Evaluation of the Potential Effects of SSR149415 on the Hypothalamic-pituitary-adrenal Axis in Outpatients With Major Depressive Disorder

Study Overview
=================
Brief Summary
-----------------
Primary Objective: - To evaluate the effects of two fixed doses of SSR149415 (250 mg bid and 100 mg bid) on hypothalamic-pituitary-adrenal axis function in patients with major depressive disorder. Secondary Objectives: To evaluate the tolerability and safety of SSR149415 in patients with major depressive disorder. To evaluate the efficacy of two fixed doses of SSR149415 compared to placebo in patients with major depressive disorder. To evaluate plasma concentrations of SSR149415.

Detailed Description
-----------------
The study consisted of three segments (A, B and C). Segment A was a 1 to 4-week, drug-free, screening and baseline period. Segment B was a 4-week, double-blind period. After the last dose of double-blind study medication in Segment B, all patients had to enter Segment C, a 1-week drug-free, follow-up period. The total study duration for one patient participating in all segments of the study was 6 weeks.

Official Title
-----------------
A Double-blind, Placebo-controlled Study Evaluating the Pharmacodynamic Effects of Two Fixed Doses of SSR149415 (250 mg Bid and 100 mg Bid) on Hypothalamic-pituitary-adrenal Axis Function in Outpatients With Major Depressive Disorder

Conditions
-----------------
Major Depressive Disorder

Intervention / Treatment
-----------------
* Drug: VASOPRESSIN V1B RECEPTOR ANTAGONIST (SSR149415)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria : Diagnosis of major depressive disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition-Text Revision (DSM-IV-TR) and the Mini International Neuropsychiatric Interview (MINI) criteria. Exclusion criteria: Outpatients unwilling to be hospitalized a total of 6 nights and 8 days. Total score of less than 21 (<21) on the 17-item Hamilton Depression Rating Scale (HAM-D) at Visit 1 (Day -7) or Visit 5 (Day -1). Patients whose current depressive episode is diagnosed with psychotic features, catatonic features, seasonal pattern or post-partum onset or is secondary to a general medical disorder. Patients with alcohol dependence or abuse or substance dependence or abuse in the past 12 months according to the MINI, except nicotine or caffeine dependence. Patients who have used the following prior to entry into Segment B: any antipsychotic within 3 months; fluoxetine within 1 month; any monoamine oxidase inhibitor (MAOI) within 2 weeks; any other antidepressant, anxiolytic, sedative-hypnotic, or mood-stabilizer (lithium, anticonvulsants) within 7 days except permitted concomitant medications 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
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Twice daily | Drug: Placebo<br>* Pharmaceutical form: Capsule Route of administration: Oral<br>|
| Experimental: SSR149415 - 100mg<br>Twice daily | Drug: VASOPRESSIN V1B RECEPTOR ANTAGONIST (SSR149415)<br>* Pharmaceutical form: Capsule Route of administration: oral<br>|
| Experimental: SSR149415 - 250mg<br>Twice daily | Drug: VASOPRESSIN V1B RECEPTOR ANTAGONIST (SSR149415)<br>* Pharmaceutical form: Capsule Route of administration: oral<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cortisol plasma concentration response to Corticotropin releasing factor (CRF) administration before and after 27 days of dosing |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adrenocorticotropic hormone (ACTH) plasma concentration response to CRF administration before and after 27 days of dosing |  | 4 weeks | 
| Number of patients with adverse events |  | Up to 6 weeks | 
| Changes in Hamilton Depression Rating Scale (HAM-D) depressed mood, factor and core items scores |  | Baseline, 4 weeks | 
| Changes Clinical Global Impression (CGI) Severity and Improvement scores |  | Baseline, 4 weeks |