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

NCT ID: NCT02670538

Last Updated: 2019-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 493 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2018-01-18

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.

Conditions

Bipolar Disorder; Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Cariprazine

Intervention Type: DRUG

Cariprazine capsule one per day orally.

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.

Group Type: EXPERIMENTAL

Cariprazine

Intervention Type: DRUG

Cariprazine capsule one per day orally.

Placebo

Following a 7 to 14 days screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo capsule one per day orally.

Interventions

Cariprazine

Cariprazine capsule one per day orally.

Intervention Type: DRUG

Placebo

Matching placebo capsule one per day orally.

Intervention Type: DRUG

Other Intervention Names

Vraylar

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Forest Laboratories

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Willie Earley

Role: STUDY_DIRECTOR

Allergan

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Harmonex Neuroscience Research, Inc.

Dothan, Alabama, United States

NoesisPharma, LLC

Phoenix, Arizona, United States

Woodland International Research Group, LLC

Little Rock, Arkansas, United States

Advanced Research Center, Inc

Anaheim, California, United States

Radiant Research

Cerritos, California, United States

Collaborative Neuroscience Network, LLC

Garden Grove, California, United States

Behavioral Research Specialists, LLC

Glendale, California, United States

Excell Research, Inc.

Oceanside, California, United States

Collaborative Neuroscience Network, LLC

Torrance, California, United States

Comprehensive Clinical Research

Washington D.C., District of Columbia, United States

CNS Clinical Research Group

Coral Springs, Florida, United States

MD Clinical

Hallandale, Florida, United States

Innovative Clinical Research, Inc.

Lauderhill, Florida, United States

Innova Clinical Trials, Inc.

Miami, Florida, United States

Research Centers of America, LLC

Oakland Park, Florida, United States

Atlanta Center for Medical Research

Atlanta, Georgia, United States

Alexian Brothers Center for Psychiatric Research

Hoffman Estates, Illinois, United States

Capstone Clinical Research

Libertyville, Illinois, United States

Baber Research Group

Naperville, Illinois, United States

J. Gary Booker, MD, APMC

Shreveport, Louisiana, United States

Coastal Research Associates, Inc.

Weymouth, Massachusetts, United States

Millennium Psychiatric Associates

Creve Coeur, Missouri, United States

St. Louis Clinical Trials, LLC

St Louis, Missouri, United States

Center for Emotional Fitness

Cherry Hill, New Jersey, United States

Pharmaceutical Research Associates, Inc.

Marlton, New Jersey, United States

Brooklyn Medical Institute

Brooklyn, New York, United States

SPRI Clinical Trials, LLC

Brooklyn, New York, United States

University at Buffalo Erie County Medical Center

Buffalo, New York, United States

Manhattan Behavioral Medicine

New York, New York, United States

Eastside Comprehensive Medical Center

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 of Cincinnati - Department of Psychiatry and Behavioral Neuroscience

Cincinnati, Ohio, United States

Professional Psychiatric Services

Mason, Ohio, United States

Cutting Edge Research Group

Oklahoma City, Oklahoma, United States

Tulsa Clinical Research, LLC

Tulsa, Oklahoma, United States

Suburban Research Associates

Media, Pennsylvania, United States

Carolina Clinical Trials, Inc.

Charleston, South Carolina, United States

Houston Endoscopy and Research Center

Houston, Texas, United States

Grayline Research Center

Wichita Falls, Texas, United States

Pacific Institute of Medical Sciences

Bothell, Washington, United States

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

Burgas, , Bulgaria

MHAT "Dr. Hristo Stambolski", EOOD

Kazanlak, , Bulgaria

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

Pleven, , Bulgaria

UMHAT "Sv. Georgi", EAD

Plovdiv, , Bulgaria

DCC "Mladost M" - Varna, OOD Site 188

Varna, , Bulgaria

DCC "Mladost M" - Varna, OOD Site 194

Varna, , Bulgaria

Neuropsychiatric Hospital Ivan Barbot

Popovača, , Croatia

Clinical Hospital Center Rijeka

Rijeka, , Croatia

Polyclinic Neuron

Zagreb, , Croatia

University Hospital Center Zagreb

Zagreb, , Croatia

Clinic for Psychiatry Vrapce

Zagreb, , Croatia

Psychiatric Hospital "Sveti Ivan"

Zagreb, , Croatia

Barbara Diaz-Hernandez MD Research, Inc.

