A Trial to Assess Brexpiprazole Versus Placebo for the Treatment of Acute Manic Episodes, Associated With Bipolar I Disorder
Condition: Bipolar I Disorder; Manic Episode
MeSH terms: Mania; Bipolar Disorder
Intervention: Brexpiprazole; Placebo
Intervention description: Brexpiprazole was administered orally with flexible dosing from 2 to 4 mg/day; titrated to a maximum of 4 mg/day for 3 weeks.; Administered orally daily for 3 weeks.
Intervention MeSH terms: Brexpiprazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 333.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Brexpiprazole; Bipolar; Manic episode

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.
    

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).