Effect Of Pregabalin Treatment In Patients With Diabetic Nerve Pain Who Currently Use A Non-Steroid Anti-Inflammatory Drug (NSAID) For Another Pain

Study Overview
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Brief Summary
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This study is to test the effectiveness of pregabalin in treating nerve pain caused by diabetes. The suitable subjects will be patients who also use an non-steroid anti-inflammatory drug for another pain which is not related to the diabetic nerve pain.

Official Title
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A Study Of Pregabalin In The Treatment Of Subjects With Painful Diabetic Peripheral Neuropathy With Background Treatment Of Nsaid For Other Pain Conditions

Conditions
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Painful Diabetic Peripheral Neuropathy

Intervention / Treatment
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* Drug: pregabalin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 or 2 diabetes with painful neuropathy Currently treated with one NSAID (including COX 2 inhibitors) for a co morbid pain condition with a regular dose Meet pre-defined level of pain severity at entrance Exclusion Criteria: History of failed pregabalin treatment due to lack of efficacy at therapeutic dose Participated in a previous or ongoing pregabalin clinical trial Neurologic disorders unrelated to diabetic neuropathy that may confound the assessment of distal neuropathic pain

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1: Pregabalin<br> | Drug: pregabalin<br>* 150 - 300 mg/day in divided dose (3 time a day) for 6 weeks<br>|
| Placebo Comparator: 2: Placebo<br> | Drug: placebo<br>* matching placebo 3 time a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Diabetic Peripheral Neuropathy (DPN) Pain Based on a Numeric Rating Scale (NRS) Over the Last 7 Days of Each Treatment Period (Week 6 of Each Treatment Period) | The daily pain diary consisted of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by having chosen the appropriate number between 0 and 10. Self assessment was performed daily in the evening before bedtime on a telephone via interactive voice recognition system (IVRS) (time window for completion between 6.00 pm to midnight). The endpoint mean pain score was defined as the mean of the last 7 daily diary pain ratings while taking study drug in each treatment period - period 1 and period 2, respectively. A rating of 1 - 3 was considered as mild pain; 4 - 6 as moderate pain; and 7 - 10 as severe pain. | End of Period (includes both Visits 5 and 9) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving 30% Reduction in Mean DPN Pain Score From Baseline at the End of Each Treatment Period (Week 6 of Each Treatment Period) | Daily pain diary consisted of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by having chosen the appropriate number between 0 and 10. Self assessment was performed daily in the evening before bedtime on a telephone via IVRS (time window for completion between 6.00 pm to midnight). The endpoint mean pain score was defined as the mean of the last 7 daily diary pain ratings while taking study drug in each treatment period - period 1 and period 2, respectively. A rating of 1 - 3 was considered as mild pain; 4 - 6 as moderate pain; and 7 - 10 as severe pain. | End of Period (includes both Visits 5 and 9) | 
| Percentage of Participants Achieving 50% Reduction in Mean DPN Pain Score From Baseline at the End of Each Treatment Period (Week 6 of Each Treatment Period) | Daily pain diary consisted of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by having chosen the appropriate number between 0 and 10. Self assessment was performed daily in the evening before bedtime on a telephone via IVRS (time window for completion between 6.00 pm to midnight). The endpoint mean pain score was defined as the mean of the last 7 daily diary pain ratings while taking study drug in each treatment period - period 1 and period 2, respectively. A rating of 1 - 3 was considered as mild pain; 4 - 6 as moderate pain; and 7 - 10 as severe pain. | End of Period (includes both Visits 5 and 9) | 
| Brief Pain Inventory-Short Form (BPI-sf) Score for Pain-Severity Domain at the End of Each Treatment Period (Week 6 of Each Treatment Period) | The BPI-sf is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during a 24 hour period prior to evaluation. Four items measure pain (0: no pain; 10: worst pain possible) at its worst, least, average, and now (current pain) on an 11-point scale. Scores range from 0 - 10 with higher scores indicating greater pain severity. | End of Period (includes both Visits 5 and 9) | 
| BPI-sf Score for Pain-Interference Domain at the End of Each Treatment Period (Week 6 of Each Treatment Period) | The BPI-sf is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during a 24 hour period prior to evaluation. Seven sub-questions evaluates the level of interference of pain on daily functioning (general activity, walking, work ability, mood, enjoyment of life, relations with other people, and sleep) on an 11-point scale (0: does not interfere; 10: completely interferes). Scores range from 0 - 10 with higher scores indicating greater interference. | End of Period (includes both Visits 5 and 9) | 
| Mean Sleep Interference Rating Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | The daily sleep diary consists of an 11-point numeric rating scale with which the participant rates how painful DPN pain has interfered with their sleep during the past 24 hours. Zero indicates does not interfere with sleep and 10 indicates completely interferes (unable to sleep due to pain). Self assessment was performed daily in the evening before bedtime on a telephone via IVRS (time window for completion between 6.00 pm to midnight) after completion of the daily pain diary. | End of Period (includes both Visits 5 and 9) | 
