PI-091 - PHARMACOKINETICS, PHARMACODYNAMICS, SAFETY, AND TOLERABILITY OF CEDIROGANT FOLLOWING SINGLE AND MULTIPLE DOSES IN JAPANESE AND CHINESE HEALTHY VOLUNTEERS.

M. Mohamed¹, Y. Qian¹, R. D'Cunha¹, S. Hao¹, R. Carcereri De Prati², G. Levy³, W. Liu¹; ¹AbbVie Inc., North Chicago, IL, USA, ²AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Rhineland-Palatinate, Germany, ³Pharmacovigilance and Patient Safety, AbbVie, North Chicago, IL, USA.

Background: This study aimed to characterize the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of cedirogant, an inverse agonist of retinoic acid-related orphan receptor gamma, thymus (RORγt) currently under development for treatment of chronic plaque psoriasis, in healthy Japanese and Chinese subjects.

Methods: Japanese healthy subjects (N=24) were randomized to receive either single ascending doses of cedirogant (75, 225, and 395 mg) or placebo. Additionally, healthy Japanese (N=12) and Chinese (N=12) subjects were randomized to receive either multiple doses of cedirogant 375 mg or placebo QD for 14 days.

Results: Cedirogant median time to maximum concentration was 4 to 5 hours. The mean terminal half-life for cedirogant was approximately 25 hours after single doses in Japanese subjects and ranged from 19 to 20 hours after multiple doses in Japanese and Chinese subjects. Cedirogant PK was consistent between the two populations. At steady-state, the median accumulation ratio ranged from 1.10 to 1.32 for cedirogant maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC). Based on a linear mixed-effects analysis, ratios of central values for steady-state cedirogant Cmax and AUC ranged from 1.38 to 1.73 in Japanese or Chinese compared to Western healthy subjects. Approximately 60-80% ex-vivo IL-17A inhibition was achieved in Japanese and Chinese subjects at steady-state with 375 mg QD doses. Cedirogant was generally well tolerated. All adverse events in the study were mild and no subject was discontinued.

Conclusion: Cedirogant PK and PD were generally consistent between Japanese and Chinese healthy subjects and between Asian and Western healthy subjects. The results supported enrollment of Japanese and Chinese subjects in subsequent clinical trials for cedirogant.