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

Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02670551
• Other study ID #: RGH-MD-54
• Secondary ID: 2016-000757-13
• Status: Completed
• Phase: Phase 3
• Start date: March 17, 2016
• Est. completion date: July 19, 2017

Study information

• Verified date: January 2019
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 488
• Est. completion date: July 19, 2017
• Est. primary completion date: July 19, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 ß-human chorionic gonadotropin (ß-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

Related Conditions & MeSH terms

• Bipolar Disorder
• Depression
• Depressive Disorder

Intervention

Drug:
• Cariprazine

• Placebo

Locations

Country	Name	City	State
Bulgaria	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	Ruse
Bulgaria	Medical Centre "Doverie" AD	Sofia
Bulgaria	MHATNP "Sv.Naum", EAD	Sofia
Bulgaria	Military Medical Academy - MHAT - Sofia	Sofia
Bulgaria	UMHAT "Alexandrovska" EAD	Sofia
Bulgaria	MHAT-Targovishte, AD	Targovishte
Bulgaria	DCC "Mladost M" - Varna, OOD	Varna
Estonia	Marienthal Center of Psychiatry and Psychology	Tallinn
Estonia	West Tallinn Central Hospital	Tallinn
Estonia	Tartu University Hospital	Tartu
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas Clinics	Kaunas
Lithuania	Neuromeda, JSC	Kaunas
Lithuania	Republican Kaunas Hospital Psychiatry Clinic Mariu Division, Public Institution	Kaunas
Lithuania	Romuvos klinika, UAB	Kaunas
Lithuania	232Antakalnis Psychiatric Consultation Center, Public Institution	Vilnius
Poland	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 Domanski	Lublin
Poland	NZOZ Syntonia	Pruszcz Gdanski
Poland	Torunskie Centrum Psychiatrii Neuromed	Torun
Puerto Rico	INSPIRA Clinical Research	San Juan
United States	Lehigh Center for Clinical Research	Allentown	Pennsylvania
United States	Radiant Research	Atlanta	Georgia
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Hassman Research Institute	Berlin	New Jersey
United States	Neuro-Behavioral Clinical Research	Canton	Ohio
United States	Neurobehavioral Research, Inc.	Cedarhurst	New York
United States	Patient Priority Clinical Sites	Cincinnati	Ohio
United States	Ohio State University Department of Psychiatry	Columbus	Ohio
United States	ATP Clinical Research, Inc.	Costa Mesa	California
United States	Midwest Clinical Research Center	Dayton	Ohio
United States	iResearch Atlanta, LLC	Decatur	Georgia
United States	Synergy San Diego	Escondido	California
United States	Integrated Medical and Behavioral Associates	Glendale	California
United States	Houston Clinical Trials, LLC	Houston	Texas
United States	Red Oak Psychiatry Associates, PA	Houston	Texas
United States	CNS Healthcare	Jacksonville	Florida
United States	Core Clinical Research	Kirkland	Washington
United States	Altea Research Institute	Las Vegas	Nevada
United States	Lincoln Research, LLC	Lincoln	Rhode Island
United States	Arkansas Psychiatric Clinic Clinical Research Trials PA	Little Rock	Arkansas
United States	Apostle Clinical Trials, Inc.	Long Beach	California
United States	Northwest Behavioral Research Center	Marietta	Georgia
United States	Clinical Neuroscience Solutions	Memphis	Tennessee
United States	Medical & Behavioral Health Research, PC	New York	New York
United States	Comprehensive Psychiatric Care	Norwich	Connecticut
United States	Pacific Research Partners, LLC	Oakland	California
United States	IPS Research Company	Oklahoma City	Oklahoma
United States	Sooner Clinical Research	Oklahoma City	Oklahoma
United States	Clinical Neuroscience Solutions, Inc	Orlando	Florida
United States	Research Across America	Plano	Texas
United States	Oregon Center for Clinical Investigations, Inc.	Portland	Oregon
United States	Alliance Research Group	Richmond	Virginia
United States	St. Charles Psychiatric Associates - Midwest Research Group	Saint Charles	Missouri
United States	Oregon Center for Clinical Investigations	Salem	Oregon
United States	Artemis Institute for Clinical Research	San Diego	California
United States	Summit Research Network Seattle	Seattle	Washington
United States	Schuster Medical Research Institute	Sherman Oaks	California
United States	Psychiatric Medicine Associates, L.L.C	Skokie	Illinois
United States	Carman Research	Smyrna	Georgia
United States	Olympian Clinical Research	Tampa	Florida
United States	Viking Clinical Research	Temecula	California
United States	Family Psychiatry of The Woodlands	The Woodlands	Texas
United States	Pacific Clinical Research Medical Group	Upland	California
United States	Neuroscience Research Institute Inc.	Winfield	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Forest Laboratories

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Week 6	The Clinical Global Impressions-Severity (CGI-S) is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of other participants 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 participants." A negative change from Baseline indicates improvement.	Baseline (Week 0) to Week 6