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

Xin Gao, Xuemei He, Hiroyuki Oshima, Daisuke Miyatake, Yukio Otsuka, Kota Kato, Chunxiao Cai, Tomasz Wojtkowski, Nan Song, Yuichiro Kaneko, Aixin Shi, Xin Gao, Xuemei He, Hiroyuki Oshima, Daisuke Miyatake, Yukio Otsuka, Kota Kato, Chunxiao Cai, Tomasz Wojtkowski, Nan Song, Yuichiro Kaneko, Aixin Shi

Abstract

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 (t1/2), maximum concentration (Cmax), and time to maximum concentration (tmax) 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 tmax was 1.0-1.5h and mean t1/2 was 7.4-13.0h for all doses. In the multiple-dose period, median tmax was 1.5-2.0h. Dose-proportional increases in Cmax and AUC24h 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.

Keywords: dose-proportionality; rheumatoid arthritis; treatment; tsDMARDs.

Conflict of interest statement

DM, HO, YO, YK, KK and TW are employees of Astellas Pharma Inc. CC and NS are employees of Astellas Pharma China, Inc. AS, XG and XH have nothing to disclose. The authors report no other conflicts of interest in this work.

© 2022 Gao et al.

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
Mean (±SD) concentration-time profiles of peficitinib on Day 1, Day 8, and Day 13 (PKAS). SD was not calculated since >50% of values were below the quantitation limit at a given time point.
Figure 3
Figure 3
Continued.
Figure 3
Figure 3
Continued.
Figure 3
Figure 3
Mean (±SD) concentration-time profiles of peficitinib metabolites on Day 1, Day 8, and Day 13 (PKAS). (A) H1; (B) H2; (C) H4. SD was not calculated since >50% of values were below the quantitation limit at a given time point.

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