Clinical trial NCT02670551: Study on the Efficacy, Safety, and Tolerability of Cariprazine Relative to Placebo in Participants With Bipolar I Depression
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: 488
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 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.


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

Primary outcomes:
measure: Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Week 6
timeFrame: Baseline (Week 0) to Week 6
Secondary outcomes:
measure: Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Week 6
timeFrame: Baseline (Week 0) to Week 6
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Psychiatric Clinic Clinical Research Trials PA
state: Arkansas
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc.
state: California
city: Escondido
country: United States
facility: Synergy San Diego
state: California
city: Glendale
country: United States
facility: Integrated Medical and Behavioral Associates
state: California
city: Long Beach
country: United States
facility: Apostle Clinical Trials, Inc.
state: California
city: Oakland
country: United States
facility: Pacific Research Partners, LLC
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Sherman Oaks
country: United States
facility: Schuster Medical Research Institute
state: California
city: Temecula
country: United States
facility: Viking Clinical Research
state: California
city: Upland
country: United States
facility: Pacific Clinical Research Medical Group
state: California
city: Norwich
country: United States
facility: Comprehensive Psychiatric Care
state: Connecticut
city: Jacksonville
country: United States
facility: CNS Healthcare
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Florida
city: Tampa
country: United States
facility: Olympian Clinical Research
state: Florida
city: Atlanta
country: United States
facility: Radiant Research
state: Georgia
city: Decatur
country: United States
facility: iResearch Atlanta, LLC
state: Georgia
city: Marietta
country: United States
facility: Northwest Behavioral Research Center
state: Georgia
city: Smyrna
country: United States
facility: Carman Research
state: Georgia
city: Skokie
country: United States
facility: Psychiatric Medicine Associates, L.L.C
state: Illinois
city: Winfield
country: United States
facility: Neuroscience Research Institute Inc.
state: Illinois
city: Saint Charles
country: United States
facility: St. Charles Psychiatric Associates - Midwest Research Group
state: Missouri
city: Las Vegas
country: United States
facility: Altea Research Institute
state: Nevada
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Cedarhurst
country: United States
facility: Neurobehavioral Research, Inc.
state: New York
city: New York
country: United States
facility: Medical & Behavioral Health Research, PC
state: New York
city: Canton
country: United States
facility: Neuro-Behavioral Clinical Research
state: Ohio
city: Cincinnati
country: United States
facility: Patient Priority Clinical Sites
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Department of Psychiatry
state: Ohio
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Oklahoma City
country: United States
facility: Sooner Clinical Research
state: Oklahoma
city: Portland
country: United States
facility: Oregon Center for Clinical Investigations, Inc.
state: Oregon
city: Salem
country: United States
facility: Oregon Center for Clinical Investigations
state: Oregon
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research
state: Pennsylvania
city: Lincoln
country: United States
facility: Lincoln Research, LLC
state: Rhode Island
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions
state: Tennessee
city: Houston
country: United States
facility: Red Oak Psychiatry Associates, PA
state: Texas
city: Houston
country: United States
facility: Houston Clinical Trials, LLC
state: Texas
city: Plano
country: United States
facility: Research Across America
state: Texas
city: The Woodlands
country: United States
facility: Family Psychiatry of The Woodlands
state: Texas
city: Richmond
country: United States
facility: Alliance Research Group
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Kirkland
country: United States
facility: Core Clinical Research
state: Washington
city: Seattle
country: United States
facility: Summit Research Network Seattle
state: Washington
city: Burgas
country: Bulgaria
facility: Mental Health Centre 'Prof. Dr. Ivan Temkov', EOOD
city: Kardzhali
country: Bulgaria
facility: SPH - Kardzhali, EOOD
city: Kazanlak
country: Bulgaria
facility: MHAT "Dr. Hristo Stambolski", EOOD
city: Lovech
country: Bulgaria
facility: State Psychiatric Hospital - Lovech
city: Pleven
country: Bulgaria
facility: UMHAT 'Dr. Georgi Stranski', EAD
city: Plovdiv
country: Bulgaria
facility: UMHAT "Sv. Georgi", EAD
city: Ruse
country: Bulgaria
facility: MHC - Ruse, EOOD
city: Sofia
country: Bulgaria
facility: MHATNP "Sv.Naum", EAD
city: Sofia
country: Bulgaria
facility: UMHAT "Alexandrovska" EAD
city: Sofia
country: Bulgaria
facility: Military Medical Academy - MHAT - Sofia
city: Sofia
country: Bulgaria
facility: Medical Centre "Doverie" AD
city: Targovishte
country: Bulgaria
facility: MHAT-Targovishte, AD
city: Varna
country: Bulgaria
facility: DCC "Mladost M" - Varna, OOD
city: Tallinn
country: Estonia
facility: Marienthal Center of Psychiatry and Psychology
city: Tallinn
country: Estonia
facility: West Tallinn Central Hospital
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Kaunas
country: Lithuania
facility: Romuvos klinika, UAB
city: Kaunas
country: Lithuania
facility: Neuromeda, JSC
city: Kaunas
country: Lithuania
facility: Republican Kaunas Hospital Psychiatry Clinic Mariu Division, Public Institution
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas Clinics
city: Vilnius
country: Lithuania
facility: 232Antakalnis Psychiatric Consultation Center, Public Institution
city: Białystok
country: Poland
facility: Podlaskie Centrum Psychogeriatrii
city: Bydgoszcz
country: Poland
facility: Przychodnia Srodmiescie Sp. z o. o.
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Leszno
country: Poland
facility: Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS
city: Lublin
country: Poland
facility: Clinical Best Solutions
city: Lublin
country: Poland
facility: Specjalistyczna Praktyka Lekarska Marek Domański
city: Pruszcz Gdański
country: Poland
facility: NZOZ Syntonia
city: Toruń
country: Poland
facility: Torunskie Centrum Psychiatrii Neuromed
city: San Juan
country: Puerto Rico
facility: INSPIRA Clinical Research
Study officials:
affiliation: Forest Research Institute, Inc., an affiliate of Allergan, plc
name: Clincial Director
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 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.