An Eight-week Study of SSR411298 as Treatment for Major Depressive Disorder in Elderly Patients

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy of 3 fixed doses of SSR411298 (10, 50 or 200 mg daily) compared to placebo, in elderly patients with Major Depressive Disorder (MDD), based on the 17-item Hamilton Depression Rating Scale. Secondary objectives are: To evaluate the tolerability and safety of an 8-week treatment with SSR411298 versus placebo in elderly patients with MDD. To evaluate the effect of SSR411298 on disability, anxiety, cognitive function, sleep, pain and somatic symptoms related to depression, and bone markers. To assess SSR411298 plasma concentrations. To assess plasma endocannabinoid concentrations.

Detailed Description
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The study period for a participants is approximately 10 weeks including a screening up to 1 week, 8-week treatment and 1-week follow-up.

Official Title
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An Eight-week, Multicenter, Randomized, Double-blind, Placebo-controlled Dose-finding Study, With Escitalopram (10 mg Daily) as Active Control, to Evaluate the Efficacy, Safety and Tolerability of Three Fixed Doses of SSR411298 (10, 50, or 200 mg Daily) in Elderly Patients With Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: SSR411298
* Drug: Escitalopram
* Drug: Placebo (for SSR411298)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elderly patient with recurrent Major Depressive Disorder Exclusion Criteria: Duration of current depressive episode greater than 2 years; Mild depression as measured by standard clinical research scales; Cognitive disturbance; Significant suicide risk; Other psychiatric conditions that would obscure the results of the study; History of failure to respond to antidepressant treatment. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 60 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 |
| --- | --- |
| Experimental: SSR411298 10 mg<br>SSR411298 10 mg, one capsule once daily for 8 weeks | Drug: SSR411298<br>* Form: capsule Route: oral administration with food<br>|
| Experimental: SSR411298 50 mg<br>SSR411298 50 mg, one capsule once daily for 8 weeks | Drug: SSR411298<br>* Form: capsule Route: oral administration with food<br>|
| Experimental: SSR411298 200 mg<br>SSR411298 200 mg, one capsule once daily for 8 weeks | Drug: SSR411298<br>* Form: capsule Route: oral administration with food<br>|
| Active Comparator: Escitalopram 10 mg<br>Escitalopram 10 mg, one capsule once daily for 8 weeks | Drug: Escitalopram<br>* Form: capsule (commercial escitalopram tablets were encapsulated within opaque capsules) Route: oral administration with food<br>|
| Placebo Comparator: Placebo<br>Placebo (for SSR411298), one capsule once daily for 8 weeks | Drug: Placebo (for SSR411298)<br>* Form: capsule Route: oral administration with food<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 17-item Hamilton Depression Rating Scale (HAM-D) total score | The HAM-D consists of 17 items assessing signs and symptoms of depression. All items are scored with a severity rating from 0 (not present) to 2 or 4 (very severe), depending on the item. The minimum and maximum possible scores are 0 and 52, respectively. | 8 weeks (from D-1 (before randomization) up to D56) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale (MADRS) total score | The MADRS consists of 10 items assessing signs and symptoms of depression. All items are scored with a severity rating from 0 (not present) to 6 (most severe). The minimum and maximum possible scores are 0 and 60, respectively. | 8 weeks (from D-1 (before randomization) up to D56) | 
| Clinical Global Impression (CGI) scores | The CGI-1 Severity of Illness score is rated on a 1 to 7 point scale. The CGI-2 Improvement score is a component of the CGI; the Improvement score captures the investigator's clinical impression regarding global improvement (or worsening) on a 7-point scale. | D-1 (before randomization) and D56 | 
| HAM-D depressed mood item score, factor scores and core item score |  | 8 weeks (from D-1 (before randomization) up to D56) | 
| Geriatric Depression Scale (GDS) total score | The GDS is a 15-item self report scale used to assess the more specific aspects of depression in elderly depressed patients. | D-1 (before randomization) and D56 | 
| Sheehan Disability Scale (SDS) total score | The SDS contains 3 questions, which assesses interference in three domains, work and school, family life and home responsibilities, and social life. Each question is answered on a 10-point Likert Scale. | D-1 (before randomization) and D56 | 
| Hamilton Anxiety Rating scale (HAM-A) total score | The HAM-A consists of 14 items assessing signs and symptoms of anxiety. All items are scored with a severity rating from 0 (not present) to 2 or 4 (very severe), depending on the item. The minimum and maximum possible scores are 0 and 56 respectively. | D-1 (before randomization) and D56 | 
| Overview of Adverse Events (AE) |  | up to 9 weeks (from first study drug intake up to 7 days after last study drug intake) | 
| SSR411298 plasma concentration | Plasma concentrations of SSR411298 are determined by a validated liquid chromatography tandem mass spectrometry method with a lower limit of quantification of 10 ng/mL. | predose and 3-5 hours after study drug intake on Day 21 and Day 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Major Depressive Episode, Antidepressant