Efficacy, Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy (ADT) in Patients With Major Depressive Disorder (MDD)

A Phase 3, Double-Blind, Placebo-Controlled Study of Cariprazine as Adjunctive Therapy in Major Depressive Disorder

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

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 1022
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • Forest Investigative Site 033
  • San Juan, Puerto Rico, 00927
    • Forest Investigative Site 034
• United States
  • Arizona
    • Tucson, Arizona, United States, 85710
      • Forest Investigative Site 032
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Forest Investigative Site 018
    • Little Rock, Arkansas, United States, 72211
      • Forest Investigative Site 029
  • California
    • Cerritos, California, United States, 90703
      • Forest Investigative Site 084
    • Culver City, California, United States, 90230
      • Forest Investigative Site 085
    • Garden Grove, California, United States, 92845
      • Forest Investigative Site 082
    • Newport Beach, California, United States, 92660
      • Forest Investigative Site 022
    • Oceanside, California, United States, 92056
      • Forest Investigative Site 004
    • Rancho Mirage, California, United States, 92270
      • Forest Investigative Site 090
    • Redlands, California, United States, 92374
      • Forest Investigative Site 078
    • Redlands, California, United States, 92374
      • Forest Investigative Site 080
    • San Diego, California, United States, 92103
      • Forest Investigative Site 007
    • San Diego, California, United States, 92108
      • Forest Investigative Site 054
    • Temecula, California, United States, 92591
      • Forest Investigative Site 031
  • Colorado
    • Denver, Colorado, United States, 80239
      • Forest Investigative Site 048
  • Florida
    • Coral Springs, Florida, United States, 33067
      • Forest Investigative Site 037
    • Fort Myers, Florida, United States, 33912
      • Forest Investigative Site 053
    • Hallandale Beach, Florida, United States, 33009
      • Forest Investigative Site 023
    • Hialeah, Florida, United States, 33012
      • Forest Investigative Site 071
    • Leesburg, Florida, United States, 34748
      • Forest Investigative Site 006
    • Miami, Florida, United States, 33145
      • Forest Investigative Site 026
    • Miami, Florida, United States, 33165
      • Forest Investigative Site 075
    • North Miami, Florida, United States, 33161
      • Forest Investigative Site 027
    • North Miami, Florida, United States, 33161
      • Forest Investigative Site 074
    • Oakland Park, Florida, United States, 33334
      • Forest Investigative Site 036
    • Orlando, Florida, United States, 32803
      • Forest Investigative Site 051
    • South Miami, Florida, United States, 33143
      • Forest Investigative Site 044
    • Tampa, Florida, United States, 33613
      • Forest Investigative Site 008
    • Winter Park, Florida, United States, 32789
      • Forest Investigative Site 019
  • Georgia
    • Atlanta, Georgia, United States, 30306
      • Forest Investigative Site 060
    • Atlanta, Georgia, United States, 30331
      • Forest Investigative Site 024
    • Marietta, Georgia, United States, 30060
      • Forest Investigative Site 017
    • Smyrna, Georgia, United States, 30080-6315
      • Forest Investigative Site 047
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Forest Investigative Site 070
    • Hoffman Estates, Illinois, United States, 60169
      • Forest Investigative Site 013
    • Libertyville, Illinois, United States, 60048
      • Forest Investigative Site 063
    • Maywood, Illinois, United States, 60153
      • Forest Investigative Site 062
    • Naperville, Illinois, United States, 60563
      • Forest Investigative Site 072
    • Oak Brook, Illinois, United States, 60523
      • Forest Investigative Site 010
    • Skokie, Illinois, United States, 60076
      • Forest Investigative Site 068
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Forest Investigative Site 061
    • Lafayette, Indiana, United States, 47905
      • Forest Investigative Site 042
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Forest Investigative Site 065
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Forest Investigative Site 073
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • Forest Investigative Site 049
    • Rockville, Maryland, United States, 20850
      • Forest Investigative Site 077
    • Rockville, Maryland, United States, 20852
      • Forest Investigative Site 012
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Forest Investigative Site 046
    • Natick, Massachusetts, United States, 01760
      • Forest Investigative Site 045
  • Missouri
    • Saint Charles, Missouri, United States, 63304
      • Forest Investigative Site 086
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Forest Investigative Site 014
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Forest Investigative Site 058
  • New York
    • Bronx, New York, United States, 10467
      • Forest Investigative Site 076
    • Brooklyn, New York, United States, 11214
      • Forest Investigative Site 028
    • New York, New York, United States, 10023
      • Forest Investigative Site 016
    • New York, New York, United States, 10028
      • Forest Investigative Site 083
    • Staten Island, New York, United States, 10305
      • Forest Investigative Site 025
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Forest Investigative Site 050
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Forest Investigative Site 067
  • Ohio
    • Canton, Ohio, United States, 44718
      • Forest Investigative Site 088
    • Cincinnati, Ohio, United States, 45215
      • Forest Investigative Site 089
    • Cincinnati, Ohio, United States, 45219
      • Forest Investigative Site 011
    • Cincinnati, Ohio, United States, 45227
      • Forest Investigative Site 015
    • Columbus, Ohio, United States, 43210
      • Forest Investigative Site 055
    • Mason, Ohio, United States, 45040
      • Forest Investigative Site 066
    • Middleburg Heights, Ohio, United States, 44130
      • Forest Investigative Site 064
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Forest Investigative Site 035
    • Oklahoma City, Oklahoma, United States, 73112
      • Forest Investigative Site 038
    • Oklahoma City, Oklahoma, United States, 73112
      • Forest Investigative Site 039
  • Oregon
    • Portland, Oregon, United States, 97210
      • Forest Investigative Site 003
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Forest Investigative Site 052
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • Forest Investigative Site 059
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Forest Investigative Site 001
  • Texas
    • Austin, Texas, United States, 78732
      • Forest Investigative Site 079
    • Houston, Texas, United States, 77008
      • Forest Investigative Site 005
    • The Woodlands, Texas, United States, 77381
      • Forest Investigative Site 087
    • Wichita Falls, Texas, United States, 76309
      • Forest Investigative Site 069
  • Utah
    • Orem, Utah, United States, 84058
      • Forest Investigative Site 030
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Forest Investigative Site 041
  • Washington
    • Bellevue, Washington, United States, 98007
      • Forest Investigative Site 081
    • Seattle, Washington, United States, 98104
      • Forest Investigative Site 043
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53227
      • Forest Investigative Site 056
    • Waukesha, Wisconsin, United States, 53188
      • Forest Investigative Site 057

