A Study With Lido-Patch and Placebo Plaster in Patients Suffering From Postherpetic Neuralgia (PHN)

Study Overview
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Brief Summary
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This study investigated the efficacy of the Lido-Patch (lidocaine 5% medicated plaster) in treatment of pain caused by PHN which is a neuropathic pain syndrome (nerve-related pain conditions) following an acute attack of herpes zoster (shingles).

Detailed Description
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Participants were treated up to 10 weeks in this study: an 8-week Run-in Phase of open-label treatment with Lido-Patch was followed by a 2-day to 14-day Double-blind Phase with Lido-Patch or Placebo Patch treatment. Only participants responding to open-label treatment with Lido-Patch were included in the Double-blind Phase. In a Follow-up Phase without treatment, the safety of participants was monitored for 1-2 weeks. Alternatively, patch application could be continued for up to 12 months in the clinical study KF10004/02.

Official Title
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A Double-blind, Multicentre, Multiple-dose, Enriched Enrolment, Randomized-withdrawal, Parallel-group Phase III Study With Lido-Patch and Corresponding Placebo Plaster in Patients Suffering From Postherpetic Neuralgia (PHN)

Conditions
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Post Herpetic Neuralgia

Intervention / Treatment
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* Drug: Lidocaine 5% medicated Plaster
* Drug: Placebo Plaster


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for the Run-in Phase: Adult participants, male and female, with a minimum age of 50 years at screening. Participants who had postherpetic neuralgia (PHN) for at least 3 months after healing of a herpes zoster skin rash. Pain score of at least 4, based on an 11-point numerical rating scale (NRS) (scale of 0-10), at the screening and enrolment visit. The pain assessment is the participant's recall of the pain intensity since the previous week. Written informed consent given. Randomization Criteria: Participants must be regularly (minimum every second day) using the Lido-Patch for control of pain in the last 4 weeks of the run-in phase. The participant must wait for pain to increase before applying a new patch. The participants' average daily pain intensity (with patch on) must be 7 or less on an 11-point NRS (scale of 0-10), and must increase during the phases when a patch is not worn, during Week 8 of the Run-in Phase. Before randomization, the participant must have an average relief with Lido-Patch of moderate or better, on a 6-item scale (worse, no pain relief, slight, moderate, a lot, complete) during Week 8 of the Run-in Phase. Exclusion Criteria: Participation in another study of investigational drugs or devices parallel to, or less than 30 days before screening, or previous participation in this study. Known to or suspected of not being able to comply with the study protocol. Any clinically significant condition that would, in the investigator's opinion, preclude study participation for instance alcohol, medication or drug dependency, neurotic personality, psychiatric illness, epilepsy or suicide risk. Pregnancy or nursing mother. Woman in childbearing age without satisfactory contraception. Hypersensitivity to lidocaine or amide-type local anesthetic drugs. Active herpes zoster lesion or dermatitis of any origin at the affected site with PHN. Evidence of another cause for pain in the area affected by herpes zoster in addition to PHN, such as lumbar radiculopathy, surgery or trauma, if this could confound assessment or self-evaluation of the pain due to post herpetic neuralgia. Participants who had neurological ablation by block or neurosurgical intervention for control of pain in PHN. Participants using topically applied analgesic compounds on the PHN affected area. Presence of other severe pain that could confound assessment or self-evaluation of the pain due to PHN. Participants with severe hepatic disorder and/or alanine or aspartate aminotransferase equal to or above 3-fold the upper limit of normal (ULN). Participants with severe renal disorder and/or increased serum creatinine equal to or above 1.5-fold the upper limit of normal (ULN). Participants who are undergoing active treatment for cancer, are known to be infected with the human immunodeficiency virus (HIV), or being acutely and intensively immunosuppressed following transplantation.

