The Objective of This Study is to Evaluate the Efficacy, Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy (ADT) in Patients With Major Depressive Disorder (MDD) Who Have Had an Inadequate Response to Antidepressants Alone

A Double-Blind, Placebo-Controlled Study of Cariprazine as an Adjunct to Antidepressants in the Treatment of Patients With Major Depressive Disorder Who Have Had an Inadequate Response to Antidepressants Alone

The objective of this study is to evaluate the efficacy, safety and tolerability of cariprazine as an adjunctive treatment to antidepressant therapy (ADT) in patients with MDD who have had an inadequate response to antidepressants alone.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Cariprazine; Drug: Placebo; Drug: Antidepressant Therapy (ADT)

• Study Type: Interventional
• Enrollment (Actual): 752
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Chatham, Ontario, Canada, N7L 1C1
      • Chatham-Kent Clinical Trials /ID# 235707
    • Ottawa, Ontario, Canada, K1C 1T1
      • Introspect Clinical Research Centre /ID# 235987
    • Ottawa, Ontario, Canada, K1Z 1G3
      • Recherches Neuro-Hippocampe Inc. d/b/a Ottawa Memory Clinic /ID# 235890
  • Quebec
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • Diex Recherche Sherbrooke Inc. /ID# 234385
• Czechia
  • Brno, Czechia, 602 00
    • Saint Anne s.r.o. /ID# 235060
  • Brno, Czechia, 615 00
    • MUDr. Marta Holanova /ID# 235126
  • Hradec Kralove, Czechia, 503 41
    • Neuropsychiatriehk s.r.o. /ID# 236195
  • Plzen, Czechia, 301 00
    • A-SHINE s.r.o. /ID# 236370
  • Prague 10, Czechia, 100 00
    • CLINTRIAL s.r.o. /ID# 237794
  • Praha, Czechia, 186 00
    • INEP medical s.r.o. /ID# 236291
  • Praha, Hlavni Mesto
    • Praha 6, Praha, Hlavni Mesto, Czechia, 160 00
      • Medical Services Prague /ID# 235109
• Finland
  • Helsinki, Finland, 00260
    • Helsingin psykiatripalvelu /ID# 235090
  • Helsinki, Finland, 00270
    • Mederon Oy /ID# 235057
  • Kuopio, Finland, 70100
    • Savon Psykiatripalvelu Oy /ID# 235028
  • Oulu, Finland, 90100
    • Oulu Mentalcare Oy /ID# 235089
  • Rauma, Finland, 26100
    • Satakunnan Psykiatripalvelu Oy /ID# 234936
  • Tampere, Finland, 33200
    • Psykiatri- ja psykologikeskus Mentoria /ID# 235091
• Poland
  • Bia?ystok, Poland, 15-464
    • Wlokiennicza Med /ID# 235105
  • Bialystok, Poland, 15-404
    • MlynowaMed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk /ID# 235065
  • Bydgoszcz, Poland, 85-080
    • Przychodnia Srodmiescie Sp. Z o.o. /ID# 236197
  • Bydgoszcz, Poland, 85-156
    • Med-Art /Id# 234986
  • Chelmno, Poland, 86-200
    • Poradnia Zdrowia Psychicznego /ID# 234750
  • Kielce, Poland, 25-411
    • Centrum Zdrowia Psychicznego BioMed - Jan Latala /ID# 235064
  • Leszno, Poland, 64-100
    • Nzop Mentis /Id# 235062
  • Lublin, Poland, 20-831
    • Centrum Medyczne Neuromedica /ID# 235615
  • Sosnowiec, Poland, 41-200
    • Krzysztof Klinke Prywatny Gabinet Psychiatryczny /ID# 235061
  • Torun, Poland, 87-100
    • Gabinet Lekarski Torunskie Centrum Psychiatrii Neuromed /ID# 235001
  • Torun, Poland, 87-100
    • Osrodek Badan Klinicznych Clinsante /ID# 234990
  • Wroclaw, Poland, 50-227
    • Przychodnia Lekarsko-Psychologiczna PERSONA /ID# 235007
  • Lodzkie
    • Belchatow, Lodzkie, Poland, 97-400
      • Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski /ID# 234851
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-109
      • Centrum Medyczne Luxmed /ID# 235110
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-546
      • Centrum Badan Klinicznych PI-House sp. z o.o. /ID# 237466
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland, 70-486
      • Zachodniopomorski Instytut Psychoterapii /ID# 236549
• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • INSPIRA Clinical Research /ID# 234542
• Serbia
  • Belgrade, Serbia, 11000
    • Bel Medic - General Hospital /ID# 236171
  • Belgrade, Serbia, 11040
    • Clinical Hospital Center Dr Dragisa Misovic - Dedinje /ID# 234299
  • Belgrade, Serbia, 11108
    • Institute of Mental Health /ID# 236481
  • Kovin, Serbia, 26220
    • Special Hospital for Psychiatric Diseases Kovin /ID# 234691
  • Novi Knezevac, Serbia, 23330
    • Specialized Hospital for Neuropsychiatric Diseases Sveti Vracevi /ID# 234716
  • Vršac, Serbia, 13000
    • Special Psychiatric Hospital /ID# 235152
  • Beograd
    • Belgrade, Beograd, Serbia, 11000
      • Military Medical Academy /ID# 237062
    • Belgrade, Beograd, Serbia, 11000
      • University Clinical Center Serbia /ID# 237747
  • Nisavski Okrug
    • NIS, Nisavski Okrug, Serbia, 18000
      • University Clinical Center of Nis /ID# 236973
  • Sumadijski Okrug
    • Kragujevac, Sumadijski Okrug, Serbia, 34000
      • University Clinical Center Kragujevac /ID# 237750
    • Kragujevac, Sumadijski Okrug, Serbia, 34000
      • University Clinical Center Kragujevac /ID# 237752
    • Kragujevac, Sumadijski Okrug, Serbia, 34000
      • University Clinical Center Kragujevac /ID# 237753
• Slovakia
  • Bratislava, Slovakia, 811 07
    • J&J SMART Ltd. /ID# 235902
  • Bratislava, Slovakia, 820 07
    • Psychiatrická ambulancia MENTUM /ID# 235020
  • Bratislava, Slovakia, 851 01
    • Vavrusova Consulting s.r.o. /ID# 235022
  • Kosice, Slovakia, 040 01
    • EPAMED s.r.o. /ID# 234830
  • Liptovsky Mikulas, Slovakia, 031 23
    • Liptovska nemocnica s poliklinikou MUDr. Ivana Stodolu Liptovsky Mikulas /ID# 235216
  • Rimavska Sobota, Slovakia, 979 01
    • Psycholine s.r.o /ID# 235081
  • Svidnik, Slovakia, 089 01
    • Centrum zdravia R.B.K sro /ID# 235085
  • Vranov nad Toplou, Slovakia, 093 01
    • Crystal Comfort s.r.o. /ID# 235083
• United States
  • Alabama
    • Dothan, Alabama, United States, 36303
