The Use of Rotigotine for Treatment of Reducing Signs and Symptoms of Fibromyalgia in Adults.

Study Overview
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Brief Summary
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This trial is to investigate the efficacy and safety of rotigotine as compared to placebo in reducing signs and symptoms of fibromyalgia syndrome. The effects of rotigotine on pain, sleep, general activity, mood, and quality of life, and the use of rescue medication to treat pain will be assessed.

Detailed Description
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The overall post-Baseline duration of treatment was 13 weeks. The trial consisted of a 4-week Titration Phase, an 8-week Maintenance Phase, a 1-week De-escalation Phase, and a 2-week Safety Follow-Up Phase. If subjects met the eligibility criteria, they were randomized to receive rotigotine 4 mg/24 hrs, rotigotine 8 mg/24 hrs, or placebo during the Maintenance Phase. During the 4-week Titration Phase, subjects assigned to rotigotine were titrated at weekly intervals of 2 mg/24 hrs until they reached 4 mg/24 hrs or 8 mg/24 hrs. All subjects who completed the 4-week Titration Phase entered an 8-week Maintenance Phase and were maintained at their randomized dose (rotigotine 4 mg/24 hrs, rotigotine 8 mg/24 hrs, or placebo). No dose adjustment was allowed during the Maintenance Phase. The Treatment Phase was defined as the combined Titration and Maintenance Phases.

Official Title
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A Parallel, Randomized, Double-Blind, Placebo-Controlled, Multicenter Proof of Concept Trial to Assess the Efficacy and Safety of 2 Different Doses of Rotigotine in Subjects With Signs and Symptoms Associated With Fibromyalgia Syndrome

Conditions
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Fibromyalgia Syndrome

Intervention / Treatment
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* Drug: Rotigotine
* Drug: Rotigotine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is male or female, 18 to 65 years of age (inclusive) Subject fulfills all 3 points of the American College of Rheumatology (ACR) definition for diagnosis of fibromyalgia (pain, stiffness, and/or sleep disorder) Subject must complete an adequate washout period for excluded medications, as necessary, prior to beginning the Baseline Diary Phase Subject has at least moderate pain that is defined as an average pain intensity of ≥5 on an 11-point Likert pain scale (0-10) during the 7 days prior to Baseline Subject must have at least 5 morning and 5 evening Likert pain scale scores for the 7 days immediately prior to Visit 2 and the average daily pain score over these 7 days must be ≥5 (average daily pain score is determined as follows: calculate the mean of the morning and evening scores separately using all pain scores for the 7 days immediately prior to Visit 2; add the mean morning and evening scores and divide by 2) Subject has a score of ≥50 on Fibromyalgia Impact Questionnaire (FIQ), with a score of 100 representing severe disease at Baseline Exclusion Criteria: Subject has symptomatic regional or structural rheumatic disease (eg, knee or hip osteoarthritis, bursitis, tendonitis), rheumatic autoimmune disease or inflammatory rheumatic disease, such as systemic lupus erythematosus (SLE), mild primary osteoarthritis of the hand(s) is allowed Subject has diagnosed neuropathic pain syndrome Subject has received therapy with a dopamine agonist (eg, pramipexole, ropinirole) for 3 months or longer that was not considered effective in managing fibromyalgia symptoms Subject is receiving disability or is involved in litigation related to fibromyalgia syndrome Subject has significant psychopathology as determined by the investigator based on results of the Structural Clinical Interview for DSM-IV Diagnosis (SCID-I). The SCID-I must be administered by a physician or clinical psychologist trained to administer the instrument Subject has evidence of an impulse control disorder according to the Jay Modified Minnesota Impulsive Disorders Interview (MIDI) Subject has any medical condition that, in the opinion of the investigator, could jeopardize or compromise the subject's ability to participate in this trial Subject has orthostatic hypotension with a decrease of blood pressure (BP) from supine to standing position of ≥20 mmHg in systolic blood pressure (SBP) or of ≥10 mmHg in diastolic blood pressure (DBP) taken from the 5-minute supine value and the 1- and/or 3-minute standing measurements, or supine SBP <105 mmHg at Baseline