Ages Eligible for Study
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Minimum Age: 50 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: Sequential Assignment
Interventional Model Description: An enriched enrolment, randomized-withdrawal, parallel-group design was applied. Only participants responding to open-label active treatment were included into the Double-blind Phase. The study comprised: A non-controlled, open-label enrichment phase with Lido-Patch treatment (Run-in Phase). A double-blind, randomized-withdrawal phase (Double-blind Phase). Upon request of the participant, treatment could be continued in the clinical study KF10004/02. A Follow-up Phase without treatment for participants not continuing in KF10004/02.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lido-Patch (Open-label Run-in Phase)<br>All participants applied up to 3 Lido-Patches (lidocaine 5% medicated plaster) per day (depending on the size of PHN area). Patches were applied topically for up to 12 hours per day (patch free interval: at least 12 hours) at the site of skin affected by painful PHN. | Drug: Lidocaine 5% medicated Plaster<br> <br> * Other names: Neurodol Tissugel (Trade Mark);|
| Experimental: Lido-Patch (Double-blind Phase)<br>Up to 3 patches (lidocaine 5% medicated plaster) per day (depending on the size of PHN area) were applied topically for up to 12 hours per day (patch free interval: at least 12 hours) at the site of skin affected by painful PHN. | Drug: Lidocaine 5% medicated Plaster<br> <br> * Other names: Neurodol Tissugel (Trade Mark);|
| Placebo Comparator: Placebo Patch (Double-blind Phase)<br>Up to 3 placebo plasters per day (depending on the size of PHN area) were applied topically for up to 12 hours per day (patch free interval: at least 12 hours) at the site of skin affected by painful PHN. | Drug: Placebo Plaster<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-exit in Double-blind Phase Due to Lack of Efficacy | The time to exit was defined as the number of days after randomization where worsening of the pain relief score by 2 or more categories on a 6-item pain relief scale (verbal rating scale, VRS) on 2 consecutive days in comparison to the average pain relief in Week 8 of the Run-in Phase was reported. The average pain relief in Week 8 of the enrichment phase was to be stated by the participant at the randomization visit. The VRS comprised the categories 1 = worse, 2 = no pain relief, 3 = slight, 4 = moderate, 5 = a lot, 6 = complete. | From Day 1 until time to exit in Double-blind Phase (maximum Day 14) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Pain Intensity: NRS | Pain intensity was assessed as pain right now directly before patch application and before patch removal, and as 24-hour average pain before patch removal using an 11-point Numeric Rating Scale (NRS from 0 = no pain to 10 = pain as bad as you can imagine). | From screening visit (Week -1) to end of Double-blind Phase visit (Week 10) | 
| Daily Pain Relief | Pain relief was defined as relief at the time point directly before patch removal in comparison to the time point directly before patch application. Pain relief was assessed using a 6-item relief scale (VRS) with categories 1 = worse, 2 = no pain relief, 3 = slight, 4 = moderate, 5 = a lot, and 6 = complete. | From screening visit (Week -1) to end of Double-blind Phase visit (Week 10) | 
| Weekly Average 24-hour Pain Intensity: NRS | The weekly average of the 24-hour average pain intensity was calculated based on corresponding daily pain intensities over the last week before the respective visit. Pain intensities were assessed using an 11-point Numeric Rating Scale (NRS from 0 = no pain to 10 = pain as bad as you can imagine). | During Run-in Phase (visits after 1 and 4 weeks), after 8 weeks, and after 10 weeks (Double-blind Phase) | 
| Weekly Average Current Pain Intensity: NRS | The weekly average of the current pain (pain right now) intensities before patch application or before patch removal were calculated based on corresponding daily pain intensities over the last week before the respective visit. Pain intensities were assessed using an 11-point Numeric Rating Scale (NRS from 0 = no pain to 10 = pain as bad as you can imagine). | During Run-in Phase (visits after 1 and 4 weeks), after 8 weeks, and after 10 weeks (Double-blind Phase) | 
| Weekly Average Pain Relief: VRS | The weekly average pain relief was calculated based on daily pain relief over the last week before visit. Pain relief was assessed using a 6-item relief scale (VRS) with categories 1 = worse, 2 = no pain relief, 3 = slight, 4 = moderate, 5 = a lot, and 6 = complete. | During Run-in Phase (visits after 1 and 4 weeks), after 8 weeks, and after 10 weeks (Double-bind Phase) | 
| Weekly Worst Pain Intensity: NRS | Weekly worst pain intensity was assessed in the last week before the visit using an 11-point NRS (from 0 = no pain to 10 = pain as bad as you can imagine). | During Run-in Phase (visits after 1 and 4 weeks), after 8 weeks, and after 10 weeks (Double-blind Phase) | 
| Weekly Average Pain Intensity: NRS | Weekly average pain intensity was assessed in the last week before the visit using an 11-point NRS (from 0 = no pain to 10 = pain as bad as you can imagine). | During Run-in Phase (visits after 1 and 4 weeks), after 8 weeks, and after 10 weeks (Double-blind Phase) | 
| Weekly Least Pain Intensity: NRS | Weekly least pain intensity was assessed in the last week before the respective visit using an 11-point NRS (from 0 = no pain to 10 = pain as bad as you can imagine). | During Run-in Phase (visits after 1 and 4 weeks), after 8 weeks, and after 10 weeks (Double-blind Phase) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lidocaine, Post herpetic neuralgia, Herpes zoster