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:

• Patients who have provided consent prior to any specific procedure
• Meet the The Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) criteria for Major Depressive Disorder (MDD)
• Have a minimum score of 20 on 17-Item Hamilton Depression (HAMD-17) rating scale at Visits 1 and 2

Exclusion Criteria:

• Patients who do not meet DSM-IV-TR criteria for MDD

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Placebo + ADT Lead-in; Antidepressant therapy (ADT) as prescribed by the investigator plus single-blind placebo for 8 weeks.	Drug: Placebo; Dose-matched placebo capsule once per day; Drug: Antidepressant Therapy (ADT); ADT such as bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, paroxetine or vilazodone as prescribed by the physician.
Placebo Comparator: Placebo + ADT (Double-Blind); Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to dose-matched placebo, once per day, oral administration plus ADT for 8 weeks (up to Week 16).	Drug: Placebo; Dose-matched placebo capsule once per day; Drug: Antidepressant Therapy (ADT); ADT such as bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, paroxetine or vilazodone as prescribed by the physician.
Experimental: Cariprazine + ADT (Double-Blind); Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to cariprazine, 1.5 to 4.5 milligrams (mg) per day, oral administration plus ADT for 8 weeks (up to Week 16).	Drug: Antidepressant Therapy (ADT); ADT such as bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, paroxetine or vilazodone as prescribed by the physician.; Drug: Cariprazine; Cariprazine capsules 1.5 to 4.5 mg/day
Other: Placebo + ADT (Continued Treatment); Following the 8 week ADT plus single blind placebo lead-in period, participants who were ADT responders continued treatment with ADT plus placebo for an additional 8 weeks.	Drug: Placebo; Dose-matched placebo capsule once per day; Drug: Antidepressant Therapy (ADT); ADT such as bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, paroxetine or vilazodone as prescribed by the physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Asberg Depression Rating Scale (MADRS) at Baseline in the Double-Blind Period	The MADRS is a clinician-rated scale to assess depressive symptomatology during the past week. Patients are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating and lack of interest. Each item is scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity for a total possible score of 0 to 60.	Baseline (Week 8)
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in the Double-Blind Period	The MADRS is a clinician-rated scale to assess depressive symptomatology during the past week. Participants are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating and lack of interest. Each item is scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity for a total possible score of 0 to 60. A negative change from Baseline indicates improvement. Mixed-effects model for repeated measures (MMRM) with treatment group, study center, visit, and treatment group-by-visit interaction as fixed effects, and the baseline value and baseline by-visit interaction as the covariates was used for analyses.	Baseline (Week 8) to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Sheehan Disability Scale (SDS) Score in the Double-Blind Period	The Sheehan Disability Scale (SDS) is a 3-item patient-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point continuum from 0 (no impairment) to 10 (most severe). The 3 individual scores are summed for a total possible score of 0 (unimpaired) to 30 (highly impaired). A negative change from Baseline indicates improvement. MMRM with treatment group, study center, visit, and treatment group-by-visit interaction as fixed effects, and the baseline value and baseline by-visit interaction as the covariates was used for analyses.	Baseline (Week 8) to Week 16

Collaborators and Investigators

• Sponsor: Forest Laboratories
• Collaborators: Gedeon Richter Ltd.
• Investigators: Study Director: Willie Earley, MD, Allergan

Publications and helpful links

General Publications

• Earley WR, Guo H, Nemeth G, Harsanyi J, Thase ME. Cariprazine Augmentation to Antidepressant Therapy in Major Depressive Disorder: Results of a Randomized, Double-Blind, Placebo-Controlled Trial. Psychopharmacol Bull. 2018 Jun 20;48(4):62-80.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2012
• Primary Completion (Actual): June 24, 2016
• Study Completion (Actual): June 24, 2016

Study Registration Dates

• First Submitted: October 25, 2012
• First Submitted That Met QC Criteria: October 26, 2012
• First Posted (Estimate): October 29, 2012

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 23, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: MDD; Major Depressive Disorder
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major; Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Cariprazine; Antidepressive Agents
• Other Study ID Numbers: RGH-MD-72