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

NCT01838876 | Completed Phase 3 Results FDA Drug

• 1 other identifier: RGH-MD-76
• Study Type: interventional
• Target: 442
• Locations: 2 countries
• Sites: 90

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).

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder; MDD; Depression

Outcome Measures

Primary Outcomes (9)

• 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

Study Arms (1)

Cariprazine + ADT

EXPERIMENTAL

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; Drug: Antidepressant Therapy (ADT)

Interventions

Cariprazine DRUG

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.

Cariprazine + ADT

Antidepressant Therapy (ADT) DRUG

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

Cariprazine + ADT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Forest Laboratories: lead
• Gedeon Richter Ltd.: collaborator

Study Sites (90)

Forest Investigative Site 032

Tucson, Arizona, 85710, United States

Location

Forest Investigative Site 109

Tucson, Arizona, 85724, United States

Location

Forest Investigative Site 105

Fayetteville, Arkansas, 72703, United States

Location

Forest Investigative Site 018

Little Rock, Arkansas, 72211, United States

Location

Forest Investigative Site 029

Little Rock, Arkansas, 72211, United States

Location

Forest Investigative Site 082

Garden Grove, California, 92845, United States

Location

Forest Investigative Site 107

Long Beach, California, 90822, United States

Location

Forest Investigative Site 104

National City, California, 91950, United States

Location

Forest Investigative Site 022

Newport Beach, California, 92660, United States

Location

Forest Investigative Site 004

Oceanside, California, 92056, United States

Location

Forest Investigative Site 078

Rancho Mirage, California, 92270, United States

Location

Forest Investigative Site 080

Redlands, California, 92374, United States

Location

Forest Investigative Site 113

San Diego, California, 92102, United States

Location

Forest Investigative Site 054

San Diego, California, 92108, United States

Location

Forest Investigative Site 007

San Diego, California, 92123, United States

Location

Forest Investigative Site 031

Temecula, California, 92591, United States

Location

Forest Investigative Site 048

Denver, Colorado, 80239, United States

Location

Forest Investigative Site 114

Norwich, Connecticut, 06360, United States

Location

Forest Investigative Site 037

Coral Springs, Florida, 33067, United States

Location

Forest Investigative Site 053

Fort Myers, Florida, 33912, United States

Location

Forest Investigative Site 023

Hallandale, Florida, 33009, United States

Location

Forest Investigative Site 071

Hialeah, Florida, 33012, United States

Location

Forest Investigative Site 006

Leesburg, Florida, 34748, United States

Location

Forest Investigative Site 112

Maitland, Florida, 32751, United States

Location

Forest Investigative Site 026

Miami, Florida, 33145, United States

Location

Forest Investigative Site 075

Miami, Florida, 33165, United States

Location

Forest Investigative Site 027

North Miami, Florida, 33161, United States

Location

Forest Investigative Site 074

North Miami, Florida, 33161, United States

Location

Forest Investigative Site 036

Oakland Park, Florida, 33334, United States

Location

Forest Investigative Site 051

Orlando, Florida, 32803, United States

Location

Forest Investigative Site 044

South Miami, Florida, 33143, United States

Location

Forest Investigative Site 008

Tampa, Florida, 33613, United States

Location

Forest Investigative Site 019

Winter Park, Florida, 32789, United States

Location

Forest Investigative Site 060

Atlanta, Georgia, 30329, United States

Location

Forest Investigative Site 024

Atlanta, Georgia, 30331, United States

Location

Forest Investigative Site 017

Marietta, Georgia, 30060, United States

Location

Forest Investigative Site 047

Smyrna, Georgia, 30080, United States

Location

Forest Investigative Site 070

Chicago, Illinois, 60612, United States

Location

Forest Investigative Site 013

Hoffman Estates, Illinois, 60169, United States

Location

Forest Investigative Site 063

Libertyville, Illinois, 60048, United States

Location

Forest Investigative Site 062

Maywood, Illinois, 60153, United States

Location

Forest Investigative Site 072

Naperville, Illinois, 60563, United States

Location

Forest Investigative Site 010

Oak Brook, Illinois, 60523, United States

Location

