Effect of High-Fat Food on the Pharmacokinetic Profile and Safety of SAF-189s, an ALK/ROS1 Inhibitor, in Healthy Chinese Adults

药代动力学 最大值 交叉研究 餐食 医学 不利影响 内科学 动物科学 胃肠病学 内分泌学 生物 安慰剂 病理 替代医学
作者
Huiling Qin,Yan Tan,Lei Diao,Ai‐Min Hui,Zhuli Wu,Yongchun Zhou,Juan Sun,Xiao Xiang,Jingjun Qiu,Wei Hu
出处
期刊:Drugs in R & D [Springer Nature]
卷期号:23 (4): 465-473 被引量:1
标识
DOI:10.1007/s40268-023-00446-2
摘要

This study was conducted to investigate the effect of high-fat meals on the pharmacokinetics (PK) and safety profile of SAF-189s, a novel ALK/ROS1 inhibitor.This was a single-center, phase I, open-label, crossover study in which healthy adults (≥18 years) were randomized (1:1) to two sequences of SAF-189s administration (fasted-fed or fed-fasted) separated by a 14-day washout. After a ≥10-h overnight fast, volunteers received SAF-189s 160 mg orally in a fasted state or 30 min after a high-fat, high-calorie meal. Similarity of pharmacokinetic parameters was concluded if the 90% CI for the geometric mean ratio (GMR) between the fed and fasted group fell within the predefined range of 0.80-1.25.In total, 24 subjects were enrolled and 23 completed the study. SAF-189s maximum plasma concentration (Cmax; GMR: 109.1% [90% CI 103.1-115.4]) was comparable under fed (high-fat meal, n = 24) versus fasted (n = 23) conditions, with no effect on area under the plasma concentration-time curve from time 0 to t (AUC0-t; GMR: 105.1% [90% CI 100.3-110.2]) and AUC from time 0 to infinity (AUC0-∞; GMR: 105.5% [90% CI, 100.6-110.6]). In both groups, the median time to maximum plasma concentration (tmax) was around 6 h and mean plasma half-life (t½) was around 35 h. Fed administration led to a lower incidence of treatment-emergent adverse events (TEAEs; 29.2% vs 54.2%), including gastrointestinal disorders (4.2% vs 41.7%) and headache (0.0% vs 12.5%), versus fasted administration.A high-fat meal had minimal effect on the pharmacokinetic profile of SAF-189s compared with a fasted state following a single dose of 160 mg. Administration with a high-fat meal led to a lower incidence of TEAEs.
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