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 Major Depressive Disorder (MDD) Who Have Had an Inadequate Response to Antidepressants Alone

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 who have had an inadequate response to antidepressants alone.

Official Title
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A Double-Blind, Placebo-Controlled Study of Cariprazine as an Adjunct to Antidepressants in the Treatment of Patients With Major Depressive Disorder Who Have Had an Inadequate Response to Antidepressants Alone

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: Written informed consent has been obtained. Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable (eg, Written Authorization for Use and Release of Health and Research Study Information [US sites] and written Data Protection consent [EU sites]). Participant must be an outpatient at the time of Visit 1 (Screening). Participant meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for MDD based on Structured Clinical Interview for DSM-5 (SCID-5), with a current major depressive episode of at least 8 weeks and not exceeding 24 months in duration at Visit 1/Screening. A diagnosis of MDD with psychotic features will be acceptable. Diagnosis of MDD confirmed through a formal adjudication process. Participant demonstrates ability to follow study instructions and likely to complete all required visits. Participant must have an inadequate response, as measured by the modified antidepressant treatment response questionnaire (ATRQ), to 1 to 3 antidepressants administered during the current episode at an adequate dose (as per package insert) and for at least 6 weeks duration, with at least one dose escalation during the current depressive episode. Only one antidepressant (of sufficient dose per package insert and taken for at least 6 weeks) will be allowed at randomization and Participants must agree to continue taking the same ADT dosing regimen through completion of Visit 6/early termination (ET). Participants who are taking more than one antidepressant at Screening, regardless of the indication, will need to discontinue all other antidepressants prior to Visit 2 (Baseline). Male and female Participants must agree to use a medically acceptable and highly effective method of birth control during the course of the entire study. Women of childbearing potential (only) must have a negative serum β-human chorionic gonadotropin pregnancy test prior to Visit 2. Exclusion Criteria: Diagnosis of any current psychiatric diagnosis other than MDD (including those with current intellectual development disability) with the exception of specific phobias. Participant has a history of intolerance or hypersensitivity to cariprazine or other drugs of the same class or to rescue medications.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + ADT<br>Cariprazine matching placebo capsules, orally, once daily in addition to their ongoing antidepressant therapy (ADT) [same antidepressant and dose of ADT they were on at the Baseline] during the Double-blind Treatment Period, up to Week 6. | Drug: Placebo<br>* Placebo supplied in capsules<br>Drug: Antidepressant Therapy (ADT)<br>* ADT as prescribed by the physician per standard of care in clinical practice.<br>|
| Experimental: Cariprazine 1.5 mg/day + ADT<br>Cariprazine 1.5 mg capsules, orally, once daily in addition to their ongoing ADT (same antidepressant and dose of ADT they were on at the Baseline) during the Double-blind Treatment Period, up to Week 6. | Drug: Cariprazine<br>* Cariprazine supplied in capsules<br>* Other names: VRAYLAR®;Drug: Antidepressant Therapy (ADT)<br>* ADT as prescribed by the physician per standard of care in clinical practice.<br>|
| Experimental: Cariprazine 3 mg/day + ADT<br>Cariprazine 1.5 mg capsules, orally, once daily for 2 weeks starting at the Baseline, titrated to 3.0 mg capsules, orally, once daily from Week 2 through Week 6 in addition to their ongoing ADT (same antidepressant and dose of ADT) during the Double-blind Treatment Period, up to Week 6. | Drug: Cariprazine<br>* Cariprazine supplied in capsules<br>* Other names: VRAYLAR®;Drug: Antidepressant Therapy (ADT)<br>* ADT as prescribed by the physician per standard of care in clinical practice.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 6 in the MADRS (Montgomery-Åsberg Depression Rating Scale) Total Score | The MADRS is a 10-item, clinician-rated scale that evaluates the participant's depressive symptomatology during the past week. Participants were rated on items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each item was scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity. The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change from Baseline indicates improvement. Mixed-effects Model for Repeated Measures (MMRM) was used for analyses. | Baseline and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 6 in the Clinical Global Impressions-Severity (CGI-S) Score | The CGI-S is a clinician-rated scale used to rate the severity of the participant's current state of mental illness compared with MDD population. The participant was rated on a scale from 1 to 7, where 1=normal, not at all ill and 7=among the most extremely ill participants. Higher score indicates worsening of mental illness. A negative change from Baseline indicates improvement. MMRM was used for analyses. | Baseline and Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDD