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

NCT02670538 | Completed Phase 3 Results

• 2 other identifiers: RGH-MD-532016-000756-98
• Study Type: interventional
• Target: 493
• Locations: 8 countries
• Sites: 89

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS)

  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 Outcomes (1)

• Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score

  Baseline (Week 0) to Week 6

Study Arms (3)

Cariprazine 3.0 mg

EXPERIMENTAL

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 1.5 mg

EXPERIMENTAL

Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.

Drug: Cariprazine

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Cariprazine DRUG

Cariprazine capsule one per day orally.

Also known as: Vraylar

Cariprazine 1.5 mg; Cariprazine 3.0 mg

Placebo DRUG

Matching placebo capsule one per day orally.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Forest Laboratories: lead

Study Sites (89)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Harmonex Neuroscience Research, Inc.

Dothan, Alabama, 36303, United States

Location

NoesisPharma, LLC

Phoenix, Arizona, 85032, United States

Location

Woodland International Research Group, LLC

Little Rock, Arkansas, 72211, United States

Location

Advanced Research Center, Inc

Anaheim, California, 92805, United States

Location

Radiant Research

Cerritos, California, 90703, United States

Location

Collaborative Neuroscience Network, LLC

Garden Grove, California, 92845, United States

Location

Behavioral Research Specialists, LLC

Glendale, California, 91206, United States

Location

Excell Research, Inc.

Oceanside, California, 92056, United States

Location

Collaborative Neuroscience Network, LLC

Torrance, California, 90502, United States

Location

Comprehensive Clinical Research

Washington D.C., District of Columbia, 20016, United States

Location

CNS Clinical Research Group

Coral Springs, Florida, 33067, United States

Location

MD Clinical

Hallandale, Florida, 33009, United States

Location

Innovative Clinical Research, Inc.

Lauderhill, Florida, 33319, United States

Location

Innova Clinical Trials, Inc.

Miami, Florida, 33133, United States

Location

Research Centers of America, LLC

Oakland Park, Florida, 33334, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

Alexian Brothers Center for Psychiatric Research

Hoffman Estates, Illinois, 60169, United States

Location

Capstone Clinical Research

Libertyville, Illinois, 60048, United States

Location

Baber Research Group

Naperville, Illinois, 60563, United States

Location

J. Gary Booker, MD, APMC

Shreveport, Louisiana, 71104, United States

Location

Coastal Research Associates, Inc.

Weymouth, Massachusetts, 02190, United States

Location

Millennium Psychiatric Associates

Creve Coeur, Missouri, 63141, United States

Location

St. Louis Clinical Trials, LLC

St Louis, Missouri, 63141, United States

Location

Center for Emotional Fitness

Cherry Hill, New Jersey, 08002, United States

Location

Pharmaceutical Research Associates, Inc.

Marlton, New Jersey, 08053, United States

Location

Brooklyn Medical Institute

Brooklyn, New York, 11214, United States

Location

SPRI Clinical Trials, LLC

Brooklyn, New York, 11235, United States

Location

University at Buffalo Erie County Medical Center

Buffalo, New York, 14215, United States

Location

Manhattan Behavioral Medicine

New York, New York, 10036, United States

Location

Eastside Comprehensive Medical Center

New York, New York, 10128, United States

Location

Finger Lakes Clinical Research

Rochester, New York, 14618, United States

Location

Clinical Trials of America, Inc

Hickory, North Carolina, 28601, United States

Location

University of Cincinnati - Department of Psychiatry and Behavioral Neuroscience

Cincinnati, Ohio, 45219, United States

Location

Professional Psychiatric Services

Mason, Ohio, 45040, United States

Location

Cutting Edge Research Group

Oklahoma City, Oklahoma, 73116, United States

Location

Tulsa Clinical Research, LLC

Tulsa, Oklahoma, 74104, United States

Location

Suburban Research Associates

Media, Pennsylvania, 19063, United States

Location

Carolina Clinical Trials, Inc.

Charleston, South Carolina, 29407, United States

Location

Houston Endoscopy and Research Center

Houston, Texas, 77079, United States

Location

Grayline Research Center

Wichita Falls, Texas, 76309, United States

Location

Pacific Institute of Medical Sciences

Bothell, Washington, 98011, United States

Location

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

Burgas, 8001, Bulgaria

Location

MHAT "Dr. Hristo Stambolski", EOOD

Kazanlak, 6100, Bulgaria

Location

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

Pleven, 5800, Bulgaria

Location

UMHAT "Sv. Georgi", EAD

Plovdiv, 4000, Bulgaria

Location

DCC "Mladost M" - Varna, OOD Site 188

Varna, 9020, Bulgaria

Location

DCC "Mladost M" - Varna, OOD Site 194

Varna, 9020, Bulgaria

Location

Neuropsychiatric Hospital Ivan Barbot

Popovača, 44317, Croatia

Location

Clinical Hospital Center Rijeka

Rijeka, 51000, Croatia

Location

Polyclinic Neuron

Zagreb, 10000, Croatia

Location

University Hospital Center Zagreb

Zagreb, 10000, Croatia

Location

Clinic for Psychiatry Vrapce

Zagreb, 10090, Croatia

Location

Psychiatric Hospital "Sveti Ivan"

Zagreb, 10090, Croatia

Location

Barbara Diaz-Hernandez MD Research, Inc.

