Safety and Efficacy of Cariprazine as an Adjunctive to Antidepressant Therapy in Major Depressive Disorder

A Double-Blind, Placebo-Controlled Study of Cariprazine (RGH-188) as Adjunctive Therapy in Major Depressive Disorder

An outpatient study to evaluate the safety and efficacy of cariprazine as adjunct to antidepressant therapy (ADT) in participants with major depressive disorder (MDD) who have an inadequate response to ADT alone. This clinical study compared cariprazine + ADT with placebo + ADT in outpatients with a diagnosis of MDD and an inadequate response to ADT. The study consisted of approximately 2 weeks of screening and washout followed by 8 weeks of double-blind treatment followed by a 1 week safety follow-up.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Cariprazine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 819
• Phase: Phase 2

Contacts and Locations

Study Locations

• Estonia
  • Tallinn, Estonia, 10614
    • Forest Investigative Site 203
  • Tallinn, Estonia, 10617
    • Forest Investigative Site 201
  • Tallinn, Estonia, 11615
    • Forest Investigative Site 206
  • Tallinn, Estonia, 13517
    • Forest Investigative Site 205
  • Tartu, Estonia, 50406
    • Forest Investigative Site 204
  • Tartu, Estonia, 50417
    • Forest Investigative Site 208
  • Tartu, Estonia, 51014
    • Forest Investigative Site 207
  • Võru, Estonia, 65608
    • Forest Investigative Site 202
• Finland
  • Helsinki, Finland, 100
    • Forest Investigative Site 301
  • Helsinki, Finland, 100
    • Forest Investigative Site 302
  • Helsinki, Finland, 100
    • Forest Investigative Site 304
  • Helsinki, Finland, 40100
    • Forest Investigative Site 303
  • Kuopio, Finland, 70110
    • Forest Investigative Site 305
  • Oulu, Finland, 90100
    • Forest Investigative Site 308
  • Pori, Finland, 28100
    • Forest Investigative Site 307
• Slovakia
  • Banska Stiavnica, Slovakia, 96901
    • Forest Investigative Site 602
  • Bardejov, Slovakia, 08501
    • Forest Investigative Site 603
  • Bratislava, Slovakia, 82007
    • Forest Investigative Site 604
  • Bratislava, Slovakia, 85101
    • Forest Investigative Site 606
  • Michalovce, Slovakia, 7101
    • Forest Investigative Site 601
  • Rimavska Sobota, Slovakia, 97901
    • Forest Investigative Site 605
  • Rimavska Sobota, Slovakia, 97912
    • Forest Investigative Site 607
• Sweden
  • Lund, Sweden, 22222
    • Forest Investigative Site 803
  • Malmö, Sweden, 21152
    • Forest Investigative Site 802
  • Stockholm, Sweden, 17145
    • Forest Investigative Site 801
• Ukraine
  • Kharkiv, Ukraine, 61068
    • Forest Investigative Site 703
  • Kharkiv, Ukraine, 61068
    • Forest Investigative Site 704
  • Kyiv, Ukraine, 02660
    • Forest Investigative Site 702
  • Kyiv, Ukraine, 04080
    • Forest Investigative Site 701
  • Lugansk, Ukraine, 91045
    • Forest Investigative Site 710
  • Odesa, Ukraine, 65014
    • Forest Investigative Site 709
  • Vinnytsia, Ukraine, 21005
    • Forest Investigative Site 706
  • Kherson
    • Stepanivka, Kherson, Ukraine, 73488
      • Forest Investigative Site 705
• United States
  • California
    • Garden Grove, California, United States, 92845
      • Forest Investigative Site 077
    • National City, California, United States, 91950
      • Forest Investigative Site 019
    • Oceanside, California, United States, 92056
      • Forest Investigative Site 039
    • Orange, California, United States, 92868
      • Forest Investigative Site 015
    • Orange, California, United States, 92868
      • Forest Investigative Site 050
    • Redlands, California, United States, 92374
      • Forest Investigative Site 008
    • Sherman Oaks, California, United States, 91403
      • Forest Investigative Site 066
  • Florida
    • Gainesville, Florida, United States, 32607
      • Forest Investigative Site 063
    • Jacksonville, Florida, United States, 32256
      • Forest Investigative Site 029
    • Kissimmee, Florida, United States, 34741
      • Forest Investigative Site 012
    • Miami, Florida, United States, 33183
      • Forest Investigative Site 023
    • Orlando, Florida, United States, 32806
      • Forest Investigative Site 026
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Forest Investigative Site 062
    • Smyrna, Georgia, United States, 30080
      • Forest Investigative Site 065
  • Kansas
    • Prairie Village, Kansas, United States, 66206
      • Forest Investigative Site 074
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Forest Investigative Site 040
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Forest Investigative Site 068
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Forest Investigative Site 061
    • Marlton, New Jersey, United States, 08053
      • Forest Investigative Site 038
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Forest Investigative Site 030
  • New York
    • Brooklyn, New York, United States, 11235
      • Forest Investigative Site 076
    • Mount Kisco, New York, United States, 10549
      • Forest Investigative Site 037
    • New York, New York, United States, 10021
      • Forest Investigative Site 067
    • New York, New York, United States, 10168
      • Forest Investigative Site 049
  • Ohio
    • Canton, Ohio, United States, 44718
      • Forest Investigative Site 047
    • Dayton, Ohio, United States, 45417
      • Forest Investigative Site 021
  • Oregon
    • Portland, Oregon, United States, 97210
      • Forest Investigative Site 022
    • Salem, Oregon, United States, 97301
      • Forest Investigative Site 027
  • Pennsylvania
    • Bridgeville, Pennsylvania, United States, 15017
      • Forest Investigative Site 069
    • Philadelphia, Pennsylvania, United States, 19139
      • Forest Investigative Site 025
    • Reading, Pennsylvania, United States, 19604
      • Forest Investigative Site 031
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Forest Investigative Site 048
  • Texas
    • Austin, Texas, United States, 78731
      • Forest Investigative Site 024
    • Dallas, Texas, United States, 75231
      • Forest Investigative Site 020
    • Houston, Texas, United States, 77054
      • Forest Investigative Site 070
    • San Antonio, Texas, United States, 78229
      • Forest Investigative Site 080
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Forest Investigative Site 028
  • Washington
    • Bellevue, Washington, United States, 98007
      • Forest Investigative Site 032
    • Kirkland, Washington, United States, 98033
      • Forest Investigative Site 034

