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

NCT ID: NCT02670551

Last Updated: 2019-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 488 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-17
• Study Completion Date: 2017-07-19

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.

Conditions

Bipolar Disorder; Depression

Study Design

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

Study Groups

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Cariprazine 1.5 mg

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

Group Type: EXPERIMENTAL

Cariprazine

Intervention Type: DRUG

Cariprazine 3.0 mg

Following 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.

Group Type: EXPERIMENTAL

Cariprazine

Intervention Type: DRUG

Interventions

Cariprazine

Intervention Type: DRUG

Placebo

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 --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

• 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

Clincial Director

Role: STUDY_DIRECTOR

Forest Research Institute, Inc., an affiliate of Allergan, plc

Locations

Arkansas Psychiatric Clinic Clinical Research Trials PA

Little Rock, Arkansas, United States

ATP Clinical Research, Inc.

Costa Mesa, California, United States

Synergy San Diego

Escondido, California, United States

Integrated Medical and Behavioral Associates

Glendale, California, United States

Apostle Clinical Trials, Inc.

Long Beach, California, United States

Pacific Research Partners, LLC

Oakland, California, United States

Artemis Institute for Clinical Research

San Diego, California, United States

Schuster Medical Research Institute

Sherman Oaks, California, United States

Viking Clinical Research

Temecula, California, United States

Pacific Clinical Research Medical Group

Upland, California, United States

Comprehensive Psychiatric Care

Norwich, Connecticut, United States

CNS Healthcare

Jacksonville, Florida, United States

Clinical Neuroscience Solutions, Inc

Orlando, Florida, United States

Olympian Clinical Research

Tampa, Florida, United States

Radiant Research

Atlanta, Georgia, United States

iResearch Atlanta, LLC

Decatur, Georgia, United States

Northwest Behavioral Research Center

Marietta, Georgia, United States

Carman Research

Smyrna, Georgia, United States

Psychiatric Medicine Associates, L.L.C

Skokie, Illinois, United States

Neuroscience Research Institute Inc.

Winfield, Illinois, United States

St. Charles Psychiatric Associates - Midwest Research Group

Saint Charles, Missouri, United States

Altea Research Institute

Las Vegas, Nevada, United States

Hassman Research Institute

Berlin, New Jersey, United States

Neurobehavioral Research, Inc.

Cedarhurst, New York, United States

Medical & Behavioral Health Research, PC

New York, New York, United States

Neuro-Behavioral Clinical Research

Canton, Ohio, United States

Patient Priority Clinical Sites

Cincinnati, Ohio, United States

Ohio State University Department of Psychiatry

Columbus, Ohio, United States

Midwest Clinical Research Center

Dayton, Ohio, 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

Oregon Center for Clinical Investigations

Salem, Oregon, United States

Lehigh Center for Clinical Research

Allentown, Pennsylvania, United States

Lincoln Research, LLC

Lincoln, Rhode Island, United States

Clinical Neuroscience Solutions

Memphis, Tennessee, United States

Red Oak Psychiatry Associates, PA

Houston, Texas, United States

Houston Clinical Trials, LLC

Houston, Texas, United States

Research Across America

Plano, Texas, United States

Family Psychiatry of The Woodlands

The Woodlands, Texas, United States

Alliance Research Group

Richmond, Virginia, United States

Northwest Clinical Research Center

Bellevue, Washington, United States

Core Clinical Research

Kirkland, Washington, United States

Summit Research Network Seattle

Seattle, Washington, United States

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

Burgas, , Bulgaria

SPH - Kardzhali, EOOD

Kardzhali, , Bulgaria

MHAT "Dr. Hristo Stambolski", EOOD

Kazanlak, , Bulgaria

State Psychiatric Hospital - Lovech

Lovech, , Bulgaria

UMHAT 'Dr. Georgi Stranski', EAD

Pleven, , Bulgaria

UMHAT "Sv. Georgi", EAD

Plovdiv, , Bulgaria

MHC - Ruse, EOOD

Rousse, , Bulgaria

MHATNP "Sv.Naum", EAD

Sofia, , Bulgaria

UMHAT "Alexandrovska" EAD

Sofia, , Bulgaria

Military Medical Academy - MHAT - Sofia

Sofia, , Bulgaria

Medical Centre "Doverie" AD

Sofia, , Bulgaria

MHAT-Targovishte, AD

Targovishte, , Bulgaria

DCC "Mladost M" - Varna, OOD

Varna, , Bulgaria

Marienthal Center of Psychiatry and Psychology

Tallinn, , Estonia

West Tallinn Central Hospital

Tallinn, , Estonia

Tartu University Hospital

Tartu, , Estonia

Romuvos klinika, UAB

Kaunas, , Lithuania

Neuromeda, JSC

Kaunas, , Lithuania

Republican Kaunas Hospital Psychiatry Clinic Mariu Division, Public Institution

Kaunas, , Lithuania

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, , Lithuania

232Antakalnis Psychiatric Consultation Center, Public Institution

Vilnius, , Lithuania

Podlaskie Centrum Psychogeriatrii

Bialystok, , Poland

Przychodnia Srodmiescie Sp. z o. o.

Bydgoszcz, , Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS

Leszno, , Poland

Clinical Best Solutions

Lublin, , Poland

Specjalistyczna Praktyka Lekarska Marek Domański

Lublin, , Poland

NZOZ Syntonia

Pruszcz Gdański, , Poland

Torunskie Centrum Psychiatrii Neuromed

Torun, , Poland

INSPIRA Clinical Research

San Juan, , Puerto Rico

Countries

United States; Bulgaria; Estonia; Lithuania; Poland; Puerto Rico

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 W, Burgess MV, Rekeda L, Dickinson R, Szatmari B, Nemeth G, McIntyre RS, Sachs GS, Yatham LN. Cariprazine Treatment of Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Phase 3 Study. Am J Psychiatry. 2019 Jun 1;176(6):439-448. doi: 10.1176/appi.ajp.2018.18070824. Epub 2019 Mar 8.

Reference Type: DERIVED

PMID: 30845817 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-000757-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RGH-MD-54

Identifier Type: -

Identifier Source: org_study_id