Clinical trial NCT02670538: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bipolar Disorder
Depression
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
First posted: 2016-02-01
Enrollment: 493
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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
  * 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 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:

  * 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

Primary outcomes:
measure: Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: Baseline (Week 0) to Week 6
Secondary outcomes:
measure: Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score
timeFrame: Baseline (Week 0) to Week 6
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Dothan
country: United States
facility: Harmonex Neuroscience Research, Inc.
state: Alabama
city: Phoenix
country: United States
facility: NoesisPharma, LLC
state: Arizona
city: Little Rock
country: United States
facility: Woodland International Research Group, LLC
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Research Center, Inc
state: California
city: Cerritos
country: United States
facility: Radiant Research
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Glendale
country: United States
facility: Behavioral Research Specialists, LLC
state: California
city: Oceanside
country: United States
facility: Excell Research, Inc.
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Washington
country: United States
facility: Comprehensive Clinical Research
state: District of Columbia
city: Coral Springs
country: United States
facility: CNS Clinical Research Group
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Lauderhill
country: United States
facility: Innovative Clinical Research, Inc.
state: Florida
city: Miami
country: United States
facility: Innova Clinical Trials, Inc.
state: Florida
city: Oakland Park
country: United States
facility: Research Centers of America, LLC
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Hoffman Estates
country: United States
facility: Alexian Brothers Center for Psychiatric Research
state: Illinois
city: Libertyville
country: United States
facility: Capstone Clinical Research
state: Illinois
city: Naperville
country: United States
facility: Baber Research Group
state: Illinois
city: Shreveport
country: United States
facility: J. Gary Booker, MD, APMC
state: Louisiana
city: Weymouth
country: United States
facility: Coastal Research Associates, Inc.
state: Massachusetts
city: Creve Coeur
country: United States
facility: Millennium Psychiatric Associates
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Clinical Trials, LLC
state: Missouri
city: Cherry Hill
country: United States
facility: Center for Emotional Fitness
state: New Jersey
city: Marlton
country: United States
facility: Pharmaceutical Research Associates, Inc.
state: New Jersey
city: Brooklyn
country: United States
facility: Brooklyn Medical Institute
state: New York
city: Brooklyn
country: United States
facility: SPRI Clinical Trials, LLC
state: New York
city: Buffalo
country: United States
facility: University at Buffalo Erie County Medical Center
state: New York
city: New York
country: United States
facility: Manhattan Behavioral Medicine
state: New York
city: New York
country: United States
facility: Eastside Comprehensive Medical Center
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Hickory
country: United States
facility: Clinical Trials of America, Inc
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati - Department of Psychiatry and Behavioral Neuroscience
state: Ohio
city: Mason
country: United States
facility: Professional Psychiatric Services
state: Ohio
city: Oklahoma City
country: United States
facility: Cutting Edge Research Group
state: Oklahoma
city: Tulsa
country: United States
facility: Tulsa Clinical Research, LLC
state: Oklahoma
city: Media
country: United States
facility: Suburban Research Associates
state: Pennsylvania
city: Charleston
country: United States
facility: Carolina Clinical Trials, Inc.
state: South Carolina
city: Houston
country: United States
facility: Houston Endoscopy and Research Center
state: Texas
city: Wichita Falls
country: United States
facility: Grayline Research Center
state: Texas
city: Bothell
country: United States
facility: Pacific Institute of Medical Sciences
state: Washington
city: Burgas
country: Bulgaria
facility: Mental Health Centre 'Prof. Dr. Ivan Temkov', EOOD
city: Kazanlak
country: Bulgaria
facility: MHAT "Dr. Hristo Stambolski", EOOD
city: Pleven
country: Bulgaria
facility: UMHAT 'Dr. Georgi Stranski', Dept. of Psychiatry
city: Plovdiv
country: Bulgaria
facility: UMHAT "Sv. Georgi", EAD
city: Varna
country: Bulgaria
facility: DCC "Mladost M" - Varna, OOD Site 188
city: Varna
country: Bulgaria
facility: DCC "Mladost M" - Varna, OOD Site 194
city: Popovača
country: Croatia
facility: Neuropsychiatric Hospital Ivan Barbot
city: Rijeka
country: Croatia
facility: Clinical Hospital Center Rijeka
city: Zagreb
country: Croatia
facility: Polyclinic Neuron
city: Zagreb
country: Croatia
facility: University Hospital Center Zagreb
city: Zagreb
country: Croatia
facility: Clinic for Psychiatry Vrapce
city: Zagreb
country: Croatia
facility: Psychiatric Hospital "Sveti Ivan"
city: San Juan
country: Puerto Rico
facility: Barbara Diaz-Hernandez MD Research, Inc.
