Efficacy Study Measuring the Impact of Pregabalin on Peripheral Neuropathic Pain.

Study Overview
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Brief Summary
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This study will measure the impact of treatment with pregabalin in adult men and women who have a diagnosis of peripheral neuropathic pain (pain caused by a primary lesion of the peripheral nervous system such as Diabetic peripheral Neuropathy and Postherpetic Neuralgia).

Official Title
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A Randomized, Placebo-Controlled Trial of the Efficacy and Safety of Pregabalin in the Treatment of Subjects With Peripheral Neuropathic Pain

Conditions
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Neuropathic Pain

Intervention / Treatment
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* Drug: Pregabalin (Lyrica)
* Drug: Pregabalin (Lyrica)
* Drug: Pregabalin (Lyrica)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects presenting a diagnosis of peripheral neuropathic pain, defined as pain caused by a lesion of the peripheral nervous system manifesting with sensory symptoms and signs, for at least 6 months at screening. At baseline, subjects must have completed at least 4 daily pain diaries and must have a mean weekly pain score equal or greater than 4. Exclusion Criteria: Presence of any of the following diagnoses: Cervical or lumbo-sacral radiculopathy; Operated or non-operated chronic low back pain Carpal tunnel syndrome or any other entrapment-related neuropathic pain (defined as pain associated with focal nerve lesion produced by constriction or mechanical distortion of the nerve, within a fibrous or fibro-osseous tunnel, or by a fibrous band) ; Complex regional pain syndrome (type 1 and 2); Fibromyalgia.