Forest Investigative Site 068

Skokie, Illinois, 60076, United States

Location

Forest Investigative Site 061

Indianapolis, Indiana, 46260, United States

Location

Forest Investigative Site 042

Lafayette, Indiana, 47905, United States

Location

Forest Investigative Site 065

Overland Park, Kansas, 66211, United States

Location

Forest Investigative Site 073

New Orleans, Louisiana, 70115, United States

Location

Forest Investigative Site 049

Gaithersburg, Maryland, 20877, United States

Location

Forest Investigative Site 077

Rockville, Maryland, 20850, United States

Location

Forest Investigative Site 110

Rockville, Maryland, 20852, United States

Location

Forest Investigative Site 046

Boston, Massachusetts, 02131, United States

Location

Forest Investigative Site 045

Natick, Massachusetts, 01760, United States

Location

Forest Investigative Site 103

Saint Charles, Missouri, 63304, United States

Location

Forest Investigative Site 106

Berlin, New Jersey, 08009, United States

Location

Forest Investigative Site 014

Toms River, New Jersey, 08755, United States

Location

Forest Investigative Site 058

Albuquerque, New Mexico, 87109, United States

Location

Forest Investigative Site 028

Brooklyn, New York, 11214, United States

Location

Forest Investigative Site 016

New York, New York, 10023, United States

Location

Forest Investigative Site 025

Staten Island, New York, 10305, United States

Location

Forest Investigative Site 076

The Bronx, New York, 10467, United States

Location

Forest Investigative Site 050

Durham, North Carolina, 27710, United States

Location

Forest Investigative Site 067

Bismarck, North Dakota, 58501, United States

Location

Forest Investigative Site 011

Cincinnati, Ohio, 45219, United States

Location

Forest Investigative Site 015

Cincinnati, Ohio, 45227, United States

Location

Forest Investigative Site 055

Columbus, Ohio, 43210, United States

Location

Forest Investigative Site 066

Mason, Ohio, 45040, United States

Location

Forest Investigative Site 064

Middleburg Heights, Ohio, 44130, United States

Location

Forest Investigative Site 038

Oklahoma City, Oklahoma, 72112, United States

Location

Forest Investigative Site 035

Oklahoma City, Oklahoma, 73103, United States

Location

Forest Investigative Site 039

Oklahoma City, Oklahoma, 73112, United States

Location

Forest Investigative Site 003

Portland, Oregon, 97210, United States

Location

Forest Investigative Site 052

Allentown, Pennsylvania, 18104, United States

Location

Forest Investigative Site 102

Norristown, Pennsylvania, 19403, United States

Location

Forest Investigative Site 059

Lincoln, Rhode Island, 02865, United States

Location

Forest Investigative Site 001

Charleston, South Carolina, 29425, United States

Location

Forest Investigative Site 079

Austin, Texas, 78732, United States

Location

Forest Investigative Site 005

Houston, Texas, 77008, United States

Location

Forest Investigative Site 108

The Woodlands, Texas, 77381, United States

Location

Forest Investigative Site 069

Wichita Falls, Texas, 76309, United States

Location

Forest Investigative Site 111

Murray, Utah, 84123, United States

Location

Forest Investigative Site 041

Charlottesville, Virginia, 22903, United States

Location

Forest Investigative Site 081

Bellevue, Washington, 98007, United States

Location

Forest Investigative Site 100

Bothell, Washington, 98011, United States

Location

Forest Investigative Site 043

Seattle, Washington, 98104, United States

Location

Forest Investigative Site 101

Middleton, Wisconsin, 53562, United States

Location

Forest Investigative Site 056

Milwaukee, Wisconsin, 53227, United States

Location

Forest Investigative Site 057

Waukesha, Wisconsin, 53188, United States

Location

Forest Investigative Site 033

San Juan, 00918, Puerto Rico

Location

Forest Investigative Site 034

San Juan, 00927, Puerto Rico

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

cariprazine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Results Point of Contact

• Title: Therapeutic Area, Head
• Organization: Allergan

clinicaltrials@allergan.com

714-246-4500

Study Officials

• Willie Earley, MD

  Allergan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2013
• First Posted: April 24, 2013
• Study Start: April 29, 2013
• Primary Completion: July 27, 2015
• Study Completion: July 27, 2015
• Last Updated: August 21, 2019
• Results First Posted: August 21, 2019

Record last verified: 2019-07

Locations

PR (2); US (88)