A Phase 3b Multicenter Study of Pregabalin in Fibromyalgia Subjects Who Have Comorbid Depression

Study Overview
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Brief Summary
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The intent of this study is to identify and treat fibromyalgia subjects with comorbid depression who are receiving an SSRI (selective serotonin reuptake inhibitor) or SNRI (selective norepinephrine reuptake inhibitor) primarily for their depression and to determine whether pregabalin demonstrates improvement relative to placebo in improving pain associated with fibromyalgia.

Official Title
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A Phase 3b Multicenter, Double-blind, Randomized, Placebo-controlled, 2-way Crossover Study Of Pregabalin In The Treatment Of Fibromyalgia With Concurrent Antidepressant Therapy For Comorbid Depression (Protocol A0081275)

Conditions
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Fibromyalgia

Intervention / Treatment
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* Drug: Pregabalin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women of any race or ethnicity who are at least 18 years of age. Adult women and men with a diagnosis of fibromyalgia and stable depression (major depressive disorder, depression not otherwise specified (NOS), or dysthymia) who have been taking an antidepressant (SSRI or SNRI) primarily for their depression for at least 3 months. Exclusion Criteria: Have failed pregabalin treatment due to lack of improvement of symptoms at doses of greater than or equal to 300 mg daily, cannot tolerate pregabalin or any pregabalin ingredient, or participated in a pregabalin clinical trial. If the subject has taken pregabalin and discontinued for reason other than lack of improvement or intolerance, then they will be eligible. Pregabalin use within the last 30 days (prior to V1) is not permitted. Patients with severe or unstable depression are not eligible. Patients with other types of pain or conditions that may make it difficult to evaluate fibromyalgia symptoms are not eligible Any subject considered at risk of suicide or self harm based on investigator judgment and/or the details of a risk assessment

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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pregabalin<br>Group 1 as Pregabalin vs. Placebo (cross over study in which period one has this group) | Drug: Pregabalin<br>* Pregabalin 300 or 450 mg/day dosed BID ( twice a day) for 14 weeks; 150 mg/day starting dose<br>|
| Placebo Comparator: Placebo<br>Group 2 as placebo vs. pregabalin (cross over study in which period two will have this group) | Drug: placebo<br>* placebo capsules twice a day for 14 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean NRS Pain Score at End of Period. | The daily pain diary consists of an 11-point numeric scale (NRS) ranging from 0 (no pain) to 10 (worst possible pain). Participants describe their pain during the past 24 hours by choosing the appropriate number between 0 and 10. The endpoint mean pain scores for Period 1 and Period 2 are defined as the mean of the last 7 non-missing daily diary pain ratings while taking study medication in the double-blind phase during Period 1 and Period 2, respectively. | End of each period, at Weeks 6 and 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fibromyalgia Impact Questionnaire (FIQ) Score at Baseline. | This was a 20-item participant reported outcome instrument. It contained 10 subscales, which were combined to yield a total score. The first 11 questions were related specifically to physical functioning subscale, ranging from 0 to 10. The remaining 9 questions assessed pain, fatigue, stiffness, difficulty working, and symptoms of anxiety and depression ranging from 0 to 10. The higher values indicated greater impairment. All 20 were combined to form a total score ranging from 0 to 100, provides an estimation of fibromyalgia impact with higher scores indicating more impairment. The severity categorizations for the FIQ are: less than 40 (mild), 40-60 (moderate), and above 60 (severe). | Baseline | 
| FIQ Score at End of Period. | This was a 20-item participant reported outcome instrument. It contained 10 subscales, which were combined to yield a total score. The first 11 questions were related specifically to physical functioning subscale, ranging from 0 to 10. The remaining 9 questions assessed pain, fatigue, stiffness, difficulty working, and symptoms of anxiety and depression ranging from 0 to 10. The higher values indicated greater impairment. All 20 were combined to form a total score ranging from 0 to 100, provides an estimation of fibromyalgia impact with higher scores indicating more impairment. The severity categorizations for the FIQ are: less than 40 (mild), 40-60 (moderate), and above 60 (severe). | End of each period, at Weeks 6 and 14 | 
| Patient Global Impression of Change (PGIC) at the End of Period 1. | PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). | End of Period 1 at Week 6 | 
| Percentage of Participants With >=30% and >=50% Pain Reduction Based on Daily Pain Diary. | Participant with at least a 30% reduction in mean pain score from baseline (at randomization) to the endpoint at the end of each period (Visits 6 and 12) is considered a 30% responder, for the respective period. Similarly, a subject with at least a 50% reduction in mean pain score from baseline (at randomization) to the endpoint at the end of each period (Visits 6 and 12) is considered a 50% responder, for the respective period. | Visits 2, 6, and 12 | 
| Subjective Sleep Questionnaire - Mean Sleep Quality at End of Period. | Subjective Sleep Questionnaire included 5 items: participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night. Subjective rating of quality of sleep during the past night was done by selecting a number between 0 (very poor) and 10 (excellent). Mean sleep quality was calculated as the mean of the last seven days, the potential range of responses was therefore 0-10. | End of each period, at Weeks 6 and 14 | 
| Subjective Sleep Questionnaire - Mean Subjective Wake After Sleep Onset at End of Period. | Subjective Sleep Questionnaire included, participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (numeric rating scale) for the previous night. Subjective wake after sleep onset was the subjective estimate of the total amount of time the participant was awake after initial sleep onset until final awakening. | End of each period, at Weeks 6 and 14 | 
| Subjective Sleep Questionnaire - Mean Latency to Sleep Onset at End of Period. | Subjective Sleep Questionnaire included, participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (numeric rating scale) for the previous night. Subjective latency to sleep onset was the subjective estimate of the amount of time to fall asleep after lights out. | End of each period, at Weeks 6 and 14 | 
| Subjective Sleep Questionnaire - Mean Subjective Total Sleep Time at End of Period. | Subjective Sleep Questionnaire included, participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (numeric rating scale) for the previous night. Subjective total sleep time was the subjective estimate of the total amount of time the participant was asleep after lights out until final awakening. | End of each period, at Weeks 6 and 14 | 
| Subjective Sleep Questionnaire - Parameter Estimates for Subjective Number of Awakenings Per Night After Sleep Onset at End of Period. | Subjective Sleep Questionnaire included, participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (numeric rating scale) for the previous night. Subjective number of awakenings after sleep onset was the subjective estimate of the total number of times the participant awakened during the night until final awakening. | End of each period, at Weeks 6 and 14 | 
| Hospital Anxiety and Depression Scale (HADS) at Baseline. | HADS: participant rated questionnaire with 2 subscales. HADS-A (anxiety) assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D (depression) assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. | Baseline | 
| HADS at End of Period. | HADS: participant rated questionnaire with 2 subscales. HADS-A (anxiety) assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D (depression) assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. | End of each period, at Weeks 6 and 14 | 
| Mean EuroQoL 5-Dimensions (EQ-5D) Score at Baseline. | EQ-5D is a standardized, participant-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a single index value characterizing current health status using a 100-point visual analog scale (0=worst, 100=best). EQ-5D summary index is obtained with a formula that weights each level of the dimensions. The index-based score is interpreted along a continuum of 0 (death) to 1 (perfect health). | Baseline | 
| EQ-5D Score at End of Period. | EQ-5D is a standardized, participant-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a single index value characterizing current health status using a 100-point visual analog scale (0=worst, 100=best). EQ-5D summary index is obtained with a formula that weights each level of the dimensions. The index-based score is interpreted along a continuum of 0 (death) to 1 (perfect health). | End of each period, at Weeks 6 and 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pregabalin, Lyrica, depression