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

February 19, 2019 updated by: Forest Laboratories

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Fixed-Dose Clinical Trial Evaluating The Efficacy, Safety And Tolerability Of Cariprazine In Patients With Bipolar I Depression

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

493

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Burgas, Bulgaria, 8001
        • Mental Health Centre 'Prof. Dr. Ivan Temkov', EOOD
      • Kazanlak, Bulgaria, 6100
        • MHAT "Dr. Hristo Stambolski", EOOD
      • Pleven, Bulgaria, 5800
        • UMHAT 'Dr. Georgi Stranski', Dept. of Psychiatry
      • Plovdiv, Bulgaria, 4000
        • UMHAT "Sv. Georgi", EAD
      • Varna, Bulgaria, 9020
        • DCC "Mladost M" - Varna, OOD Site 188
      • Varna, Bulgaria, 9020
        • DCC "Mladost M" - Varna, OOD Site 194
  • Croatia
      • Popovača, Croatia, 44317
        • Neuropsychiatric Hospital Ivan Barbot
      • Rijeka, Croatia, 51000
        • Clinical Hospital Center Rijeka
      • Zagreb, Croatia, 10000
        • University hospital center Zagreb
      • Zagreb, Croatia, 10000
        • Polyclinic Neuron
      • Zagreb, Croatia, 10090
        • Clinic for Psychiatry Vrapce
      • Zagreb, Croatia, 10090
        • Psychiatric Hospital "Sveti Ivan"
  • Puerto Rico
      • San Juan, Puerto Rico, 00926
        • Barbara Diaz-Hernandez MD Research, Inc.
  • Romania
      • Bucuresti, Romania, 010825
        • Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila"
      • Bucuresti, Romania, 030442
        • Spitalul de Psihiatrie Titan "Dr. Constantin Gorgos"
      • Galati, Romania, 800179
        • Spitalul de Psihiatrie "Elisabeta Doamna" Galati
      • Iasi, Romania, 700282
        • Institutul de Psihiatrie Socola Iasi Site 111
      • Iasi, Romania, 700282
        • Institutul de Psihiatrie Socola Iasi Site 113
  • Serbia
      • Belgrade, Serbia, 11000
        • Clinical Center of Serbia
      • Belgrade, Serbia, 11000
        • Institute of Mental Health
      • Belgrade, Serbia, 11000
        • Clinical Center Zvezdara
      • Belgrade, Serbia, 11000
        • Clinic of Psychiatric Diseases "Dr Laza Lazarevic"
      • Belgrade, Serbia, 11000
        • General Hospital Euromedic
      • Belgrade, Serbia, 11040
        • Clinical Center "Dr. Dragisa Misovic"
      • Kragujevac, Serbia, 34000
        • Clinical Center Kragujevac Site 154
      • Kragujevac, Serbia, 34000
        • Clinical Centre Kragujevac Site 158
      • Nis, Serbia, 18000
        • Clinical Center Nis Site 150
      • Nis, Serbia, 18000
        • Clinical Center Nis Site 160
      • Novi Knezevac, Serbia, 23330
        • Specialized Hospital for Neuropsychiatric Diseases "Sveti Vracevi"
  • Slovakia
      • Bardejov, Slovakia, 08501
        • Centrum zdravia R.B.K. s.r.o.
      • Bratislava, Slovakia, 85101
        • Vavrusova Consulting s.r.o.
      • Liptovsky Mikulas, Slovakia, 03123
        • Liptovska nemocnica s poliklinikou Liptovsky Mikulas
      • Rimavská Sobota, Slovakia, 97901
        • PsychoLine s.r.o.
      • Rožňava, Slovakia, 04801
        • Nemocnica s poliklinikou sv. Barbory, Roznava a.s.
      • Vranov nad Toplou, Slovakia, 09301
        • Crystal Comfort s.r.o.
  • Ukraine
      • Glevakha, Ukraine, 08631
        • CI of Kyiv Reg.Council Reg.Psychiatric-Narcological Medical Association
      • Ivano-Frankivsk, Ukraine, 76014
        • Regional Psychoneurological Hospital #3
      • Ivano-Frankivsk, Ukraine, 76014
        • Regional Psychoneurological Hospital #3, Dept of Primary Psych Episode
      • Kharkiv, Ukraine, 61068
        • SI Inst.of Neurology, Psychiatry and Narcology of NAMS of Ukraine
      • Kherson, Ukraine, 73488
        • CI Kherson Reg. Psychiatric Hospital of Kherson RC
      • Komintern, Ukraine, 67513
        • CI Odesa Regional Psychiatric Hospital # 2
      • Lviv, Ukraine, 79017
        • CI of LRC Lviv Reg. Council Lviv Reg.Clinical Psychoneurological Dispensary
      • Odesa, Ukraine, 65006
        • CI Odesa Regional Medical Center of Mental Health
      • Smila, Ukraine, 20708
        • CI Cherkasy Regional Psychiatric Hospital of ChRC
      • Ternopil, Ukraine, 46027
        • Ternopil Reg. Communal Clinical Psychoneurological Hospital Depts of Psychiatry #2
      • Uzhgorod, Ukraine, 88000
        • Transcarpathian Regional Narcological Dispensary
      • Vinnytsia, Ukraine, 21005
        • CI O.I. Yushchenko Vinnytsia Reg. Psychoneurological Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
      • Dothan, Alabama, United States, 36303
        • Harmonex Neuroscience Research, Inc.
    • Arizona
      • Phoenix, Arizona, United States, 85032
        • NoesisPharma, LLC
    • Arkansas
      • Little Rock, Arkansas, United States, 72211
        • Woodland International Research Group, LLC
    • California
      • Anaheim, California, United States, 92805
        • Advanced Research Center, Inc
      • Cerritos, California, United States, 90703
        • Radiant Research
      • Garden Grove, California, United States, 92845
        • Collaborative Neuroscience Network, LLC
