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
Condition: Bipolar Disorder; Depression
MeSH terms: Depression; Bipolar Disorder
Intervention: Cariprazine; Placebo
Intervention description: Cariprazine capsule one per day orally.; Matching placebo capsule one per day orally.
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: 493.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

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