Pharmacokinetics, Safety, and Tolerability of Cedirogant in Healthy Japanese and Chinese Adults.

ABSTRACT

Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma, thymus (RORγt) developed for treatment of psoriasis. This study aimed to characterize pharmacokinetics, pharmacodynamics, safety, and tolerability of cedirogant following a single oral dose in Japanese participants and multiple oral doses in Japanese and Chinese participants. The single doses evaluated in healthy Japanese participants were 75, 225, and 395 mg. The multiple doses evaluated in both healthy Japanese and Chinese participants was 375 mg once daily for 14 days. Cedirogant plasma exposure increased dose proportionally with administration of single doses. Maximum cedirogant plasma concentration was reached within a median time of 4-5 hours after dosing. The harmonic mean elimination half-life ranged from 19 to 25 hours. Cedirogant pharmacokinetics were similar between Japanese and Chinese participants. Compared with healthy Western participants in a cross-study analysis, steady-state cedirogant plasma exposure was 38%-73% higher in Japanese or Chinese participants. Ex vivo interleukin-17 inhibition increased in a dose-dependent manner and was maximized by 375 mg once-daily doses. The cedirogant regimens tested were generally well tolerated, and no new safety issues were identified. The results supported enrollment of Japanese and Chinese subjects in subsequent clinical trials for cedirogant.