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 |
| --- | --- |
| Experimental: 1<br> | Drug: Pregabalin (Lyrica)<br>* pregabalin 150mg/day (75mg BID)<br>|
| Experimental: 2<br> | Drug: Pregabalin (Lyrica)<br>* pregabalin 300 mg/day (150mg BID)<br>|
| Experimental: 3<br> | Drug: Pregabalin (Lyrica)<br>* pregabalin 600/day (300mg BID)<br>|
| Placebo Comparator: 4<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropathic Pain in Subjects With Peripheral Neuropathic Pain Conditions During the Double-blind Phase | Pain score end of Double-Blind treatment = mean of last 7 available pain scores from daily pain diary while on Double-Blind treatment. A Daily Pain Rating Score : 11- point numerical scale ranging from 0 (no pain) to 10 (worst possible pain). | 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weekly Mean Pain Scores During the Single-blind Treatment Phase | Pain score at Week 0 and Week 4, end of single-bind treatment. Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11- point numerical scale ranging from 0 (no pain) to 10 (worst possible pain). | 0 and 4 weeks | 
| Weekly Mean Pain Scores During the Double Blind Treatment Phase | Mean Pain scores for weeks 4, 5, 6, 7, 8 and 9. Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11-point numerical scale ranging from 0 (no pain) to 10 (worst possible pain). | Week 4 - 9 | 
| Change in Pain Scores During Double Blind Treatment Phase | Change in Mean Pain score = Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11-point numerical scale ranging from 0 (no pain) to 10 (worst possible pain). | 9 weeks | 
| Number of Subjects With >= 30% Reduction in Mean Pain Score During Single-blind Treatment | Responders = ≥30% reduction in mean pain score at end of single-blind treatment phase compared to weekly mean pain score at baseline. Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11-point numerical scale ranging from 0 (no pain) to 10 (worst possible pain). | Week 4 (end of single-blind treatment phase) | 
| Mean Pain Score for Responders at End of Single-blind Treatment Phase. Change From Baseline of Mean of Last 7 Available Pain Scores From Daily Pain Diary While on Single-blind Treatment. | Daily Pain Rating Score:11-point numerical scale 0 (no pain) to 10 (worst possible pain). Responders = ≥30% reduction in mean pain score at end of single-blind treatment phase compared to weekly mean pain score at baseline. | Week 4 | 
| Mean Pain Score for Non-responders at End of Single-blind Treatment Phase | Change from baseline of mean of last 7 available pain scores from daily pain diary while on single-blind treatment. Daily Pain Rating Score:11-point numerical scale 0 (no pain) to 10 (worst possible pain). Non-Responders = <30% reduction in mean pain score at end of single-blind treatment phase compared to weekly mean pain score at baseline. | Week 4 | 
| Categorized Daily Pain Score | Mean number of days in each pain category. DPRS Daily Pain Rating Score Categories: No pain (score 0), Mild pain (scores 1-3), Moderate pain (scores 4-6), Severe pain (scores 7-10) | Week 9 | 
| Time to Meaningful Increase in Pain During Double-blind Treatment Phase (Number of Participants) | Number of participants who experienced a meaningful increase in pain also includes participants who took rescue medication for pain due to peripheral neuropathic pain or discontinued from the study . | Week 9 | 
| Mean Sleep Interference Score | Mean Sleep Interference (SI) score at end of Double-Blind treatment = mean of last 7 available SI scores from daily SI diary while on Double-Blind treatment. Daily SI rating scale (DSIS) consists of an 11-point numerical scale : Zero means pain does not interfere with sleep and 10 means pain completely interferes with sleep. | Week 9 | 
| Weekly Mean Sleep Interference Scores During the Single-Blind Treatment Phase | Sleep Interference (SI) score at Week 0 and Week 4, end of single-bind treatment. Mean of last 7 available SI scores from daily SI diary while on single-blind treatment. Daily SI rating scale (DSIS) consists of an 11-point numerical scale : Zero means pain does not interfere with sleep and 10 means pain completely interferes with sleep. | 0 and 4 weeks | 
| Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase | Mean Sleep Interference scores for weeks 4, 5, 6, 7, 8 and 9. Mean of last 7 available SI scores from daily SI diary while on single-blind treatment. Daily SI rating scale (DSIS) consists of an 11-point numerical scale : Zero means pain does not interfere with sleep and 10 means pain completely interferes with sleep. | Week 9 | 
| Change in Sleep Interference Scores During Double Blind Treatment Phase | Change in Mean SI score: Mean SI score at observation minus mean SI score at week 4. Mean SI Score = mean of last 7 available SI scores from daily SI diary while on single-blind treatment. Daily SI rating scale (DSIS) is 11-point numerical scale : Zero means pain does not interfere with sleep and 10 means pain completely interferes with sleep. | 9 weeks | 
| Intensity of Neuropathic Pain -Visual Analog Scale (NeP - VAS) | Change in Scale from randomization to Week 9. Scale to measure Neuropathic Pain -Visual Analog Scale (NeP - VAS): the subject places a mark on the VAS scale (0 to 100) where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. | Week 4, Week 9 | 
| Change in Hospital Anxiety and Depression Scale Responses | Mean Change from Randomization in Score from Hospital Anxiety and Depression Scale (HADS): 2 subscales, measuring anxiety (HADS-A)and depression (HADS-D). 7 items in each subscale assessed on a scale of 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). which yields the score ranging 0-21. | Week 9 | 
| Change in Pain Treatment Satisfaction Scale (PTSS) | Mean Change: score from observation minus score from randomization: PTSS Impact module of 8-items & Satisfaction module of 6-items; item scores 1-5. Mean score for each module transformed onto scale 0- 100, where score 0 =worst possible response and score 100 =best possible response: Score =[(5 - mean non-missing items)*100]/4. | Week 9 | 
| Patient Global Impression of Change (PGIC) Categories by Number of Subjects | Number of subjects that responded to PGIC Categories. PGIC is a subject-rated instrument that measures change in the subject's overall status on a 7-point scale. Scores range from 1 (very much improved) to 7 (very much worse). | Week 9 | 
| Change in Modified Brief Pain Inventory (mBPI) for Pain Interference or Pain Severity. | Mean Change from Randomization: score at mBPI observation minus score at randomization. mBPI is extent to which pain interferes with daily activities on a 0 (no interference) to 10 (completely interfered) scale. | Week 9 | 
| Change in Euro Quality of Life (EQ-5D) Health State Profile and Visual Analog Scale Components | two components to the EQ-5D: a Health State Profile (scores from five domains are used to calculate the utility score :0 refers to dead and a score of 1 refers to perfect health) and a Visual Analogue Scale (VAS) (0 represents the worst imaginable health state and 100 represents the best imaginable health state) | Week 9 |