| Hospital Anxiety and Depression Scale - Anxiety (HADS-A) Total Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | The Hospital Anxiety and Depression Scale (HADS) is a 14- item self-administered questionnaire that consists of 2 scales, one measuring anxiety (HADS-A), and the other measuring depression (HADS-D). Each subscale consists of 7 statements and the participant responds as to how each item applies to him/her over the past week on 4- point response scale. Separate scores are calculated for anxiety and depression and a score (ranging from 0 to 21) is obtained for each subscale. The higher the score, the more severe the anxiety or depression. | End of Period (includes both Visits 5 and 9) | 
| HADS-D Total Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | HADS is a 14- item self-administered questionnaire that consists of 2 scales, one measuring anxiety (HADS-A), and the other measuring depression (HADS-D). Each subscale consists of 7 statements and the participant responds as to how each item applies to him/her over the past week on 4- point response scale. Separate scores are calculated for anxiety and depression and a score (ranging from 0 to 21) is obtained for each subscale. The higher the score, the more severe the anxiety or depression. | End of Period (includes both Visits 5 and 9) | 
| Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) Total Quality of Life (TQOL) Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on quality of life of participants with diabetic neuropathy. All symptoms (1 - 7) are scored as either 1 or 0, indicating presence or absence of the symptom. With exception of questions 31 and 32, the other items are scored according to the 5-point Likert Scale (0 - 4, no problem to severe problem). In question 31, good, the middle item, is scored as 0, very good as -1, excellent as -2, fair as 1, and poor as 2. In question 32, about the same, the middle item, is scored as 0, somewhat better as -1, much better as -2, somewhat worse as 1, and much worse as 2. TQOL score should be summed as follow: sum (Σ) (1 - 7, 8 - 35). The (sub)scales are calculated without weighting of any kind, and reported as the integer sum of listed questionnaire items (range: -4 - 136). The QOL-DN version that was administered in this study was modified with a 2-week recall period. | End of Period (includes both Visits 5 and 9) | 
| Norfolk QOL-DN Symptoms Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess the impact of diabetic neuropathy on quality of life of participants with diabetic neuropathy. All symptoms (1 - 7) are scored as either 1 or 0, indicating presence or absence of the symptom. Item 9 is scored according to the 5-point Likert Scale (0 - 4, no problem to severe problem). The symptoms domain score should be summed as follow: Σ (1 - 7, 9). The scales and subscales are calculated without weighting of any kind, and reported as the integer sum of the listed questionnaire items (range: 0 - 32). The QOL-DN version that was administered in this study was modified with a 2-week recall period. | End of Period (includes both Visits 5 and 9) | 
| Norfolk QOL-DN Activities of Daily Living Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess the impact of diabetic neuropathy on quality of life of participants with diabetic neuropathy. The items are scored according to the 5-point Likert Scale (0 - 4, no problem to severe problem). Activities of the daily living domain score should be summed as follow: Σ (12, 22, 23, 25, 26). Scales and subscales are calculated without weighting of any kind, and reported as integer sum of listed questionnaire items (range: 0 - 20). The QOL-DN version that was administered in the study was modified with a 2-week recall period. | End of Period (includes both Visits 5 and 9) | 
| Norfolk QOL-DN Physical Functioning / Large Fiber Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess the impact of diabetic neuropathy on quality of life of participants with diabetic neuropathy. With exception of questions 31 and 32, items are scored according to the 5-point Likert Scale (0 - 4, no problem to severe problem). In question 31, good, middle item, is scored as 0, very good as -1 , excellent as -2, fair as 1, and poor as 2. In question 32, about the same, middle item, is scored as 0, somewhat better as -1, much better as -2, somewhat worse as 1, and much worse as 2. Physical functioning / large fiber domain score should be summed as follow: Σ (8, 11, 13 - 15, 24, 27 - 35). Scales and subscales are calculated without weighting of any kind, and reported as integer sum of listed questionnaire items (range: -4 - 56). QOL-DN version that was administered in the study was modified with a 2-week recall period. | End of Period (includes both Visits 5 and 9) | 
| Norfolk QOL-DN Small Fiber Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on quality of life of participants with diabetic neuropathy. The items are scored according to the 5-point Likert Scale (0 - 4, no problem to severe problem). The small fiber domain score should be summed as follow: Σ (10, 16, 17, 18). Scales and subscales are calculated without weighting of any kind, and reported as integer sum of the listed questionnaire items (range: 0 - 16). The QOL-DN version that was administered in this study was modified with a 2-week recall period. | End of Period (includes both Visits 5 and 9) | 
| Norfolk QOL-DN Autonomic Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess the impact of diabetic neuropathy on quality of life of participants with diabetic neuropathy. The items are scored according to the 5-point Likert Scale (0 - 4, no problem to severe problem). The autonomic domain score should be summed as follow: Σ (19, 20, 21). The scales and subscales are calculated without weighting of any kind, and reported as the integer sum of the listed questionnaire items (range: 0 - 12). The QOL-DN version that was administered in this study was modified with a 2-week recall period. | End of Period (includes both Visits 5 and 9) | 
