Pregabalin Peripheral Neuropathic Pain Study

Study Overview
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Brief Summary
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To evaluate the efficacy of pregabalin, using a flexible, optimized dose schedule with dose adjustment based on Daily Pain Rating Scale (DPRS), compared to placebo in subjects with peripheral neuropathic pain.

Official Title
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A 10-Week, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pregabalin (150 mg - 600 mg/Day) Using a Flexible, Optimized Dose Schedule in Subjects With Peripheral Neuropathic Pain

Conditions
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Diabetic Neuropathies, Neuralgia

Intervention / Treatment
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* Drug: pregabalin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of peripheral neuropathic pain syndrome, including diabetic peripheral neuropathy (DPN), postherpetic neuralgia (PHN), or post-traumatic neuropathic pain (including post-surgical), confirmed by a qualified pain specialist. Subjects must have completed at least 4 daily pain diaries during the 7 days prior to Visit 2 and have an average pain score of ≥4 over the 7 days prior to Visit 2 (randomization). Exclusion Criteria: Neurologic disorders unrelated to DPN, PHN, or post-traumatic neuropathic pain (including post-surgical), that may confuse or confound the assessment of neuropathic pain. Presence of any severe pain associated with conditions other than DPN, PHN, or post-traumatic neuropathic pain (including post-surgical) that may confound the assessment or self evaluation of the pain due to DPN, PHN, or post-traumatic neuropathic pain (including post-surgical). Creatinine clearance < 30 mL/min (estimated from serum creatinine, body weight, age, and sex using the Cockcroft and Gault equation in Appendix E). Maximum dose for subjects with creatinine clearance of 30 to 60 mL/min is 300 mg/day

