Pharmacokinetics, Pharmacodynamics, and Safety of ASP015K (Peficitinib), a New Janus Kinase Inhibitor, in Healthy Subjects
Pharmacokinetics, Pharmacodynamics, and Safety of ASP015K (Peficitinib), a New Janus Kinase Inhibitor, in Healthy Subjects
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DOI：
10.1002/cpdd.273
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发表时间：
2016-11-01
影响因子：
2
通讯作者：
Zhu, Tong
中科院分区：
文献类型：
--
作者：
Cao, Ying Jun;Sawamoto, Taiji;Zhu, Tong
报告了两项随机化、双盲、安慰剂对照研究，旨在评价ASP 015 K（peficitinib）（一种Janus激酶（JAK）抑制剂）在健康受试者中的药代动力学、药效学和安全性。单次给药研究包括7个男性组（3-300 mg）和2个女性组（30或200 mg），n = 8/组（每组6例接受ASP 015 K，2例接受安慰剂）。多次给药研究包括1个女性组和3个男性组，n = 12/组（每组9例接受ASP 015 K治疗，3例接受安慰剂治疗），接受ASP 015 K（30 mg）或安慰剂，每12小时一次（每天两次），持续14天。在单次给药研究中，血浆ASP 015 K浓度与剂量成比例增加。食物使ASP 015 K暴露量（AUC（inf））增加27%。平均JAK抑制峰值随剂量增加而增加，从ASP 015 K 3 mg给药后4小时（中位数）的6%增加至ASP 015 K 300 mg给药后2小时（中位数）的93%（范围，89%-98%）。在多次给药研究中，ASP 015 K血浆暴露量在第3天达到稳态。在第14天，平均ASP 015 K峰值浓度比首次给药后高38%-65%; 100或200 mg每日两次后的峰值JAK抑制> 85%。最常见的不良事件（AE）为中性粒细胞减少、头痛和腹痛;未发生严重AE。ASP 015 K有效剂量的安全性结果支持进一步的临床开发。
Two randomized, double-blind, placebo-controlled studies are reported that had the objective to evaluate the pharmacokinetics, pharmacodynamics, and safety of ASP015K (peficitinib), a Janus kinase (JAK) inhibitor, in healthy subjects. The single-dose study included 7 male groups (3-300 mg) and 2 female groups (30 or 200 mg), n = 8/group (6 on ASP015K and 2 on placebo in each group). The multiple-dose study included 1 female and 3 male groups, n = 12/group (9 on ASP015K and 3 on placebo in each group), who received ASP015K (30 mg) or placebo every 12 hours (twice a day) for 14 days. In the single-dose study, plasma ASP015K concentration increased dose-proportionally. Food increased ASP015K exposure (AUC(inf)) by 27%. Mean peak JAK inhibition increased with dose, from 6% at 4 hours (median) following ASP015K 3 mg to 93% (range, 89%-98%) at 2 hours (median) after ASP015K 300 mg. In the multiple-dose study, ASP015K plasma exposure reached steady state by day 3. On day 14, mean ASP015K peak concentration was 38%-65% higher than after the first dose; peak JAK inhibition following 100 or 200 mg twice daily was >85%. The most common adverse events (AEs) were neutropenia, headache, and abdominal pain; no serious AEs occurred. The safety findings at pharmacologically effective doses of ASP015K support further clinical development.