Efficacy, Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy (ADT) in Patients With Major Depressive Disorder (MDD)

Study Overview
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Brief Summary
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The objective of this study is to evaluate the efficacy, safety and tolerability of cariprazine as an adjunctive treatment to antidepressant therapy (ADT) in patients with MDD

Official Title
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A Phase 3, Double-Blind, Placebo-Controlled Study 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: Placebo
* 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 specific procedure Meet the The Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) criteria for Major Depressive Disorder (MDD) Have a minimum score of 20 on 17-Item Hamilton Depression (HAMD-17) rating scale at Visits 1 and 2 Exclusion Criteria: Patients who do not meet 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Placebo + ADT Lead-in<br>Antidepressant therapy (ADT) as prescribed by the investigator plus single-blind placebo for 8 weeks. | Drug: Placebo<br>* Dose-matched placebo capsule once per day<br>Drug: Antidepressant Therapy (ADT)<br>* ADT such as bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, paroxetine or vilazodone as prescribed by the physician.<br>|
| Placebo Comparator: Placebo + ADT (Double-Blind)<br>Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to dose-matched placebo, once per day, oral administration plus ADT for 8 weeks (up to Week 16). | Drug: Placebo<br>* Dose-matched placebo capsule once per day<br>Drug: Antidepressant Therapy (ADT)<br>* ADT such as bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, paroxetine or vilazodone as prescribed by the physician.<br>|
| Experimental: Cariprazine + ADT (Double-Blind)<br>Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to cariprazine, 1.5 to 4.5 milligrams (mg) per day, oral administration plus ADT for 8 weeks (up to Week 16). | Drug: Cariprazine<br>* Cariprazine capsules 1.5 to 4.5 mg/day<br>Drug: Antidepressant Therapy (ADT)<br>* ADT such as bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, paroxetine or vilazodone as prescribed by the physician.<br>|
| Other: Placebo + ADT (Continued Treatment)<br>Following the 8 week ADT plus single blind placebo lead-in period, participants who were ADT responders continued treatment with ADT plus placebo for an additional 8 weeks. | Drug: Placebo<br>* Dose-matched placebo capsule once per day<br>Drug: Antidepressant Therapy (ADT)<br>* ADT such as bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, paroxetine or vilazodone as prescribed by the physician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale (MADRS) at Baseline in the Double-Blind Period | The MADRS is a clinician-rated scale to assess depressive symptomatology during the past week. Patients are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating and lack of interest. Each item is scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity for a total possible score of 0 to 60. | Baseline (Week 8) | 
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in the Double-Blind Period | The MADRS is a clinician-rated scale to assess depressive symptomatology during the past week. Participants are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating and lack of interest. Each item is scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity for a total possible score of 0 to 60. A negative change from Baseline indicates improvement. Mixed-effects model for repeated measures (MMRM) with treatment group, study center, visit, and treatment group-by-visit interaction as fixed effects, and the baseline value and baseline by-visit interaction as the covariates was used for analyses. | Baseline (Week 8) to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Sheehan Disability Scale (SDS) Score in the Double-Blind Period | The Sheehan Disability Scale (SDS) is a 3-item patient-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point continuum from 0 (no impairment) to 10 (most severe). The 3 individual scores are summed for a total possible score of 0 (unimpaired) to 30 (highly impaired). A negative change from Baseline indicates improvement. MMRM with treatment group, study center, visit, and treatment group-by-visit interaction as fixed effects, and the baseline value and baseline by-visit interaction as the covariates was used for analyses. | Baseline (Week 8) to Week 16 | 

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