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

• Study Type: Interventional
• Enrollment (Actual): 759
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Kardzhali, Bulgaria, 6600
    • State Psychiatry Hospital-Kardzhali; Third Male Department /ID# 234625
  • Kazanlak, Bulgaria, 6100
    • MHAT Dr. Hristo Stambolski EOOD; Hospital Pharmacy /ID# 234773
  • Pleven, Bulgaria, 5800
    • UMHAT Dr Georgi Stranski EAD /ID# 237828
  • Plovdiv, Bulgaria, 4000
    • Medical Center Mentalcare OOD /ID# 234934
  • Plovdiv, Bulgaria, 4002
    • Clinic of Psychiatry /ID# 235878
  • Ruse, Bulgaria, 7003
    • Mental health Centre-Ruse EOOD /ID# 234775
  • Sofia, Bulgaria, 1113
    • Medical Center Sveti Naum EOOD /ID# 236069
  • Sofia, Bulgaria, 1510
    • Medical Center Hera EOOD /ID# 235859
  • Sofia, Bulgaria, 1632
    • Medical complex Doverie /ID# 238307
  • Targovishte, Bulgaria, 7700
    • Medical Centre - VAS OOD /ID# 235719
  • Varna, Bulgaria, 9020
    • Diagnostic consultative center Mladost M /ID# 236253
  • Varna, Bulgaria, 9020
    • Diagnostic consultative center Mladost M /ID# 236254
  • Veliko Tarnovo, Bulgaria, 5000
    • Mental Health Center - Veliko Tarnovo EOOD Veliko Tarnovo /ID# 236078
  • Vratsa, Bulgaria, 3000
    • Mental Health Center - Vratsa EOOD Hospital Pharmacy /ID# 235960
  • Sofia
    • Sofiya, Sofia, Bulgaria, 1431
      • UMHAT Alexandrovska EAD /ID# 237834
• Estonia
  • Tallinn, Estonia, 10617
    • West Tallinn Central Hospital /ID# 237078
  • Tallinn, Estonia, 11315
    • Marienthali Kliinik /ID# 235677
  • Tartu, Estonia, 50406
    • OU Jaanson and Laane /ID# 234985
  • Tartumaa
    • Tartu Linn, Tartumaa, Estonia, 50406
      • Tartu University Hospital /ID# 237079
• Germany
  • Berlin, Germany, 10245
    • Private Practice - Dr. Thomsen /ID# 235713
  • Berlin, Germany, 10629
    • Emovis GmbH /ID# 235010
  • Berlin, Germany, 12209
    • MVZ LIO Berlin /ID# 235711
  • Berlin, Germany, 13156
    • BAG Prof. Dr. Kunte / Dr. sc. med. A. Schulze /ID# 235970
  • Berlin, Germany, 13187
    • Arztpraxis Dr Kirsten Hahn /ID# 235958
  • Chemnitz, Germany, 09116
    • Klinikum Chemnitz gGmbH /ID# 237758
  • Westerstede, Germany, 26655
    • Studienzentrum Nord-West /ID# 236357
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60590
      • Universitaetsklinikum Frankfurt /ID# 237292
• Hungary
  • Budapest, Hungary, 1033
    • Clinexpert Kft /ID# 237266
  • Budapest, Hungary, 1084
    • Jozsefvarosi Szent Kozma Egeszsegugyi Kozpont /ID# 235095
  • Budapest, Hungary, 1085
    • Semmelweis Egyetem /ID# 237096
  • Budapest, Hungary, 1135
    • Nyiro Gyula Orszagos Pszichiatriai és Addiktologiai Intezet /ID# 235912
  • Budapest, Hungary, 1137
    • Varoskapu Rendelo - Processus Kft. /ID# 235170
  • Bacs-Kiskun
    • Kalocsa, Bacs-Kiskun, Hungary, 6300
      • Bacs-Kiskun Megyei Oktatokorhaz Szent-Kereszt Korhaz /ID# 235974
  • Baranya
    • Pecs, Baranya, Hungary, 7627
      • PsychoTech Kft. /ID# 235008
  • Heves
    • Gyöngyös, Heves, Hungary, 3200
      • Bugat Pal Korhaz /ID# 238145
  • Komarom-Esztergom
    • Tatabanya, Komarom-Esztergom, Hungary, 2800
      • Szent Borbala Korhaz /ID# 238293
  • Pest
    • Budapest, Pest, Hungary, 1036
      • Obudai Egeszsegugyi Centrum Kft. /ID# 237495
• Ukraine
  • Kyiv, Ukraine, 02192
    • KNP Kyiv City Psychoneurological Hospital /ID# 235093
  • Kyiv, Ukraine, 03049
    • Kyiv Railway Clinical Hosp No.2 /ID# 237405
  • Lviv, Ukraine, 79021
    • CNE of LOR Lviv Regional Clinical Psychiatric Hospital /ID# 236270
  • Odesa, Ukraine, 65006
    • MNCE Odesa Regional Medical Center for Mental Health /ID# 235723
  • Ternopil, Ukraine, 46002
    • Ternopil University Hospital /ID# 236819
  • Vinnytsia, Ukraine, 21005
    • Vinnytsia Regional Psycho-Neurological Hospital /ID# 235178
  • Vinnytsia, Ukraine, 21005
    • Vinnytsia Regional Psycho-Neurological Hospital /ID# 235179
  • Cherkaska Oblast
    • Smila, Cherkaska Oblast, Ukraine, 20708
