A Study With Lidocaine 5% Medicated Plaster in Patients Suffering From Postherpetic Neuralgia

An Open-label, Multicenter, Multiple-dose, Phase III Study With Lidocaine 5% Medicated Plaster in Patients Suffering From Postherpetic Neuralgia

This study was performed to evaluate the local and systemic safety profile and the analgesic efficacy of long-term treatment with lidocaine 5% medicated plaster (Lido-Patch).

The study was an open-label, multi-center, multiple-dose, Phase III study and comprised a main and an extension period. 161 participants who completed treatment in KF10004/01 (NCT03745404) and 98 newly recruited participants were enrolled.

Study Overview

• Status: Completed
• Conditions: Post Herpetic Neuralgia
• Intervention / Treatment: Drug: Lidocaine 5% medicated plaster

Detailed Description

The main period was performed in 34 sites in 12 European countries (259 participants). Treatment duration was up to 12 months. All participants applied lidocaine 5% medicated plaster (containing 700 mg lidocaine per plaster) topically at the site of the skin affected by painful PHN. Depending on the size of the affected skin area, up-to 3 plasters were simultaneously applied for up to 12 hours per day (with a plaster-free interval of at least 12 hours). Study objectives of the main period were to evaluate the local and systemic safety profile and the analgesic efficacy of lidocaine 5% medicated plaster, and to evaluate the pharmacokinetics of lidocaine and its metabolite 2,6-xylidine in the target population after multiple administrations of lidocaine 5% medicated plaster by means of population kinetics. The study results were planned to be evaluated descriptively.

102 participants who were satisfied with the treatment in the main study period entered the open-label extension period with continued treatment. 27 sites in 12 countries participated in the extension period. Enrollment in the extension period coincided with last visit of the main period of the study. Treatment duration was up to 4.4 years in the extension period. The objective of the extension period was to evaluate the long-term local and systemic safety profile and the long-term analgesic efficacy of treatment with lidocaine 5% medicated plaster in the subpopulation who had completed 12 months of treatment in the open-label main study period.

• Study Type: Interventional
• Enrollment (Actual): 259
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.
• Only for patients who had not participated in the KF10004/01 (NCT03745404) study: Pain score of at least 4, based on an 11-point numerical rating scale (NRS) (scale of 0-10), at the screening visit. The pain assessment is the participant's recall of the pain intensity since the previous week.
• Written informed consent given.

