Study of the Efficacy of a Fixed-dose Regimen of Cariprazine Compared to Placebo for Treatment of the Depressive Episode in Participants With Bipolar I Disorder

This study is designed to prospectively confirm the efficacy of a fixed-dose regimen of cariprazine 1.5 milligrams (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.


Eligibility Criteria:
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
  * Patient 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
* 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:

  * Patients with a positive cannabinoid on entry may be retested before randomization. If the patient remains positive, the patient is no longer eligible
  * Patients 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