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Titration by Week 4 to two 20 cm2 placebo patches. At all weeks, placebo patches are matched in size and appearance to active patches.<br>|
| Experimental: Rotigotine 4 mg<br>4 mg/24 hrs | Drug: Rotigotine<br>* Titration by Week 4 to two 20 cm2 patches (one placebo patch and one 4 mg/24 hrs patch)<br>* Other names: Neupro;|
| Experimental: Rotigotine 8 mg<br>8 mg/24 hrs | Drug: Rotigotine<br>* Titration by Week 4 to two 20 cm2 patches (both are 4 mg/24 hrs patches)<br>* Other names: Neupro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Average Daily Pain Score to the Last 2 Weeks of the 12-week Treatment Phase (Based on the Full Analysis Set) | The average daily pain score is calculated using an 11-point Likert scale, ranging from 0 (no pain) to 10 (worst pain ever experienced). | Baseline, Last 2 weeks of the 12-week Treatment Phase | 
| Change From Baseline in Average Daily Pain Score to the Last 2 Weeks of the 12-week Treatment Phase (Based on the Per Protocol Set) | The average daily pain score is calculated using an 11-point Likert scale, ranging from 0 (no pain) to 10 (worst pain ever experienced). | Baseline, Last 2 weeks of the 12-week Treatment Phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fibromyalgia Impact Questionnaire (FIQ) Total Score to the Last Assessment in the 12-week Treatment Phase | The Fibromyalgia Impact Questionnaire (FIQ) Total Score ranges from 0 to 100 with higher scores corresponding to a greater impact of fibromyalgia | Baseline, Last assessment in the 12-week Treatment Phase | 
| Change From Baseline in Total Myalgic Score to the Last Assessment in the 12-week Treatment Phase | Total Myalgic Score ranges from 0 to 54 with higher scores corresponding to a greater level of pain. | Baseline, Last assessment in the 12-week Treatment Phase | 
| Change From Baseline in Average Daily Interference With Sleep to the Last 2 Weeks of the 12-week Treatment Phase | Sleep scale - the subject rated quality of sleep, from 0 (very good sleep) to 10 (very poor sleep) | Baseline, Last 2 weeks of the 12-week Treatment Phase | 
| Change From Baseline in Daily Interference With General Activity to the Last 2 Weeks of the 12-week Treatment Phase | General activity scale - the subject rated how the pain had interfered with general activity, from 0 (did not interfere) to 10 (completely interfered) | Baseline, Last 2 weeks of the 12-week Treatment Phase | 
| Patient Global Impression of Change (PGIC) Assessment From Baseline to the Last Assessment in the 12-week Treatment Phase | The PGIC is a 7-point self-administered categorical rating scale in which the subject rated the change in pain since starting trial medication (from much worse [score of 1] to much better [score of 7]). | Baseline, Last assessment in the 12-week Treatment Phase | 
| Change From Baseline in Morning and Evening Pain Scores to the Last 2 Weeks of the 12-week Treatment Phase | An 11-point Likert scale was used for subjects to assess pain, from 0 (no pain) to 10 (worst pain ever experienced). | Baseline, Last 2 weeks of the 12-week Treatment Phase | 
| Number of Subjects Using Rescue Medication and Alcohol During the 12-week Treatment Phase | Subjects recorded use of rescue medication for pain in the diary daily in the evening with a Yes/No response. Use of alcohol to treat pain in the past 24 hours was recorded with a Yes/No response. | 12-week Treatment Phase | 
| Rotigotine Plasma Concentration at the End of the Maintenance Phase/Week 12 |  | End of the Maintenance Phase/Week 12 | 
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Scores to the Last Assessment in the 12-week Treatment Phase | The Hospital Anxiety and Depression Scale (HADS) is a self-administered instrument for detecting anxiety and depression in medical outpatients. Scores range from 0 to 21 for each subscale with higher scores reflecting a greater level of anxiety or depression. | Baseline, Last assessment in the 12-week Treatment Phase | 
| Change From Baseline in Fibromyalgia Symptom Scores to the Last Assessment in the 12-week Treatment Phase | All scores range from 0 to 10 with higher scores corresponding to a greater level of symptom severity. | Baseline, Last assessment in the 12-week Treatment Phase | 
| Change From Baseline in Beck Depression Inventory-II (BDI-II) Scores to the Last Assessment in the 12-week Treatment Phase | The Beck Depression Inventory-II is a 21-item questionnaire. Each item is scored on a scale of 0 to 3 with a total score ranging from 0 to 63. A higher total score is associated with more severe depressive symptoms. | Baseline, Last assessment in the 12-week Treatment Phase | 
| Number of Subjects With Presence of Impulse Control Disorders | Impulse control disorders (ICDs) are a set of psychiatric disorders in which a person is unable to control strong and often harmful impulses. They are assessed in this study using the Jay Modified Minnesota Impulsive Disorders Interview (Jay Modified MIDI), which focuses on the five most common ICDs that may be associated with dopamine agonist use: compulsive buying, compulsive gambling, compulsive eating, hypersexuality and punding (performing repetitive and/or mechanical tasks). | 12-week Treatment Phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fibromyalgia Syndrome, Rotigotine, Neupro