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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Fibromyalgia

Intervention / Treatment
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* Drug: Placebo
* Drug: Milnacipran


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Placebo tablets administered orally twice daily | Drug: Placebo<br>* Placebo tablets administered orally twice daily<br>|
| Experimental: 2<br>Milnacipran tablets administered orally twice daily | Drug: Milnacipran<br>* Milnacipran tablets administered orally twice daily<br>* Other names: Savella ®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Loss of Therapeutic Response (LTR) | 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 | From baseline Visit 3 (week 5) to Visit 7 (week 17) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Worsening in Patient Global Impression of Change (PGIC) | 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. | From baseline Visit 3 (week 5) to Visit 7 (week 17) | 
| Time to Worsening in Multidimensional Assessment of Fatigue (MAF) | 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). | From baseline Visit 3 (week 5) to Visit 7 (week 17) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Milnacipran, Pain, Durability of Effect, Loss of Therapeutic Response, Fatigue, Forest Research Institute, Savella ®