      • Glendale, California, United States, 91206
        • Behavioral Research Specialists, LLC
      • Oceanside, California, United States, 92056
        • Excell Research, Inc.
      • Torrance, California, United States, 90502
        • Collaborative Neuroscience Network, LLC
    • District of Columbia
      • Washington, District of Columbia, United States, 20016
        • Comprehensive Clinical Research
    • Florida
      • Coral Springs, Florida, United States, 33067
        • CNS Clinical Research Group
      • Hallandale Beach, Florida, United States, 33009
        • MD Clinical
      • Lauderhill, Florida, United States, 33319
        • Innovative Clinical Research, Inc.
      • Miami, Florida, United States, 33133
        • Innova Clinical Trials, Inc.
      • Oakland Park, Florida, United States, 33334
        • Research Centers of America, LLC
    • Georgia
      • Atlanta, Georgia, United States, 30331
        • Atlanta Center for Medical Research
    • Illinois
      • Hoffman Estates, Illinois, United States, 60169
        • Alexian Brothers Center for Psychiatric Research
      • Libertyville, Illinois, United States, 60048
        • Capstone Clinical Research
      • Naperville, Illinois, United States, 60563
        • Baber Research Group
    • Louisiana
      • Shreveport, Louisiana, United States, 71104
        • J. Gary Booker, MD, APMC
    • Massachusetts
      • Weymouth, Massachusetts, United States, 02190
        • Coastal Research Associates, Inc.
    • Missouri
      • Creve Coeur, Missouri, United States, 63141
        • Millennium Psychiatric Associates
      • Saint Louis, Missouri, United States, 63141
        • St. Louis Clinical Trials, LLC
    • New Jersey
      • Cherry Hill, New Jersey, United States, 08002
        • Center for Emotional Fitness
      • Marlton, New Jersey, United States, 08053
        • Pharmaceutical Research Associates, Inc.
    • New York
      • Brooklyn, New York, United States, 11235
        • SPRI Clinical Trials, LLC
      • Brooklyn, New York, United States, 11214
        • Brooklyn Medical Institute
      • Buffalo, New York, United States, 14215
        • University at Buffalo Erie County Medical Center
      • New York, New York, United States, 10036
        • Manhattan Behavioral Medicine
      • New York, New York, United States, 10128
        • Eastside Comprehensive Medical Center
      • Rochester, New York, United States, 14618
        • Finger Lakes Clinical Research
    • North Carolina
      • Hickory, North Carolina, United States, 28601
        • Clinical Trials of America, Inc
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati - Department of Psychiatry and Behavioral Neuroscience
      • Mason, Ohio, United States, 45040
        • Professional Psychiatric Services
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73116
        • Cutting Edge Research Group
      • Tulsa, Oklahoma, United States, 74104
        • Tulsa Clinical Research, LLC
    • Pennsylvania
      • Media, Pennsylvania, United States, 19063
        • Suburban Research Associates
    • South Carolina
      • Charleston, South Carolina, United States, 29407
        • Carolina Clinical Trials, Inc.
    • Texas
      • Houston, Texas, United States, 77079
        • Houston Endoscopy and Research Center
      • Wichita Falls, Texas, United States, 76309
        • Grayline Research Center
    • Washington
      • Bothell, Washington, United States, 98011
        • Pacific Institute of Medical Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cariprazine 3.0 mg
Following 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.
Drug: Cariprazine
Cariprazine capsule one per day orally.
Other Names:
  • Vraylar
Experimental: Cariprazine 1.5 mg
Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.
Drug: Cariprazine
Cariprazine capsule one per day orally.
Other Names:
  • Vraylar
Placebo Comparator: Placebo
Following a 7 to 14 days screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.
Drug: Placebo
Matching placebo capsule one per day orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS)
Time Frame: 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).
Baseline (Week 0) to Week 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score
Time Frame: Baseline (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).
Baseline (Week 0) to Week 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Forest Laboratories

Investigators

  • Study Director: Willie Earley, Allergan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 31, 2016

Primary Completion (Actual)

January 18, 2018

Study Completion (Actual)

January 18, 2018

Study Registration Dates

First Submitted

January 28, 2016

First Submitted That Met QC Criteria

January 29, 2016

First Posted (Estimate)

February 1, 2016

Study Record Updates

Last Update Posted (Actual)

March 12, 2019

Last Update Submitted That Met QC Criteria

February 19, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RGH-MD-53
  • 2016-000756-98 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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