Study Of A Controlled Release Formulation Of Pregabalin In Fibromyalgia Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of a controlled release formulation of pregabalin administered once daily as compared to placebo in the treatment of fibromyalgia. All patients will receive pregabalin; half of the patients will receive placebo at some point in the study.

Official Title
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A Phase 3 Double-blind, Randomized, Placebo-controlled, Safety And Efficacy Study Of Once Daily Controlled Release Pregabalin In The Treatment Of Patients With Fibromyalgia (Protocol A0081245)

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: Patients must have fibromyalgia. Exclusion Criteria: Patients with other painful conditions cannot participate.

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: Pregabalin<br> | Drug: pregabalin<br>* controlled release tablet; 165-495 mg/day; given once daily<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* matching placebo tablet; given once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Double-Blind Phase: Time to Loss of Therapeutic Response (LTR) | The time to loss of therapeutic response (LTR) is the time to loss of pain response (<30% pain response relative to the single-blind (SB) baseline mean pain) or withdrawal due to lack of efficacy or adverse events (in the double blind phase). | Randomization to Week 19 | 
| Double-Blind Phase: Number of Participants With Loss of Therapeutic Response (LTR) Event | Participants who did not maintain at least 30% pain response during the DB phase relative to baseline or were discontinued during DB due to lack of efficacy or an adverse event were considered to have a loss of therapeutic response. | Randomization to Week 19 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single-Blind Phase: Change From Baseline in Mean Daily Pain Score at Weeks 1, 2, 3, 4, 5, 6 | Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain). | Baseline, Weeks 1, 2, 3, 4, 5, 6 | 
| Double-Blind Phase: Change From Baseline in Mean Daily Pain Score at Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 | Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 NRS: 0 (no pain) to 10 (worst possible pain). | Baseline, Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 | 
| Double-Blind Phase: Change From Baseline in Mean Daily Pain Score at Double Blind Endpoint Visit | Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 NRS: 0 (no pain) to 10 (worst possible pain). | Baseline, Double blind endpoint visit (Week 19) | 
| Single-Blind Phase: Change From Baseline in Average Daily Tiredness Score at Weeks 1, 2, 3, 4, 5, 6 | The tiredness assessment in the daily interactive voice response system (IVRS) diary consists of an 11-point NRS ranging from zero (not tired) to 10 (extremely tired). Participants rate their tiredness due to fibromyalgia during the past 24 hours by choosing the appropriate number between 0 (not tired) and 10 (extremely tired). | Baseline, Weeks 1, 2, 3, 4, 5, 6 | 
| Double-Blind Phase: Change From Baseline in Average Daily Tiredness Score at Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 | The tiredness assessment in the daily IVRS diary consists of an 11-point NRS ranging from zero (not tired) to 10 (extremely tired). Participants rate their tiredness due to fibromyalgia during the past 24 hours by choosing the appropriate number between 0 (not tired) and 10 (extremely tired). | Baseline, Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 | 
| Double-Blind Phase: Change From Baseline in Average Daily Tiredness Score at Double Blind Endpoint Visit | The tiredness assessment in the daily IVRS diary consists of an 11-point NRS ranging from zero (not tired) to 10 (extremely tired). Participants rate their tiredness due to fibromyalgia during the past 24 hours by choosing the appropriate number between 0 (not tired) and 10 (extremely tired). | Baseline, Double blind endpoint visit (Week 19) | 
| Single-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Subjective Wake After Sleep and Subjective Latency to Sleep Onset at Weeks 1, 2, 3, 4, 5, 6 | The SSQ is designed to capture subjective behavior in participants with disrupted sleep. 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. | Baseline, Weeks 1, 2, 3, 4, 5, 6 | 
| Single-Blind Phase: Change From Baseline in Daily SSQ - Subjective Number of Awakenings After Sleep Onset at Weeks 1, 2, 3, 4, 5, 6 | The SSQ is designed to capture subjective behavior in participants with disrupted sleep. 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. | Baseline, Weeks 1, 2, 3, 4, 5, 6 | 
