Open-Label Adhesion Performance Studies of a New Lidocaine Topical System 1.8% versus Lidocaine Patches 5% and Lidocaine Medicated Plaster 5% in Healthy Subjects

Abstract

Purpose: The primary objective was to evaluate adhesion performance of the lidocaine topical system 1.8% for 12 hours in healthy human subjects in three studies: as a single product (Study 1) and versus other lidocaine topical products (lidocaine patch 5% and lidocaine medicated plaster 5% [Study 2] and generic lidocaine patch 5% [Study 3]). Safety of the lidocaine topical system 1.8%, with a skin irritation focus, was a secondary objective.

Patients and methods: All three studies were open-label, randomized, Phase 1 adhesion performance studies in healthy adult volunteers (N=125). Lidocaine topical products were applied for 12 hours per test, per study arm. Adhesion of all test products was scored at 0, 3, 6, 9, and 12 hours post-application. Skin irritation was scored after product removal or when a product detached.

Results: Overall, the majority (≥75%) of subjects treated with the lidocaine topical system 1.8% demonstrated ≥90% adhesion (FDA adhesion score 0) throughout the 12-hour administration period versus 13.6% of subjects treated with lidocaine patch 5%, 15.9% of subjects treated with lidocaine medicated plaster 5%, and 0% of subjects treated with the generic lidocaine patch 5%. There were no complete detachments with the lidocaine topical system 1.8%, whereas 4.5% of lidocaine patch 5% and lidocaine medicated plaster 5% detached, and 29% of generic lidocaine patch 5% detached. Minimal skin irritation was observed with each lidocaine topical product.

Conclusion: Across three studies, lidocaine topical system 1.8% demonstrated superior adhesion performance versus the three other products tested. Skin irritation was minimal across products and studies.

Clinicaltrialsgov: NCT04312750, NCT04320173, NCT04319926.

Keywords: adhesion; lidocaine medicated plaster; lidocaine patch; lidocaine topical system; postherpetic neuralgia.

Conflict of interest statement

Dr. Gudin has been an advisor, consultant, speaker bureau member, or shareholder in the past year for Averitas Pharma, BioDelivery Sciences International, Inc., Daiichi Sankyo, Hisamitsu Pharmaceutical Co. Inc., Nektar, Quest Diagnostics, Salix Pharmaceuticals, Scilex Pharmaceuticals Inc., and Virpax Pharmaceuticals. Dr. Webster is affiliated with PRA Health Sciences and has been an advisor or consultant for Alcobra, BioDelivery Sciences International, Inc., Bonti, Charleston Laboratories, Daiichi Sankyo, Depomed, Egalet, Elysium Pharmaceuticals, Ensysce Biosciences, Indivior, Inspirion Pharmaceuticals, Insys Therapeutics, Jefferies, KemPharm, Mallinckrodt Pharmaceuticals, Merck, Neurana, Pain Therapeutics, Pernix, Pfizer, Salix, Shionogi, Teva, Trevena, Trevi Therapeutics, Vallon, and Vector Pharma. Drs. Greuber, Vought, and Patel are employees of Scilex Pharmaceuticals Inc. Dr. Kuritzky has no relationships to disclose; the opinions in this article do not represent those of his institutional affiliation (University of Florida). The authors report no other conflicts of interest in this work.

© 2021 Gudin et al.

Figures

Figure 1

Adhesion assessments at the end of the dosing period (12 hours). The proportion of subjects with at least 90% adhesion (using the FDA adhesion rating scale) at the end of the 12-hour application period and the proportion of subjects who had experienced 0% adhesion (complete detachment) at any time point throughout the study in (A) Study 1 (n=54); (B) Study 2 (n=44); and (C) Study 3 (n=24).

Figure 2

Mean percent adhesion over time. Mean percent adhesion scores were evaluated every 3 hours over the 12-hour application period. (A) In Study 2, there was a significant difference favoring the lidocaine topical system 1.8% over the lidocaine patch 5% and lidocaine medicated plaster 5% at baseline and at each time point after application (P<0.0001). (B) In Study 3, there was a significant difference favoring the lidocaine topical system 1.8% over the generic lidocaine patch 5% at baseline and at each time point after application (P<0.0001 for all comparisons).

Figure 3

Representative adhesion performance with the FDA score (denoted in red) in Studies 2 and 3. Subjects were treated with the lidocaine topical system 1.8% (top rows in panels A and B), lidocaine patch 5% (middle row in A), lidocaine medicated plaster 5% (bottom row in A), or generic lidocaine patch 5% (bottom row in B). Photographs were taken immediately following product application (0 hours) and at the end of the study after 12 hours (±15 minutes) of wear.

Figure 4

Mean irritation scores after product removal in Study 2. Irritation at the application site was assessed at 0.5 hours (+10 minutes), 2 hours (±15 minutes), and 12 hours (±30 minutes) after product removal. Irritation was graded using an 8-point scale of dermal response . Overall mean scores across all time points were not significantly different between the lidocaine topical system 1.8% and lidocaine patch 5% or lidocaine medicated plaster 5% (P=0.1656 for both comparisons). *Horizontal line represents a score of 2, defined as definite erythema, minimal edema, or minimal papular response and is considered clinically meaningful irritation.