A Study to Compare QUTENZA With Pregabalin for the Treatment of Peripheral Neuropathic Pain (PNP) After 8 Weeks of Treatment

Study Overview
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Brief Summary
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This study is comparing the efficacy and tolerability of Qutenza with that of pregabalin in patients suffering from peripheral neuropathic pain. Treatment allocation will be to one of these treatments and the duration of the study will be about 10 weeks (assuming that from screening to treatment allocation takes 2 weeks). Participants will be asked to complete questionnaires about various aspects relating to their condition throughout the study. This study will include subjects suffering from Postherpetic Neuralgia, Peripheral Nerve Injury or Non Diabetic peripheral polyneuropathy.

Official Title
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Qutenza Versus Pregabalin in Subjects With Peripheral Neuropathic Pain: an Open-label, Randomized, Multicenter, Non-inferiority Efficacy and Tolerability Study

Conditions
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Non-diabetic Painful Peripheral Polyneuropathy, Postherpetic Neuralgia (PHN), Peripheral Nerve Injury (PNI)

Intervention / Treatment
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* Drug: Qutenza
* Drug: Pregabalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Documented diagnosis of probable or definite PNP 2. Localized and well-defined area of PNP, suitable for treatment with QUTENZA 3. Documented diagnosis at the Baseline Visit of either: Postherpetic neuralgia (PHN) with pain persisting at least 6 months since shingles vesicle crusting Peripheral nerve injury (PNI) including post-surgical or post-traumatic neuropathic pain, persisting for a minimum of 3 months Non-diabetic painful peripheral polyneuropathy with pain which has persisted for a minimum of 3 months, including (i) small-fiber neuropathy, as confirmed by quantitative sensory testing (QST), laser evoked potentials (LEP) or skin biopsy, (ii) chemotherapy induced neuropathy in subjects with stable neoplastic disease, (iii) other, adequately characterized painful peripheral polyneuropathy, based on clinical history and examination 4. Average pain score ≥4 during Screening Period, over a minimum of at least 4 consecutive days (using the average pain for the past 24 hours Numeric Pain Rating Scale (NPRS) score 5. Intact, non-irritated, dry skin over the painful area(s) to be treated 6. Is either: Naïve to treatment with pregabalin and gabapentin, OR In the opinion of the investigator, has not received an adequate trial of treatment with pregabalin or gabapentin 7. Subject is willing to receive pregabalin or QUTENZA as part of the trial 8. Females of child bearing potential must be willing to use highly effective methods of birth control during the study and for 30 days following study termination Exclusion Criteria: 1. Significant ongoing or recurrent pain of etiology other than PHN, PNI or non-diabetic painful peripheral polyneuropathy, for example: compression-related neuropathies (e.g. spinal stenosis), radiculopathy, tumor-related pain, fibromyalgia or arthritis 2. Complex Regional Pain Syndrome (CRPS, Type I or II) 3. Neuropathic pain related to previously administered radiotherapy, diabetes mellitus or HIV-AN 4. Neuropathic pain areas located only on the face, above the hairline of the scalp, and/or in proximity to mucous membranes 5. Severe loss of heat sensation in the painful area, indicative of C-fiber denervation 6. Reported daily pain score of 10 on the NPRS for at least 4 days during the Screening Period 7. Past or current history of diabetes mellitus 8. Unstable or poorly controlled hypertension or a recent history of a cardiovascular event which, in the opinion of the investigator, would put the subject at risk of adverse cardiovascular reactions related to the patch application procedure 9. Creatinine clearance (CLcr) < 60mL/min according to the Cockcroft-Gault formula 10. Untreated ongoing generalized anxiety disorder according to DSM-IV or ICD-10 criteria 11. Severe ongoing depression according to DSM-IV or ICD-10 criteria 12. Evidence of cognitive impairment including dementia that may interfere with subject's ability to complete study evaluations and recall pain levels in the past 24 hours 13. Planned elective surgery during the trial 14. Changes to stable neuropathic pain background medication in the 4 weeks prior to the Baseline Visit 15. Any prior receipt of QUTENZA patches, including blinded patches administered as part of a clinical trial 16. Hypersensitivity to capsaicin (i.e., chilli peppers