Pharmacokinetics and Safety of Single and Multiple Doses of Peficitinib (ASP015K) in Healthy Chinese Subjects.

OBJECTIVE

To investigate the pharmacokinetics and safety of peficitinib (Janus kinase inhibitor for the treatment of rheumatoid arthritis) in healthy Chinese subjects following single and multiple doses.

METHODS

This open-label, randomized study was conducted at one site in China. Subjects received peficitinib 50, 100 or 150 mg as a single dose on Day 1 (fasted) and once daily from Days 8 to 13 in the multiple-dose period (fed). Blood samples were collected before administration each day, and up to 72h post administration. Pharmacokinetic assessments included area under the concentration curve (AUC), half-life (t), maximum concentration (C), and time to maximum concentration (t) of peficitinib and its metabolites (H1, H2 and H4). Treatment-emergent adverse events (TEAEs) were evaluated.

RESULTS

Thirty-six subjects were enrolled (12 per dose group). After a single dose of peficitinib, median t was 1.0-1.5h and mean t was 7.4-13.0h for all doses. In the multiple-dose period, median t was 1.5-2.0h. Dose-proportional increases in C and AUC were observed for peficitinib and its metabolites following single and multiple doses, with minimal drug accumulation. The major metabolite was H2, with a systemic exposure of >150% of the parent AUC. Drug-related TEAEs were experienced by 5 (13.9%) and 12 (33.3%) subjects in the single- and multiple-dose periods, respectively. Following multiple doses of peficitinib, TEAEs were more frequent in higher than lower dose groups but were mild in severity with no related discontinuation or death.

CONCLUSION

Following single and multiple doses of peficitinib in healthy Chinese subjects, peficitinib demonstrated rapid absorption and was well tolerated at all doses.

CLINICALTRIALSGOV IDENTIFIER

NCT04143477.

© 2022 Gao et al.