San Juan, 00926, Puerto Rico

Location

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

Bucharest, 010825, Romania

Location

Spitalul de Psihiatrie Titan "Dr. Constantin Gorgos"

Bucharest, 030442, Romania

Location

Spitalul de Psihiatrie "Elisabeta Doamna" Galati

Galati, 800179, Romania

Location

Institutul de Psihiatrie Socola Iasi Site 111

Iași, 700282, Romania

Location

Institutul de Psihiatrie Socola Iasi Site 113

Iași, 700282, Romania

Location

Clinic of Psychiatric Diseases "Dr Laza Lazarevic"

Belgrade, 11000, Serbia

Location

Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Clinical Center Zvezdara

Belgrade, 11000, Serbia

Location

General Hospital Euromedic

Belgrade, 11000, Serbia

Location

Institute of Mental Health

Belgrade, 11000, Serbia

Location

Clinical Center "Dr. Dragisa Misovic"

Belgrade, 11040, Serbia

Location

Clinical Center Kragujevac Site 154

Kragujevac, 34000, Serbia

Location

Clinical Centre Kragujevac Site 158

Kragujevac, 34000, Serbia

Location

Clinical Center Nis Site 150

Niš, 18000, Serbia

Location

Clinical Center Nis Site 160

Niš, 18000, Serbia

Location

Specialized Hospital for Neuropsychiatric Diseases "Sveti Vracevi"

Novi Kneževac, 23330, Serbia

Location

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

Bardejov, 08501, Slovakia

Location

Vavrusova Consulting s.r.o.

Bratislava, 85101, Slovakia

Location

Liptovska nemocnica s poliklinikou Liptovsky Mikulas

Liptovský Mikuláš, 03123, Slovakia

Location

PsychoLine s.r.o.

Rimavská Sobota, 97901, Slovakia

Location

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

Rožňava, 04801, Slovakia

Location

Crystal Comfort s.r.o.

Vranov nad Topľou, 09301, Slovakia

Location

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

Hlevakha, 08631, Ukraine

Location

Regional Psychoneurological Hospital #3, Dept of Primary Psych Episode

Ivano-Frankivsk, 76014, Ukraine

Location

Regional Psychoneurological Hospital #3

Ivano-Frankivsk, 76014, Ukraine

Location

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

Kharkiv, 61068, Ukraine

Location

CI Kherson Reg. Psychiatric Hospital of Kherson RC

Kherson, 73488, Ukraine

Location

CI Odesa Regional Psychiatric Hospital # 2

Komintern, 67513, Ukraine

Location

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

Lviv, 79017, Ukraine

Location

CI Odesa Regional Medical Center of Mental Health

Odesa, 65006, Ukraine

Location

CI Cherkasy Regional Psychiatric Hospital of ChRC

Smila, 20708, Ukraine

Location

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

Ternopil, 46027, Ukraine

Location

Transcarpathian Regional Narcological Dispensary

Uzhhorod, 88000, Ukraine

Location

CI O.I. Yushchenko Vinnytsia Reg. Psychoneurological Hospital

Vinnytsia, 21005, Ukraine

Location

Related Publications (6)

• 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.

  PMID: 39520655 DERIVED

• 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.

  PMID: 33915374 DERIVED

• 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.

  PMID: 33677183 DERIVED

• 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.

  PMID: 32942346 DERIVED

• 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.

  PMID: 31969269 DERIVED

• 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.

  PMID: 31628698 DERIVED

MeSH Terms

Conditions

Bipolar Disorder; Depression

Interventions

cariprazine

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Results Point of Contact

• Title: Therapeutic Area, Head
• Organization: Allergan

clinicaltrials@allergan.com

714-246-4500

Study Officials

• Willie Earley

  Allergan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2016
• First Posted: February 1, 2016
• Study Start: March 31, 2016
• Primary Completion: January 18, 2018
• Study Completion: January 18, 2018
• Last Updated: March 12, 2019
• Results First Posted: February 5, 2019

Record last verified: 2019-02

Locations

SE (11); UA (12); RO (5); CR (6); BU (6); PR (1); SL (6); US (42)