Study on the Efficacy, Safety, and Tolerability of Cariprazine Relative to Placebo in Participants With Bipolar I Depression

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Fixed-Dose Clinical Trial Evaluating The Efficacy, Safety And Tolerability Of Cariprazine In Patients With Bipolar I Depression

This study investigates the efficacy of a fixed-dose regimen of cariprazine 1.5 milligram (mg)/day or 3 mg/day compared to placebo for treatment of the depressive episode in participants with bipolar I disorder. The safety and tolerability of the fixed-dose regimens will be evaluated.

Inclusion Criteria:

• Currently meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for bipolar I disorder without psychotic features confirmed by the administration of the Mini International Neuropsychiatric Interview (MINI), with a current major depressive episode of at least 4 weeks and not exceeding 12 months in duration
• Currently treated as an outpatient at the time of enrollment
• A verified previous manic or mixed episode. Verification must include one of the following sources: --Treatment of mania with an anti-manic agent (eg, lithium or divalproate) or antipsychotic medication with an approved indication for mania --Hospital records/Medical records --Participant report corroborated by caretaker or previous or current treating clinician
• 17-item Hamilton Depression Rating Scale (HAMD-17) total score ≥ 20
• HAMD-17 item 1 score ≥ 2
• Clinical Global Impressions-Severity (CGI-S) score ≥ 4
• Negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test (women of childbearing potential only)
• Normal physical examination, clinical laboratory test results, and electrocardiogram (ECG) results or abnormal findings that are judged not clinically significant by the Principal Investigator (PI)

Exclusion Criteria:

• Young Mania Rating Scale (YMRS) total score > 12

• Four or more episodes of a mood disturbance (depression, mania, hypomania, or mixed state) within the 12 months before Visit 1

• Any current axis 1 psychiatric diagnosis other than bipolar disorder with the exception of specific phobias

• History of meeting DSM-5 criteria for: ○ Dementia, amnesic, or other cognitive disorder ○ Schizophrenia, schizoaffective, or other psychotic disorder

  ○ Mental retardation - DSM-5-based diagnosis of borderline or antisocial personality disorder or other axis II disorder of sufficient severity to interfere with participation in this study

• History of meeting DSM-5 criteria for alcohol or substance abuse or dependence (other than nicotine or caffeine) within the 6 months before Visit 1

• Positive result on blood alcohol test or urine drug screen for any prohibited medication. Exception: ○ Participants with a positive cannabinoid on entry may be retested before randomization. If the participant remains positive, the participant is no longer eligible ○ Participants positive for opiates on entry, discussion with Study Physician is required.

• Electroconvulsive therapy in the 3 months before Visit 1

• Previous lack of response to electroconvulsive therapy

• Treatment with a depot antipsychotic drug within 1 treatment cycle before Visit 1

• Treatment with clozapine in a dose of > 50 mg/day in the past 2 years

• Prior participation in any investigational study of RGH-188 or cariprazine within the past 12 months

• Previous treatment with vagus nerve stimulation or transcranial magnetic stimulation within 6 months before Visit 1

• Prior participation with any clinical trials, involving experimental or investigational drugs, within 6 months before Visit 1 or during the study

• Initiation or termination of psychotherapy for depression within the 3 months preceding Visit 1, or plans to initiate, terminate, or change such therapy during the course of the study.

• Pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study

• Gastric bypass or any condition that would be expected to affect drug absorption (lap band procedures are acceptable if there is no problem with absorption)

• Known history of cataracts or retinal detachment

• Known human immunodeficiency virus infection

• Employee, or immediate relative of an employee, of the Sponsor, any of its affiliates or partners, or the study center