Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Clinical Pharmacology and Exploratory Development, Astellas Pharma Inc., Tokyo, Japan.
Drug Des Devel Ther. 2022 May 9;16:1365-1381. doi: 10.2147/DDDT.S359501. eCollection 2022.
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.
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.
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.
Following single and multiple doses of peficitinib in healthy Chinese subjects, peficitinib demonstrated rapid absorption and was well tolerated at all doses.
NCT04143477.
研究健康中国受试者单次和多次给药后培非替尼（治疗类风湿关节炎的 Janus 激酶抑制剂）的药代动力学和安全性。
这是一项在中国的一个研究中心进行的开放标签、随机研究。受试者在第 1 天（禁食）单次接受培非替尼 50、100 或 150mg 治疗，在多次给药期（进食）每天接受一次培非替尼治疗，连续 13 天。每天给药前和给药后 72h 内采集血样。药代动力学评估包括培非替尼及其代谢物（H1、H2 和 H4）的浓度-时间曲线下面积（AUC）、半衰期（t）、最大浓度（C）和达峰时间（t）。评估治疗中出现的不良事件（TEAE）。
共纳入 36 名受试者（每组 12 名）。单次给药后，所有剂量的培非替尼中位 t 为 1.0-1.5h，平均 t 为 7.4-13.0h。在多次给药期间，中位 t 为 1.5-2.0h。培非替尼及其代谢物在单次和多次给药后呈剂量比例增加，药物蓄积最小。主要代谢物是 H2，其全身暴露量是母体 AUC 的>150%。单次和多次给药期间，分别有 5 名（13.9%）和 12 名（33.3%）受试者发生与药物相关的 TEAE。在多次给予培非替尼后，高剂量组的 TEAE 发生率高于低剂量组，但严重程度均为轻度，无相关停药或死亡。
在健康中国受试者中单次和多次给予培非替尼后，培非替尼显示出快速吸收，在所有剂量下均具有良好的耐受性。
临床试验.gov 标识符：NCT04143477。