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, except previous participation in the KF10004/01 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 PHN.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lidocaine 5% medicated plaster; Up to 3 plasters were applied per day.	Drug: Lidocaine 5% medicated plaster; Topical application at the site of skin affected by painful PHN for up to 12 hours per day (plaster-free interval at least 12 hours).; Other Names: Versatis (Trade Mark); Lidoderm (Trade Mark); Neurodol Tissugel (Trade Mark)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment emergent adverse events (main study period)	Treatment emergent adverse events (TEAEs) were continually monitored through the main period of the study (12 months). Incidences were calculated based on all events reported up to 12 months. No primary endpoint was defined for this study.	From first plaster application up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain relief (main study period): verbal rating scale	Pain relief was assessed starting 1 week (new participants) or 6 weeks after treatment initiation (participants from KF10004/01) until the final visit of the main study period. The average pain relief during the last week before the visit was assessed using a 6-item verbal rating scale (VRS) with categories 1 = worse, 2 = no pain relief, 3 = slight, 4 = moderate, 5 = a lot, and 6 = complete.	After 1, 6, 12, 18, 26, 34, 42, and 52 weeks (or early withdrawal)
Pain intensity (main study period): Numeric Rating Scale	The participant's recall of worst, least, and average pain intensity in the last week prior to each visit were assessed using an 11-point Numeric Rating Scale (NRS from 0 = no pain to 10 = pain as bad as you can imagine).	At screening/enrollment and after 1, 6, 12, 18, 26, 34, 42, and 52 weeks (or early withdrawal)
Pain relief (extension period): verbal rating scale	The participant's recall of average pain relief during plaster application in the last week prior to each visit in the extension period was assessed using a 6-item VRS with categories 1 = worse, 2 = no pain relief, 3 = slight, 4 = moderate, 5 = a lot, and 6 = complete.	Every 6 months after first plaster application in the extension period up to 4.4 years (or early withdrawal)
Number of participants with treatment emergent adverse events (extension period)	Treatment emergent adverse events were continually monitored for or asked about at each visit scheduled every 6 months in the extension period. The extension period lasted for up to 4.4 years and included a follow-up visit (1-2 weeks after last regular 6-month visit [or early withdrawal]). Adverse event incidences were calculated based on all events reported in the extension period.	Every 6 months after first plaster application in the extension period up to 4.4 years (including a follow-up visit 1-2 weeks after last regular 6-month visit or early withdrawal)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Allodynia severity rating (main study period)	Allodynia severity was rated using the following categorical scale: 0 = no pain or discomfort to touch; 1 = uncomfortable, but tolerable to touch; 2 = painful; 3 = extremely painful, participant cannot stand touching. The test was conducted by means of a brush (type N12). The painful PHN area was stroked with the brush and the intensity of allodynic pain was assessed by the participant.	At screening/enrollment, and after 1, 6, 12, 18, 26, 34, 42, and 52 weeks (or early withdrawal)
Clinical Global Impression of Change (CGIC) (main study period)	Investigators were asked to describe their overall impression of the change of the participant's condition/pain by answering the following question: "Compared to the patient's condition at admission to the project, how much has he/she changed?" The categorical scale comprises the categories not assessed = 0, very much improved = 1, much improved = 2, minimally improved = 3, no change = 4, minimally worse = 5, much worse = 6, and very much worse = 7.	At 26 weeks of treatment in the main study period and at the final visit (at 52 weeks, or early withdrawal)
Short Form-36 Quality of Life Index (SF-36) (main study period)	The Short Form 36 Quality of Life Index (SF-36 [Trade Mark]) standard version with a 4-week recall period was used as a self-assessment. Eleven questions were answered on binomial (Yes/No) or on 3-, 5-, or 6-point categorical scales to generate the 8 raw scales (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, Mental Health). Higher values of the raw scales represent a better outcome. The raw scales were converted into a transformed scale (transformed scale = [(actual raw score - lowest possible raw score) / possible raw score range] x 100).	At screening, and after 12, 26, 42, and 52 weeks (or early withdrawal)
Short Form McGill Pain Questionnaire (SF-MPQ) (main study period)	The SF-MPQ includes 15 words (11 sensory, 4 affective). Each word or phrase is rated on a 4-point intensity scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). In addition, the 6-point Present Pain Intensity (PPI) rating (no pain, mild, discomforting, distressing, horrible, excruciating) is included as is a visual analogue scale for rating pain intensity. Total score as well as sensory and affective sub-scores were calculated.	At screening, and after 12, 26, 42, and 52 weeks (or early withdrawal)
Clinical Global Impression of Change (CGIC) (extension period)	Investigators were asked to describe their overall impression of the change of the participant's condition/pain by answering the following question: "Compared to the patient's condition at admission to the project, how much has he/she changed?" (categories: not assessed = 0, very much improved = 1, much improved = 2, minimally improved = 3, no change = 4, minimally worse = 5, much worse = 6, very much worse = 7).	Every 6 months after first plaster application in the extension period up to 4.4 years (or early withdrawal)
Patient's Global Impression of Change (PGIC) (extension period)	Participants were asked to describe their overall impression of change of their condition/pain by answering the following question: "Compared to your pain at admission to the project, how much has it changed?" (categories: not assessed = 0, very much improved = 1, much improved = 2, minimally improved = 3, no change = 4, minimally worse = 5, much worse = 6, very much worse = 7).	Every 6 months after first plaster application in the extension period up to 4.4 years (or early withdrawal)
Investigator's Global Evaluation of the IMP (extension period)	The assessment of the investigational medicinal product (IMP) was made on a 5-point categorical scale (poor, fair, good, very good, excellent). Investigators responded to the following question: "How would you rate the study medication the patient received for pain?"	Every 6 months after first plaster application in the extension period up to 4.4 years (or early withdrawal)
Patient's Global Evaluation of the IMP (extension period)	The assessment of the IMP was made on a 5-point categorical scale (poor, fair, good, very good, excellent). Participants responded to the following question: "How would you rate the study medication you received for pain?"	Every 6 months after first plaster application in the extension period up to 4.4 years (or early withdrawal)
Change in concomitant medication (main and extension period)	For each participant, the number of different medications taken for PHN symptoms was determined at enrollment into the and at the last assessment in the study. Participants were classified into 5 groups: 0, 1, 2, 3, and more than 3 different substances taken. Shifts were determined for enrollment to last assessment in the study.	At enrollment into main study period; at last assessment in extension period (up to 5.4 years after enrollment)

Collaborators and Investigators

• Sponsor: Grünenthal GmbH
• Investigators: Study Director: Grünenthal Study Director, Grünenthal GmbH

Publications and helpful links

General Publications

• Hans G, Sabatowski R, Binder A, Boesl I, Rogers P, Baron R. Efficacy and tolerability of a 5% lidocaine medicated plaster for the topical treatment of post-herpetic neuralgia: results of a long-term study. Curr Med Res Opin. 2009 May;25(5):1295-305. doi: 10.1185/03007990902901368.
• Sabatowski R, Hans G, Tacken I, Kapanadze S, Buchheister B, Baron R. Safety and efficacy outcomes of long-term treatment up to 4 years with 5% lidocaine medicated plaster in patients with post-herpetic neuralgia. Curr Med Res Opin. 2012 Aug;28(8):1337-46. doi: 10.1185/03007995.2012.707977. Epub 2012 Jul 18. Erratum In: Curr Med Res Opin. 2014 Feb;30(2):329-30.

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2003
• Primary Completion (Actual): July 12, 2005
• Study Completion (Actual): February 12, 2009

Study Registration Dates

• First Submitted: November 27, 2018
• First Submitted That Met QC Criteria: December 4, 2018
• First Posted (Actual): December 5, 2018

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: lidocaine; post-herpetic neuralgia
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Neuralgia, Postherpetic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine
• Other Study ID Numbers: KF10004/02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No