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

NCT02670551 | Completed Phase 3 Results

• 2 other identifiers: RGH-MD-542016-000757-13
• Study Type: interventional
• Target: 488
• Locations: 6 countries
• Sites: 74

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Score at 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.

  Baseline (Week 0) to Week 6

Secondary Outcomes (1)

• Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Week 6

  Baseline (Week 0) to Week 6

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Cariprazine 1.5 mg

EXPERIMENTAL

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

Drug: Cariprazine

Cariprazine 3.0 mg

EXPERIMENTAL

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.

Drug: Cariprazine

Interventions

Cariprazine DRUG

Also known as: VRAYLAR®

Cariprazine 1.5 mg; Cariprazine 3.0 mg

Placebo DRUG

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 --Participant 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
• 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)

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: ○ 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.

Sponsors & Collaborators

• Forest Laboratories: lead

Study Sites (74)

Arkansas Psychiatric Clinic Clinical Research Trials PA

Little Rock, Arkansas, 72211, United States

Location

ATP Clinical Research, Inc.

Costa Mesa, California, 92626, United States

Location

Synergy San Diego

Escondido, California, 92025, United States

Location

Integrated Medical and Behavioral Associates

Glendale, California, 91204, United States

Location

Apostle Clinical Trials, Inc.

Long Beach, California, 90813, United States

Location

Pacific Research Partners, LLC

Oakland, California, 94612, United States

Location

Artemis Institute for Clinical Research

San Diego, California, 92103, United States

Location

Schuster Medical Research Institute

Sherman Oaks, California, 91403, United States

Location

Viking Clinical Research

Temecula, California, 92591, United States

Location

Pacific Clinical Research Medical Group

Upland, California, 91786, United States

Location

Comprehensive Psychiatric Care

Norwich, Connecticut, 06360, United States

Location

CNS Healthcare

Jacksonville, Florida, 32256, United States

Location

Clinical Neuroscience Solutions, Inc

Orlando, Florida, 32801, United States

Location

Olympian Clinical Research

Tampa, Florida, 33609, United States

Location

Radiant Research

Atlanta, Georgia, 30328, United States

Location

iResearch Atlanta, LLC

Decatur, Georgia, 30030, United States

Location

Northwest Behavioral Research Center

Marietta, Georgia, 30060, United States

Location

Carman Research

Smyrna, Georgia, 30080, United States

Location

Psychiatric Medicine Associates, L.L.C

Skokie, Illinois, 60076, United States

Location

Neuroscience Research Institute Inc.

Winfield, Illinois, 60190, United States

Location

St. Charles Psychiatric Associates - Midwest Research Group

Saint Charles, Missouri, 63304, United States

Location

Altea Research Institute

Las Vegas, Nevada, 89102, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

Neurobehavioral Research, Inc.

Cedarhurst, New York, 11516, United States

Location

Medical & Behavioral Health Research, PC

New York, New York, 10023, United States

Location

Neuro-Behavioral Clinical Research

Canton, Ohio, 44718, United States

Location

Patient Priority Clinical Sites

Cincinnati, Ohio, 45215, United States

Location

Ohio State University Department of Psychiatry

Columbus, Ohio, 43210, United States

Location

Midwest Clinical Research Center

Dayton, Ohio, 45417, United States

Location

IPS Research Company

Oklahoma City, Oklahoma, 73103, United States

Location

Sooner Clinical Research

Oklahoma City, Oklahoma, 73112, United States

Location

Oregon Center for Clinical Investigations, Inc.

Portland, Oregon, 97214, United States

Location

Oregon Center for Clinical Investigations

Salem, Oregon, 97301, United States

Location

Lehigh Center for Clinical Research

Allentown, Pennsylvania, 18104, United States

Location

Lincoln Research, LLC

Lincoln, Rhode Island, 02865, United States

Location

Clinical Neuroscience Solutions

Memphis, Tennessee, 38119, United States

Location

Red Oak Psychiatry Associates, PA

Houston, Texas, 77090, United States

Location

Houston Clinical Trials, LLC

Houston, Texas, 77098, United States

Location

Research Across America

Plano, Texas, 75093, United States

Location

Family Psychiatry of The Woodlands

The Woodlands, Texas, 77381, United States

Location

Alliance Research Group

Richmond, Virginia, 23230, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Core Clinical Research

Kirkland, Washington, 98033, United States

Location

Summit Research Network Seattle

Seattle, Washington, 98104, United States

Location

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

Burgas, 8000, Bulgaria

Location

SPH - Kardzhali, EOOD

Kardzhali, 6600, Bulgaria

Location

MHAT "Dr. Hristo Stambolski", EOOD

Kazanlak, 6100, Bulgaria

Location

State Psychiatric Hospital - Lovech

Lovech, 5500, Bulgaria

Location

UMHAT 'Dr. Georgi Stranski', EAD

Pleven, 5800, Bulgaria

Location

UMHAT "Sv. Georgi", EAD

Plovdiv, 4000, Bulgaria

Location

MHC - Ruse, EOOD

Rousse, 7003, Bulgaria

Location

MHATNP "Sv.Naum", EAD

Sofia, 1113, Bulgaria

Location

UMHAT "Alexandrovska" EAD

Sofia, 1431, Bulgaria

Location

Military Medical Academy - MHAT - Sofia

Sofia, 1606, Bulgaria

Location

Medical Centre "Doverie" AD

Sofia, 1632, Bulgaria

Location

MHAT-Targovishte, AD

Targovishte, 7700, Bulgaria

Location

DCC "Mladost M" - Varna, OOD

Varna, 9020, Bulgaria

Location

Marienthal Center of Psychiatry and Psychology

Tallinn, 10617, Estonia

Location

West Tallinn Central Hospital

Tallinn, 13517, Estonia

Location

Tartu University Hospital

Tartu, 50417, Estonia

Location

Romuvos klinika, UAB

Kaunas, 44279, Lithuania

Location

Neuromeda, JSC

Kaunas, 50185, Lithuania

Location

Republican Kaunas Hospital Psychiatry Clinic Mariu Division, Public Institution

Kaunas, 53136, Lithuania

Location

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, LT-50009, Lithuania

Location

232Antakalnis Psychiatric Consultation Center, Public Institution

Vilnius, 10204, Lithuania

Location

Podlaskie Centrum Psychogeriatrii

Bialystok, 15-756, Poland

Location

Przychodnia Srodmiescie Sp. z o. o.

Bydgoszcz, 85-080, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS

Leszno, 64-100, Poland

Location

Clinical Best Solutions

Lublin, 20-045, Poland

Location

Specjalistyczna Praktyka Lekarska Marek Domański

Lublin, 20-442, Poland

Location

NZOZ Syntonia

Pruszcz Gdański, 83-000, Poland

Location

Torunskie Centrum Psychiatrii Neuromed

Torun, 87-100, Poland

Location

INSPIRA Clinical Research

San Juan, 00918, Puerto Rico

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 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.

  PMID: 30845817 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

• Clincial Director

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

  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 17, 2016
• Primary Completion: July 19, 2017
• Study Completion: July 19, 2017
• Last Updated: January 30, 2019
• Results First Posted: January 30, 2019

Record last verified: 2019-01

Locations

ES (3); US (44); PR (1); BU (13); PL (8); LI (5)