      • Harmonex /ID# 236936
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group /ID# 236349
  • California
    • Anaheim, California, United States, 92804-3738
      • California Pharmaceutical Research Institute /ID# 236731
    • Colton, California, United States, 92324
      • Axiom Research /ID# 236267
    • Costa Mesa, California, United States, 92627
      • Global Clinical Trials /ID# 235059
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Research - Orange County /ID# 237637
    • Glendale, California, United States, 91206-4261
      • Behavioral Research Specialists, LLC /ID# 236622
    • Imperial, California, United States, 92251-9401
      • Sun Valley Research Center /ID# 236560
    • Oceanside, California, United States, 92054
      • North County Clinical Research /ID# 235014
    • Oceanside, California, United States, 92056
      • Excell Research, Inc /ID# 237717
    • Orange, California, United States, 92868
      • NRC Research Institute /ID# 234632
    • Redlands, California, United States, 92374-4555
      • Anderson Clinical Research /ID# 236624
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research /ID# 237408
    • Sherman Oaks, California, United States, 91403-2109
      • California Neuroscience Research Medical Group, Inc. /ID# 236636
    • Sherman Oaks, California, United States, 91403
      • Schuster Medical Research Institute /ID# 236445
    • Upland, California, United States, 91786-3676
      • Pacific Clinical Research Management Group /ID# 234378
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • MCB Clinical Research Centers /ID# 236927
  • Connecticut
    • Cromwell, Connecticut, United States, 06416
      • CT Clinical Research /ID# 234638
  • Florida
    • Fort Lauderdale, Florida, United States, 33319
      • Innovative Clinical Research /ID# 235186
    • Fort Myers, Florida, United States, 33912
      • Gulfcoast Clinical Research Center /ID# 236280
    • Miami, Florida, United States, 33133
      • Innova Clinical Trials /ID# 237376
    • Miami, Florida, United States, 33183
      • International Research Associates, LLC /ID# 237410
    • Orange City, Florida, United States, 32763
      • Medical Research Group of Central Florida /ID# 237326
    • Orlando, Florida, United States, 32801-2986
      • Clinical Neuroscience Solutions, Inc /ID# 236604
    • Palm Bay, Florida, United States, 32905
      • Space Coast Neuropsychiatric Research Institute /ID# 235766
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research /ID# 234696
    • Atlanta, Georgia, United States, 30341
      • Institute for Advanced Medical Research /ID# 234992
    • Savannah, Georgia, United States, 31405
      • iResearch Savannah /ID# 236082
    • Smyrna, Georgia, United States, 30082-2629
      • Iris Research Inc. /ID# 234995
  • Illinois
    • Naperville, Illinois, United States, 60563
      • AMR Conventions Research /ID# 236262
  • Kansas
    • Prairie Village, Kansas, United States, 66208
      • Collective Medical Research /ID# 236397
  • Massachusetts
    • Boston, Massachusetts, United States, 02131-2515
      • Boston Clinical Trials /ID# 236558
    • New Bedford, Massachusetts, United States, 02740
      • BTC of New Bedford /ID# 236381
    • South Weymouth, Massachusetts, United States, 02190
      • The Coastal Research Associates Inc /ID# 235056
    • Springfield, Massachusetts, United States, 01103
      • Sisu at Renaissance Medical Group /ID# 236198
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002-3008
      • Center for Emotional Fitness /ID# 236630
    • Toms River, New Jersey, United States, 08755-6434
      • Bio Behavioral Health, Inc /ID# 238209
  • New York
    • Brooklyn, New York, United States, 11235-5660
      • SPRI Clinical Trails /ID# 236657
    • Mount Kisco, New York, United States, 10549-3028
      • Bioscience Research /ID# 234961
    • New York, New York, United States, 10017-1921
      • Fieve Clinical Research, Inc. /ID# 236632
    • New York, New York, United States, 10128
      • Eastside Comprehensive Medical Center LLC /ID# 236094
  • North Carolina
    • Hickory, North Carolina, United States, 28601
      • Clinical Trials America /ID# 237636
  • Ohio
    • Avon Lake, Ohio, United States, 44012
      • Quest Therapeutics of Avon Lake /ID# 236281
    • Cincinnati, Ohio, United States, 45215-2123
      • Patient Priority Clinical Sites, LLC /ID# 236743
    • Middleburg Heights, Ohio, United States, 44130
      • North Star Medical Research LL /ID# 235076
    • West Chester, Ohio, United States, 45069
      • CincyScience /ID# 236387
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute (LHSI) /ID# 237612
    • Tulsa, Oklahoma, United States, 74136
      • Central States Research /ID# 238295
  • Oregon
    • Salem, Oregon, United States, 97301
      • Oregon Ctr for Clin Inv /ID# 237463
  • Pennsylvania
    • Plymouth Meeting, Pennsylvania, United States, 19462
      • Keystone Clinical Studies LLC /ID# 238153
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Psychiatric Consultants PC /ID# 235838
    • Memphis, Tennessee, United States, 38119-5202
      • Research Strategies of Memphis /ID# 236629
  • Texas
    • Friendswood, Texas, United States, 77546
      • Earle Research /ID# 236660
    • Plano, Texas, United States, 75093
      • AIM Trials /ID# 236366
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc /ID# 237864
    • The Woodlands, Texas, United States, 77381
      • Family Psychiatry of The Woodlands /ID# 236423
  • Vermont
    • Woodstock, Vermont, United States, 05091-9795
      • Woodstock Research Center /ID# 236653
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • SSM Health Dean Medical Group /ID# 238103