| Euro QoL-5 Dimensions (EQ-5D) Mobility Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | EQ-5D is a participant-completed 5-item questionnaire designed to assess health related quality of life in terms of a single index value or utility score. There are 5 dimensions: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. Each dimension is rated on a 3-point response scale (no problems, some/moderate problems, extreme problems) and the scores are combined to form a single index utility value between 0 and 1 with higher scores indicating better health. | End of Period (includes both Visits 5 and 9) | 
| EQ-5D Self-Care Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | EQ-5D is a participant-completed 5-item questionnaire designed to assess health related quality of life in terms of a single index value or utility score. There are 5 dimensions: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. Each dimension is rated on a 3-point response scale [1 = no problems, 2 = some/moderate problems, 3 = extreme problems] and the scores are combined to form a single index utility value between 0 and 1 with higher scores indicating better health. | End of Period (includes both Visits 5 and 9) | 
| EQ-5D Usual Activities Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | EQ-5D is a participant-completed 5-item questionnaire designed to assess health related quality of life in terms of a single index value or utility score. There are 5 dimensions: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. Each dimension is rated on a 3-point response scale [1 = no problems, 2 = some/moderate problems, 3 = extreme problems] and the scores are combined to form a single index utility value between 0 and 1 with higher scores indicating better health. | End of Period (includes both Visits 5 and 9) | 
| EQ-5D Pain / Discomfort Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | EQ-5D is a participant-completed 5-item questionnaire designed to assess health related quality of life in terms of a single index value or utility score. There are 5 dimensions: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. Each dimension is rated on a 3-point response scale [1 = no problems, 2 = some/moderate problems, 3 = extreme problems] and the scores are combined to form a single index utility value between 0 and 1 with higher scores indicating better health. | End of Period (includes both Visits 5 and 9) | 
| EQ-5D Anxiety / Depression Domain Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | EQ-5D is a participant-completed 5-item questionnaire designed to assess health related quality of life in terms of a single index value or utility score. There are 5 dimensions: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. Each dimension is rated on a 3-point response scale [1 = no problems, 2 = some/moderate problems, 3 = extreme problems] and the scores are combined to form a single index utility value between 0 and 1 with higher scores indicating better health. | End of Period (includes both Visits 5 and 9) | 
| EQ-5D Dolan 1997 Index Summary Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | EQ-5D is a participant-completed 5-item questionnaire designed to assess health related quality of life in terms of a single index value or utility score. There are 5 dimensions: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. Each dimension is rated on a 3-point response scale [1 = no problems, 2 = some/moderate problems, 3 = extreme problems] and the scores are combined to form a single index utility value between 0 and 1 with higher scores indicating better health. The utility score is calculated using the Dolan 1997 algorithm and the revised version which was provided to the EuroQol Group by Dolan in 2001 - but later published in medical care in 2002. | End of Period (includes both Visits 5 and 9) | 
| EQ-5D Dolan 2002 Index Summary Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) | EQ-5D is a participant-completed 5-item questionnaire designed to assess health related quality of life in terms of a single index value or utility score. There are 5 dimensions: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. Each dimension is rated on a 3-point response scale [1 = no problems, 2 = some/moderate problems, 3 = extreme problems] and the scores are combined to form a single index utility value between 0 and 1 with higher scores indicating better health. The utility score is calculated using the Dolan 1997 algorithm and the revised version which was provided to the EuroQol Group by Dolan in 2001 - but later published in medical care in 2002. | End of Period (includes both Visits 5 and 9) | 
| Patient Global Impression of Change (PGIC) Score at the End of Period 1 (Week 6) - Original Scores | The PGIC is a participant-rated instrument that measures the participant's assessment of change in his/her overall status on a scale ranging from 1 (very much improved) to 7 (very much worse). Due to the crossover design, PGIC was analyzed at the end of period 1 (V5). | End of Period 1 (V5) | 
| PGIC Score at the End of Period 1 (Week 6) - Categorized Scores | The PGIC is a participant-rated instrument that measures the participant's assessment of change in his/her overall status on a scale ranging from 1 (very much improved) to 7 (very much worse). Original scores (7 different scores) and categorized scores (4 different scores) were provided. Categorized scores were very much improved (consisting of very much improved and much improved); any improvement (consisting of very much improved, much improved, and minimally improved); no change (consisting of no change); and any worsening (consisting of minimally worse, much worse, and very much worse). Due to the crossover design, PGIC was analyzed at the end of period 1 (V5). | End of Period 1 (V5) |