      • Cherkasy regional psychiatric hospital of the CRC /ID# 234513
  • Dnipropetrovska Oblast
    • Kryvbas Village, Dnipropetrovska Oblast, Ukraine, 53054
      • Geikivka multidisciplinary hospital for psychiatric care /ID# 234498
  • Ivano-Frankivska Oblast
    • Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine, 76014
      • KNP Prykarpatskyi Regional Clinical Centre of Mental Health /ID# 234999
  • Kharkivska Oblast
    • Kharkiv, Kharkivska Oblast, Ukraine, 61068
      • SI Institution Neurology Psychiatry and Narcology NAMS of Ukraine /ID# 236336
    • Kharkiv, Kharkivska Oblast, Ukraine, 61068
      • SI Institution Neurology Psychiatry and Narcology NAMS of Ukraine /ID# 236338
    • Kharkiv, Kharkivska Oblast, Ukraine, 61068
      • SI Institution Neurology Psychiatry and Narcology NAMS of Ukraine /ID# 236340
  • Khersonska Oblast
    • Stepanivka Village, Khersonska Oblast, Ukraine, 73488
      • Kherson Regional Psychiatric Institution for Psychiatric Care /ID# 234509
  • Odeska Oblast
    • Oleksandrivka Village, Odeska Oblast, Ukraine, 67513
      • Odesa regional psychiatric hospital 2 of the ORC /ID# 234505
  • Zakarpatska Oblast
    • Uzhgorod, Zakarpatska Oblast, Ukraine, 88000
      • KNP Zakarpatskyi Regional MC of Mental Health and Medicine of Dependencies /ID# 234499
• United Kingdom
  • Blackpool, United Kingdom, FY2 0JH
    • MAC Clinical Research /ID# 235938
  • Blackpool, United Kingdom, FY2 0JH
    • MAC Clinical Research /ID# 235941
  • Blackpool, United Kingdom, FY2 0JH
    • MAC Clinical Research /ID# 235945
  • Blackpool, United Kingdom, FY2 0JH
    • MAC Clinical Research /ID# 239078
  • Manchester, United Kingdom, M13 9NQ
    • MAC Clinical Research-Manchester /ID# 235940
  • Devon
    • Plymouth, Devon, United Kingdom, PL5 3JB
      • Knowle House Surgery /ID# 235025
  • Surrey
    • Chertsey, Surrey, United Kingdom, KT16 0AE
      • St. Peter's Hospital Surrey and Borders Partnership NHS FT /ID# 235725
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012-2707
      • Alea Research /ID# 234789
  • Arkansas
    • Little Rock, Arkansas, United States, 72209-7040
      • Atria Clinical Research /ID# 237988
    • Rogers, Arkansas, United States, 72758-6442
      • Woodland Research Northwest, LLC /ID# 236641
  • California
    • Anaheim, California, United States, 92804-3738
      • California Pharmaceutical Research Institute /ID# 236732
    • Anaheim, California, United States, 92805
      • Advanced Research Center /ID# 237957
    • Colton, California, United States, 92324
      • Axiom Research /ID# 236268
    • Costa Mesa, California, United States, 92626-4607
      • ATP Clinical Research, Inc /ID# 236619
    • Culver City, California, United States, 90230-6632
      • ProScience Research Group /ID# 236442
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Research - Orange County /ID# 237639
    • Irvine, California, United States, 92614
      • Irvine Clinical Research /ID# 237409
    • La Habra, California, United States, 90631-3842
      • Omega Clinical Trials LLC /ID# 238168
    • Lemon Grove, California, United States, 91945-2956
      • Synergy San Diego /ID# 236654
    • Redlands, California, United States, 92374-4555
      • Anderson Clinical Research /ID# 236627
    • San Diego, California, United States, 92123
      • Sharp Mesa Vista Hospital /ID# 235797
    • Temecula, California, United States, 92591-6200
      • Viking Clinical Research /ID# 236614
  • Florida
    • Clearwater, Florida, United States, 33756
      • Olympian Clinical Research /ID# 237417
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Hialeah, Florida, United States, 33012-5830
      • Reliable Clinical Research /ID# 234786
    • Jacksonville, Florida, United States, 32256-6039
      • CNS Healthcare - Jacksonville /ID# 238241
    • Palm Bay, Florida, United States, 32905
      • Space Coast Neuropsychiatric Research Institute /ID# 235765
