Safety and Efficacy of Levomilnacipran ER (F2695 SR) in Adults With Fatigue Associated With Major Depressive Disorder

A Double-blind, Randomized, Placebo- and Active-Controlled Study of F2695 SR in Adult Patients With Fatigue Associated With Major Depressive Disorder

The purpose of the study is to evaluate the efficacy, safety and tolerability of Levomilnacipran ER for the treatment of fatigue associated with major depressive disorder (MDD).

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Levomilnacipran ER; Drug: Paroxetine, Sertraline, Citalopram or Fluoxetine.; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 262
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Forest Investigative Site 010
  • Arkansas
    • Little Rock, Arkansas, United States, 72223
      • Forest Investigative Site 002
  • California
    • Cerritos, California, United States, 90703
      • Forest Investigative Site 001
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Forest Investigative Site 014
    • Jacksonville, Florida, United States, 32216
      • Forest Investigative Site 006
    • Orange City, Florida, United States, 32763
      • Forest Investigative Site 017
    • Orlando, Florida, United States, 32806
      • Forest Investigative Site 005
    • Tampa, Florida, United States, 33613
      • Forest Investigative Site 012
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Forest Investigative Site 009
  • Illinois
    • Joliet, Illinois, United States, 60435
      • Forest Investigative Site 016
  • Louisiana
    • New Orleans, Louisiana, United States, 70122
      • Forest Investigative Site 004
  • Massachusetts
    • Boston, Massachusetts, United States, 02135
      • Forest Investigative Site 022
  • New York
    • Bronx, New York, United States, 10467
      • Forest Investigative Site 011
    • Cedarhurst, New York, United States, 11516
      • Forest Investigative Site 015
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Forest Investigative Site 003
    • Dayton, Ohio, United States, 45417
      • Forest Investigative Site 013
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • Forest Investigative Site 020
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Forest Investigative Site 018
  • Texas
    • Dallas, Texas, United States, 75235
      • Forest Investigative Site 008
  • Wisconsin
    • Middleton, Wisconsin, United States, 53562
      • Forest Investigative Site 007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women, 18-65 years old
• Currently meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) criteria for Major Depressive Disorder
• The patient's current depressive episode must be at least 4 weeks in duration

Exclusion Criteria:

• Women who are pregnant, women who will be breastfeeding during the study, and women of child-bearing potential who are not practicing a reliable method of birth control

• Patients with a history of meeting DSM-IV-TR criteria for:

  1. any manic or hypomanic episode;
  2. schizophrenia or any other psychotic disorder;
  3. obsessive-compulsive disorder.
• Patients who are considered a suicide risk

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 40 -120 mg/day Levomilnacipran ER capsules, oral administration	Drug: Levomilnacipran ER; Drug: Levomilnacipran ER (40 -120 mg/day) Study drug is to be given orally, in capsule form, once daily for 8 weeks
Active Comparator: 2; Randomized to treatment with 1 of 4 Selective Serotonin Reuptake Inhibitors (SSRIs) - Paroxetine, Sertraline, Citalopram or Fluoxetine Oral administration, once daily dosing	Drug: Paroxetine, Sertraline, Citalopram or Fluoxetine.; Paroxetine (20, 40, or 60 mg/day) to be given orally, in capsule form, once daily for 8 weeks, or Sertraline (50, 100, or 150 mg/day) to be given orally, in capsule form, once daily for 8 weeks, or Citalopram (20, 40, or 60 mg/day) to be given orally, in capsule form, once daily for 8 weeks or Fluoxetine (20, 40, or 60 mg/day) to be given orally, in capsule form, once daily for 8 weeks
Placebo Comparator: 3; Matching placebo capsules, oral administration	Drug: Placebo; Matching placebo capsules, oral administration, once daily dosing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinical Global Impression of Severity (CGI-S) for Fatigue Score	The CGI-S is a clinician-rated scale that rates the severity of the patient's current state of fatigue based on the Investigator's clinical opinion with regard to the patient population with Major Depressive Disorder (MDD). Patient were rated on a scale from 1 to 7, with 1 indicating a normal state and 7 indicating that the patient was among the most extremely fatigued	From Baseline to Week 8
Change in Patient Global Impressions of Severity (PGI-S) for Fatigue Score	The PGI-S is a clinician-rated scale that rates was used to rate the severity of the patient's current state of overall fatigue. Patients were rated on a scale from 1 to 7, with 1 indicating no symptoms of fatigue and 7 indicating extreme fatigue.	From Baseline to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cognitive and Physical Functioning Questionnaire (CPFQ), Last Observation Carried Forward	The Cognitive and Physical Functioning Questionnaire is a patient-rated, 7-item scale used to measure cognitive and executive dysfunction in mood and anxiety disorders. The CPFQ is sensitive to change with treatment and displays convergent validity by significant correlations with other measures of sleepiness, fatigue, apathy, and neuropsychological functioning. Patients are rated on a scale from 1 to 6 for seven common complaints of depressed patients reporting fatigue or cognitive/executive problems-with 1 indicating greater than normal functioning, 2 indicating normal functioning, and 3 to 6 indicating degrees of impaired functioning. The CPFQ ranges from the best possible score of 7 (greater than normal functioning) to the worst possible score of 42 (totally absent).	From Baseline to Week 8

Collaborators and Investigators

• Sponsor: Forest Laboratories

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: December 3, 2010
• First Submitted That Met QC Criteria: December 3, 2010
• First Posted (Estimate): December 6, 2010

Study Record Updates

• Last Update Posted (Estimate): August 6, 2014
• Last Update Submitted That Met QC Criteria: August 5, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Depression; Fatigue; Major Depressive Disorder
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Fatigue; Disease; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Cytochrome P-450 CYP2D6 Inhibitors; Sertraline; Citalopram; Paroxetine; Fluoxetine; Milnacipran; Levomilnacipran
• Other Study ID Numbers: LVM-MD-06