Randomized, Double-Blind, Multicenter, Placebo-Controlled Study Of Pregabalin For Pain Associated With Diabetic Peripheral Neuropathy

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of pregabalin at 300 mg/day and 600 mg/day (BID) in patients with painful diabetic peripheral neuropathy.

Official Title
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Randomized, Double-Blind, Multicenter, Placebo-Controlled Study To Evaluate Efficacy And Safety Of Pregabalin (CI-1008) In The Treatment For Pain Associated With Diabetic Peripheral Neuropathy

Conditions
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Diabetic Neuropathy, Painful

Intervention / Treatment
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* Drug: placebo
* Drug: pregabalin
* Drug: pregabalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Visual Analogue Scale (VAS) of pain is higher than 40 mm. Diagnosis of type 1 or 2 diabetes mellitus for at least 1 year Exclusion Criteria: Malignancy within the past 2 years. Neurologic disorders unrelated to diabetic neuropathy that may confuse the assessment of neuropathy 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* Dosage: placebo, oral administration, Treatment duration: 13 weeks (1-week titration and 12-week fixed dose)<br>|
| Experimental: Pregabalin 300 mg/day<br> | Drug: pregabalin<br>* Dosage: 300 mg/day (150 mg bid), oral administration, Treatment duration: 13 weeks (1-week titration and 12-week fixed dose)<br>|
| Experimental: Pregabalin 600 mg/day<br> | Drug: pregabalin<br>* Dosage: 600 mg/day (300 mg bid), oral administration, Treatment duration: 13 weeks (1-week titration and 12-week fixed dose)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Study Endpoint in Mean Weekly Pain Scores | Change from baseline: Score at study endpoint minus score at baseline. Study endpoint is defined as the mean of the last seven entries of the daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) while on study medication up to and including day after last dose. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline to Study Endpoint in Mean Weekly Pain Scores by Groups of Subjects With Expected Similar Plasma Concentrations | Change from baseline: Score at study endpoint minus score at baseline. Study endpoint is defined as the mean of the last seven entries of the daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) while on study medication up to and including day after last dose. Subjects are classified by exposure to pregabalin, which is estimated by creatinine clearance (CLcr). | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Number of Responders | A responder is defined as a subject with a 50% reduction in weekly mean pain score from baseline to study endpoint. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline at Week 1 in Mean Weekly Pain Scores | The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 1. Change from baseline: Score at Week 1 minus score at baseline | From baseline to Week 1 | 
| Change From Baseline at Week 2 in Mean Weekly Pain Scores | The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 2. Change from baseline: Score at Week 2 minus score at baseline | From baseline to Week 2 | 
| Change From Baseline at Week 3 in Mean Weekly Pain Scores | The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 3. Change from baseline: Score at Week 3 minus score at baseline | From baseline to Week 3 | 
| Change From Baseline at Week 4 in Mean Weekly Pain Scores | The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 4. Change from baseline: Score at Week 4 minus score at baseline | From baseline to Week 4 | 
| Change From Baseline at Week 5 in Mean Weekly Pain Scores | The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 5. Change from baseline: Score at Week 5 minus score at baseline | From baseline to Week 5 | 
| Change From Baseline at Week 6 in Mean Weekly Pain Scores | The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 6. Change from baseline: Score at Week 6 minus score at baseline | From baseline to Week 6 | 
| Change From Baseline at Week 7 in Mean Weekly Pain Scores | The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 7. Change from baseline: Score at Week 7 minus score at baseline | From baseline to Week 7 | 
| Change From Baseline at Week 8 in Mean Weekly Pain Scores | The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 8. Change from baseline: Score at Week 8 minus score at baseline | From baseline to Week 8 | 
| Change From Baseline at Week 9 in Mean Weekly Pain Scores | The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 9. Change from baseline: Score at Week 9 minus score at baseline | From baseline to Week 9 | 
| Change From Baseline at Week 10 in Mean Weekly Pain Scores | The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 10. Change from baseline: Score at Week 10 minus score at baseline | From baseline to Week 10 | 
| Change From Baseline at Week 11 in Mean Weekly Pain Scores | The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 11. Change from baseline: Score at Week 11 minus score at baseline | From baseline to Week 11 | 
| Change From Baseline at Week 12 in Mean Weekly Pain Scores | The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 12. Change from baseline: Score at Week 12 minus score at baseline | From baseline to Week 12 | 
| Change From Baseline at Week 13 in Mean Weekly Pain Scores | The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 13. Change from baseline: Score at Week 13 minus score at baseline | From baseline to Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Physical Functioning | The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Role Limitations-Physical | The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Bodily Pain | The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Short Form 36-Item (SF-36) Health Survey: General Health Perception | The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Social Functioning | The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Role Limitations-Emotional | The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Vitality | The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Mental Health | The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Mean Sleep Interference Scores | The mean change from baseline in the weekly mean sleep interference score at study endpoint. Score range is from 0-10. Higher scores indicate more severe interference with sleep. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Short-Form McGill Pain Questionnaire: Sensory Scores | The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Sensory score ranges from 0-33. Higher scores indicate more severe pain. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Short-Form McGill Pain Questionnaire: Affective Scores | The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Affective score ranges from 0-12. Higher scores indicate more severe pain. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Short-Form McGill Pain Questionnaire: Total Scores | The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Total score ranges from 0-45. Higher scores indicate more severe pain. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Short-Form McGill Pain Questionnaire: Visual Analogue Scale Scores | The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Visual Analogue Scale Score ranges from 0-100 mm. Higher scores indicate more severe pain. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Short-Form McGill Pain Questionnaire: Present Pain Intensity Scores | The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Present pain intensity score ranges from 0-5. Higher scores indicate more severe pain. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Sleep Disturbance | The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for sleep disturbance ranges from 0-100. Higher scores indicate more severe pain. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Snoring | The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for snoring ranges from 0-100. Higher scores indicate more of the attribute. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Sleep Shortness of Breath or Headache | The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for sleep shortness of breath or headache ranges from 0-100. Higher scores indicate more of the attribute. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Quantity of Sleep | The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for quantity of sleep ranges from 0-24. Higher scores indicate more of the attribute named in the subscale. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Sleep Adequacy | The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for sleep adequacy ranges from 0-100. Higher scores indicate more of the attribute. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Somnolence | The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for somnolence ranges from 0-100. Higher scores indicate more of the attribute. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Overall Sleep Problems Index | The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for overall sleep problems index ranges from 0-100. Higher scores indicate more of the attribute. | From baseline to Week 13 or up to study discontinuation (Study Endpoint) | 
| Clinical Global Impression of Change | Clinical Global Impression of Change is a clinician-rated instrument that measures change in patient's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). | Week 13 or up to discontinuation | 
| Patient Global Impression of Change | The Patient Global Impression of Change is a patient-rated instrument that measures change in patient's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). | Week 13 or up to discontinuation |