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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

Phase 3
Completed
Conditions
Bipolar Disorder
Depression
Interventions
Drug: Placebo
Registration Number
NCT02670538
Lead Sponsor
Forest Laboratories
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
493
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboFollowing a 7 to 14 days screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.
Cariprazine 1.5 mgCariprazineFollowing a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.
Cariprazine 3.0 mgCariprazineFollowing a 7 to 14 days screening/washout period, cariprazine 1.5 milligrams (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.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS)Baseline (Week 0) to Week 6

MADRS is a 10-item, clinician-rated scale that evaluates the participants depressive symptomatology during the past week. Participants were rated on items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each of the 10 items was scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity for a total possible score of 0 (best) to 60 (worst). A negative change from Baseline indicates improvement. Mixed-effects Model for Repeated Measures (MMRM) with fixed factors (treatment group, pooled study center, and visit), baseline (a covariate), and interactions (treatment group by visit, baseline by visit).

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Clinical Global Impressions-Severity (CGI-S) ScoreBaseline (Week 0) to Week 6

CGI-S is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of other patients the physician has observed. The participant was rated on a scale from 1 to 7, with 1 indicating a "normal state" and 7 indicating "among the most extremely ill patients". A negative change from Baseline indicates improvement. MMRM with fixed factors (treatment group, pooled study center, and visit), baseline (a covariate), and interactions (treatment group by visit, baseline by visit).

Trial Locations

Locations (88)

Atlanta Center for Medical Research

🇺🇸

Atlanta, Georgia, United States

Mental Health Centre 'Prof. Dr. Ivan Temkov', EOOD

🇧🇬

Burgas, Bulgaria

Polyclinic Neuron

🇭🇷

Zagreb, Croatia

Clinical Center Nis Site 150

🇷🇸

Nis, Serbia

Centrum zdravia R.B.K. s.r.o.

🇸🇰

Bardejov, Slovakia

CI O.I. Yushchenko Vinnytsia Reg. Psychoneurological Hospital

🇺🇦

Vinnytsia, Ukraine

CI Kherson Reg. Psychiatric Hospital of Kherson RC

🇺🇦

Kherson, Ukraine

Transcarpathian Regional Narcological Dispensary

🇺🇦

Uzhgorod, Ukraine

Alexian Brothers Center for Psychiatric Research

🇺🇸

Hoffman Estates, Illinois, United States

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Harmonex Neuroscience Research, Inc.

🇺🇸

Dothan, Alabama, United States

CNS Clinical Research Group

🇺🇸

Coral Springs, Florida, United States

Baber Research Group

🇺🇸

Naperville, Illinois, United States

Collaborative Neuroscience Network, LLC

🇺🇸

Torrance, California, United States

Millennium Psychiatric Associates

🇺🇸

Creve Coeur, Missouri, United States

Barbara Diaz-Hernandez MD Research, Inc.

🇵🇷

San Juan, Puerto Rico

Coastal Research Associates, Inc.

🇺🇸

Weymouth, Massachusetts, United States

Professional Psychiatric Services

🇺🇸

Mason, Ohio, United States

Center for Emotional Fitness

🇺🇸

Cherry Hill, New Jersey, United States

UMHAT 'Dr. Georgi Stranski', Dept. of Psychiatry

🇧🇬

Pleven, Bulgaria

Institutul de Psihiatrie Socola Iasi Site 111

🇷🇴

Iasi, Romania

Innovative Clinical Research, Inc.

🇺🇸

Lauderhill, Florida, United States

Clinical Center of Serbia

🇷🇸

Belgrade, Serbia

Cutting Edge Research Group

🇺🇸

Oklahoma City, Oklahoma, United States

SPRI Clinical Trials, LLC

🇺🇸

Brooklyn, New York, United States

Grayline Research Center

🇺🇸

Wichita Falls, Texas, United States

Eastside Comprehensive Medical Center

🇺🇸

New York, New York, United States

UMHAT "Sv. Georgi", EAD

🇧🇬

Plovdiv, Bulgaria

Brooklyn Medical Institute

🇺🇸

Brooklyn, New York, United States

Pharmaceutical Research Associates, Inc.

🇺🇸

Marlton, New Jersey, United States

Tulsa Clinical Research, LLC

🇺🇸

Tulsa, Oklahoma, United States

Psychiatric Hospital "Sveti Ivan"

🇭🇷

Zagreb, Croatia

Regional Psychoneurological Hospital #3, Dept of Primary Psych Episode

🇺🇦

Ivano-Frankivsk, Ukraine

DCC "Mladost M" - Varna, OOD Site 188

🇧🇬

Varna, Bulgaria

CI of Kyiv Reg.Council Reg.Psychiatric-Narcological Medical Association

🇺🇦

Glevakha, Ukraine

Regional Psychoneurological Hospital #3

🇺🇦

Ivano-Frankivsk, Ukraine

CI Odesa Regional Medical Center of Mental Health

🇺🇦

Odesa, Ukraine

CI Odesa Regional Psychiatric Hospital # 2

🇺🇦

Komintern, Ukraine

SI Inst.of Neurology, Psychiatry and Narcology of NAMS of Ukraine

🇺🇦

Kharkiv, Ukraine

Innova Clinical Trials, Inc.