    • Tampa, Florida, United States, 33606
      • University of South Florida /ID# 234386
  • Georgia
    • Alpharetta, Georgia, United States, 30022-1142
      • Institute for Advanced Medical Research /ID# 236672
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta, LLC /ID# 237389
    • Marietta, Georgia, United States, 30060
      • Psych Atlanta /ID# 235835
  • Illinois
    • Libertyville, Illinois, United States, 60048-5341
      • Capstone Clinical Research /ID# 236546
    • Lincolnwood, Illinois, United States, 60712
      • Pillar Clinical Research /ID# 235702
    • Winfield, Illinois, United States, 60190
      • NeuroPsychiatric Research Practice & Associate LTD /ID# 234636
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
      • Lake Charles Clinical Trials /ID# 237723
    • Shreveport, Louisiana, United States, 71104
      • J. Gary Booker MD APMC /ID# 234514
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Pharmasite Research, Inc. /ID# 237395
    • Gaithersburg, Maryland, United States, 20877
      • CBH Health LLC /ID# 234536
  • Michigan
    • Ann Arbor, Michigan, United States, 48105-3205
      • Michigan Clinical Research Institute /ID# 234792
    • Bloomfield Hills, Michigan, United States, 48302
      • NeuroBehavioral Medicine Group /ID# 236671
  • Mississippi
    • Flowood, Mississippi, United States, 39232-8839
      • Precise Research Centers /ID# 236598
  • Missouri
    • Saint Louis, Missouri, United States, 63132
      • Millennium Psychiatric Associates LLC /ID# 235989
  • Nebraska
    • Lincoln, Nebraska, United States, 68526-9474
      • Alivation Research /ID# 236583
  • Nevada
    • Las Vegas, Nevada, United States, 89102-1955
      • Altea Research Institute /ID# 236726
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute /ID# 237501
  • New York
    • Brooklyn, New York, United States, 11229-3576
      • Integrative Clinical Trials /ID# 236656
    • New York, New York, United States, 10036
      • Manhattan Behavioral Medicine PLLC /ID# 236314
    • Rochester, New York, United States, 14618-1609
      • Finger Lakes Clinical Research /ID# 236578
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • New Hope Clinical Research Inc. /ID# 234557
    • Raleigh, North Carolina, United States, 27609
      • Richard Weisler MD, PA & Assoc /ID# 237424
  • Ohio
    • Avon Lake, Ohio, United States, 44012
      • Quest Therapeutics of Avon Lake /ID# 236282
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Trial and Consulting /ID# 236271
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Department of Psychiatry /ID# 234583
    • West Chester, Ohio, United States, 45069
      • CincyScience /ID# 236391
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73106
      • IPS Research Company /ID# 237671
    • Oklahoma City, Oklahoma, United States, 73112
      • Sooner Clinical Research /ID# 236346
  • Oregon
    • Portland, Oregon, United States, 97214-2569
      • Oregon Center for Clinical Investigations, Inc. - Portland /ID# 236649
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104-5034
      • Lehigh Center for Clinical Research /ID# 236702
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center /ID# 235909
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Psychiatric Consultants PC /ID# 235839
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions - Memphis /ID# 237476
  • Texas
    • Austin, Texas, United States, 78737
      • Austin Clinical Trial Partners /ID# 236551
    • Austin, Texas, United States, 78759-5290
      • BioBehavioral Research of Austin /ID# 236477
    • Bellaire, Texas, United States, 77401-2928
      • Houston Clinical Trials /ID# 234442
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, LP /ID# 236275
    • Friendswood, Texas, United States, 77546
      • Earle Research /ID# 236661
    • Houston, Texas, United States, 77090-2641
      • Red Oak Psychiatry Associates /ID# 236600
