Clinical Trial Evaluating the Efficacy, Safety, and Tolerability of Cariprazine in a Dose-Reduction Paradigm in the Prevention of Relapse in Participants With Schizophrenia

A Double-Blind, Placebo-Controlled, Randomized Withdrawal, Multicenter Clinical Trial Evaluating the Efficacy, Safety, and Tolerability of Cariprazine in a Dose-Reduction Paradigm in the Prevention of Relapse in Patients With Schizophrenia

1. To evaluate the efficacy and safety of cariprazine at a target dose of 4.5 milligram per day (mg/d) compared with placebo in prevention of relapse in patients with schizophrenia
2. To evaluate the efficacy and safety of cariprazine at a target dose of 3.0 mg/d compared with placebo in prevention of relapse in patients with schizophrenia who were initially stabilized on a target dose of 4.5 mg/d

Study Overview

• Status: Terminated
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Cariprazine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 587
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Burgas, Bulgaria, 8000
    • Mental Health Centre - Prof.Dr.Ivan Temkov-Burgas
  • Kardzhali, Bulgaria, 6600
    • State Psychiatry Hospital
  • Kazanlak, Bulgaria, 6100
    • MHAT Dr. Hristo Stambolski" EOOD; Department of Psychiatry
  • Lovech, Bulgaria, 5500
    • State Psyciiatric Hospital - Lovech
  • Pleven, Bulgaria, 5800
    • UMHAT Dr. Georgi Stranski, EAD
  • Ruse, Bulgaria, 7003
    • Mental health Centre-Ruse EOOD
  • Targovishte, Bulgaria, 7700
    • MHAT-Targovishte, AD
  • Varna, Bulgaria, 9000
    • DCC Mladost M - Varna, OOD
  • Veliko Tarnovo, Bulgaria, 5000
    • Mental Health Center - Veliko Tarnovo EOOD, Veliko Tarnovo
  • Vratsa, Bulgaria, 3000
    • Mental Health Center - Vratsa EOOD, Vratsa
• Korea, Republic of
  • Busan, Korea, Republic of, 47392
    • Inje University Busan Paik Hospital
  • Busan, Korea, Republic of, 48108
    • Inje University Heaundae Paik Hospital
  • Gwangju, Korea, Republic of, 61469
    • Chonnam National University Hospital
  • Incheon, Korea, Republic of, 405-760
    • Gachon University Gil Medical Center
  • Jeju, Korea, Republic of, 63241
    • Jeju National University Hospital
• Malaysia
  • Ipoh, Malaysia, 30450
    • University Kuala Lumpur
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Center
  • Kuching, Malaysia, 93250
    • Hospital Sentosa
• Poland
  • Bydgoszcz, Poland, 85-094
    • Szpital Uniwersytecki Nr.1 im. Dr. A. Jurasza, Klinika Psychiatrii
  • Chełmno, Poland, 86-200
    • Samodzielny Publiczny Zespół Opieki Zdrowotnej
  • Gdansk, Poland, 80-546
    • Centrum Badan Klinicznych PI-House
  • Lublin, Poland, 20-589
    • Specjalistyczna Praktyka Lekarska
  • Poznan, Poland, 60744
    • Indywidualna Specjalistyczna Praktyka
• Puerto Rico
  • San Juan, Puerto Rico, 918
    • INSPIRA Clinical Research
• Romania
  • Brasov, Romania, 500079
    • Spitalul de Psihiatrie si Neurologie Brasov
  • Bucharest, Romania, 60011
    • Armys Clinical Emergency Central Hospital Prof Dr Carol Davila
  • București, Romania, 30447
    • Spitalul de Psihiatrie TITAN "Dr. Constantin Gorgoș", Bulevardul Nicolae Grigorescu, Nr. 41
  • București, Romania, 60222
    • CETTT SF Stelian Hospital
  • Targu Mures, Romania, 540142
    • Spital Clinic Judetean Tg. Mures
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia
  • Belgrade, Serbia, 11000
    • Institute of Mental Health
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center Dr. Dragisa Misovic-Dedinje
  • Kovin, Serbia, 26220
    • Special Hospital for Psychiatric Diseases "Kovin"
  • Kragujevac, Serbia, 34000
    • Clinical Centre Kragujevac
  • Kragujevac, Serbia, 3400
    • Clinical Centre Kragujevac
  • Novi Knezevac, Serbia, 23330
    • Specialized Hospital for Neuropsychiatric Diseases Sveti Vracevi
  • Novi Sad, Serbia, 21000
    • Clinic for Psychiatry, Clinical Centre of Vojvodina
• Taiwan
  • New Taipei City, Taiwan, 23142
    • Taipei Tzu Chi Hospital
  • Tainan City, Taiwan, 70428
    • National Cheng Kung University Hospital
  • Taipei City, Taiwan, 112
    • Department of Psychiatry, Taipei Veterans General Hospital, Taiwan
• Thailand
  • Mueang Nonthaburi, Thailand, 50100
    • Suan Prung Psychiatric Hospital
• Ukraine
  • Ivano-Frankivsk, Ukraine, 76014
    • Regional Psychonevrological Hospital #3
  • Kharkiv, Ukraine, 61068
    • SI Institute of Neurology, Psychiatry and Narcology of NAMSU
  • Kharkiv, Ukraine, 31068
    • Kharkiv regional clinical psychiatric hospital #3
  • Kharkiv, Ukraine, 61068
    • Institute of Neurology, Psychiatry and Narcology of the NAMS of Ukraine
  • Kyiv, Ukraine, 03049
    • Kyiv Railway Clinical Hospital #2 of Branch "Health Center" of the Public Joint Stock Company "Ukrainian Railway"v
  • Kyiv, Ukraine, 04080
    • Kyiv Regional Medical Incorporation "Psychiatry"
  • Kyiv, Ukraine, 53054
    • Geikivka multidisciplinary hospital for psychiatric care
