Clinical trial NCT03745404: A Study With Lido-Patch and Placebo Plaster in Patients Suffering From Postherpetic Neuralgia (PHN)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post Herpetic Neuralgia
Keywords: Post herpetic neuralgia
Lidocaine
Herpes zoster
Lead sponsor: Grünenthal GmbH
Sponsor class: INDUSTRY
First posted: 2018-11-19
Enrollment: 265
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time-to-exit in Double-blind Phase Due to Lack of Efficacy
timeFrame: From Day 1 until time to exit in Double-blind Phase (maximum Day 14)
Secondary outcomes:
measure: Daily Pain Intensity: NRS
timeFrame: From screening visit (Week -1) to end of Double-blind Phase visit (Week 10)
measure: Daily Pain Relief
timeFrame: From screening visit (Week -1) to end of Double-blind Phase visit (Week 10)
measure: Weekly Average 24-hour Pain Intensity: NRS
timeFrame: During Run-in Phase (visits after 1 and 4 weeks), after 8 weeks, and after 10 weeks (Double-blind Phase)
measure: Weekly Average Current Pain Intensity: NRS
timeFrame: During Run-in Phase (visits after 1 and 4 weeks), after 8 weeks, and after 10 weeks (Double-blind Phase)
measure: Weekly Average Pain Relief: VRS
timeFrame: During Run-in Phase (visits after 1 and 4 weeks), after 8 weeks, and after 10 weeks (Double-bind Phase)
measure: Weekly Worst Pain Intensity: NRS
timeFrame: During Run-in Phase (visits after 1 and 4 weeks), after 8 weeks, and after 10 weeks (Double-blind Phase)
measure: Weekly Average Pain Intensity: NRS
timeFrame: During Run-in Phase (visits after 1 and 4 weeks), after 8 weeks, and after 10 weeks (Double-blind Phase)
measure: Weekly Least Pain Intensity: NRS
timeFrame: During Run-in Phase (visits after 1 and 4 weeks), after 8 weeks, and after 10 weeks (Double-blind Phase)
Other outcomes:
measure: Chronic Pain Sleep Inventory (CPSI)
timeFrame: From screening at each visit up to the final visit (Week 10) [6 time points in total]
measure: Short Form McGill Pain Questionnaire (SF-MPQ)
timeFrame: At screening visit (Week -1), randomization visit (Week 8), and final visit (Week 10)
measure: Clinical Global Impression of Change (CGIC)
timeFrame: Withdrawal visit (end of Run-in Phase) or final visit (end of Double-blind Phase)
measure: Short Form-36 Quality of Life Index (SF-36)
timeFrame: At screening visit (Week -1), randomization visit (Week 8), and final visit (Week 10)
measure: Allodynia Assessment
timeFrame: From screening at each visit up to Week 10 (6 time points in total)
Locations:
Study officials:
affiliation: Grünenthal GmbH
name: Grünenthal Study Director
role: STUDY_DIRECTOR
References:
citation: Binder A, Bruxelle J, Rogers P, Hans G, Bosl I, Baron R. Topical 5% lidocaine (lignocaine) medicated plaster treatment for post-herpetic neuralgia: results of a double-blind, placebo-controlled, multinational efficacy and safety trial. Clin Drug Investig. 2009;29(6):393-408. doi: 10.2165/00044011-200929060-00003.