Safety and Efficacy of Cariprazine as an Adjunctive to Antidepressant Therapy in Major Depressive Disorder

Study Overview
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Brief Summary
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An outpatient study to evaluate the safety and efficacy of cariprazine as adjunct to antidepressant therapy (ADT) in participants with major depressive disorder (MDD) who have an inadequate response to ADT alone. This clinical study compared cariprazine + ADT with placebo + ADT in outpatients with a diagnosis of MDD and an inadequate response to ADT. The study consisted of approximately 2 weeks of screening and washout followed by 8 weeks of double-blind treatment followed by a 1 week safety follow-up.

Official Title
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A Double-Blind, Placebo-Controlled Study of Cariprazine (RGH-188) as Adjunctive Therapy in Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Placebo
* Drug: Cariprazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female outpatients 18 to 65 years of age, inclusive. Currently meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for moderate to severe major depressive disorder (MDD). Current major depressive episode of at least 8 weeks and not exceeding 24 months in duration. Ongoing inadequate response to protocol allowed antidepressant therapy (ADT). Exclusion Criteria: Principal DSM-IV-TR-based diagnosis of an axis I disorder, other than MDD, Women who are pregnant, or planning to become pregnant or breastfeed during the study or not practicing reliable contraception that will continue through out the study. History of meeting DSM-IV-TR criteria for: Depressive episode with psychotic or catatonic features. Manic, hypomanic or mixed episode, including bipolar disorder and substance induced manic, hypomanic or mixed episode. Schizophrenia, schizoaffective, or other psychotic disorder. Obsessive-compulsive disorder. Bulimia or anorexia nervosa. Dementia, amnesic, or other cognitive disorder. Mental retardation. Participants considered a suicide risk.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received placebo orally once a day for 8 weeks. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment. | Drug: Placebo<br>* Placebo was supplied in capsules<br>|
| Experimental: Cariprazine 1-2 mg<br>Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2 and 1.0 mg on Days 3-7. At the investigator's discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 1.0 or 1.5 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 1.0, 1.5, or 2.0 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment. | Drug: Cariprazine<br>* Cariprazine was supplied in capsules.<br>|
| Experimental: Cariprazine 2-4.5 mg<br>Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2, 1.0 mg on Day 3, 1.5 mg on Day 4, and 2.0 mg on Days 5-7. At the investigator's discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 2.0 or 3.0 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 2.0, 3.0, or 4.5 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment. | Drug: Cariprazine<br>* Cariprazine was supplied in capsules.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 8 | The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement. | Baseline to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Sheehan Disability Scale (SDS) Total Score at Week 8 | The SDS measures an individual's perception of the extent to which his or her emotional symptoms are disrupting his or her functioning in 3 domains, work/school, social life/leisure activities, and family life/home responsibilities. The participant is asked to rate the degree to which their functioning is impaired on an 11-point scale, ranging from 0 (not at all) to 10 (extremely). Scores of 0 to 3 indicate mild functional impairment, 4 to 6 indicate moderate functional impairment, and 7 to 9 indicate marked functional impairment. The scores for the 3 domains are summed into a total score that ranges from 0 (unimpaired) to 30 (highly impaired). A higher score indicates greater impairment. A negative change score indicates improvement. | Baseline to Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major depressive disorder, Depression