| Single-Blind Phase: Change From Baseline in Daily SSQ - Subjective Total Sleep Time at Weeks 1, 2, 3, 4, 5, 6 | The SSQ is designed to capture subjective behavior in participants with disrupted sleep. 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. | Baseline, Weeks 1, 2, 3, 4, 5, 6 | 
| Single-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Sleep Quality at Weeks 1, 2, 3, 4, 5, 6 | The SSQ is designed to capture subjective behavior in participants with disrupted sleep. 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. Participants rated quality of sleep during the past night 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 at each week was therefore 0 (very poor) -10 (excellent), where higher scores indicated better quality of sleep. | Baseline, Weeks 1, 2, 3, 4, 5, 6 | 
| Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Subjective Wake After Sleep Onset and Subjective Latency to Sleep Onset at Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 | The SSQ is designed to capture subjective behavior in participants with disrupted sleep. 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. | Baseline, Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 | 
| Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Subjective Number of Awakenings After Sleep Onset at Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 | The SSQ is designed to capture subjective behavior in participants with disrupted sleep. 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. | Baseline, Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 | 
| Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Subjective Total Sleep Time at Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 | The SSQ is designed to capture subjective behavior in participants with disrupted sleep. 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 total sleep time was the subjective estimate of the total amount of time the participant was asleep after lights out until final awakening. | Baseline, Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 | 
| Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Sleep Quality at Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 | The SSQ is designed to capture subjective behavior in participants with disrupted sleep. 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. Participants rated quality of sleep during the past night 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 at each week was therefore 0 (very poor) -10 (excellent), where higher scores indicated better quality of sleep. | Baseline, Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 | 
| Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Subjective Wake After Sleep Onset and Subjective Latency to Sleep Onset at Double Blind Endpoint Visit | The SSQ is designed to capture subjective behavior in participants with disrupted sleep. 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. | Baseline, Double blind endpoint visit (Week 19) | 
| Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Subjective Number of Awakenings After Sleep Onset at Double Blind Endpoint Visit | The SSQ is designed to capture subjective behavior in participants with disrupted sleep. 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. | Baseline, Double blind endpoint visit (Week 19) | 
| Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Subjective Total Sleep Time at Double Blind Endpoint Visit | The SSQ is designed to capture subjective behavior in participants with disrupted sleep. 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. | Baseline, Double blind endpoint visit (Week 19) | 
| Double-Blind Phase: Change From Baseline in Daily Subjective Sleep Questionnaire (SSQ) - Sleep Quality at Double Blind Endpoint Visit | The SSQ is designed to capture subjective behavior in participants with disrupted sleep. 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. Participants rated quality of sleep during the past night by selecting a number between 0 (very poor) and 10 (excellent). | Baseline, Double blind endpoint visit (Week 19) | 
| Single-Blind Phase: Change From Baseline in Weekly Pain Score at Week 6 (1 Week Recall Period) | Weekly pain scores were calculated from the daily pain diary. Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 NRS: 0 (no pain) to 10 (worst possible pain). | Baseline, Week 6 | 
| Double-Blind Phase: Change From Baseline in Weekly Pain Score at Week 19 (1 Week Recall Period) | Weekly pain scores were calculated from the daily pain diary. Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 NRS: 0 (no pain) to 10 (worst possible pain). | Baseline, Week 19 | 
