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

Conditions: Bipolar Disorder; Depression

Summary: 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