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

Phase 3
Completed
Conditions
Major Depressive Disorder
Interventions
Drug: Antidepressant Therapy (ADT)
Registration Number
NCT01838876
Lead Sponsor
Forest Laboratories
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
442
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Cariprazine + ADTAntidepressant Therapy (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.
Cariprazine + ADTCariprazineCariprazine, 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.
Primary Outcome Measures
NameTimeMethod
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign ParametersBaseline (Week 0) to up to 26 weeks in the Treatment Period plus a 2-week Safety Follow-up Period (Up to 28 weeks)

Vital sign parameters included blood pressure, pulse rate, body mass index (BMI), weight, and waist circumference. The investigator assessed the results for clinical significance.

Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG)Baseline (Week 0) to up to 26 weeks

A standard 12-lead ECG was performed. The investigator determined the clinical significance of the ECG findings using the central ECG interpretation laboratory report.

Number of Participants With Newly Emergent Adverse Events (NEAEs) in the Safety Follow-up Period2 weeks following the 26-week Treatment 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.

Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory ParametersBaseline (Week 0) to up to 26 weeks in the Treatment Period

Clinical laboratory parameters included tests of hematology, chemistry, urinalysis and prolactin. The investigator assessed the results for clinical significance.

Number of Participants With Extrapyramidal Symptom (EPS)-Related TEAEsFirst 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)

Extrapyramidal symptoms are drug-induced movement disorders such as dystonia, akathisia, parkinsonism, bradykinesia, tremor, and tardive dyskinesia.

Number of Participants in the Most Severe Suicidal Ideation and Suicidal Behavior Recorded on the C-SSRS During the Treatment PeriodBaseline (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

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.

Number of Participants With Treatment-Emergent Ocular EventsFirst 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)

A TEAE is an AE that occurs or worsens after receiving study drug. Ocular events are adverse events related to the eye.

Change From Baseline in the Arizona Sexual Experiences Scale (ASEX) ScoreBaseline (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

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.

Number of Participants With Treatment-emergent Adverse Events (TEAEs) in the Treatment PeriodFirst 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)

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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (90)

Forest Investigative Site 049

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Gaithersburg, Maryland, United States

Forest Investigative Site 077

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Rockville, Maryland, United States

Forest Investigative Site 033

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San Juan, Puerto Rico

Forest Investigative Site 034

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San Juan, Puerto Rico

Forest Investigative Site 113

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San Diego, California, United States

Forest Investigative Site 075

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Miami, Florida, United States

Forest Investigative Site 046

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Boston, Massachusetts, United States

Forest Investigative Site 011

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Cincinnati, Ohio, United States

Forest Investigative Site 015

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Cincinnati, Ohio, United States

Forest Investigative Site 043

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Seattle, Washington, United States

Forest Investigative Site 005

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Houston, Texas, United States

Forest Investigative Site 007

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San Diego, California, United States

Forest Investigative Site 004

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Oceanside, California, United States

Forest Investigative Site 082

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Garden Grove, California, United States

Forest Investigative Site 022

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Newport Beach, California, United States

Forest Investigative Site 107

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Long Beach, California, United States

Forest Investigative Site 078

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Rancho Mirage, California, United States

Forest Investigative Site 070

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Chicago, Illinois, United States

Forest Investigative Site 059

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Lincoln, Rhode Island, United States

Forest Investigative Site 108

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The Woodlands, Texas, United States

Forest Investigative Site 081

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Bellevue, Washington, United States

Forest Investigative Site 101

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Middleton, Wisconsin, United States

Forest Investigative Site 050

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Durham, North Carolina, United States

Forest Investigative Site 039

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Oklahoma City, Oklahoma, United States

Forest Investigative Site 003

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Portland, Oregon, United States

Forest Investigative Site 008

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Tampa, Florida, United States

Forest Investigative Site 056

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Milwaukee, Wisconsin, United States

Forest Investigative Site 032

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Tucson, Arizona, United States

Forest Investigative Site 109

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Tucson, Arizona, United States