  • Lviv, Ukraine, 79021
    • KNP of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital"
  • Odesa, Ukraine, 65006
    • Odessa Regional Medical Centre of Mental Health
  • Odesa, Ukraine, 67513
    • Odesa Regional Psychiatric Hospital No.2 of the ORC
  • Petrivka, Ukraine, 73488
    • Kherson Regional Psychiatric Institution for Psychiatric Care
  • Smila, Ukraine, 20704
    • Cherkasy regional psychiatric hospital of the CRC
  • Vinnytsia, Ukraine, 21005
    • CI O.I. Yuschenko VRPsH Depts No.14 and No.15 M.I. Pyrogov VNMU
  • Vinnytsia, Ukraine, 21005
    • VNMU
• United States
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Pillar Clinical Research
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group
    • Rogers, Arkansas, United States, 72758
      • Woodland Research Northwest, LLC
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center, Inc.
    • Bellflower, California, United States, 90706
      • CITrials - Bellflower
    • Cerritos, California, United States, 90703
      • Synexus Clinical Research US, Inc.
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research, Inc.
    • Costa Mesa, California, United States, 92626
      • California Pharmaceutical Research Institute, Inc.
    • Culver City, California, United States, 90230
      • ProScience Research Group
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Research Network, LLC.
    • Glendale, California, United States, 91206
      • Behavioral Research Specialists, LLC
    • La Habra, California, United States, 90631
      • Omega Clinical Trials
    • Lemon Grove, California, United States, 91945
      • Synergy San Diego
    • Long Beach, California, United States, 90807
      • Alliance Research
    • Oceanside, California, United States, 92056
      • Excell Research, Inc
    • Orange, California, United States, 92868
      • Orange County Neuropsychiatric Research Center, LLC
    • Pico Rivera, California, United States, 90660
      • CNRI-Los Angeles
    • San Diego, California, United States, 92103-8229
      • University of California San Diego
    • Sherman Oaks, California, United States, 91423
      • Schuster Medical Research Institute
    • Torrance, California, United States, 90502
      • Collaborative Neuroscience Research, LLC
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • Wilks & Safirstein MD PA D/B/A MD Clinical
    • Hialeah, Florida, United States, 33012
      • Southern Winds Hospital
    • Hollywood, Florida, United States, 33024
      • Research Centers of America
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research
    • Atlanta, Georgia, United States, 30328
      • Synexus Clinical Research, Inc
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta LLC
    • Dunwoody, Georgia, United States, 30338
      • Atlanta Behavioral Research, LLC
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • AMITA Health Alexian Brothers Center for Psychiatric Research
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Louisiana Clinical Research
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • CBH Health LLC
  • Nevada
    • Las Vegas, Nevada, United States, 85012
      • Altea Research
    • Las Vegas, Nevada, United States, 89102
      • Alea Research Institute
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
  • New York
    • Cedarhurst, New York, United States, 11516
      • Neurobehavioral Research, Inc.
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • New Hope Clinical Research
  • Ohio
    • Beavercreek, Ohio, United States, 45431
      • Clinical Inquest Center Ltd.
    • Columbus, Ohio, United States, 43210
      • OSY Psychiatry Department
    • Mason, Ohio, United States, 45069
      • Professional Psychiatric Services
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 23112
      • Sooner Clinical Research
  • Texas
    • Austin, Texas, United States, 78754
      • Community Clinical Research, Inc.
    • Richardson, Texas, United States, 75042
      • Pillar Clinical Research
    • Richardson, Texas, United States, 75080
      • Pillar Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 62 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of schizophrenia for a minimum of 1 year before Visit 1 (Screening).
• Ability to follow study instructions, complete study assessment tools with minimal assistance and no alteration to the assessment tools, and likely to complete all required visits.
• Participant meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for schizophrenia as determined by Structured Clinical Interview for DSM-5 (SCID-5).
• Positive and Negative Syndrome Scale (PANSS) total score >= 70 and <= 120 at Visit 1 and Visit 2 (Day 1).
• Rating of at least 4 (moderate) on at least 2 of the following 4 PANSS positive symptoms; P1: delusions; P2: conceptual disorganization; P3: hallucinatory behaviour; P6: suspiciousness/persecution at Visit 1 and Visit 2.

