Efficacy, Safety and Tolerability of Agomelatine in the Prevention of Relapse of Major Depressive Disorder

Study Overview
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Brief Summary
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This study will demonstrate the efficacy of agomelatine (AGO178) 25 mg and 50 mg in the prevention of relapse in patients with Major Depressive Disorder (MDD). Eligible patients will undergo open-label treatment for 20 to 26 weeks, depending on response to treatment. Patients demonstrating stable response at the end of the open-label treatment phase will be assigned to receive agomelatine or placebo for 52 weeks.

Official Title
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A 52-week, Randomized, Double-blind, Placebo-controlled, Multi-center, Parallel-group Study of the Long-term Efficacy, Tolerability and Safety of Agomelatine 25 and 50 mg in the Prevention of Relapse of Major Depressive Disorder (MDD) Following Open-label Treatment of 16-24 Weeks

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: agomelatine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adults, 18 through 70 years of age, inclusive Diagnosis of Major Depressive Disorder, recurrent episode, according to Diagnostic and Statistical Manual of Mental Disorders - 4th Edition (DSM-IV) criteria A history of at least two previous episodes of Major Depression plus the current episode Hamilton Depression Rating Scale (HAM-D17) total score ≥ 22 at Screening and Baseline Exclusion Criteria: History of bipolar disorder (I or II), schizophrenia, schizoaffective disorder, eating disorder, or obsessive compulsive disorder Any current Axis I disorder other than major depressive disorder which is the focus of treatment Substance or alcohol abuse in the last 30 days, dependence in the last 6 months Use of any psychoactive medication after the screening visit Patients who have been previously treated with agomelatine Female patients of childbearing potential who are not using effective contraception Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: agomelatine<br> <br> |
| Experimental: 2<br> | Drug: agomelatine<br> <br> |
| Placebo Comparator: 3<br> | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to relapse, where relapse is defined by the occurrence of any one of the following: |  | Primary efficacy variable is measured from randomization to relapse | 
| Hamilton Depression Rating Scale total score ≥16 at two consecutive visits; |  | Primary efficacy variable is measured from randomization to relapse | 
| hospitalization due to depression; |  | Primary efficacy variable is measured from randomization to relapse | 
| suicide attempt or suicide; |  | Primary efficacy variable is measured from randomization to relapse | 
| discontinuation due to lack of efficacy according to Investigator judgment. |  | Primary efficacy variable is measured from randomization to relapse | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who demonstrate clinical improvement at the end of the double-blind continuation phase, where improvement is defined by a score of 1 or 2 on the Clinical Global Impression Improvement (CGI-I) scale. |  | Secondary efficacy variables will be measured from randomization to the end of the Double-Blind continuation Phase | 
| Proportion of patients experiencing relapse during the double-blind continuation phase. |  | Secondary efficacy variables will be measured from randomization to the end of the Double-Blind continuation Phase | 
| Proportion of patients who achieve remission at the end of the double-blind continuation phase, where remission is defined by a total score of ≤7 on the HAM-D. |  | Secondary efficacy variables will be measured from randomization to the end of the Double-Blind continuation Phase | 
| Change from randomization to the end of the double-blind continuation phase, on the Hospital Anxiety and Depression (HAD) total score and subscale scores. |  | Secondary efficacy variables will be measured from randomization to the end of the Double-Blind continuation Phase | 

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