A Randomized, Open-Label, Bioequivalence Study of Lidocaine Topical System 1.8% and Lidocaine Patch 5% in Healthy Subjects

Jeffrey Gudin, Charles Argoff, Jeffrey Fudin, Emileigh Greuber, Kip Vought, Kalpana Patel, Sri Nalamachu, Jeffrey Gudin, Charles Argoff, Jeffrey Fudin, Emileigh Greuber, Kip Vought, Kalpana Patel, Sri Nalamachu

Abstract

Purpose: This study was designed to characterize drug delivery with lidocaine topical system 1.8% vs lidocaine patch 5% through 2 PK studies.

Patients and methods: Two Phase 1, single-center, open-label, randomized PK studies were performed in healthy adults. In Study 1, 56 subjects received a single intravenous bolus of 0.7 mg/kg of lidocaine as a lead-in to allow for the accurate determination of apparent dose of both products. After a 7-day washout period, subjects were randomized to receive either lidocaine topical system 1.8% or lidocaine patch 5% for 12 hours followed by another 7-day washout period, after which subjects crossed over to receive the other treatment for 12 hours. In Study 2, 54 subjects were randomized to receive either lidocaine topical system 1.8% or lidocaine patch 5% for 12 hours. After a 7-day washout period, subjects crossed over to receive the other treatment. Adhesion and skin irritation assessments were performed after application of the products in Study 2. In both studies, serial blood samples were collected to measure the plasma concentration of lidocaine after product application. Safety assessments and adverse events were monitored in both studies.

Results: The comparative PK analysis demonstrated that the two products, despite their difference in drug load and strength, are bioequivalent. Both products were well tolerated. In Study 2, dermal response scores (skin tolerability after removal) were similar between lidocaine topical system 1.8% and lidocaine patch 5%, with a mean irritation score per patch <1 (barely perceptible erythema), which is not considered to be clinically significant.

Conclusion: Bioequivalence was demonstrated between lidocaine topical system 1.8% and lidocaine patch 5%. A comparison of the single-time adhesion scores at 12 hours in Study 2 favored lidocaine topical system 1.8% over lidocaine patch 5%. Both products were well tolerated as a single application in healthy adult human subjects.

Clinicaltrialsgov: NCT04144192, NCT04149938.

Keywords: lidocaine; pharmacokinetics; postherpetic neuralgia; topical.

Conflict of interest statement

The abstract of this paper was presented at the PAINWeek 2018 Conference (September 4–8, 2018; Las Vegas, NV) as a poster presentation with interim findings. The poster’s abstract was published in “Poster Abstracts” in 2018 Postgraduate Medicine: Patel K, Gudin J, Vought K, Shah M, Grimes D, LaStella P, Greuber E. A Randomized, Comparative Pharmacokinetic (PK) Study of ZTlido™ Lidocaine Topical System 1.8% (36 mg) Versus Lidoderm® Lidocaine Patch 5% (700 mg). (2018) PAINWeek Abstract Book 2018, Postgrad Med, 130:sup1, 1–91, DOI: 10.1080/00325481.2018.1512253. In the past year, Dr. Gudin has been an advisor, consultant, or speaker’s bureau member for Averitas Pharma, BioDelivery Sciences International, Inc., Daiichi Sankyo, Hisamitsu Pharmaceutical Co. Inc., Nektar Therapeutics, Salix Pharmaceuticals, and Scilex Pharmaceuticals Inc. Dr. Fudin has been an advisor, consultant, or speaker’s bureau member for Abbott Laboratories, AcelRx Pharmaceuticals, Acutis Diagnostics Inc., AstraZeneca, BioDelivery Sciences International, Inc., Daiichi Sankyo, Firstox Laboratories, GlaxoSmithKline, Human Half-Cell, Inc., Quest Diagnostics, Salix Pharmaceuticals, and Scilex Pharmaceuticals Inc. Dr. Nalamachu has been a consultant/speaker and has received honorarium and grants from Allergan, AstraZeneca, BioDelivery Sciences International, Inc., Collegium Pharmaceuticals, Daiichi Sankyo, Depomed (Assertio Therapeutics), Eli Lilly and Company, Endo Pharmaceuticals, Ferring Pharmaceuticals, Insys Pharmaceuticals, Pernix Therapeutics, Pfizer Inc., Purdue Pharmaceuticals, and Scilex Pharmaceuticals Inc. Drs. Vought and Greuber have patent application 62/762753 pending to Scilex Pharmaceuticals Inc., and Dr Vought is head of R&D responsible for the design and conduct of the study. Drs. Greuber, Patel, and Vought are employees of Scilex Pharmaceuticals Inc., and they report grants and personal fees from Scilex Pharmaceuticals Inc. The authors report no other conflicts of interest in this work.

© 2020 Gudin et al.

Figures

Figure 1
Figure 1
Mean lidocaine plasma concentrations versus time profiles for IV lidocaine 0.7 mg/kg, semilog scale (N = 56) (Study 1). Time = 0 is pre-dose measurement. Abbreviation: IV, intravenous.
Figure 2
Figure 2
Mean lidocaine plasma concentrations versus time profiles for lidocaine topical system 1.8% (N = 56) and lidocaine patch 5%, semilog scale (N = 54) (Study 1). Time = 0 is pre-dose measurement.
Figure 3
Figure 3
Mean lidocaine plasma concentrations versus time profiles for lidocaine topical system 1.8% and lidocaine patch 5% (Study 2).
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7319520/bin/JPR-13-1485-g0001.jpg

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