Clinical trial NCT03765697: A Study With Lidocaine 5% Medicated Plaster in Patients Suffering From Postherpetic Neuralgia
Official title: An Open-label, Multicenter, Multiple-dose, Phase III Study With Lidocaine 5% Medicated Plaster in Patients Suffering From Postherpetic Neuralgia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post Herpetic Neuralgia
Keywords: post-herpetic neuralgia
lidocaine
Lead sponsor: Grünenthal GmbH
Sponsor class: INDUSTRY
First posted: 2018-12-05
Enrollment: 259
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with treatment emergent adverse events (main study period)
timeFrame: From first plaster application up to 12 months
Secondary outcomes:
measure: Pain relief (main study period): verbal rating scale
timeFrame: After 1, 6, 12, 18, 26, 34, 42, and 52 weeks (or early withdrawal)
measure: Pain intensity (main study period): Numeric Rating Scale
timeFrame: At screening/enrollment and after 1, 6, 12, 18, 26, 34, 42, and 52 weeks (or early withdrawal)
measure: Pain relief (extension period): verbal rating scale
timeFrame: Every 6 months after first plaster application in the extension period up to 4.4 years (or early withdrawal)
measure: Number of participants with treatment emergent adverse events (extension period)
timeFrame: 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 outcomes:
measure: Allodynia severity rating (main study period)
timeFrame: At screening/enrollment, and after 1, 6, 12, 18, 26, 34, 42, and 52 weeks (or early withdrawal)
measure: Clinical Global Impression of Change (CGIC) (main study period)
timeFrame: At 26 weeks of treatment in the main study period and at the final visit (at 52 weeks, or early withdrawal)
measure: Short Form-36 Quality of Life Index (SF-36) (main study period)
timeFrame: At screening, and after 12, 26, 42, and 52 weeks (or early withdrawal)
measure: Short Form McGill Pain Questionnaire (SF-MPQ) (main study period)
timeFrame: At screening, and after 12, 26, 42, and 52 weeks (or early withdrawal)
measure: Clinical Global Impression of Change (CGIC) (extension period)
timeFrame: Every 6 months after first plaster application in the extension period up to 4.4 years (or early withdrawal)
measure: Patient's Global Impression of Change (PGIC) (extension period)
timeFrame: Every 6 months after first plaster application in the extension period up to 4.4 years (or early withdrawal)
measure: Investigator's Global Evaluation of the IMP (extension period)
timeFrame: Every 6 months after first plaster application in the extension period up to 4.4 years (or early withdrawal)
measure: Patient's Global Evaluation of the IMP (extension period)
timeFrame: Every 6 months after first plaster application in the extension period up to 4.4 years (or early withdrawal)
measure: Change in concomitant medication (main and extension period)
timeFrame: At enrollment into main study period; at last assessment in extension period (up to 5.4 years after enrollment)
Locations:
Study officials:
affiliation: Grünenthal GmbH
name: Grünenthal Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.