Study on the Efficacy, Safety, and Tolerability of Cariprazine Relative to Placebo in Participants With Bipolar I Depression
Condition: Bipolar Disorder; Depression
MeSH terms: Depression; Depressive Disorder; Bipolar Disorder
Intervention: Cariprazine; Placebo
Intervention MeSH terms: Cariprazine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 488.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      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.
    

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 --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