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

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: SSR411298; Drug: Escitalopram; Drug: Placebo (for SSR411298)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 527
• Phase: Phase 2

Contacts and Locations

Study Locations

• Chile
  • Santiago, Chile
    • Sanofi-Aventis Administrative Office
• Mexico
  • Mexico, Mexico
    • Sanofi-Aventis Administrative Office
• Romania
  • Bucuresti, Romania
    • Sanofi-Aventis Administrative Office
• Russian Federation
  • Moscow, Russian Federation
    • Sanofi-Aventis Administrative Office
• Slovakia
  • Brastislava, Slovakia
    • Sanofi-Aventis Administrative Office
• South Africa
  • Midrand, South Africa
    • Sanofi-Aventis Administrative Office
• Ukraine
  • Kiev, Ukraine
    • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SSR411298 10 mg; SSR411298 10 mg, one capsule once daily for 8 weeks	Drug: SSR411298; Form: capsule Route: oral administration with food
EXPERIMENTAL: SSR411298 50 mg; SSR411298 50 mg, one capsule once daily for 8 weeks	Drug: SSR411298; Form: capsule Route: oral administration with food
EXPERIMENTAL: SSR411298 200 mg; SSR411298 200 mg, one capsule once daily for 8 weeks	Drug: SSR411298; Form: capsule Route: oral administration with food
ACTIVE_COMPARATOR: Escitalopram 10 mg; Escitalopram 10 mg, one capsule once daily for 8 weeks	Drug: Escitalopram; Form: capsule (commercial escitalopram tablets were encapsulated within opaque capsules) Route: oral administration with food
PLACEBO_COMPARATOR: Placebo; Placebo (for SSR411298), one capsule once daily for 8 weeks	Drug: Placebo (for SSR411298); Form: capsule Route: oral administration with food

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (ACTUAL): February 1, 2010
• Study Completion (ACTUAL): February 1, 2010

Study Registration Dates

• First Submitted: January 13, 2009
• First Submitted That Met QC Criteria: January 13, 2009
• First Posted (ESTIMATE): January 14, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): March 15, 2013
• Last Update Submitted That Met QC Criteria: March 14, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Depression; Antidepressant; Major Depressive Episode
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram
• Other Study ID Numbers: DFI10560; 2008-001718-26 (EUDRACT_NUMBER)