A Randomized, Crossover, Pharmacokinetic and Adhesion Performance Study of a Lidocaine Topical System 1.8% During Physical Activity and Heat Treatment in Healthy Subjects

Abstract

Purpose: This study compares the pharmacokinetic (PK) profile, adhesion, and safety of lidocaine topical system 1.8%, a novel lidocaine topical system approved to treat postherpetic neuralgia, under conditions of heat and exercise vs normal conditions.

Materials and methods: This open-label, 3-period, 3-treatment crossover study randomized 12 healthy adults to receive three lidocaine topical systems 1.8% during each of three treatment periods, with 7-day washouts between treatments. The product was applied to the mid-lower back and was removed after 12 hours. During Treatment A, subjects exercised on a bicycle for 30 minutes at 0, 2.5, 5.5, and 8.5 hours. During Treatment B, heat (temperature set at 36.7-40.3°C) was applied at 0 and 8.5 hours. Treatment C was normal conditions. The PK profile of each subject under exercise and heat conditions was compared to normal conditions. Skin irritation, adhesion, and adverse events were assessed.

Results: Twelve subjects completed the study. Exposure to external heat resulted in increased peak plasma concentration of lidocaine with a mean Cmax of 160.3±100.1 ng/mL vs 97.6±36.9 ng/mL under normal conditions, with no effect on the extent of exposure (AUC). Concentrations returned to normal within 4 hours after the heat was removed. No clinically relevant differences in absorption were observed under exercise conditions with a mean Cmax of 90.5±25.4 ng/mL and no effect on the extent (AUC) of lidocaine exposure was observed relative to normal conditions. No systems detached during the study. Adverse events were mild, with none leading to discontinuation.

Conclusion: Transient heat exposure resulted in increased lidocaine plasma concentrations compared to normal conditions, whereas exercise had no effect. The effects of heat appear to be immediate, reversible, and below systemic therapeutic threshold in antiarrhythmic treatment (1000-1500 ng/mL), and well below the safe systemic threshold of 5000 ng/mL. Lidocaine topical system 1.8% remained adhered to the skin and was well tolerated under all conditions. ClinicalTrials.gov: NCT04150536.

Keywords: dermal; herpes zoster; neuropathic pain; shingles.

Conflict of interest statement

Dr Jeffrey Fudin is a speaker for Abbott Laboratories, AstraZeneca, and Acutis Diagnostics, Inc; part of the advisory board, speakers bureau, and consulting for AcelRx Pharmaceuticals, BioDelivery Sciences International, GlaxoSmithKline (GSK), Salix Pharmaceuticals, and Daiichi-Sankyo Incorporated; received non-financial support by collaborating publications for Scilex Pharmaceuticals; consultant for Firstox; advisory board for Human Half-Cell, Inc and Quest Diagnostics, outside the submitted work. Drs. Greuber, Vought, and Patel are full-time employees of Scilex Pharmaceuticals Inc. Dr Vought has a patent 62/762,753 pending to Scilex Pharmaceuticals Inc and was responsible for the design and conduct of the study. Dr. Nalamachu has been a consultant/speaker and has received an honorarium from BDSI, DSI, Endo, Insys, Scilex Pharmaceuticals Inc., Purdue, Pfizer Inc., Eli Lilly and Company, Collegium Pharmaceutical, Pernix Therapeutics, Daiichi-Sankyo, and AstraZeneca. Dr Erica Wegrzyn reports personal fees from Remitigate LLC and Tower Health Pain & Addiction Symposium; is an Associate Editor in Chief for Journal of Pain Research, outside the submitted work. The authors report no other conflicts of interest in this work.

© 2020 Fudin et al.

Figures

Figure 1

Mean plasma lidocaine concentration after application of three lidocaine topical systems (1.8%; 108 mg) vs time with physical exercise, heat exposure, and under normal conditions. Treatment A: with physical exercise; Treatment B: with heating; Treatment C: under normal conditions.