Forest Investigative Site 018

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Little Rock, Arkansas, United States

Forest Investigative Site 105

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Fayetteville, Arkansas, United States

Forest Investigative Site 029

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Little Rock, Arkansas, United States

Forest Investigative Site 104

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National City, California, United States

Forest Investigative Site 080

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Redlands, California, United States

Forest Investigative Site 054

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San Diego, California, United States

Forest Investigative Site 048

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Denver, Colorado, United States

Forest Investigative Site 031

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Temecula, California, United States

Forest Investigative Site 053

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Fort Myers, Florida, United States

Forest Investigative Site 023

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Hallandale Beach, Florida, United States

Forest Investigative Site 114

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Norwich, Connecticut, United States

Forest Investigative Site 037

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Coral Springs, Florida, United States

Forest Investigative Site 071

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Hialeah, Florida, United States

Forest Investigative Site 026

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Miami, Florida, United States

Forest Investigative Site 112

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Maitland, Florida, United States

Forest Investigative Site 006

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Leesburg, Florida, United States

Forest Investigative Site 027

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North Miami, Florida, United States

Forest Investigative Site 074

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North Miami, Florida, United States

Forest Investigative Site 036

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Oakland Park, Florida, United States

Forest Investigative Site 044

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South Miami, Florida, United States

Forest Investigative Site 060

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Atlanta, Georgia, United States

Forest Investigative Site 019

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Winter Park, Florida, United States

Forest Investigative Site 017

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Marietta, Georgia, United States

Forest Investigative Site 024

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Atlanta, Georgia, United States

Forest Investigative Site 047

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Smyrna, Georgia, United States

Forest Investigative Site 013

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Hoffman Estates, Illinois, United States

Forest Investigative Site 063

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Libertyville, Illinois, United States

Forest Investigative Site 062

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Maywood, Illinois, United States

Forest Investigative Site 072

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Naperville, Illinois, United States

Forest Investigative Site 010

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Oak Brook, Illinois, United States

Forest Investigative Site 061

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Indianapolis, Indiana, United States

Forest Investigative Site 068

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Skokie, Illinois, United States

Forest Investigative Site 065

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Overland Park, Kansas, United States

Forest Investigative Site 045

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Natick, Massachusetts, United States

Forest Investigative Site 110

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Rockville, Maryland, United States

Forest Investigative Site 106

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Berlin, New Jersey, United States

Forest Investigative Site 014

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Toms River, New Jersey, United States

Forest Investigative Site 028

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Brooklyn, New York, United States

Forest Investigative Site 016

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New York, New York, United States

Forest Investigative Site 025

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Staten Island, New York, United States

Forest Investigative Site 067

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Bismarck, North Dakota, United States

Forest Investigative Site 066

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Mason, Ohio, United States

Forest Investigative Site 055

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Columbus, Ohio, United States

Forest Investigative Site 038

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Oklahoma City, Oklahoma, United States

Forest Investigative Site 064

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Middleburg Heights, Ohio, United States

Forest Investigative Site 035

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Oklahoma City, Oklahoma, United States

Forest Investigative Site 102

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Norristown, Pennsylvania, United States

Forest Investigative Site 052

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Allentown, Pennsylvania, United States

Forest Investigative Site 069

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Wichita Falls, Texas, United States

Forest Investigative Site 111

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Murray, Utah, United States

Forest Investigative Site 041

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Charlottesville, Virginia, United States

Forest Investigative Site 100

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Bothell, Washington, United States

Forest Investigative Site 057

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Waukesha, Wisconsin, United States

Forest Investigative Site 042

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Lafayette, Indiana, United States

Forest Investigative Site 103

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Saint Charles, Missouri, United States

Forest Investigative Site 051

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Orlando, Florida, United States

Forest Investigative Site 073

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New Orleans, Louisiana, United States

Forest Investigative Site 058

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Albuquerque, New Mexico, United States

Forest Investigative Site 076

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Bronx, New York, United States

Forest Investigative Site 001

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Charleston, South Carolina, United States

Forest Investigative Site 079

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Austin, Texas, United States

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