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent has been obtained.
• Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable (eg, Written Authorization for Use and Release of Health and Research Study Information [US sites] and written Data Protection consent [EU sites]).
• Participant must be an outpatient at the time of Visit 1 (Screening).
• Participant meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for MDD based on Structured Clinical Interview for DSM-5 (SCID-5), with a current major depressive episode of at least 8 weeks and not exceeding 24 months in duration at Visit 1/Screening. A diagnosis of MDD with psychotic features will be acceptable.
• Diagnosis of MDD confirmed through a formal adjudication process.
• Participant demonstrates ability to follow study instructions and likely to complete all required visits.
• Participant must have an inadequate response, as measured by the modified antidepressant treatment response questionnaire (ATRQ), to 1 to 3 antidepressants administered during the current episode at an adequate dose (as per package insert) and for at least 6 weeks duration, with at least one dose escalation during the current depressive episode.
• Only one antidepressant (of sufficient dose per package insert and taken for at least 6 weeks) will be allowed at randomization and Participants must agree to continue taking the same ADT dosing regimen through completion of Visit 6/early termination (ET). Participants who are taking more than one antidepressant at Screening, regardless of the indication, will need to discontinue all other antidepressants prior to Visit 2 (Baseline).
• Male and female Participants must agree to use a medically acceptable and highly effective method of birth control during the course of the entire study.
• Women of childbearing potential (only) must have a negative serum β-human chorionic gonadotropin pregnancy test prior to Visit 2.

