Study of Milnacipran for the Treatment of Fibromyalgia

A Phase III Pivotal, Multicenter, Double-blind, Randomized, Placebo-Controlled Monotherapy Study of Milnacipran for the Treatment of Fibromyalgia.

The purpose of this study was to demonstrate the efficacy and safety of milnacipran at a dosage of 100 mg/day in the treatment of the fibromyalgia syndrome or the pain associate with fibromyalgia.

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Drug: Placebo; Drug: Milnacipran 100mg

• Study Type: Interventional
• Enrollment (Actual): 1025
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Tuscaloosa, Alabama, United States, 35406
      • Forest Investigative Site
  • California
    • Fresno, California, United States, 93710
      • Forest Investigative Site
    • Pismo Beach, California, United States, 93449
      • Forest Investigative Site
    • Vista, California, United States, 92083
      • Forest Investigative Site
  • Florida
    • St. Petersburg, Florida, United States, 33702
      • Forest Investigative Site
    • St. Petersburg, Florida, United States, 33709
      • Forest Investigative Site
    • Stuart, Florida, United States, 34996
      • Forest Investigative Site
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Forest Investigative Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Forest Investigative Site
    • Worcester, Massachusetts, United States, 01610
      • Forest Investigative Site
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Forest Investigative Site
  • New Jersey
    • Haddon Heights, New Jersey, United States, 08035
      • Forest Investigative Site
  • New York
    • Johnson City, New York, United States, 13790
      • Forest Investigative Site
    • Syracuse, New York, United States, 13210
      • Forest Investigative Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Forest Investigative Site
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Forest Investigative Site
    • Columbus, Ohio, United States, 43212
      • Forest Investigative Site
    • Toledo, Ohio, United States, 43623
      • Forest Investigative Site
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Forest Investigative Site
  • Pennsylvania
    • Mechanicsburg, Pennsylvania, United States, 17055
      • Forest Investigative Site
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Forest Investigative Site
    • Greer, South Carolina, United States, 29651
      • Forest Investigative Site
  • Texas
    • Richardson, Texas, United States, 75080
      • Forest Investigative Site
  • Virginia
    • Virginia Beach, Virginia, United States, 23454
      • Forest Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of fibromyalgia defined by 1990 American College of Rheumatology (ACR) Criteria

Exclusion Criteria:

• psychiatric illness,
• depression,
• suicidal risk,
• substance abuse,
• pulmonary dysfunction,
• renal impairment,
• active cardiac disease,
• liver disease,
• autoimmune disease,
• cancer,
• inflammatory bowel disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo, oral administration, twice daily for 12 weeks	Drug: Placebo; Placebo, oral administration, twice daily for 12 weeks
Experimental: Milnacipran; Milnacipran 100mg/day (50mg BID [twice a day])	Drug: Milnacipran 100mg; Milnacipran 100mg per day (50mg BID [twice a day])

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Syndrome Responder Status	Composite Syndrome Responder Status is the number of responders based on 3 domains: (1) 30% reduction in pain (as recorded in the Patient Experience Diary [PED], electronic diary, during the morning report; 24 hour recall); (2) patient global impression of change (PGIC) score of "very much improved" and "much improved;" and (3) physical function improvement of 6 or more points on Short Form-36 Physical Component Summary (SF-36 PCS)	At the end of the three-month stable dose treatment phase
Composite Pain Responder Status	Composite Pain Responder Status is the number of responders based on two domains: (1) 30% reduction in pain (as recorded in the Patient Experience Diary [PED], electronic diary, during the morning report; 24 hour recall); and (2) Patient Global Impression of Change (PGIC) score of "very much improved" or "much improved."	At the end of three-month stable dose treatment phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-Weighted Average of Patient Experience Diary (PED) Reported Morning 24-Hour Recall Pain Scores for Weeks 1-12 of the Stable Dose Phase	Time-weighted average (area under the curve [AUC]) of the weekly average Patient Experience Diary (PED)-reported morning recall pain scores for weeks 1 through 12 of the stable dose treatment phase is the area under the Patient Experience Diary (PED)-time curve estimated using the trapezoidal method and normalized by time. PED is the Patient Experience Diary, an electronic diary system used for collection of patient self-reported pain data. Outcome measure is assessed using the VAS Pain Intensity Scale from 0-100 millimeters anchored at 0 mm (no pain) to 100 mm (worst possible pain).	Weeks 1 through 12 of the stable dose treatment phase (Visit TX0-TX12)
Time-Weighted Average of Patient Global Impression of Change (PGIC) From Visit TX0-TX12.	Time-weighted average (area under the curve [AUC]) for Patient Global Impression of Change (PGIC) from Visit TX0-TX12 is the area under the PGIC-time curve estimated using the trapezoidal method and normalized by time. PGIC is an efficacy assessment on a scale of 1-7 taken at visits TX0-TX12. The wording of the assessment is as follows: "Since the start of the study, overall my fibromyalgia is:" 1=Very Much Improved, 2=Much Improved, 3=Minimally Improved, 4=No Change, 5=Minimally Worse, 6=Much Worse, and 7-Very Much Worse.	Weeks 1-12 (Visit TX0-TX12) of the stable dose treatment phase
Change From Baseline in the Multi-Dimensional Fatigue Inventory (MFI) Total Score at Visit TX12.	Change from Baseline in the Multi-Dimensional Fatigue Inventory (MFI) total score at TX12. Negative differences indicate decrease of fatigue. MFI is a subjective report of fatigue symptoms consisting of 20 items that can be scored to produce 5 dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. The MFI is a 1-5 scale with 1="yes, that is true" and 5="no, that is not true."	Baseline through end of week 12 (Visit TX12)
Time-Weighted Average of the Short Form-36 Physical Component Summary (SF-36 PCS) Score From Visit TX0-TX12	Short Form-36 (SF-36): pt. questionnaire (36 questions) which give rise to 8 domains & 2 component summaries (mental and physical); assessing quality of life, health & functional status. SF-36 PCS: weighted summary of physical function using all 8 domains. Scores are standardized so that the range for all domains and component summaries is 0 (worst possible score) to 100 (best possible score). Higher scores indicate better health or functional status. SF-36 PCS AUC (Area under the Curve): estimated using trapezoidal method, normalized by time.	Weeks 1-12 (Visit TX0-TX12) of the stable dose treatment phase

Collaborators and Investigators

• Sponsor: Forest Laboratories
• Collaborators: Cypress Bioscience, Inc.

Publications and helpful links

General Publications

• Saxe PA, Arnold LM, Palmer RH, Gendreau RM, Chen W. Short-term (2-week) effects of discontinuing milnacipran in patients with fibromyalgia. Curr Med Res Opin. 2012 May;28(5):815-21. doi: 10.1185/03007995.2012.677418. Epub 2012 Apr 10.
• Arnold LM, Gendreau RM, Palmer RH, Gendreau JF, Wang Y. Efficacy and safety of milnacipran 100 mg/day in patients with fibromyalgia: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010 Sep;62(9):2745-56. doi: 10.1002/art.27559.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: April 11, 2006
• First Submitted That Met QC Criteria: April 11, 2006
• First Posted (Estimate): April 13, 2006

Study Record Updates

• Last Update Posted (Estimate): January 20, 2010
• Last Update Submitted That Met QC Criteria: January 14, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Keywords: Fibromyalgia
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Milnacipran; Levomilnacipran
• Other Study ID Numbers: MLN-MD-03