Exclusion Criteria:

• Currently meeting DSM-5 criteria for any of the following:
• Schizoaffective disorder, schizophreniform disorder, and other psychotic disorders
• Bipolar I and II disorder
• Autism spectrum disorder, intellectual development disorder, delirium, major/minor neurocognitive disorder
• History of meeting DSM-5 criteria for substance-related disorders (excluding caffeine-related and tobacco-related disorders) within the prior 3 months before Visit 1.
• Prior participation in any clinical trials involving experimental or investigational drugs within 6 months before Visit 1 or planned during the study.
• Female Participants who are pregnant, planning to become pregnant during the course of the study, or are currently lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cariprazine 4.5 mg/day (Open-label Treatment Period); Cariprazine 1.5 mg capsules orally once daily at Week 1, titrated to 3.0 mg capsules orally once daily at Week 2 and then titrated to 4.5 mg orally once daily from Week 3 through Week 18 in the Open-label Treatment Period.	Drug: Cariprazine; Cariprazine capsules, oral administration, once daily.
Placebo Comparator: Placebo (Double-blind Treatment Period); Cariprazine placebo-matching capsules orally once daily from Week 19 through Week 44 in Double-blind Treatment Period.	Drug: Placebo; Matching placebo capsules, oral administration, once daily.
Experimental: Cariprazine 3.0 mg/day (Double-blind Treatment Period); Cariprazine 3.0 mg capsules orally once daily from Week 19 through Week 44 in Double-blind Treatment Period.	Drug: Cariprazine; Cariprazine capsules, oral administration, once daily.
Experimental: Cariprazine 4.5 mg/day (Double-blind Treatment Period); Cariprazine 4.5 mg capsules orally once daily from Week 19 through Week 44 in Double-blind Treatment Period.	Drug: Cariprazine; Cariprazine capsules, oral administration, once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Relapse During Double-blind Treatment Period	Time to Relapse is the number of days from randomization to first relapse. Relapse is defined as any 1 of the following: Increase in Positive and Negative Syndrome Scale(PANSS) by ≥30% for participants who had total score of ≥50 at randomization or ≥10-point increased score with total score <50 at randomization [PANSS=30 questions where 1=absence of symptoms to 7=extremely severe symptom;total score=30 to 210;higher score more severe symptoms]; Increase in Clinical Global Impression-Severity (CGI-S) score by 2 or more points [1=normal to 7=among most extremely ill]; Score of >4 on 1 or more of 7 PANSS items:P1-delusions,P2-conceptual disorganization,P3-hallucinatory behavior,P6-suspiciousness,P7-hostility,G8-uncooperativeness,G14-poor impulse control; Deliberate self-injury; Initiation of treatment with mood stabilizer,antidepressant,antipsychotics or benzodiazepine that exceeds specified allowance; Psychiatric hospitalization; Exacerbation of psychiatric illness	Randomization (Week 18) to End of Treatment (Week 44)

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2018
• Primary Completion (Actual): February 11, 2021
• Study Completion (Actual): February 11, 2021

Study Registration Dates

• First Submitted: July 10, 2018
• First Submitted That Met QC Criteria: July 10, 2018
• First Posted (Actual): July 20, 2018

Study Record Updates

• Last Update Posted (Actual): April 11, 2022
• Last Update Submitted That Met QC Criteria: April 7, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Cariprazine
• Other Study ID Numbers: RGH-MD-24; 2017-000818-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing, please refer to the link below.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No