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

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo; Drug: VASOPRESSIN V1B RECEPTOR ANTAGONIST (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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Bridgewater, New Jersey, United States
      • Sanofi-Aventis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	Time Frame
Number of patients with adverse events	Up to 6 weeks
Adrenocorticotropic hormone (ACTH) plasma concentration response to CRF administration before and after 27 days of dosing	4 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

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Griebel G, Beeske S, Stahl SM. The vasopressin V(1b) receptor antagonist SSR149415 in the treatment of major depressive and generalized anxiety disorders: results from 4 randomized, double-blind, placebo-controlled studies. J Clin Psychiatry. 2012 Nov;73(11):1403-11. doi: 10.4088/JCP.12m07804. Epub 2012 Oct 16.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): August 1, 2007
• Study Completion (Actual): August 1, 2007

Study Registration Dates

• First Submitted: May 23, 2012
• First Submitted That Met QC Criteria: May 24, 2012
• First Posted (Estimate): May 25, 2012

Study Record Updates

• Last Update Posted (Estimate): May 25, 2012
• Last Update Submitted That Met QC Criteria: May 24, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Natriuretic Agents; Hemostatics; Coagulants; Vasoconstrictor Agents; Antidiuretic Agents; Vasopressins; Arginine Vasopressin
• Other Study ID Numbers: PDY5467