San Juan, , Puerto Rico

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

Bucharest, , Romania

Spitalul de Psihiatrie Titan "Dr. Constantin Gorgos"

Bucharest, , Romania

Spitalul de Psihiatrie "Elisabeta Doamna" Galati

Galati, , Romania

Institutul de Psihiatrie Socola Iasi Site 111

Iași, , Romania

Institutul de Psihiatrie Socola Iasi Site 113

Iași, , Romania

Clinic of Psychiatric Diseases "Dr Laza Lazarevic"

Belgrade, , Serbia

Clinical Center of Serbia

Belgrade, , Serbia

Clinical Center Zvezdara

Belgrade, , Serbia

General Hospital Euromedic

Belgrade, , Serbia

Institute of Mental Health

Belgrade, , Serbia

Clinical Center "Dr. Dragisa Misovic"

Belgrade, , Serbia

Clinical Center Kragujevac Site 154

Kragujevac, , Serbia

Clinical Centre Kragujevac Site 158

Kragujevac, , Serbia

Clinical Center Nis Site 150

Niš, , Serbia

Clinical Center Nis Site 160

Niš, , Serbia

Specialized Hospital for Neuropsychiatric Diseases "Sveti Vracevi"

Novi Kneževac, , Serbia

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

Bardejov, , Slovakia

Vavrusova Consulting s.r.o.

Bratislava, , Slovakia

Liptovska nemocnica s poliklinikou Liptovsky Mikulas

Liptovský Mikuláš, , Slovakia

PsychoLine s.r.o.

Rimavská Sobota, , Slovakia

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

Rožňava, , Slovakia

Crystal Comfort s.r.o.

Vranov nad Topľou, , Slovakia

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

Hlevakha, , Ukraine

Regional Psychoneurological Hospital #3, Dept of Primary Psych Episode

Ivano-Frankivsk, , Ukraine

Regional Psychoneurological Hospital #3

Ivano-Frankivsk, , Ukraine

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

Kharkiv, , Ukraine

CI Kherson Reg. Psychiatric Hospital of Kherson RC

Kherson, , Ukraine

CI Odesa Regional Psychiatric Hospital # 2

Komintern, , Ukraine

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

Lviv, , Ukraine

CI Odesa Regional Medical Center of Mental Health

Odesa, , Ukraine

CI Cherkasy Regional Psychiatric Hospital of ChRC

Smila, , Ukraine

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

Ternopil, , Ukraine

Transcarpathian Regional Narcological Dispensary

Uzhhorod, , Ukraine

CI O.I. Yushchenko Vinnytsia Reg. Psychoneurological Hospital

Vinnytsia, , Ukraine

Countries

United States; Bulgaria; Croatia; Puerto Rico; Romania; Serbia; Slovakia; Ukraine

References

McIntyre RS, Llorca PM, Aronin LC, Yu J, Nguyen HB. Effect of Cariprazine on Anhedonia in Patients with Bipolar I Depression: Post Hoc Analysis of Three Randomized Placebo-Controlled Clinical Trials. Adv Ther. 2025 Jan;42(1):246-260. doi: 10.1007/s12325-024-03009-2. Epub 2024 Nov 9.

Reference Type: DERIVED

PMID: 39520655 (View on PubMed)

Citrome L, Yatham LN, Patel MD, Barabassy A, Hankinson A, Earley WR. Cariprazine and akathisia, restlessness, and extrapyramidal symptoms in patients with bipolar depression. J Affect Disord. 2021 Jun 1;288:191-198. doi: 10.1016/j.jad.2021.03.076. Epub 2021 Mar 31.

Reference Type: DERIVED

PMID: 33915374 (View on PubMed)

Thase ME, Harrington A, Calabrese J, Montgomery S, Niu X, Patel MD. Evaluation of MADRS severity thresholds in patients with bipolar depression. J Affect Disord. 2021 May 1;286:58-63. doi: 10.1016/j.jad.2021.02.043. Epub 2021 Feb 20.

Reference Type: DERIVED

PMID: 33677183 (View on PubMed)

Yatham LN, Vieta E, McIntyre RS, Jain R, Patel M, Earley W. Broad Efficacy of Cariprazine on Depressive Symptoms in Bipolar Disorder and the Clinical Implications. Prim Care Companion CNS Disord. 2020 Sep 17;22(5):20m02611. doi: 10.4088/PCC.20m02611.

Reference Type: DERIVED

PMID: 32942346 (View on PubMed)

Earley WR, Burgess M, Rekeda L, Hankinson A, McIntyre RS, Suppes T, Calabrese JR, Yatham LN. A pooled post hoc analysis evaluating the safety and tolerability of cariprazine in bipolar depression. J Affect Disord. 2020 Feb 15;263:386-395. doi: 10.1016/j.jad.2019.11.098. Epub 2019 Nov 22.

Reference Type: DERIVED

PMID: 31969269 (View on PubMed)

Earley WR, Burgess MV, Khan B, Rekeda L, Suppes T, Tohen M, Calabrese JR. Efficacy and safety of cariprazine in bipolar I depression: A double-blind, placebo-controlled phase 3 study. Bipolar Disord. 2020 Jun;22(4):372-384. doi: 10.1111/bdi.12852. Epub 2019 Nov 6.

Reference Type: DERIVED

PMID: 31628698 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-000756-98

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RGH-MD-53

Identifier Type: -

Identifier Source: org_study_id