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: 1<br> | Drug: pregabalin<br>* 150-600mg/day, BID<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Pain Rating Scale (DPRS)- Mean Pain Score (ITT Population) | DPRS is 11-point rating scale from 0 (no pain) to 10 (worst possible pain). Subjects instructed to describe their pain (daily upon awakening) during preceding 24 hrs by choosing the appropriate number between 0-10. Mean endpoint pain score was obtained from the last 7 available DPRS scores of the daily pain diary while subject on study medication. | Endpoint- Week 8 or Early Discontinuation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Pain Rating Scale (DPRS)- Number of 30% Responders (With Respect to Pain Scores) | DPRS consists of an 11-point rating scale ranging from 0 (no pain) to 10 (worst possible pain). A 30% responder at endpoint is a subject who has a 30% or more reduction in mean pain score at endpoint compared to baseline | Endpoint- Week 8 or Early Discontinuation | 
| Daily Pain Rating Scale (DPRS)- Number of 50% Responders (With Respect to Pain Scores) | DPRS consists of an 11-point rating scale ranging from 0 (no pain) to 10 (worst possible pain). A 50% responder at endpoint is a subject who has a 50% or more reduction in mean pain score at endpoint compared to baseline. | Endpoint- Week 8 or Early Discontination | 
| Daily Pain Rating Scale (DPRS)- Weekly Mean Pain Score | DPRS is 11-point rating scale (0=no pain to 10=worst possible pain). Subjects instructed to describe pain (upon awakening) during preceding 24 hrs by choosing appropriate number between 0-10. Mean endpoint pain score obtained from last 7 available DPRS scores of daily pain diary while subject on study medication. Overall Comparison=8-week average. | Weeks 1 to 8 | 
| Duration Adjusted Average Change (DAAC) of (Adjusted) Mean Pain Score | DAAC is a score used to assess treatment effects averaged over the entire length of the study. DAAC from baseline to weekly mean pain score was derived by calculating the mean of all post-baseline scores minus baseline mean pain score, and then weighing this according to the proportion of the planned study duration the subject actually completed. | Weeks 1 to 8 | 
| Mean Sleep Interference Score Based on Daily Sleep Interference Scale (DSIS). | DSIS consists of an 11-point rating scale (0 = pain did not interfere with sleep to 10 = completely interfered with sleep). Higher score indicating greater level of sleep disturbance. | Endpoint- Week 8 or Early Discontinuation | 
| Mean Sleep Score as Computed by DSIS. | DSIS consists of an 11-point rating scale ranging from 0 = pain did not interfere with sleep to 10 = pain completely interfered with sleep. Overall Comparison= 8-week average. | Weeks 1 to 8 | 
| Medical Outcome Study (MOS) Sleep Disturbance | MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Sleep Disturbance sub-scale scores range from 0 to 100, lower scores indicate less disturbance. | Week 8 | 
| Medical Outcome Study (MOS) Snoring Score | MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Snoring sub-scale scores range from 0 to 100, lower scores indicate less snoring. | Week 8 | 
| Medical Outcome Study (MOS) Awaken Short of Breath or Headache | MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Awaken Short of Breath or with a Headache sub-scale scores range from 0 to 100, lower scores indicate less difficulty. | Week 8 | 
| Medical Outcome Study (MOS) Sleep Quantity | MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Sleep Quantity sub-scale scores range from 0 to 24 (number of hours slept). | Week 8 | 
| Medical Outcome Study (MOS) Optimal Sleep: Number of Participants With Optimal Sleep | MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Optimal Sleep sub-scale score is a binary outcome derived from Sleep Quantity (SQ): the response is YES (or 1) if SQ = 7 or 8 hours per night. | Week 8 | 
| Medical Outcome Study (MOS) Sleep Adequacy | MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Sleep Adequacy sub-scale scores range from 0 to 100, higher scores indicate greater sleep adequacy. | Week 8 | 
| Medical Outcome Study (MOS) Somnolence | MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Somnolence sub-scale scores range from 0 to 100, lower scores indicate less somnolence. | Week 8 | 
| Medical Outcome Study (MOS) Overall Sleep Problems Index | MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Overall Sleep Problems Index is a 9-item sub-scale; scores range from 0 to 100, lower scores indicate fewer sleep problems. | Week 8 | 
| Euro Quality of Life (QOL) (EQ-5D) Utility Score | EQ-5D, a subject-completed questionnaire, assesses health-related QOL. QOL Health State Profile (HSP) is designed to record subject's level of current health across 5 domains (mobility, self-care, usual activities, pain/discomfort & anxiety/depression); scores are used to calculate EQ-5D Utility Score; range: -0.594 to 1.000 (from worst to best). | Week 8 | 
| Euro Quality of Life (EQ-5D) Visual Analog Scale (VAS) | EQ-5D is a subject-completed questionnaire to assess health-related QOL (Health State Profile (HSP) & Visual Analog Scale (VAS)). The VAS is designed to rate the subject's current health state on a scale from 0 to 100 where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. | Week 8 | 
| Hospital Anxiety and Depression Scale- Anxiety (HADS-A) Score | HADS-A consists of 7 items that are assessed by a score of 0 = no anxiety to 3 = severe feeling of anxiety. The anxiety subscale determines a state of generalized anxiety (including anxious mood, restlessness, anxious thoughts, panic attacks). Score range = 0 to 21; higher scores indicate a greater intensity of anxiety | Week 8 | 
| Hospital Anxiety and Depression Scale- Depression (HADS-D) Score | HADS-D consists of 7 items that are assessed by a score of 0 = no depression to 3 = severe feeling of depression. The depression subscale focuses on the state of lost interest and diminished pleasure response (lowering of hedonic tone). Score range = 0 to 21; higher scores indicate a greater intensity of depression | Week 8 | 
| Patient Global Impression of Change (PGIC) | PGIC is a subject-rated instrument that measured change in subject's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improved = minimally improved, much improved, and very much improved; Worse = minimally worse, much worse, and very much worse. | Week 8 | 
| Clinical Global Impression of Change (CGIC) | CGIC is a clinician-rated instrument that assesses the subject's overall global improvement on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improved = minimally improved, much improved, and very much improved; Worse = minimally worse, much worse, and very much worse. | Week 8 | 
| Duration Adjusted Average Change (DAAC) of (Unadjusted) Mean Pain Score | DAAC is a score used to assess treatment effects averaged over the entire length of the study. DAAC from baseline to weekly mean pain score was derived by calculating the mean of all post-baseline scores minus baseline mean pain score, and then weighing this according to the proportion of the planned study duration the subject actually completed. | Weeks 1 to 8 |