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: Cariprazine
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

Group	Intervention	Description
Cariprazine + ADT	Antidepressant 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 + ADT	Cariprazine	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Parameters	Baseline (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 Period	2 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 Parameters	Baseline (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 TEAEs	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)	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 Period	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	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 Events	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)	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) Score	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	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 Period	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)	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

Name	Time	Method

Trial Locations

Locations (90): 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 105
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Fayetteville, Arkansas, United States
Forest Investigative Site 018
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Little Rock, Arkansas, United States
Forest Investigative Site 029
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Little Rock, Arkansas, United States
Forest Investigative Site 082
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Garden Grove, California, United States
Forest Investigative Site 107
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Long Beach, California, United States
Forest Investigative Site 104
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National City, California, United States
Forest Investigative Site 022
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Newport Beach, California, United States
Forest Investigative Site 004
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Oceanside, California, United States
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Forest Investigative Site 032
🇺🇸Tucson, Arizona, United States