Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder

A Phase 3, Long-term, Open-label Study of Safety and Tolerability of Cariprazine as Adjunctive Therapy in Major Depressive Disorder

The objective of this study is to evaluate the long-term safety and tolerability of cariprazine as an adjunctive treatment to antidepressant therapy (ADT) in patients with Major Depressive Disorder (MDD).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 442
• 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
    • Tucson, Arizona, United States, 85724
      • Forest Investigative Site 109
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Forest Investigative Site 105
    • Little Rock, Arkansas, United States, 72211
      • Forest Investigative Site 018
    • Little Rock, Arkansas, United States, 72211
      • Forest Investigative Site 029
  • California
    • Garden Grove, California, United States, 92845
      • Forest Investigative Site 082
    • Long Beach, California, United States, 90822
      • Forest Investigative Site 107
    • National City, California, United States, 91950
      • Forest Investigative Site 104
    • 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 078
    • Redlands, California, United States, 92374
      • Forest Investigative Site 080
    • San Diego, California, United States, 92108
      • Forest Investigative Site 054
    • San Diego, California, United States, 92102
      • Forest Investigative Site 113
    • San Diego, California, United States, 92123
      • Forest Investigative Site 007
    • Temecula, California, United States, 92591
      • Forest Investigative Site 031
  • Colorado
    • Denver, Colorado, United States, 80239
      • Forest Investigative Site 048
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Forest Investigative Site 114
  • 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
    • Maitland, Florida, United States, 32751
      • Forest Investigative Site 112
    • 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, 30331
      • Forest Investigative Site 024
    • Atlanta, Georgia, United States, 30329
      • Forest Investigative Site 060
    • Marietta, Georgia, United States, 30060
      • Forest Investigative Site 017
    • Smyrna, Georgia, United States, 30080
      • 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 110
  • 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 103
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Forest Investigative Site 106
    • 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
    • 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
    • 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 039
    • Oklahoma City, Oklahoma, United States, 72112
      • Forest Investigative Site 038
  • Oregon
    • Portland, Oregon, United States, 97210
      • Forest Investigative Site 003
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Forest Investigative Site 052
    • Norristown, Pennsylvania, United States, 19403
      • Forest Investigative Site 102
  • 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 108
    • Wichita Falls, Texas, United States, 76309
      • Forest Investigative Site 069
  • Utah
    • Murray, Utah, United States, 84123
      • Forest Investigative Site 111
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Forest Investigative Site 041
  • Washington
    • Bellevue, Washington, United States, 98007
      • Forest Investigative Site 081
    • Bothell, Washington, United States, 98011
      • Forest Investigative Site 100
    • Seattle, Washington, United States, 98104
      • Forest Investigative Site 043
  • Wisconsin
    • Middleton, Wisconsin, United States, 53562
      • Forest Investigative Site 101
    • 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: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who have provided consent prior to any study specific procedures
• Meets the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for MDD
• New patients must have ongoing inadequate response to protocol allowed ADTs as reported in Antidepressant Treatment Response Questionnaire (ATRQ)
• For rollover patients from RGH-MD-72 [NCT01715805], completion of Study RGH-MD-72 (either double-blind or single-blind treatment periods) with continued ADT treatment.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cariprazine + ADT; Cariprazine, flexible dose (titrated to a dose of 3.0 milligrams (mg) adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability), oral administration, once daily plus antidepressant drug therapy (ADT) for 26 weeks.

