Intervention: Cariprazine
Trial phase: Phase 3
ATC code: N05AX15
SMILES: CN(C)C(=O)N[C@H]1CC[C@H](CCN2CCN(c3cccc(Cl)c3Cl)CC2)CC1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 158
Group description: Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 2 weeks increased to cariprazine 3.0 mg capsule, one per day orally beginning on Day 15 for 4 weeks.
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