543 An evaluator blinded study to evaluate the cumulative irritation potential of topically-applied GSK2894512 cream in healthy subjects

Abstract

Topical drugs that come into contact with skin need to be evaluated for their potential to induce skin irritation in a controlled clinical setting. GSK2894512 is a novel anti-inflammatory agent that is currently under development as a cream for the topical treatment of atopic dermatitis (AD) and plaque psoriasis. GSK2894512 was investigated earlier in 4 clinical studies (N=282) for its safety and efficacy. It was found to be efficacious with no noted related safety signals in both AD and psoriasis patients, other than some application site reactions suggestive of contact dermatitis. This constituted a trigger to conduct a standard 21 day cumulative skin irritation study (healthy volunteer, multicenter, randomized, controlled, evaluator blinded) of 3 concentrations of GSK2894512 cream (0.5%, 1%, and 2%) under occlusive (n=6) and semi occlusive (n=40) conditions. The study was conducted from 30-Oct-2013 to 02-Jul-2014. In the present study (funded by GSK), GSK2894512 cream induced clinically-relevant skin irritation in all subjects. The intensity of the skin irritations was dose dependent, as shown by higher cumulative irritation scores with increasing GSK2894512 concentration. The cream vehicle also showed some irritant properties. All observed skin irritations were fully reversible after the discontinuation of treatment with GSK2894512 cream or vehicle cream, and did not require any medical intervention to treat them. Such dose-dependent relationships are typical for skin irritation but not for (contact) skin allergy. The skin irritation induced by the cream vehicle alone likely contributed to the overall irritation caused by the drug product (active substance and its vehicle). Other than the observed skin irritation, no serious events and few AEs occurred overall. None of the AEs were judged by the investigator to be related to GSK2894512. Future studies will be conducted utilizing a modified formulation, which may mitigate irritation.