Drug: Cariprazine; Cariprazine capsules 0.5 mg, 1.0 mg, and 1.5 mg; Cariprazine doses 1.5, 3.0, or 4.5 mg/day (d); patients will be titrated to a starting dose of 3.0 mg/d. Patients can stay on 3.0 mg/d or the dose can be adjusted to 1.5 mg or 4.5 mg based on investigator's judgment of response and tolerability. Oral administration.; Drug: Antidepressant Therapy (ADT); ADT such as citalopram, escitalopram, fluoxetine, sertraline, paroxetine, vilazodone, venlafaxine, desvenlafaxine, duloxetine or bupropion prescribed in accordance with its respective FDA approved package insert for each drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) in the Treatment Period	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (i.e. laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A TEAE is an AE that occurs or worsens after receiving study drug.	First dose of study drug to last dose of study drug in the 26-week Treatment Period and within 30 days of last dose of study drug for participants who did not participate in the 2-week Safety Follow-up Period (Up to 30 weeks)
Number of Participants With Newly Emergent Adverse Events (NEAEs) in the Safety Follow-up Period	An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (i.e. laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A NEAE is a new AE that occurred during the 2-week Safety Follow-up Period.	2 weeks following the 26-week Treatment Period
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters	Clinical laboratory parameters included tests of hematology, chemistry, urinalysis and prolactin. The investigator assessed the results for clinical significance.	Baseline (Week 0) to up to 26 weeks in the Treatment Period
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters	Vital sign parameters included blood pressure, pulse rate, body mass index (BMI), weight, and waist circumference. The investigator assessed the results for clinical significance.	Baseline (Week 0) to up to 26 weeks in the Treatment Period plus a 2-week Safety Follow-up Period (Up to 28 weeks)
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG)	A standard 12-lead ECG was performed. The investigator determined the clinical significance of the ECG findings using the central ECG interpretation laboratory report.	Baseline (Week 0) to up to 26 weeks
Number of Participants With Extrapyramidal Symptom (EPS)-Related TEAEs	Extrapyramidal symptoms are drug-induced movement disorders such as dystonia, akathisia, parkinsonism, bradykinesia, tremor, and tardive dyskinesia.	First dose of study drug to last dose of study drug in the 26-week Treatment Period plus a 2-week Safety Follow-up Period or within 30 days of last dose of study drug for participants who did not participate in the Safety Follow-up Period (Up to 30 weeks)
Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment Period	The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior. Suicidal ideation is classified on a 5-item scale: 1 (wish to be dead) to 5 (active suicidal ideation with specific plan and intent). The C-SSRS also captures information about the intensity of ideation, specifically the frequency, duration, controllability, deterrents, and reasons for the most severe types of ideation. Suicidal behavior is classified on a 5-item scale: 0 (no suicidal behavior to 4 (actual attempt). More than 1 classification can be selected provided they represent separate episodes.	Baseline (Lead-in study Baseline for roll-over participants and prior to first dose in this study for new participants) to Week 26 in this study
Number of Participants With Treatment-Emergent Ocular Events	A TEAE is an AE that occurs or worsens after receiving study drug. Ocular events are adverse events related to the eye.	First dose of study drug to last dose of study drug in the 26-week Treatment Period plus a 2-week Safety Follow-up Period or within 30 days of last dose of study drug for participants who did not participate in the Safety Follow-up Period (Up to 30 weeks)
Change From Baseline in the Arizona Sexual Experiences Scale (ASEX) Score	The ASEX is a participant-completed scale to evaluate overall sexual experiences over the previous 7 days consisting of 5 questions answered on a scale of 1 (best) to 6 (worst) for a total possible score of 3 to 30 (2 questions were only answered if the participant was sexually active in the past week), higher score indicates greater sexual dysfunction. There are different forms for males and females. A negative change from Baseline indicates improvement.	Baseline (Lead-in study Baseline for roll-over participants and prior to first dose of this study for new participants) to End of Treatment (Up to Week 26) in this study

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2013
• Primary Completion (Actual): July 27, 2015
• Study Completion (Actual): July 27, 2015

Study Registration Dates

• First Submitted: April 22, 2013
• First Submitted That Met QC Criteria: April 23, 2013
• First Posted (Estimate): April 24, 2013

Study Record Updates

• Last Update Posted (Actual): August 21, 2019
• Last Update Submitted That Met QC Criteria: July 29, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Depression; 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-76

Drug and device information, study documents

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