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Study on the Efficacy, Safety, and Tolerability of Cariprazine Relative to Placebo in Participants With Bipolar I Depression

Phase 3
Completed
Conditions
Bipolar Disorder
Depression
Interventions
Drug: Placebo
Registration Number
NCT02670551
Lead Sponsor
Forest Laboratories
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
488
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboFollowing a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks.
Cariprazine 1.5 mgCariprazineFollowing a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks.
Cariprazine 3.0 mgCariprazineFollowing a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 milligram (mg) capsule, one per day, orally beginning on Day 15 for 4 weeks.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Week 6Baseline (Week 0) to Week 6

The Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item, clinician-rated scale that evaluates the participant's 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.

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

The Clinical Global Impressions-Severity (CGI-S) is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of other participants 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 participants." A negative change from Baseline indicates improvement.

Trial Locations

Locations (74)

Carman Research

🇺🇸

Smyrna, Georgia, United States

Neuroscience Research Institute Inc.

🇺🇸

Winfield, Illinois, United States

Midwest Clinical Research Center

🇺🇸

Dayton, Ohio, United States

Viking Clinical Research

🇺🇸

Temecula, California, United States

Pacific Research Partners, LLC

🇺🇸

Oakland, California, United States

Pacific Clinical Research Medical Group

🇺🇸

Upland, California, United States

Research Across America

🇺🇸

Plano, Texas, United States

SPH - Kardzhali, EOOD

🇧🇬

Kardzhali, Bulgaria

Medical & Behavioral Health Research, PC

🇺🇸

New York, New York, United States

CNS Healthcare

🇺🇸

Jacksonville, Florida, United States

UMHAT 'Dr. Georgi Stranski', EAD

🇧🇬

Pleven, Bulgaria

UMHAT "Alexandrovska" EAD

🇧🇬

Sofia, Bulgaria

Medical Centre "Doverie" AD

🇧🇬

Sofia, Bulgaria

Neuromeda, JSC

🇱🇹

Kaunas, Lithuania

Core Clinical Research

🇺🇸

Kirkland, Washington, United States

Lincoln Research, LLC

🇺🇸

Lincoln, Rhode Island, United States

UMHAT "Sv. Georgi", EAD

🇧🇬

Plovdiv, Bulgaria

DCC "Mladost M" - Varna, OOD

🇧🇬

Varna, Bulgaria

Podlaskie Centrum Psychogeriatrii

🇵🇱

Białystok, Poland

Uniwersyteckie Centrum Kliniczne

🇵🇱

Gdańsk, Poland

NZOZ Syntonia

🇵🇱

Pruszcz Gdański, Poland

Oregon Center for Clinical Investigations

🇺🇸

Salem, Oregon, United States

Marienthal Center of Psychiatry and Psychology

🇪🇪

Tallinn, Estonia

Przychodnia Srodmiescie Sp. z o. o.

🇵🇱

Bydgoszcz, Poland

MHATNP "Sv.Naum", EAD

🇧🇬

Sofia, Bulgaria

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

🇧🇬

Burgas, Bulgaria

MHAT "Dr. Hristo Stambolski", EOOD

🇧🇬

Kazanlak, Bulgaria

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

🇱🇹

Kaunas, Lithuania

Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS

🇵🇱

Leszno, Poland

Torunskie Centrum Psychiatrii Neuromed

🇵🇱

Toruń, Poland

INSPIRA Clinical Research

🇵🇷

San Juan, Puerto Rico

MHC - Ruse, EOOD

🇧🇬

Ruse, Bulgaria

Specjalistyczna Praktyka Lekarska Marek Domański

🇵🇱

Lublin, Poland

ATP Clinical Research, Inc.

🇺🇸

Costa Mesa, California, United States

Northwest Behavioral Research Center

🇺🇸

Marietta, Georgia, United States

Psychiatric Medicine Associates, L.L.C

🇺🇸

Skokie, Illinois, United States

Hassman Research Institute

🇺🇸

Berlin, New Jersey, United States

Neuro-Behavioral Clinical Research

🇺🇸

Canton, Ohio, United States

Ohio State University Department of Psychiatry

🇺🇸

Columbus, Ohio, United States

Family Psychiatry of The Woodlands

🇺🇸

The Woodlands, Texas, United States

Artemis Institute for Clinical Research

🇺🇸

San Diego, California, United States

Altea Research Institute

🇺🇸

Las Vegas, Nevada, United States

Patient Priority Clinical Sites

🇺🇸

Cincinnati, Ohio, United States

Red Oak Psychiatry Associates, PA

🇺🇸

Houston, Texas, United States

Houston Clinical Trials, LLC

🇺🇸

Houston, Texas, United States

Summit Research Network Seattle

🇺🇸

Seattle, Washington, United States

IPS Research Company

🇺🇸

Oklahoma City, Oklahoma, United States

Sooner Clinical Research

🇺🇸

Oklahoma City, Oklahoma, United States

Oregon Center for Clinical Investigations, Inc.

🇺🇸

Portland, Oregon, United States

MHAT-Targovishte, AD

🇧🇬

Targovishte, Bulgaria

Arkansas Psychiatric Clinic Clinical Research Trials PA

🇺🇸

Little Rock, Arkansas, United States

Integrated Medical and Behavioral Associates

🇺🇸

Glendale, California, United States

Synergy San Diego

🇺🇸

Escondido, California, United States

Schuster Medical Research Institute

🇺🇸

Sherman Oaks, California, United States

iResearch Atlanta, LLC

🇺🇸

Decatur, Georgia, United States

Apostle Clinical Trials, Inc.

🇺🇸

Long Beach, California, United States

Comprehensive Psychiatric Care

🇺🇸

Norwich, Connecticut, United States

St. Charles Psychiatric Associates - Midwest Research Group

🇺🇸

Saint Charles, Missouri, United States

Military Medical Academy - MHAT - Sofia

🇧🇬

Sofia, Bulgaria

Neurobehavioral Research, Inc.

🇺🇸

Cedarhurst, New York, United States

Lehigh Center for Clinical Research

🇺🇸

Allentown, Pennsylvania, United States

Alliance Research Group

🇺🇸

Richmond, Virginia, United States

Clinical Neuroscience Solutions

🇺🇸

Memphis, Tennessee, United States

Northwest Clinical Research Center

🇺🇸

Bellevue, Washington, United States

State Psychiatric Hospital - Lovech

🇧🇬

Lovech, Bulgaria

West Tallinn Central Hospital

🇪🇪

Tallinn, Estonia

Republican Kaunas Hospital Psychiatry Clinic Mariu Division, Public Institution

🇱🇹

Kaunas, Lithuania

Tartu University Hospital

🇪🇪

Tartu, Estonia

232Antakalnis Psychiatric Consultation Center, Public Institution

🇱🇹

Vilnius, Lithuania

Clinical Best Solutions

🇵🇱

Lublin, Poland

Romuvos klinika, UAB

🇱🇹

Kaunas, Lithuania

Clinical Neuroscience Solutions, Inc

🇺🇸

Orlando, Florida, United States

Olympian Clinical Research

🇺🇸

Tampa, Florida, United States

Radiant Research

🇺🇸

Atlanta, Georgia, United States

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