Dataset Information

A Randomized, Crossover, Adhesion Performance and Pharmacokinetic Study of a Lidocaine Topical System Under Conditions of Water Exposure in Healthy Subjects.

ABSTRACT:

Purpose

This study compares the adhesion performance, pharmacokinetic profile, and safety of lidocaine topical system 1.8%, which is approved to treat postherpetic neuralgia, under conditions of swimming and showering versus normal conditions.

Patients and methods

This open-label, 3-period, 3-treatment crossover study randomized 24 healthy adults to receive one lidocaine topical system during each of three treatment periods; subjects either swam in a heated swimming pool for 15 minutes 4.0 hours post-product application (swimming), showered for 10 minutes 8.0 hours after product application (showering), or the product remained dry throughout the treatment period (normal conditions). The product was applied to the mid-upper back and was removed after 12 hours. The pharmacokinetic profile of each subject under water exposure conditions was compared to subjects under normal conditions. Skin irritation, adhesion, and adverse events were assessed.

Results

Twenty-four (24) subjects enrolled and 23 completed the study. Exposure to water resulted in lifting of the topical systems. There were two complete detachments, as well as seven occurrences of major lifting (more than 50% detached) after water exposure. The topical systems were immediately pressed down and/or reapplied after observing lifting and remained adhered to for the rest of the 12-hour application period. No clinically relevant differences in systemic absorption were observed under either showering or swimming conditions. The topical systems were well tolerated, with only mild adverse events, none leading to discontinuation.

Conclusion

These data show that while water exposure can cause the topical system to lift or detach, the lidocaine topical system 1.8% is capable of being reapplied and maintains adhesion for up to 12 hours of wear with no clinically significant changes in drug delivery.

Clinicaltrialsgov

NCT04784728.

SUBMITTER: Vought K

PROVIDER: S-EPMC8379683 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Similar Datasets

Project description:PurposeThis 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 methodsThis 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.ResultsTwelve 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.ConclusionTransient 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.

Project description:PurposeThis study was designed to characterize drug delivery with lidocaine topical system 1.8% vs lidocaine patch 5% through 2 PK studies.Patients and methodsTwo 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.ResultsThe 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.ConclusionBioequivalence 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.ClinicaltrialsgovNCT04144192, NCT04149938.