city: Bucuresti
country: Romania
facility: Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila"
city: Bucuresti
country: Romania
facility: Spitalul de Psihiatrie Titan "Dr. Constantin Gorgos"
city: Galati
country: Romania
facility: Spitalul de Psihiatrie "Elisabeta Doamna" Galati
city: Iasi
country: Romania
facility: Institutul de Psihiatrie Socola Iasi Site 111
city: Iasi
country: Romania
facility: Institutul de Psihiatrie Socola Iasi Site 113
city: Belgrade
country: Serbia
facility: Clinic of Psychiatric Diseases "Dr Laza Lazarevic"
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Clinical Center Zvezdara
city: Belgrade
country: Serbia
facility: General Hospital Euromedic
city: Belgrade
country: Serbia
facility: Institute of Mental Health
city: Belgrade
country: Serbia
facility: Clinical Center "Dr. Dragisa Misovic"
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac Site 154
city: Kragujevac
country: Serbia
facility: Clinical Centre Kragujevac Site 158
city: Nis
country: Serbia
facility: Clinical Center Nis Site 150
city: Nis
country: Serbia
facility: Clinical Center Nis Site 160
city: Novi Knezevac
country: Serbia
facility: Specialized Hospital for Neuropsychiatric Diseases "Sveti Vracevi"
city: Bardejov
country: Slovakia
facility: Centrum zdravia R.B.K. s.r.o.
city: Bratislava
country: Slovakia
facility: Vavrusova Consulting s.r.o.
city: Liptovsky Mikulas
country: Slovakia
facility: Liptovska nemocnica s poliklinikou Liptovsky Mikulas
city: Rimavská Sobota
country: Slovakia
facility: PsychoLine s.r.o.
city: Rožňava
country: Slovakia
facility: Nemocnica s poliklinikou sv. Barbory, Roznava a.s.
city: Vranov nad Toplou
country: Slovakia
facility: Crystal Comfort s.r.o.
city: Glevakha
country: Ukraine
facility: CI of Kyiv Reg.Council Reg.Psychiatric-Narcological Medical Association
city: Ivano-Frankivsk
country: Ukraine
facility: Regional Psychoneurological Hospital #3, Dept of Primary Psych Episode
city: Ivano-Frankivsk
country: Ukraine
facility: Regional Psychoneurological Hospital #3
city: Kharkiv
country: Ukraine
facility: SI Inst.of Neurology, Psychiatry and Narcology of NAMS of Ukraine
city: Kherson
country: Ukraine
facility: CI Kherson Reg. Psychiatric Hospital of Kherson RC
city: Komintern
country: Ukraine
facility: CI Odesa Regional Psychiatric Hospital # 2
city: Lviv
country: Ukraine
facility: CI of LRC Lviv Reg. Council Lviv Reg.Clinical Psychoneurological Dispensary
city: Odesa
country: Ukraine
facility: CI Odesa Regional Medical Center of Mental Health
city: Smila
country: Ukraine
facility: CI Cherkasy Regional Psychiatric Hospital of ChRC
city: Ternopil
country: Ukraine
facility: Ternopil Reg. Communal Clinical Psychoneurological Hospital Depts of Psychiatry #2
city: Uzhgorod
country: Ukraine
facility: Transcarpathian Regional Narcological Dispensary
city: Vinnytsia
country: Ukraine
facility: CI O.I. Yushchenko Vinnytsia Reg. Psychoneurological Hospital
Study officials:
affiliation: Allergan
name: Willie Earley
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.