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

Autor: Qin H; Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China., Tan Y; Shanghai Fosun Pharmaceutical Development Co., Ltd., 1289 Yishan Road, Shanghai, 200233, China., Diao L; Shanghai Fosun Pharmaceutical Development Co., Ltd., 1289 Yishan Road, Shanghai, 200233, China., Hui AM; EnCureGen Pharma, 9 Yayingshi Road, Huangpu District, Guangzhou, 510700, China., Wu Z; Shanghai Fosun Pharmaceutical Development Co., Ltd., 1289 Yishan Road, Shanghai, 200233, China., Zhou Y; Wanbang Biopharmaceuticals, 6 Yangshan Road, Economic Zone, Xuzhou, 221004, Jiangsu, China., Sun J; Shanghai Fosun Pharmaceutical Development Co., Ltd., 1289 Yishan Road, Shanghai, 200233, China., Xiang X; Shanghai Fosun Pharmaceutical Development Co., Ltd., 1289 Yishan Road, Shanghai, 200233, China., Qiu J; Shanghai Fosun Pharmaceutical Development Co., Ltd., 1289 Yishan Road, Shanghai, 200233, China., Hu W; Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China. huwei@ahmu.edu.cn.
Jazyk: angličtina
Zdroj: Drugs in R&D [Drugs R D] 2023 Dec; Vol. 23 (4), pp. 465-473. Date of Electronic Publication: 2023 Nov 07.
DOI: 10.1007/s40268-023-00446-2
Abstrakt: Background and Objectives: 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.
Methods: 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.
Results: In total, 24 subjects were enrolled and 23 completed the study. SAF-189s maximum plasma concentration (C max ; 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 (AUC 0-t ; GMR: 105.1% [90% CI 100.3-110.2]) and AUC from time 0 to infinity (AUC 0-∞ ; GMR: 105.5% [90% CI, 100.6-110.6]). In both groups, the median time to maximum plasma concentration (t max ) was around 6 h and mean plasma half-life (t ½ ) 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.
Conclusions: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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