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

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