Discontinuation Study of the Durability of Effect of Milnacipran for the Treatment of Fibromyalgia

• ClinicalTrials.gov Identifier: NCT01014585
• Recruitment Status: Completed
• First Posted: November 17, 2009
• Results First Posted: September 7, 2011
• Last Update Posted: September 7, 2011
• Sponsor: Forest Laboratories
• Collaborator: Cypress Bioscience, Inc.
• Information provided by (Responsible Party): Forest Laboratories

Tracking Information

• First Submitted Date: November 13, 2009
• First Posted Date: November 17, 2009
• Results First Submitted Date: June 7, 2011
• Results First Posted Date: September 7, 2011
• Last Update Posted Date: September 7, 2011
• Study Start Date: November 2009
• Actual Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 2, 2011)

Time to Loss of Therapeutic Response (LTR) [ Time Frame: From baseline Visit 3 (week 5) to Visit 7 (week 17) ]

Time to loss of therapeutic response is defined as the time from the first dose of double-blind investigational product to the first visit when a patient has a < 30% reduction in Visual Analog Scale (VAS) pain score from pre-milnacipran exposure OR a worsening of fibromyalgia requiring, in the judgment of the investigator, an alternative treatment

• Original Primary Outcome Measures (submitted: November 16, 2009): Loss of therapeutic response (LTR), defined as a < 30% reduction in Visual Analog Scale (VAS) pain score from pre-milnacipran exposure OR a worsening of fibromyalgia requiring, in the judgment of the Investigator, an alternative treatment [ Time Frame: 12 weeks randomized treatment period ]

Current Secondary Outcome Measures (submitted: September 2, 2011)

• Time to Worsening in Patient Global Impression of Change (PGIC) [ Time Frame: From baseline Visit 3 (week 5) to Visit 7 (week 17) ]
  Time to worsening in Patient Global Impression of Change is defined as the time from the first dose of double-blind investigational product to the first visit when a patient has a PGIC score of 6 or 7. The PGIC is an efficacy assessment on a scale of 1-7 taken at visits 4, 5, 6 and 7. 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.
• Time to Worsening in Multidimensional Assessment of Fatigue (MAF) [ Time Frame: From baseline Visit 3 (week 5) to Visit 7 (week 17) ]
  Time to worsening in MAF is defined as the time from the first dose of double-blind investigational product to the first visit when a patient has a 10-point increase from baseline in the global index of fatigue in MAF. Scores range from 1 (no fatigue) to 50 (severe fatigue). The MAF contains 16 items measuring 4 dimensions of fatigue: severity, distress, degree of interference in activities of daily living, and timing. Fourteen of the items contain numerical rating scales (increasing in severity); the remaining 2 items have multiple-choice responses (decreasing in severity).

Original Secondary Outcome Measures (submitted: November 16, 2009)

• Patient Global Impression of Change (PGIC) [ Time Frame: 12 weeks randomized treatment period ]
• Multidimensional Assessment of Fatigue (MAF) [ Time Frame: 12 weeks randomized treatment period ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Discontinuation Study of the Durability of Effect of Milnacipran for the Treatment of Fibromyalgia
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-Controlled Discontinuation Study of the Durability of Effect of Milnacipran for the Treatment of Fibromyalgia in Patients Receiving Long-term Milnacipran Treatment
• Brief Summary: The purpose of this study is to evaluate the durability of effect of milnacipran for the treatment of fibromyalgia in patients receiving long-term milnacipran treatment and to characterize the effects of milnacipran on multiple symptoms of fibromyalgia, as demonstrated by changes in symptoms following the discontinuation of milnacipran.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Fibromyalgia

Intervention

• Drug: Placebo
  Placebo tablets administered orally twice daily
• Drug: Milnacipran
  Milnacipran tablets administered orally twice daily
  Other Name: Savella ®

Study Arms

• Placebo Comparator: 1
  Placebo tablets administered orally twice daily
  Intervention: Drug: Placebo
• Experimental: 2
  Milnacipran tablets administered orally twice daily
  Intervention: Drug: Milnacipran

• Publications *: Clauw DJ, Mease PJ, Palmer RH, Trugman JM, Wang Y. Continuing efficacy of milnacipran following long-term treatment in fibromyalgia: a randomized trial. Arthritis Res Ther. 2013 Aug 16;15(4):R88. doi: 10.1186/ar4268.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 2, 2011): 340
• Original Estimated Enrollment (submitted: November 16, 2009): 425
• Study Completion Date: Not Provided
• Actual Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Currently participating in Study MLN-MD-06
• Receiving a stable dosage of milnacipran (50-200 mg/d) at Screening/Enrollment (Visit 1)

Exclusion Criteria:

• Significant risk of suicide
• History of mania, bipolar disorder, psychotic disorder, schizophrenia, or a current episode of major depressive disorder
• Myocardial infarction and/or stroke within the prior 12 months
• Mean systolic blood pressure > 180 mm Hg or mean diastolic blood pressure > 110 mm Hg at Screening (Visit 1)
• Active liver disease
• Severe renal impairment
• Platelet and bleeding disorders
• Female patients who are pregnant or breastfeeding

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01014585
• Other Study ID Numbers: MLN-MD-27
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Forest Laboratories
• Original Responsible Party: James Perhach, PhD, Executive Director, Clinical Development, Forest Research Institute Inc, a subsidiary of Forest Laboratories Inc.
• Current Study Sponsor: Forest Laboratories
• Original Study Sponsor: Same as current
• Collaborators: Cypress Bioscience, Inc.

Investigators

• Study Director: Joel Trugman, MD; Forest Research Institute Inc., A Subsidiary of Forest Laboratories Inc

• PRS Account: Forest Laboratories
• Verification Date: September 2011