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

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01838876
• Other study ID #: RGH-MD-76
• Status: Completed
• Phase: Phase 3
• Start date: April 29, 2013
• Est. completion date: July 27, 2015

Study information

• Verified date: July 2019
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 442
• Est. completion date: July 27, 2015
• Est. primary completion date: July 27, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Disease
• Major Depressive Disorder

Intervention

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.
• 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

Locations

Country	Name	City	State
Puerto Rico	Forest Investigative Site 033	San Juan
Puerto Rico	Forest Investigative Site 034	San Juan
United States	Forest Investigative Site 058	Albuquerque	New Mexico
United States	Forest Investigative Site 052	Allentown	Pennsylvania
United States	Forest Investigative Site 024	Atlanta	Georgia
United States	Forest Investigative Site 060	Atlanta	Georgia
United States	Forest Investigative Site 079	Austin	Texas
United States	Forest Investigative Site 081	Bellevue	Washington
United States	Forest Investigative Site 106	Berlin	New Jersey
United States	Forest Investigative Site 067	Bismarck	North Dakota
United States	Forest Investigative Site 046	Boston	Massachusetts
United States	Forest Investigative Site 100	Bothell	Washington
United States	Forest Investigative Site 076	Bronx	New York
United States	Forest Investigative Site 028	Brooklyn	New York
United States	Forest Investigative Site 001	Charleston	South Carolina
United States	Forest Investigative Site 041	Charlottesville	Virginia
United States	Forest Investigative Site 070	Chicago	Illinois
United States	Forest Investigative Site 011	Cincinnati	Ohio
United States	Forest Investigative Site 015	Cincinnati	Ohio
United States	Forest Investigative Site 055	Columbus	Ohio
United States	Forest Investigative Site 037	Coral Springs	Florida
United States	Forest Investigative Site 048	Denver	Colorado
United States	Forest Investigative Site 050	Durham	North Carolina
United States	Forest Investigative Site 105	Fayetteville	Arkansas
United States	Forest Investigative Site 053	Fort Myers	Florida
United States	Forest Investigative Site 049	Gaithersburg	Maryland
United States	Forest Investigative Site 082	Garden Grove	California
United States	Forest Investigative Site 023	Hallandale Beach	Florida
United States	Forest Investigative Site 071	Hialeah	Florida
United States	Forest Investigative Site 013	Hoffman Estates	Illinois
United States	Forest Investigative Site 005	Houston	Texas
United States	Forest Investigative Site 061	Indianapolis	Indiana
United States	Forest Investigative Site 042	Lafayette	Indiana
United States	Forest Investigative Site 006	Leesburg	Florida
United States	Forest Investigative Site 063	Libertyville	Illinois
United States	Forest Investigative Site 059	Lincoln	Rhode Island
United States	Forest Investigative Site 018	Little Rock	Arkansas
United States	Forest Investigative Site 029	Little Rock	Arkansas
United States	Forest Investigative Site 107	Long Beach	California
United States	Forest Investigative Site 112	Maitland	Florida
United States	Forest Investigative Site 017	Marietta	Georgia
United States	Forest Investigative Site 066	Mason	Ohio
United States	Forest Investigative Site 062	Maywood	Illinois
United States	Forest Investigative Site 026	Miami	Florida
United States	Forest Investigative Site 075	Miami	Florida
United States	Forest Investigative Site 064	Middleburg Heights	Ohio
United States	Forest Investigative Site 101	Middleton	Wisconsin
United States	Forest Investigative Site 056	Milwaukee	Wisconsin
United States	Forest Investigative Site 111	Murray	Utah
United States	Forest Investigative Site 072	Naperville	Illinois
United States	Forest Investigative Site 045	Natick	Massachusetts
United States	Forest Investigative Site 104	National City	California
United States	Forest Investigative Site 073	New Orleans	Louisiana
United States	Forest Investigative Site 016	New York	New York
United States	Forest Investigative Site 022	Newport Beach	California
United States	Forest Investigative Site 102	Norristown	Pennsylvania
United States	Forest Investigative Site 027	North Miami	Florida
United States	Forest Investigative Site 074	North Miami	Florida
United States	Forest Investigative Site 114	Norwich	Connecticut
United States	Forest Investigative Site 010	Oak Brook	Illinois
United States	Forest Investigative Site 036	Oakland Park	Florida
United States	Forest Investigative Site 004	Oceanside	California
United States	Forest Investigative Site 035	Oklahoma City	Oklahoma
United States	Forest Investigative Site 038	Oklahoma City	Oklahoma
United States	Forest Investigative Site 039	Oklahoma City	Oklahoma
United States	Forest Investigative Site 051	Orlando	Florida
United States	Forest Investigative Site 065	Overland Park	Kansas
United States	Forest Investigative Site 003	Portland	Oregon
United States	Forest Investigative Site 078	Rancho Mirage	California
United States	Forest Investigative Site 080	Redlands	California
United States	Forest Investigative Site 077	Rockville	Maryland
United States	Forest Investigative Site 110	Rockville	Maryland
United States	Forest Investigative Site 103	Saint Charles	Missouri
United States	Forest Investigative Site 007	San Diego	California
United States	Forest Investigative Site 054	San Diego	California
United States	Forest Investigative Site 113	San Diego	California
United States	Forest Investigative Site 043	Seattle	Washington
United States	Forest Investigative Site 068	Skokie	Illinois
United States	Forest Investigative Site 047	Smyrna	Georgia
United States	Forest Investigative Site 044	South Miami	Florida
United States	Forest Investigative Site 025	Staten Island	New York
United States	Forest Investigative Site 008	Tampa	Florida
United States	Forest Investigative Site 031	Temecula	California
United States	Forest Investigative Site 108	The Woodlands	Texas
United States	Forest Investigative Site 014	Toms River	New Jersey
United States	Forest Investigative Site 032	Tucson	Arizona
United States	Forest Investigative Site 109	Tucson	Arizona
United States	Forest Investigative Site 057	Waukesha	Wisconsin
United States	Forest Investigative Site 069	Wichita Falls	Texas
United States	Forest Investigative Site 019	Winter Park	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Forest Laboratories	Gedeon Richter Ltd.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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
Primary	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)
Primary	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
Primary	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)
Primary	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
Primary	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)
Primary	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