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:

• Male or female outpatients 18 to 65 years of age, inclusive.
• Currently meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for moderate to severe major depressive disorder (MDD).
• Current major depressive episode of at least 8 weeks and not exceeding 24 months in duration.
• Ongoing inadequate response to protocol allowed antidepressant therapy (ADT).

Exclusion Criteria:

• Principal DSM-IV-TR-based diagnosis of an axis I disorder, other than MDD,
• Women who are pregnant, or planning to become pregnant or breastfeed during the study or not practicing reliable contraception that will continue through out the study.

• History of meeting DSM-IV-TR criteria for:

  1. Depressive episode with psychotic or catatonic features.
  2. Manic, hypomanic or mixed episode, including bipolar disorder and substance induced manic, hypomanic or mixed episode.
  3. Schizophrenia, schizoaffective, or other psychotic disorder.
  4. Obsessive-compulsive disorder.
  5. Bulimia or anorexia nervosa.
  6. Dementia, amnesic, or other cognitive disorder.
  7. Mental retardation.
• Participants considered a suicide risk.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo orally once a day for 8 weeks. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.	Drug: Placebo; Placebo was supplied in capsules
Experimental: Cariprazine 1-2 mg; Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2 and 1.0 mg on Days 3-7. At the investigator's discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 1.0 or 1.5 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 1.0, 1.5, or 2.0 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.	Drug: Cariprazine; Cariprazine was supplied in capsules.
Experimental: Cariprazine 2-4.5 mg; Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2, 1.0 mg on Day 3, 1.5 mg on Day 4, and 2.0 mg on Days 5-7. At the investigator's discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 2.0 or 3.0 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 2.0, 3.0, or 4.5 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.	Drug: Cariprazine; Cariprazine was supplied in capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 8	The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.	Baseline to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Sheehan Disability Scale (SDS) Total Score at Week 8	The SDS measures an individual's perception of the extent to which his or her emotional symptoms are disrupting his or her functioning in 3 domains, work/school, social life/leisure activities, and family life/home responsibilities. The participant is asked to rate the degree to which their functioning is impaired on an 11-point scale, ranging from 0 (not at all) to 10 (extremely). Scores of 0 to 3 indicate mild functional impairment, 4 to 6 indicate moderate functional impairment, and 7 to 9 indicate marked functional impairment. The scores for the 3 domains are summed into a total score that ranges from 0 (unimpaired) to 30 (highly impaired). A higher score indicates greater impairment. A negative change score indicates improvement.	Baseline to Week 8

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Durgam S, Earley W, Guo H, Li D, Nemeth G, Laszlovszky I, Fava M, Montgomery SA. Efficacy and safety of adjunctive cariprazine in inadequate responders to antidepressants: a randomized, double-blind, placebo-controlled study in adult patients with major depressive disorder. J Clin Psychiatry. 2016 Mar;77(3):371-8. doi: 10.4088/JCP.15m10070.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2011
• Primary Completion (Actual): December 12, 2013
• Study Completion (Actual): December 12, 2013

Study Registration Dates

• First Submitted: November 8, 2011
• First Submitted That Met QC Criteria: November 9, 2011
• First Posted (Estimate): November 10, 2011

Study Record Updates

• Last Update Posted (Actual): May 1, 2018
• Last Update Submitted That Met QC Criteria: March 29, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Depression; 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
• Other Study ID Numbers: RGH-MD-75