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Juan Wu,1,2 Hongrong Xu,1 Hui Li,1 Lei Ma,3 Juan Chen,3 Fei Yuan,1 Lei Sheng,1 Chao Liu,1 Weili Chen,1 Xuening Li1 1Department of Clinical Pharmacology & Cancer Center, ZhongShan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Pharmacy, Shanghai Children’s Medical Center, School of Medicine, Shanghai JiaoTong University, Shanghai, People’s Republic of China; 3Haihe Biopharma Co., Ltd, Shanghai, People’s Republic of ChinaCorrespondence: Xuening Li, Department of Clinical Pharmacology & Cancer Center, ZhongShan Hospital, Fudan University, 180 Fenglin Road, Shanghai, People’s Republic of China, 200032, Tel +86 21 3158 7860, Fax +86 21 3158 7866, Email li.xuening@zs-hospital.sh.cnObjective: This study aimed to investigate the effect of food on the pharmacokinetics and safety profiles of SCC244, a novel oral c-Met inhibitor in healthy Chinese male subjects.Methods: It was a randomized, open-label, and 3-period crossover design, single-dose phase I clinical trial. A total of 18 healthy male subjects were enrolled. These subjects received a single oral 300 mg dose of SCC244 with a 14-day washout between each period. Blood samples were collected at the designated time points and determined using a validated liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters were calculated by noncompartmental methods. Tolerability was assessed by physical examination, vital sign measurements, 12-lead ECG, clinical laboratory tests, and adverse events (AEs) monitoring throughout the study.Results: Eighteen eligible subjects were enrolled in the study. The ratios (90% CI) of Cmax values for SCC244 in high-fat and low-fat meal states to that observed in fasted state were 194.8% (174.3– 217.7%) and 194.6% (174.1– 217.5%), respectively. The ratios of AUC0-t and AUC0-inf in the high-fat meal state versus the fasted state were 237.4% (208.7– 270.0%) and 235.9% (207.5– 268.3%), respectively. The ratios of AUC0-t and AUC0-inf in the low-fat meal state versus the fasted state were 219.2% (192.7– 249.3%) and 218.3% (192.0– 248.3%), respectively. Median Tmax values and mean t1/2 were similar in all groups. The most common AEs were headache, blood fibrinogen decreased, head discomfort, dizziness, and protein urine presence. All AEs were Common Terminology Criteria for Adverse Events (CTCAE) grade 1 (except 1 case of grade 2) and have resolved by the end of the study.Conclusion: The bioavailability of the tablet formulation of SCC244 was significantly increased when administered with high- and low-fat meals. However, the meals did not affect the median Tmax and t1/2. Safety under different fed conditions was comparable to fasted conditions in this study.Keywords: SCC244, c-Met inhibitor, food effect, pharmacokinetics, safety |
