Safety and Efficacy of Milnacipran in Pediatric Patients With Primary Fibromyalgia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, efficacy, and pharmacokinetics of milnacipran in pediatric patients aged 13 to 17 years with primary fibromyalgia.

Detailed Description
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8 weeks open-label treatment period with milnacipran. Followed by randomization to 8-weeks double blind treatment period for eligible patients

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-Controlled Withdrawal Study to Evaluate the Safety, Tolerability, and Efficacy of Milnacipran in Pediatric Patients With Primary Fibromyalgia

Conditions
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Primary Fibromyalgia

Intervention / Treatment
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* Drug: Milnacipran
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of primary fibromyalgia 13-17 years of age To be eligible for screening, have average pain rating in the previous week of at least 3 but no more than 9 on an 11-point numeric rating scale To be eligible to enter into the open-label treatment period, have a 1-week mean of daily pain ratings of at least 3 but no more than 9 (11-point numeric rating scale) in the week before Baseline (Visit 2) To be eligible for randomization and entry into the double-blind treatment period, have a decrease of at least 50% in 1-week mean of daily pain ratings (11-point numeric rating scale) before Randomization (Visit 7) compared with the 1-week mean of daily pain ratings, in the week before Baseline (Visit 2) Unsatisfactory response to nonpharmacologic fibromyalgia treatment. Exclusion Criteria: Severe psychiatric illness Severe renal impairment Evidence of active liver disease Pregnant or breastfeeding Significant risk of suicidality Unable, unwilling or inadvisable to discontinue prohibited medications History of alcohol abuse or drug abuse or dependence, within previous year Current systemic infection Autoimmune disease History of seizure disorder (other than febrile seizures)

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 17 Years

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 |
| --- | --- |
| Experimental: Milnacipran<br>oral administration, twice daily dosing | Drug: Milnacipran<br>* Maximum tolerated dose (50, 75, or 100 mg/day tablets) was determined during the open label phase of the study. Oral administration, twice daily dosing<br>* Other names: Savella;|
| Placebo Comparator: Placebo<br>oral administration, twice daily dosing | Drug: Placebo<br>* matching placebo tablets daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Loss of Therapeutic Response (LTR) Following Randomization to Milnacipran or Placebo. | During the open-label period, 20 patients out of 116 enrolled had a reduction from baseline (Visit 2) of at least 50% in their pain, were classified as responders and were randomized (Visit 7). A Loss of Therapeutic Response was said to occur if, during the double-blind treatment period, any of the following occurred: • A worsening of fibromyalgia requiring an alternate treatment OR • An increase in 1-week mean of daily pain ratings (11-point numeric rating scale) to greater than 70% of Baseline (Visit 2) OR • Withdrawal from the study for any reason except withdrawals due to extenuating circumstances | Change from Visit 7 (Week 8) to Visit 10 (Week 16) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Global Impression of Severity (PGIS) | The wording of the PGIS assessment was as follows: Considering all aspects of your illness, how do you evaluate the severity of your fibromyalgia? The possible responses to this question were 1. Normal, not at all ill 2. Borderline ill 3. Mildly ill 4. Moderately ill 5. Severely ill 6. Extremely ill | Change from Visit 7 (Week 8) to Visit 10 (Week 16) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fibromyalgia, Pediatric Fibromyalgia, Adolescent Fibromyalgia, milnacipran, Savella, loss of therapeutic response, Forest Research Institute, Pain, Fatigue, Serotonin Norepinephrine Reuptake Inhibitors, Randomized Withdrawal