Placebo-controlled Safety and Efficacy Study of Pregabalin in Subjects With Post-traumatic Peripheral Neuropathic Pain

Study Overview
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Brief Summary
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This study is designed to investigate if pregabalin is effective in treating neuropathic (nerve) pain resulting from peripheral nerve trauma due to a traumatic or surgical event such as, for example, motor vehicle accident, fall, sports injury, knee or hip replacement, hernia repair, thoracotomy, mastectomy, focal/localized burns or crush injury.

Official Title
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A Randomized Double Blind Placebo Controlled Parallel Group Study Of The Efficacy And Safety Of Pregabalin (Bid) In Subjects With Post-traumatic Peripheral Neuropathic Pain

Conditions
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Neuropathic Pain

Intervention / Treatment
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* Drug: pregabalin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have chronic peripheral neuropathic pain present for than 6 months after a traumatic or surgical event such as, for example, motor vehicle accident, fall, sports injury, knee or hip replacement, hernia repair, thoracotomy, mastectomy, focal/localized burns or crush injury. Subjects must be literate and have the ability (unaided) to understand and use the interactive voice response system (IVRS), have daily access to a telephone in order to complete the IVRS assessments each day, perform telephone visits and complete all required assessments/forms. Subjects must have sufficient post-traumatic neuropathic pain at screening and baseline. Exclusion Criteria: Subjects with neuropathic pain due to diabetic peripheral neuropathy (DPN), post herpetic neuralgia (PHN), HIV, trigeminal neuralgia (TGN), carpal tunnel syndrome (CTS) or with central neuropathic pain (for example, due to spinal cord injury) or with Complex Regional Pain Syndrome (CRPS, Type I or Type II). Subjects with other pain that may confound assessment or self-evaluation of the peripheral neuropathic pain. Subjects who have failed pregabalin treatment due to lack of efficacy with an adequate course of therapy at doses greater than or equal to 150 mg/day, who have previously participated in a pregabalin clinical trial or who have been treated with pregabalin at any time during the 6 month period prior to screening. Subjects with epilepsy; pernicious anemia; hematological illnesses; known HIV infection; any clinically unstable cardiovascular (including a myocardial infarction [heart attack] in the 3 months prior to screening), hematological, autoimmune, endocrine, renal, hepatic (including chronic hepatitis B, hepatitis B within the 3 months prior to screening) respiratory, or gastrointestinal disease; symptomatic peripheral vascular disease including intermittent claudication; uncontrolled diabetes mellitus; untreated hypothyroidism. Subjects with a diagnosis of DSM-IV TR Axis I disorder (including, for example, schizophrenia, bipolar disorder) with the exceptions of Generalized Anxiety Disorder (GAD) or major depression that is clinically stable. Subjects considered at risk of suicide or self-harm based on investigator judgment and/or details of a risk assessment. Use of prohibited medications in the absence of appropriate washout periods.