    • Plano, Texas, United States, 75093
      • AIM Trials /ID# 236369
    • Richardson, Texas, United States, 75080
      • Pillar Clinical Research LLC /ID# 234465
  • Vermont
    • Woodstock, Vermont, United States, 05091
      • Neuropsychiatric Associates LLC/DBA Woodstock Research Center /ID# 236087
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center /ID# 237584
    • Everett, Washington, United States, 98201
      • Core Clinical Research /ID# 236405

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 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]).
• Patient must be an outpatient at the time of Visit 1 (Screening).
• Patient meets the DSM-5 criteria for MDD based on 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.
• Patient demonstrates ability to follow study instructions and likely to complete all required visits.
• Patient must have an inadequate response, as measured by the modified 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 patients must agree to continue taking the same ADT dosing regimen through completion of Visit 6/ET. Patients 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 patients 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.
• Patient 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
Experimental: Cariprazine 1.5 mg/Day + ADT; During the double blind treatment period (6 weeks), participants will take 1 capsule of cariprazine 1.5mg, orally, per day in addition to their ongoing ADT (Same antidepressant and dose of ADT they were on at the Visit 2 baseline).	Drug: Cariprazine; Cariprazine supplied in capsules
Experimental: Cariprazine 3 mg/Day + ADT; During the double blind treatment period (6 weeks), participants will take 1 capsule of cariprazine 1.5mg, orally, per day for two weeks in addition to their ongoing ADT (Same antidepressant and dose of ADT they were on at the Visit 2 baseline). They will then titrate to Cariprazine 3 mg, orally per day, in addition to their ADT starting at Visit 4 (Week 2).	Drug: Cariprazine; Cariprazine supplied in capsules
Placebo Comparator: Placebo + ADT; During the double blind treatment period (6 weeks), participants will take 1 capsule of placebo, orally, per day in addition to their ongoing ADT (Same antidepressant and dose of ADT they were on at the Visit 2 baseline).	Drug: Placebo; Placebo supplied in capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Score Change From Baseline to Week 6 in the MADRS (Montgomery-Åsberg Depression Rating Scale)	The MADRS is a 10-item, clinician-rated scale that evaluates the patient's depressive symptomatology during the past week. Patients are 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 is scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity. mITT Population included all randomized participants who had ≥1 postbaseline assessment of the MADRS total score. Number of subjects analyzed are the number of participants with data available 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 scores indicate worsening of mental illness. A negative change from Baseline indicates improvement. MMRM was used for analyses. mITT Population included all randomized participants who had ≥1 postbaseline assessment of the MADRS total score. Number of subjects analyzed are the number of participants with data available for analyses.	Baseline and Week 6

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2018
• Primary Completion (Actual): September 30, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: November 8, 2018
• First Submitted That Met QC Criteria: November 8, 2018
• First Posted (Actual): November 13, 2018

Study Record Updates

• Last Update Posted (Actual): October 25, 2022
• Last Update Submitted That Met QC Criteria: September 29, 2022
• Last Verified: September 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
• Other Study ID Numbers: 3111-301-001; 2018-002782-19 (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