🇺🇸

Miami, Florida, United States

Houston Endoscopy and Research Center

🇺🇸

Houston, Texas, United States

Capstone Clinical Research

🇺🇸

Libertyville, Illinois, United States

DCC "Mladost M" - Varna, OOD Site 194

🇧🇬

Varna, Bulgaria

Advanced Research Center, Inc

🇺🇸

Anaheim, California, United States

Woodland International Research Group, LLC

🇺🇸

Little Rock, Arkansas, United States

NoesisPharma, LLC

🇺🇸

Phoenix, Arizona, United States

Behavioral Research Specialists, LLC

🇺🇸

Glendale, California, United States

Excell Research, Inc.

🇺🇸

Oceanside, California, United States

MD Clinical

🇺🇸

Hallandale Beach, Florida, United States

Comprehensive Clinical Research

🇺🇸

Washington, District of Columbia, United States

Research Centers of America, LLC

🇺🇸

Oakland Park, Florida, United States

J. Gary Booker, MD, APMC

🇺🇸

Shreveport, Louisiana, United States

St. Louis Clinical Trials, LLC

🇺🇸

Saint Louis, Missouri, United States

Manhattan Behavioral Medicine

🇺🇸

New York, New York, United States

Finger Lakes Clinical Research

🇺🇸

Rochester, New York, United States

Clinical Trials of America, Inc

🇺🇸

Hickory, North Carolina, United States

University at Buffalo Erie County Medical Center

🇺🇸

Buffalo, New York, United States

University of Cincinnati - Department of Psychiatry and Behavioral Neuroscience

🇺🇸

Cincinnati, Ohio, United States

Carolina Clinical Trials, Inc.

🇺🇸

Charleston, South Carolina, United States

Suburban Research Associates

🇺🇸

Media, Pennsylvania, United States

Pacific Institute of Medical Sciences

🇺🇸

Bothell, Washington, United States

Clinical Centre Kragujevac Site 158

🇷🇸

Kragujevac, Serbia

Clinical Center Zvezdara

🇷🇸

Belgrade, Serbia

Institute of Mental Health

🇷🇸

Belgrade, Serbia

CI of LRC Lviv Reg. Council Lviv Reg.Clinical Psychoneurological Dispensary

🇺🇦

Lviv, Ukraine

Neuropsychiatric Hospital Ivan Barbot

🇭🇷

Popovača, Croatia

Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila"

🇷🇴

Bucuresti, Romania

Spitalul de Psihiatrie Titan "Dr. Constantin Gorgos"

🇷🇴

Bucuresti, Romania

General Hospital Euromedic

🇷🇸

Belgrade, Serbia

Clinical Center Nis Site 160

🇷🇸

Nis, Serbia

University Hospital Center Zagreb

🇭🇷

Zagreb, Croatia

Clinical Center "Dr. Dragisa Misovic"

🇷🇸

Belgrade, Serbia

Liptovska nemocnica s poliklinikou Liptovsky Mikulas

🇸🇰

Liptovsky Mikulas, Slovakia

Nemocnica s poliklinikou sv. Barbory, Roznava a.s.

🇸🇰

Rožňava, Slovakia

Crystal Comfort s.r.o.

🇸🇰

Vranov nad Toplou, Slovakia

MHAT "Dr. Hristo Stambolski", EOOD

🇧🇬

Kazanlak, Bulgaria

Clinical Hospital Center Rijeka

🇭🇷

Rijeka, Croatia

Spitalul de Psihiatrie "Elisabeta Doamna" Galati

🇷🇴

Galati, Romania

Clinic for Psychiatry Vrapce

🇭🇷

Zagreb, Croatia

Institutul de Psihiatrie Socola Iasi Site 113

🇷🇴

Iasi, Romania

Clinic of Psychiatric Diseases "Dr Laza Lazarevic"

🇷🇸

Belgrade, Serbia

Clinical Center Kragujevac Site 154

🇷🇸

Kragujevac, Serbia

Specialized Hospital for Neuropsychiatric Diseases "Sveti Vracevi"

🇷🇸

Novi Knezevac, Serbia

Vavrusova Consulting s.r.o.

🇸🇰

Bratislava, Slovakia

PsychoLine s.r.o.

🇸🇰

Rimavská Sobota, Slovakia

CI Cherkasy Regional Psychiatric Hospital of ChRC

🇺🇦

Smila, Ukraine

Ternopil Reg. Communal Clinical Psychoneurological Hospital Depts of Psychiatry #2

🇺🇦

Ternopil, Ukraine

Radiant Research

🇺🇸

Cerritos, California, United States

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