Xin Gao1, Xuemei He1, Hiroyuki Oshima2, Daisuke Miyatake2, Yukio Otsuka2, Kota Kato3, Chunxiao Cai4, Tomasz Wojtkowski5, Nan Song6, Yuichiro Kaneko7, Aixin Shi1. 1. Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China. 2. Clinical Pharmacology and Exploratory Development, Astellas Pharma Inc., Tokyo, Japan. 3. Analysis & Pharmacokinetics Research Labs., Astellas Pharma Inc., Ibaraki, Japan. 4. Development Medical Department, Astellas (China) Investment Co., Ltd, Beijing, People's Republic of China. 5. Data Science Development, Astellas Pharma US, Inc., Northbrook, IL, USA. 6. Development Division Biostatistics and Statistical Programming, Astellas (China) Investment Co., Ltd, Beijing, People's Republic of China. 7. Biostatistics Group, Japan-Asia Data Science, Development, Astellas Pharma Inc, Tokyo, Japan.
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.
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.
Authors: Josef S Smolen; Robert B M Landewé; Johannes W J Bijlsma; Gerd R Burmester; Maxime Dougados; Andreas Kerschbaumer; Iain B McInnes; Alexandre Sepriano; Ronald F van Vollenhoven; Maarten de Wit; Daniel Aletaha; Martin Aringer; John Askling; Alejandro Balsa; Maarten Boers; Alfons A den Broeder; Maya H Buch; Frank Buttgereit; Roberto Caporali; Mario Humberto Cardiel; Diederik De Cock; Catalin Codreanu; Maurizio Cutolo; Christopher John Edwards; Yvonne van Eijk-Hustings; Paul Emery; Axel Finckh; Laure Gossec; Jacques-Eric Gottenberg; Merete Lund Hetland; Tom W J Huizinga; Marios Koloumas; Zhanguo Li; Xavier Mariette; Ulf Müller-Ladner; Eduardo F Mysler; Jose A P da Silva; Gyula Poór; Janet E Pope; Andrea Rubbert-Roth; Adeline Ruyssen-Witrand; Kenneth G Saag; Anja Strangfeld; Tsutomu Takeuchi; Marieke Voshaar; René Westhovens; Désirée van der Heijde Journal: Ann Rheum Dis Date: 2020-01-22 Impact factor: 19.103