or Over-the-counter [OTC] capsaicin products), any QUTENZA excipients, local anesthetics, or adhesives 17. Treatment with pregabalin or gabapentin within 2 months prior to the Baseline Visit 18. Hypersensitivity to pregabalin or any of the excipients 19. Use of opioids exceeding a total daily dose of morphine of 200 mg/day, or equivalent; or any intravenous opioids or tapentadol, regardless of dose, within 7 days preceding the Baseline Visit 20. Use of any topical pain medication, such as non-steroidal anti-inflammatory drugs, menthol, methyl salicylate, local anesthetics (including patch containing lidocaine), steroids or capsaicin products on the painful areas to be treated within 7 days preceding the Baseline Visit 21. Chemotherapy within 3 months of the Baseline Visit, except maintenance hormone treatment 22. Use of any investigational agent within 30 days prior to Baseline Visit 23. Active substance abuse or history of chronic substance abuse within 1 year prior to screening; or any prior chronic substance abuse (including alcoholism) likely to re-occur during the study period as judged by the investigator 24. Female subjects of child-bearing potential with a positive serum or urine pregnancy test prior to treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Qutenza<br>Cutaneous patch | Drug: Qutenza<br>* Cutaneous patch<br>* Other names: Capsaicin;|
| Active Comparator: Pregabalin<br>Oral capsule | Drug: Pregabalin<br>* Oral capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects in each arm who achieve at least 30% decrease in the average pain for the past 24 hours Numeric Pain Rating Scale (NPRS) score from baseline to week 8 |  | Baseline and week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects in each arm who achieve optimal Therapeutic effect | Optimal therapeutic effect is defined as: No change in background chronic pain medication and no discontinuation of study drug due to lack of efficacy or tolerability prior to Week 8 At least a 30% reduction in the average pain for the past 24 hours NPRS score, from baseline to Week 8, and No moderate or severe adverse drug reactions (ADRs) during the stable Treatment Period | Baseline and week 8 | 
| Proportion of subjects who achieve at least a 30% decrease in the average pain for the past 24 hours | NPRS score from baseline to the mean of all scores recorded between Week 1 (Day 8) and Week 8 (Day 57) | Baseline to Week 8 | 
| Proportion of subjects who achieve at least a 50% decrease in the average pain for the past 24 hours | NPRS score from baseline to week 8, and from baseline to the mean of all scores recorded between Week 1 (Day 8) and Week 8 (Day 57) | Baseline to Week 8 | 
| Absolute and percent change in average pain for the past 24 hours | NPRS score from baseline to Week 8, and from baseline to the mean of all scores recorded between Weeks 1 to 8 | Baseline to Week 8 | 
| Time to onset of pain relief (in days) | Assessed by at least a 30% reduction in average pain for the past 24 hours NPRS score | Up to 8 weeks | 
| Overall subject status using Patient Global Impression of Change (PGIC) questionnaire |  | At Weeks 4 and 8 | 
| Change in the Medical Outcomes Study (MOS) 6-Item Cognitive Functioning Scale |  | Baseline to Week 8 | 
| MOS - Sleep Scale |  | Baseline to Weeks 4 and 8 | 
| Change in the EQ-5D-5L (Euroqol-5 dimensions-5 levels) total score |  | Baseline to Week 8 | 
| Treatment satisfaction | As assessed by: Proportion of subjects who discontinue study drug or withdraw from the study due to either a lack of efficacy or tolerability Treatment Satisfaction Questionnaire for Medication (TSQM) questionnaire at Week 4 and Week 8 | Baseline to Weeks 4 and 8 | 
| Treatment satisfaction - continuance of treatment | As assessed by willingness to continue treatment at Week 8 | Week 8 | 
| Time to reach optimal maintenance dose for pregabalin |  | Baseline to Week 8 | 
| Healthcare Resource use | Number of contacts with health professionals | Baseline to Week 8 | 
| Tolerability (Assessed by the number, severity and duration of ADRs) | Collected as self-rated health-related complaints by the subject and then medically confirmed and causality assigned by the investigator | Baseline to Week 8 | 
| Change in intensity and area of allodynia |  | Baseline to Week 8 | 
| Changes in sensory symptoms | Assessed using Neuropathic Pain Symptom Inventory (NPSI) scores | Baseline to Week 8 | 
| Reduction in pain | By the pattern of sensory symptoms as defined using NPSI scores at baseline. | Baseline to Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post herpetic neuralgia, Qutenza, NGX-4010, Peripheral Neuropathic Pain, Pregabalin