A Trial to Assess Brexpiprazole Versus Placebo for the Treatment of Acute Manic Episodes Associated With Bipolar I Disorder

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 will also demonstrate the safety and tolerability of brexpiprazole in
the study population of males and females aged 18 to 65 years (inclusive, at time of
consent).

Inclusion Criteria:

- Male or female subjects, ages 18 to 65 years, inclusive, at the time of informed
consent.

- Subjects willing to discontinue all prohibited medications to meet protocol-required
washouts prior to and during the trial period.

- Subjects 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 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" is defined as an intervention that occurred rather than
one that was recommended.

- YMRS score of ≥ 24 at screening & baseline

Exclusion Criteria:

- Sexually active male or WOCBP (women of childbearing potential) who do 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 IMP.

- Females who are breastfeeding and/or who have a positive pregnancy test result prior
to receiving trial medication.

- Subjects considered unresponsive to clozapine or who are only responsive to
cloazapine.

- Subjects 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, subjects with borderline, paranoid, histrionic,
schizotypal, schizoid, or antisocial personality disorder. All other current diagnoses
must be discussed with the medical monitor.

- Subjects whose current manic episode has lasted for more than 4 weeks overall, or who
have required hospitalization > 21 days for the current acute episode at the time of
the screening visit, excluding hospitalization for psychosocial reasons.

- Subject with manic symptoms better accounted for by another general medical condition
or direct physiological effect of substance (eg. medication)

- Subjects who have had electroconvulsive treatment within the past 2 months.

- Subjects with a positive drug screen for cocaine or other illicit drugs

- Abnormal laboratory test results, vital signs or ECG results, unless based on
investigator's judgment the findings are not medically significant or would not affect
the trial results.

- Rapid cyclers with more than 6 episodes in previous year

- Subjects with uncontrolled hypo/hyperthyroidism

- Subjects with uncontrolled hypertension or symptomatic hypotension or orthostatic
hypotension.

- Subject with epilepsy or history of seizures

- Subjects 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.

- Subjects who currently have clinically significant neurological, hepatic, renal,
metabolic, hematological, immunological, cardiovascular, pulmonary, or
gastrointestinal disorders

- Subjects who received brexpiprazole in any prior clinical trial or currently taking
commercially available brexpiprazole (Rexulti®).