hospital
city: Ternopil'
country: Ukraine
facility: Ternopil Regional Municipal Clinical Psychoneurolgical Hospital
city: Vinnytsia
country: Ukraine
facility: Communal Establishment "Acad. O.I. Iushchenko Vinnytsia Regional Psychoneurologic Hospital"
Study officials:
affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.
name: Matthew Leoni, M.D.
role: STUDY_DIRECTOR
References: