PII-060

S. Lee,1 F. Jiang,1 J. Lee,1 J. Chung,2 I. Jang,1 H. Lee,1 K. Yu,1 K. Jang1; 1Seoul National University College of Medicine and Hospital, Seoul, Korea, Republic of, 2Seoul National University College of Medicine and Bundang Hospital, Sungnam, Korea, Republic of

BACKGROUND: DWP05195, a low molecular weight transient receptor potential vanilloid 1(TRPV1) antagonist, is under clinical development for pain management. The purpose of this first-in-human study was to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DWP05195 after single oral administration in healthy male volunteers.
METHODS: A randomized, double-blind, placebo-controlled, single-dose, dose-escalation from 10 mg to 600 mg study was conducted in 80 healthy volunteers. Blood and urine samples for PK analysis were collected up to 72 hours after dosing. PD evaluations were done by measuring heat-pain threshold (HPtr) and heat-pain tolerance (HPtol). Safety evaluations were performed throughout the study.
RESULTS: The maximum plasma concentrations (Cmax) and the area under the plasma concentration-time curve from zero to the last measurable time (AUClast) increased as the dose of DWP05195 increased, proportionally in dose groups of 100 mg or higher. HPtr or HPtol in the DWP05195 treatment groups generally increased when compared to the placebo group. HPtr and HPtol compared to the baseline increased dose-dependently in dose groups higher than 100 mg, and the AUEC (0-8 hours) was significantly greater in the 600 mg dose group.
CONCLUSION: DWP05195 was well tolerated up to 600 mg when administered as a single dose and the systemic exposure increased as the dose increased. HPtr and HPtol increased dose-dependently at a dose above 100 mg.