A first-in-human, double-blind, placebo-controlled, randomized, dose escalation study of DWP05195, a novel TRPV1 antagonist, in healthy volunteers

Jieon Lee, Bo-Hyung Kim, Kyung-Sang Yu, Hee Sun Kim, Ji Duck Kim, Joo-Youn Cho, SeungHwan Lee, Namyi Gu

DWP05195 is a transient receptor potential vanilloid 1 (TRPV1) antagonist developed for managing pain. The purpose of this study was to evaluate the pharmacodynamics pharmacokinetics, safety, and tolerability of DWP05195 in healthy subjects. This was a first-in-human randomized, double-blinded, placebo-controlled, dose escalation study. DWP05195 or placebo was administered as a single dose of 10-600 mg in the single-dose study and as 100-400 mg once daily for 8 days in the multiple-dose studies. Each study group consisted of 10 subjects (study drug-to-placebo ratio was 8:2). For pharmacodynamics assessment, the heat pain threshold (HPtr), heat pain tolerance (HPtol), perfusion intensity, and flare area ratio of cutaneous blood flow were measured. Safety and tolerability were evaluated throughout the study. The maximum plasma concentrations and area under the plasma concentration-time curve from zero to the last measurable time dose-dependently increased. HPtr and HPtol tended to increase more after DWP05195 administration than after placebo administration. HPtr and HPtol tended to dose-dependently increase after administration of DWP05195. Cutaneous blood flow was reduced as the dose of DWP05195 increased during the multiple-dose study. DWP05195 was well tolerated up to 600 and 400 mg single- and multiple-dose administrations, respectively. The pharmacological activity of DWP05195, measured using HPtr and HPtol, increased as expected in a dose-dependent manner owing to increased systemic exposure, indicating that DWP05195 can be used as a TRPV1 antagonist for pain management.