Exclusion Criteria:

• Diagnosis of any current psychiatric diagnosis other than MDD (including those with current intellectual development disability) with the exception of specific phobias.
• Participant has a history of intolerance or hypersensitivity to cariprazine or other drugs of the same class or to rescue medications.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo + ADT; Cariprazine matching placebo capsules, orally, once daily in addition to their ongoing antidepressant therapy (ADT) [same antidepressant and dose of ADT they were on at the Baseline] during the Double-blind Treatment Period, up to Week 6.	Drug: Placebo; Placebo supplied in capsules; Drug: Antidepressant Therapy (ADT); ADT as prescribed by the physician per standard of care in clinical practice.
Experimental: Cariprazine 1.5 mg/day + ADT; Cariprazine 1.5 mg capsules, orally, once daily in addition to their ongoing ADT (same antidepressant and dose of ADT they were on at the Baseline) during the Double-blind Treatment Period, up to Week 6.	Drug: Cariprazine; Cariprazine supplied in capsules; Other Names: VRAYLAR®; Drug: Antidepressant Therapy (ADT); ADT as prescribed by the physician per standard of care in clinical practice.
Experimental: Cariprazine 3 mg/day + ADT; Cariprazine 1.5 mg capsules, orally, once daily for 2 weeks starting at the Baseline, titrated to 3.0 mg capsules, orally, once daily from Week 2 through Week 6 in addition to their ongoing ADT (same antidepressant and dose of ADT) during the Double-blind Treatment Period, up to Week 6.	Drug: Cariprazine; Cariprazine supplied in capsules; Other Names: VRAYLAR®; Drug: Antidepressant Therapy (ADT); ADT as prescribed by the physician per standard of care in clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 6 in the MADRS (Montgomery-Åsberg Depression Rating Scale) Total Score	The 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 item 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. The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change from Baseline indicates improvement. Mixed-effects Model for Repeated Measures (MMRM) was used for analyses.	Baseline and Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 6 in the Clinical Global Impressions-Severity (CGI-S) Score	The CGI-S is a clinician-rated scale used to rate the severity of the participant's current state of mental illness compared with MDD population. The participant was rated on a scale from 1 to 7, where 1=normal, not at all ill and 7=among the most extremely ill participants. Higher score indicates worsening of mental illness. A negative change from Baseline indicates improvement. MMRM was used for analyses.	Baseline and Week 6

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

Helpful Links

• VRAYLAR® (cariprazine) capsules prescribing information.

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2018
• Primary Completion (Actual): September 6, 2021
• Study Completion (Actual): September 6, 2021

Study Registration Dates

• First Submitted: November 9, 2018
• First Submitted That Met QC Criteria: November 9, 2018
• First Posted (Actual): November 13, 2018

Study Record Updates

• Last Update Posted (Actual): September 21, 2022
• Last Update Submitted That Met QC Criteria: August 26, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: MDD
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Cariprazine; Antidepressive Agents
• Other Study ID Numbers: 3111-302-001; 2018-003164-31 (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
• product manufactured in and exported from the U.S.: No