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 |
| --- | --- |
| Active Comparator: pregabalin<br> | Drug: pregabalin<br>* capsules, 150-600 mg/day administered in divided doses twice a day for 15 weeks after randomization<br>* Other names: Lyrica, PD-144723;|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* capsules, placebo for pregabalin administered in divided doses twice a day for 15 weeks after randomization<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Mean Pain Score | This is based on the daily pain dairy and is defined as the baseline mean pain diary score. The Daily Pain Diary consists of an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst possible pain). Subjects describe their pain during the past 24 hours by choosing the appropriate number between 0 and 10. | Baseline | 
| Change From Baseline to Week 15 in Weekly Mean Pain Score | This is based on the daily pain diary and is defined as the change from baseline to week 15 in mean pain diary score. The Daily Pain Diary consists of an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst possible pain). Subjects describe their pain during the past 24 hours by choosing the appropriate number between 0 and 10. | up to Week 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Global Impression of Change (PGIC) at Week 15 | A self administered instrument that measures changes in participants' overall status on a scale ranging from 1 (very much improved) to 7 (very much worse). The PGIC is based on the Clinical Global Impression of Change, which is a validated scale. | Week 15 | 
| Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS) | This is an 11-point NRS ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep [unable to sleep due to pain]). Participants describe how pain has interfered with their sleep during the past 24 hours. Please note that the data for Baseline (raw scores) have been included in the below table to read the change from Baseline data in context. Note: Weekly mean SIRS scores were derived from the daily sleep diary and calculated as the mean of the available scores in the 7 days. Generally, week 'n' mean SIRS scores were defined as the mean of the 7 daily diary SIRS scores from Day 2+7 (n-1) to Day 1+7*n. For participants with multiple diary scores collected on the same day, the average of all non-missing scores for that day was used in any analyses or data listings. Overall is the pooled average sleep interference score for each subject across all post-baseline/randomization weeks. | up to Week 15 | 
| Change From Baseline in Pain Severity Index (Brief Pain Inventory-short Form [BPI-sf]) | A self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during the 24 hour period prior to evaluation. The BPI-sf consists of 5 questions. Four items measure pain on 11-point response scales from 0 (No Pain) to 10 (Pain as bad as you can imagine). In the above scale, score 0 indicates the better outcome whereas score 10 indicates the worse outcome. | Week 15 | 
| Change From Baseline in Pain Interference Index (BPI-sf) | BPI-sf is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during the 24 hour period prior to evaluation. It consists of 7 sub-questions that evaluates the level of pain interference with daily functioning on 11-point response scales from 0 (does not interfere) to 10 (completely interferes). The BPI-sf pain interference index was calculated as average of the seven individual pain interference scores. | Week 15 | 
| Change From Baseline to Endpoint in Quality of Life Using EuroQol (EQ-5D) Health State Profile Scores | A self-administered 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 and the scores are combined to form a single index value between 0 and 1 with higher scores being more positive (better health status). The EQ-5D was completed by the subject at week-0 and week-15/ET where 30% responder and 50% responder status would be defined for each participants based on the percent change from baseline (week 0/Randomization) to each visit week in mean pain score and participant global impression of change (PGIC). PGIC is a self-administered instrument that measures change in participant's overall status on a scale ranging from 1 (very much improved) to 7 (very much worse). It is based on the Clinical Global Impression of Change CGIC), which is a validated scale. | Week 15 | 
| Baseline Scores in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score. | MOS-SS is a self administered measure consisting of twelve items that assess the key constructs of sleep. Instrument scored results in 7 subscales: sleep disturbance, snoring, awaken short of breath or with headache, quantity of sleep, optimal sleep, sleep adequacy, somnolence. Two index measures that assess sleep disturbance was also constructed to provide composite scores. Sleep disturbance, snoring, somnolence, awaken short of breath, and the 9 items sleep problems index all have score ranges from 0 (no sleep problems) to 100 (greater sleep problems), therefore a negative change indicates improvement. Sleep adequacy is scored 0 (least sleep adequacy) to 100 (better sleep adequacy), therefore a positive change indicates improvement. Quantity of sleep is scored 0 (less quantity of sleep) to 24 (greater quantity of sleep), therefore a positive change indicates improvement. Optimal sleep is scored Yes if average hours of sleep is in range of 7-8 hours. | Baseline | 
| Mean Change From Baseline in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score. | MOS-SS is a self administered measure consisting of twelve items that assess the key constructs of sleep. Instrument scored results in 7 subscales: sleep disturbance, snoring, awaken short of breath or with headache, quantity of sleep, optimal sleep, sleep adequacy, somnolence. Two index measures that assess sleep disturbance was also constructed to provide composite scores. Sleep disturbance, snoring, somnolence, awaken short of breath, and the 9 items sleep problems index all have score ranges from 0 (no sleep problems) to 100 (greater sleep problems), therefore a negative change indicates improvement. Sleep adequacy is scored 0 (least sleep adequacy) to 100 (better sleep adequacy), therefore a positive change indicates improvement. Quantity of sleep is scored 0 (less quantity of sleep) to 24 (greater quantity of sleep), therefore a positive change indicates improvement. Optimal sleep is scored Yes if average hours of sleep is in range of 7-8 hours. | Week 15 | 
| Percentage of Participants in MOS-SS With Optimal Sleep Status. | MOS-SS optimal sleep status analyzed on a scale of four parameters: any improvements, no change, any worsening and not applicable. | Week 15 | 
| Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%. | Participants with at least 30% reduction in the mean pain score from baseline to each week. Weekly mean pain NRS scores are derived from the daily pain NRS and calculated as the mean of the available scores in the 7 days. Generally, week 'n' mean pain score is defined as the mean of the 7 daily diary pain ratings from Day 2+7*(n-1) to Day 1+7*n. At least 4 entries within the last 7 days are required to calculate a mean score. Scores range from 0 (no pain) to 10 (worst possible pain), with higher scored indicating increased pain. | Week 15 | 
| Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50% | Participants with at least 50% reduction in the mean pain score from baseline to each week. Weekly mean pain NRS scores are derived from the daily pain NRS and calculated as the mean of the available scores in the 7 days. Generally, week 'n' mean pain score is defined as the mean of the 7 daily diary pain ratings from Day 2+7*(n-1) to Day 1+7*n. At least 4 entries within the last 7 days are required to calculate a mean score. Scores range from 0 (no pain) to 10 (worst possible pain), with higher scored indicating increased pain. | Week 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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post-traumatic peripheral neuropathic pain