| Change From Baseline in Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 6 - Sleep Disturbance, Snoring, Awakening Short of Breath or With a Headache, Sleep Adequacy, Somnolence, Sleep Problems Index I and Sleep Problems Index II | The MOS-SS is a validated self-administered questionnaire consisting of 12 items that assess key constructs of sleep. Instrument scoring yields 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) and two overall sleep problems indices assessing sleep over the past week. Score range for Sleep Disturbance (SD), sleep adequacy (SA), snoring, somnolence, awakening short of breath/headache was 0-100, where higher score=greater SD; greater SA; greater snoring; greater somnolence; greater shortness of breath/headache respectively. Quantity of Sleep (range-0 to 24 hours; higher scores/hours=greater quantity of sleep). Sleep Problem Index I and II: Score Range=0 to 100; higher scores =greater sleep problems. Optimal Sleep (assessed as yes or no), 'Yes' =optimal sleep (average 7-8 hours/night); 'No' =not optimal sleep. | Baseline, Week 6 | 
| Change From Baseline in Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 6- Quantity of Sleep | The MOS-SS is a validated self-administered questionnaire consisting of 12 items that assess key constructs of sleep. Instrument scoring yields 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) and two overall sleep problems indices assessing sleep over the past week. Score range for Sleep Disturbance (SD), sleep adequacy (SA), snoring, somnolence, awakening short of breath/headache was 0-100, where higher score=greater SD; greater SA; greater snoring; greater somnolence; greater shortness of breath/headache respectively. Quantity of Sleep (range-0 to 24 hours; higher scores/hours=greater quantity of sleep). Sleep Problem Index I and II: Score Range=0 to 100; higher scores =greater sleep problems. Optimal Sleep (assessed as yes or no), 'Yes' =optimal sleep (average 7-8 hours/night); 'No' =not optimal sleep. | Baseline, Week 6 | 
| Double-Blind Phase: Change From Baseline in Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 19-Sleep Disturbance, Snoring, Awakening Short of Breath or With a Headache, Sleep Adequacy, Somnolence, Sleep Problems Index I and Sleep Problems Index II | The MOS-SS is a validated self-administered questionnaire consisting of 12 items that assess key constructs of sleep. Instrument scoring yields 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) and two overall sleep problems indices assessing sleep over the past week. Score range for Sleep Disturbance (SD), sleep adequacy (SA), snoring, somnolence, awakening short of breath/headache was 0-100, where higher score=greater SD; greater SA; greater snoring; greater somnolence; greater shortness of breath/headache respectively. Quantity of Sleep (range-0 to 24 hours; higher scores/hours=greater quantity of sleep). Sleep Problem Index I and II: Score Range=0 to 100; higher scores =greater sleep problems. Optimal Sleep (assessed as yes or no), 'Yes' =optimal sleep (average 7-8 hours/night); 'No' =not optimal sleep. | Baseline, Week 19 | 
| Double-Blind Phase: Change From Baseline in Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 19- Quantity of Sleep | The MOS-SS is a validated self-administered questionnaire consisting of 12 items that assess key constructs of sleep. Instrument scoring yields 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) and two overall sleep problems indices assessing sleep over the past week. Score range for Sleep Disturbance (SD), sleep adequacy (SA), snoring, somnolence, awakening short of breath/headache was 0-100, where higher score=greater SD; greater SA; greater snoring; greater somnolence; greater shortness of breath/headache respectively. Quantity of Sleep (range-0 to 24 hours; higher scores/hours=greater quantity of sleep). Sleep Problem Index I and II: Score Range=0 to 100; higher scores =greater sleep problems. Optimal Sleep (assessed as yes or no), 'Yes' =optimal sleep (average 7-8 hours/night); 'No' =not optimal sleep. | Baseline, Week 19 | 
| Single-Blind Phase: Number of Participants Who Reported Global Impression of Change (PGIC) at Week 6 | 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). | Week 6 | 
| Double-Blind Phase: Number of Participants Who Reported Global Impression of Change (PGIC) at Week 19 | 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). | Week 19 | 
| Single-Blind Phase: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) at Week 6 | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100. Higher scores indicated a better health-related quality of life. | Baseline, Week 6 | 
| Double-Blind Phase: Change From Baseline in SF-36 Score at Week 19 | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100. Higher scores indicated a better health-related quality of life. | Baseline, Week 19 | 
