A Study Comparing Duloxetine and Placebo in the Treatment of Fibromyalgia

Study Overview
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Brief Summary
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The purpose of this study is to confirm the efficacy and safety of duloxetine 60-120 mg once daily in comparison to placebo on symptom improvement in patients meeting criteria for fibromyalgia aged 18 and older. Patients will be randomized to duloxetine or placebo, however, all patients will receive duloxetine at some point in the study.

Official Title
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Flexible Dosed Duloxetine Versus Placebo in the Treatment of Fibromyalgia

Conditions
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Fibromyalgia

Intervention / Treatment
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* Drug: duloxetine hydrochloride
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female patients aged 18 and older who meet criteria for fibromyalgia as defined by the American College of Rheumatology have a score of at least 4 on the average pain item of the Brief Pain Inventory (BPI) (modified short form) at visits 1 and 2 all females must test negative for pregnancy at the time of enrollment have a degree of understanding such that the patient can provide informed consent, complete protocol required assessments and communicate intelligibly with the investigator and study coordinator. Exclusion Criteria: have pain symptoms related to traumatic injury, structural rheumatic disease, or regional rheumatic disease that will interfere with interpretation of outcome measures have regional pain syndrome, multiple surgeries or failed back syndrome have confirmed current or previous diagnosis of rheumatoid arthritis, inflammatory arthritis, or infectious arthritis, or an autoimmune disease (i.e. systemic lupus erythematosus)

Ages Eligible for Study
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Minimum Age: 18 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: Duloxetine<br>60-120 mg, oral, every day, 12 weeks | Drug: duloxetine hydrochloride<br>* 60-120 mg, oral, every day, 12 weeks (acute blinded phase followed by a 12 week blinded continuation phase).<br>* Other names: Cymbalta;|
| Placebo Comparator: Placebo<br>oral, daily, 12 weeks | Drug: placebo<br>* oral, daily, 12 weeks (acute blinded phase followed by 12 weeks of blinded duloxetine treatment)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient's Global Impressions of Improvement (PGI-I) at Week 12 | The PGI-Improvement scale is a patient-rated instrument that measures perceived improvement in symptoms. It is a 7-point scale where a score of 1 indicates that the patient is very much improved, a score of 4 indicates that the patient has experienced no change, and a score of 7 indicates that the patient is very much worse. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Brief Pain Inventory (BPI) (Modified Short Form) at 12 Week Endpoint | BPI is a self-reported form that assesses severity of pain and the interference of pain on function. There are 4 questions assessing the severity for worst pain, least pain, and average pain in the past 24 hours, and the pain right now. Severity scores range from 0 (no pain) to 10 (pain as bad as you can imagine). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Interference scores range from 0 (does not interfere) to 10 (completely interferes). | Baseline, 12 weeks | 
| Change From Baseline in Multidimensional Fatigue Inventory (MFI) at 12 Week Endpoint | MFI is a 20-item, self-reporting instrument designed to collect data on the following 5 dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. Each dimension score is derived by summing the scores of the 4 individual items that pertain to each dimension. Item scores range from 1 to 5; thus, dimensional scores range from 4 to 20 with a higher score reflecting greater levels of fatigue. | Baseline, 12 weeks | 
| Change From Baseline in Beck Depression Inventory-II (BDI-II) at 12 Week Endpoint | BDI-II is a 21-item patient-completed questionnaire designed to assess characteristics of depression. Each item is rated on a 4-point scale (0 = not present; 3 = present in the extreme). This questionnaire will be used to rate the severity of depressive symptoms and any improvement during the course of the trial. The total score ranges from 0 to 63; the higher the score, the more severe the depressive symptoms. | Baseline, 12 weeks | 
| Change From Baseline in Clinical Global Impressions of Severity (CGI-S) at 12 Week Endpoint | The Clinical Global Impressions of Severity (CGI-Severity) scale evaluates the severity of illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). | Baseline, 12 Weeks | 
| Change From Baseline in Beck Anxiety Inventory (BAI) at 12 Week Endpoint | BAI is a 21-item patient-completed questionnaire designed to assess characteristics of anxiety. Each item is rated on a 4-point scale (0 = not present; 3 = present in the extreme). This questionnaire will be used to rate the severity of anxiety symptoms and any improvement during the course of the trial. The total score ranges from 0 to 63; the higher the score, the more severe the anxiety symptoms. | Baseline, 12 weeks | 
| Change From Baseline in 36-Item Short-form Health Survey (SF-36) at 12 Weeks | The patient-rated SF-36 consists of 36 questions covering eight health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. Two summary scores: the Physical Component Summary and the Mental Component Summary are constructed based on the eight SF-36 domains. | Baseline, 12 weeks | 
| Change From Baseline in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total Score at 12 Week Endpoint | The MGH-CPFQ is a self-report instrument consisting of seven questions pertaining to an individual's cognitive and physical well-being. Each question is rated 1 = greater than normal to 6 = totally absent. Total score ranges from 7 to 42. | Baseline, 12 weeks | 
| Change From Baseline in the Mood, Anxiety, Pain, Sleep, and Stiffness Likert Scale at 12 Week Endpoint | Likert scales are patient-rated assessments. Mood: feeling low, sad or depressed; rated 0 = not feeling low, sad or depressed to 10 = feeling extremely low, sad or depressed. Anxious: anxious feelings; rated 0 = not feeling anxious to 10 = extremely anxious. Sleep: how much patient bothered by sleep difficulties; rated 0 = not bothered to 10 = extremely bothered. Pain: how much patient bothered by painful physical discomforts; rated 0 = not bothered to 10 = extremely bothered. Stiffness: how stiff patient felt in past 24 hours; rated 0 = not felt any stiffness to 10 = felt extremely stiff. | Baseline, 12 weeks | 
| Number of Responders: 30% Improvement in Brief Pain Inventory Average Pain at 12 Week Endpoint | Response was defined as at least 30% reduction from baseline to endpoint (last observation carried forward) for BPI average pain score. BPI average pain score assesses the severity of the average pain in the past 24 hours. The average severity score ranges from 0 (no pain) to 10 (pain as bad as you can imagine). | 12 Weeks | 
| Number of Responders: 50% Improvement in Brief Pain Inventory Average Pain Score at 12 Week Endpoint | Response was defined as at least 50% reduction from baseline to endpoint (last observation carried forward) for BPI average pain score. BPI average pain score assesses the severity of the average pain in the past 24 hours. The average severity score ranges from 0 (no pain) to 10 (pain as bad as you can imagine). | 12 weeks | 
| Change From Baseline in Blood Pressure at 12 Week Endpoint |  | Baseline, 12 weeks | 
| Change From Baseline in Heart Rate at 12 Week Endpoint |  | Baseline, 12 weeks | 
| Number of Patients With Columbia Suicide Severity Rating Scale (CSSR-S) Events (Behaviors, Ideations, Acts) | C-SSRS: scale capturing occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of patients with suicidal behaviors, ideations, and acts are provided. Suicidal behavior: a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a yes answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal act: a yes answer to actual attempt or completed suicide. | Baseline through 12 Weeks | 
| Change From Baseline in Weight at 12 Week Endpoint |  | Baseline, 12 weeks |