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

Study Overview
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Brief Summary
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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).

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

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Cariprazine
* Drug: Antidepressant Therapy (ADT)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cariprazine + ADT<br>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<br>* 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.<br>Drug: Antidepressant Therapy (ADT)<br>* 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<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder, MDD, Depression