| Single-Blind Phase: Change From Baseline in Hospital Anxiety and Depression Scale (HADS) at Week 6 | HADS: participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D 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, Week 6 | 
| Double-Blind Phase: Change From Baseline in HADS Score at Week 19 | HADS: participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D 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, Week 19 | 
| Single-Blind Phase: Change From Baseline in Fibromyalgia Impact Questionnaire (FIQ) at Week 6 | The FIQ is a 20-item self-administered questionnaire. FIQ contains 10 subscales, which are combined to yield a total score. There are 11 questions that are related specifically to physical functioning (item 1). The remaining questions assess pain, fatigue, stiffness, difficulty working, and symptoms of anxiousness and depression. The FIQ is scored from 0 to 100, with higher scores indicating more impairment. | Baseline, Week 6 | 
| Double-Blind Phase: Change From Baseline in FIQ Score at Week 19 | The FIQ is a 20-item self-administered questionnaire. FIQ contains 10 subscales, which are combined to yield a total score. There are 11 questions that are related specifically to physical functioning (item 1). The remaining questions assess pain, fatigue, stiffness, difficulty working, and symptoms of anxiousness and depression. The FIQ is scored from 0 to 100, with higher scores indicating more impairment. | Baseline, Week 19 | 
| Single-Blind Phase: Change From Baseline in Multidimensional Fatigue Inventory (MFI) at Week 6 | The MFI is a 20-item, self-administered questionnaire designed to measure the following dimensions of fatigue: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. Items are summed to form subscale scores; there is no overall score. The score range is from 4 to 20, where higher scores indicate greater dysfunction. | Baseline, Week 6 | 
| Double-Blind Phase: Change From Baseline in MFI Score at Week 19 | The MFI is a 20-item, self-administered questionnaire designed to measure the following dimensions of fatigue: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. Items are summed to form subscale scores; there is no overall score. The score range is from 4 to 20, where higher scores indicate greater dysfunction. | Baseline, Week 19 | 
| Single-Blind Phase: Number of Participants With Benefit, Satisfaction, Willingness to Continue Measure (BSW) at Week 6 | The questionnaire consists of 3 single-item measures designed to captures the participant's perception of the effect of treatment in terms of the relative benefit, their satisfaction, and their intention or willingness to continue on therapy. | Week 6 | 
| Double-Blind Phase: Number of Participants With Benefit, Satisfaction, and Willingness (BSW) to Continue Data at Visit 9 (3 Component Questions) at Week 19 | The questionnaire consists of 3 single-item measures designed to captures the participant's perception of the effect of treatment in terms of the relative benefit, their satisfaction, and their intention or willingness to continue on therapy. | Week 19 | 
| Single-Blind Phase: Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire at Week 6 | WPAI: 6 question participant rated questionnaire to determine the degree to which disease state affected work productivity while at work and affected activities outside of work. Subscale scores include percent work time missed due to the health problem; percent impairment while working due to problem; percent overall work impairment due to problem; and percent activity impairment due to problem. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. | Baseline, Week 6 | 
| Double-Blind Phase: Change From Baseline WPAI Questionnaire at Week 19 | WPAI: 6 question participant rated questionnaire to determine the degree to which disease state affected work productivity while at work and affected activities outside of work. Subscale scores include percent work time missed due to the health problem; percent impairment while working due to problem; percent overall work impairment due to problem; and percent activity impairment due to problem. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. | Baseline, Week 19 | 
| Double-Blind Phase: Change From Baseline in Actigraphy Functional/Sleep Assessment - Total Daytime Activity at Double Blind End Point Visit (Week 19) | Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Total daytime activity = total activity counts during the day. | Baseline, Double blind end point visit (Week 19) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fibromyalgia, pain, pregabalin, Lyrica