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

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: NCT02670538
• Other study ID #: RGH-MD-53
• Secondary ID: 2016-000756-98
• Status: Completed
• Phase: Phase 3
• Start date: March 31, 2016
• Est. completion date: January 18, 2018

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 493
• Est. completion date: January 18, 2018
• Est. primary completion date: January 18, 2018
• 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

• 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 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:

• 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

Related Conditions & MeSH terms

• Bipolar Disorder
• Depression
• Depressive Disorder

Intervention

Drug:
• Cariprazine
Cariprazine capsule one per day orally.
• Placebo
Matching placebo capsule one per day orally.

Locations

Country	Name	City	State
Bulgaria	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
Croatia	Neuropsychiatric Hospital Ivan Barbot	Popovaca
Croatia	Clinical Hospital Center Rijeka	Rijeka
Croatia	Clinic for Psychiatry Vrapce	Zagreb
Croatia	Polyclinic Neuron	Zagreb
Croatia	Psychiatric Hospital "Sveti Ivan"	Zagreb
Croatia	University Hospital Center Zagreb	Zagreb
Puerto Rico	Barbara Diaz-Hernandez MD Research, Inc.	San Juan
Romania	Spitalul de Psihiatrie Titan "Dr. Constantin Gorgos"	Bucuresti
Romania	Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila"	Bucuresti
Romania	Spitalul de Psihiatrie "Elisabeta Doamna" Galati	Galati
Romania	Institutul de Psihiatrie Socola Iasi Site 111	Iasi
Romania	Institutul de Psihiatrie Socola Iasi Site 113	Iasi
Serbia	Clinic of Psychiatric Diseases "Dr Laza Lazarevic"	Belgrade
Serbia	Clinical Center "Dr. Dragisa Misovic"	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 Kragujevac Site 154	Kragujevac
Serbia	Clinical Centre Kragujevac Site 158	Kragujevac
Serbia	Clinical Center Nis Site 150	Nis
Serbia	Clinical Center Nis Site 160	Nis
Serbia	Specialized Hospital for Neuropsychiatric Diseases "Sveti Vracevi"	Novi Knezevac
Slovakia	Centrum zdravia R.B.K. s.r.o.	Bardejov
Slovakia	Vavrusova Consulting s.r.o.	Bratislava
Slovakia	Liptovska nemocnica s poliklinikou Liptovsky Mikulas	Liptovsky Mikulas
Slovakia	PsychoLine s.r.o.	Rimavská Sobota
Slovakia	Nemocnica s poliklinikou sv. Barbory, Roznava a.s.	Rožnava
Slovakia	Crystal Comfort s.r.o.	Vranov nad Toplou
Ukraine	CI of Kyiv Reg.Council Reg.Psychiatric-Narcological Medical Association	Glevakha
Ukraine	Regional Psychoneurological Hospital #3	Ivano-Frankivsk
Ukraine	Regional Psychoneurological Hospital #3, Dept of Primary Psych Episode	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	Uzhgorod
Ukraine	CI O.I. Yushchenko Vinnytsia Reg. Psychoneurological Hospital	Vinnytsia
United States	Advanced Research Center, Inc	Anaheim	California
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Pacific Institute of Medical Sciences	Bothell	Washington
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	Radiant Research	Cerritos	California
United States	Carolina Clinical Trials, Inc.	Charleston	South Carolina
United States	Center for Emotional Fitness	Cherry Hill	New Jersey
United States	University of Cincinnati - Department of Psychiatry and Behavioral Neuroscience	Cincinnati	Ohio
United States	CNS Clinical Research Group	Coral Springs	Florida
United States	Millennium Psychiatric Associates	Creve Coeur	Missouri
United States	Harmonex Neuroscience Research, Inc.	Dothan	Alabama
United States	Collaborative Neuroscience Network, LLC	Garden Grove	California
United States	Behavioral Research Specialists, LLC	Glendale	California
United States	MD Clinical	Hallandale Beach	Florida
United States	Clinical Trials of America, Inc	Hickory	North Carolina
United States	Alexian Brothers Center for Psychiatric Research	Hoffman Estates	Illinois
United States	Houston Endoscopy and Research Center	Houston	Texas
United States	Innovative Clinical Research, Inc.	Lauderhill	Florida
United States	Capstone Clinical Research	Libertyville	Illinois
United States	Woodland International Research Group, LLC	Little Rock	Arkansas
United States	Pharmaceutical Research Associates, Inc.	Marlton	New Jersey
United States	Professional Psychiatric Services	Mason	Ohio
United States	Suburban Research Associates	Media	Pennsylvania
United States	Innova Clinical Trials, Inc.	Miami	Florida
United States	Baber Research Group	Naperville	Illinois
United States	Eastside Comprehensive Medical Center	New York	New York
United States	Manhattan Behavioral Medicine	New York	New York
United States	Research Centers of America, LLC	Oakland Park	Florida
United States	Excell Research, Inc.	Oceanside	California
United States	Cutting Edge Research Group	Oklahoma City	Oklahoma
United States	NoesisPharma, LLC	Phoenix	Arizona
United States	Finger Lakes Clinical Research	Rochester	New York
United States	St. Louis Clinical Trials, LLC	Saint Louis	Missouri
United States	J. Gary Booker, MD, APMC	Shreveport	Louisiana
United States	Collaborative Neuroscience Network, LLC	Torrance	California
United States	Tulsa Clinical Research, LLC	Tulsa	Oklahoma
United States	Comprehensive Clinical Research	Washington	District of Columbia
United States	Coastal Research Associates, Inc.	Weymouth	Massachusetts
United States	Grayline Research Center	Wichita Falls	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Forest Laboratories

Countries where clinical trial is conducted

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

Outcome

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