PMID- 32800383 OWN - NLM STAT- MEDLINE DCOM- 20210519 LR - 20210519 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 42 IP - 9 DP - 2020 Sep TI - Effects of Food on the Pharmacokinetic Properties of Surufatinib: A Phase I, Single-dose, Randomized, Open-label Crossover Study in Healthy Subjects. PG - 1778-1786 LID - S0149-2918(20)30344-1 [pii] LID - 10.1016/j.clinthera.2020.07.010 [doi] AB - PURPOSE: Surufatinib is a potent and orally active small-molecule tyrosine kinase inhibitor targeting VEGFRs 1 to 3, FGFR-1, and CSF-1R, and thus may exert antitumor and antiangiogenic effects. The objective of this study was to determine the tolerability and effects of food intake on the pharmacokinetic properties of surufatinib in healthy Chinese subjects. METHODS: A total of 24 healthy Chinese male subjects aged between 18 and 55 years were enrolled. Subjects were administered a single dose of surufatinib 250-mg capsules in the fasted and fed states in succession. Pharmacokinetic analysis was performed through the collection of blood samples at predose and at several time points after surufatinib administration. Tolerability assessments comprised physical examination including vital sign measurements, laboratory testing, and ECG to determine adverse events (AEs). FINDINGS: The 90% CIs of the geometric mean ratios of AUC(0-t) and AUC(0-infinity) in the fasted and fed states was within 0.80 to 1.25; and for C(max), within 0.70 to 1.43, indicating that food had no effect on the bioavailability of surufatinib in these healthy Chinese male subjects. Food intake delayed the time to peak absorption of surufatinib, as the median T(max) in the fed state was longer than that in the fasted state (4.0 vs 2.0 h). Surufatinib was marginally excreted from urine (mean [SD] cumulative excretion fraction, 1.2% [0.4%]). AEs occurred in 7 of the 24 subjects (29.2%) and included upper respiratory tract infection, dizziness, merycism, intervertebral disc protrusion, influenza-like disease, hematuria, prostatitis, and elevated blood urea nitrogen. All AEs were grade 1 or 2. IMPLICATIONS: The bioavailability of surufatinib was not affected by food intake prior to dosing. However, food intake led to delated T(max) of surufatinib. The tolerability of a single oral dose of surufatinib 250 mg in the fasted and fed states was favorable in these healthy Chinese male subjects. These results indicate that surufatinib capsules could be administered before or after meals. ClinicalTrials.gov identifier: NCT02320409. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Qian, Hongjie AU - Qian H AD - Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China. FAU - Wu, Xue AU - Wu X AD - Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China. FAU - Chen, Qian AU - Chen Q AD - Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China. FAU - Li, Tingting AU - Li T AD - Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China. FAU - Wang, Wei AU - Wang W AD - Department of Emergency, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China. FAU - Jia, Jingying AU - Jia J AD - Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China. FAU - Yu, Chen AU - Yu C AD - Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China. FAU - Li, Ke AU - Li K AD - Hutchison MediPharma Ltd, Shanghai, China. FAU - Sai, Yang AU - Sai Y AD - Hutchison MediPharma Ltd, Shanghai, China. FAU - Su, Weiguo AU - Su W AD - Hutchison MediPharma Ltd, Shanghai, China. FAU - Liu, Yanmei AU - Liu Y AD - Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China. Electronic address: ymliu@shxh-centerlab.com. LA - eng SI - ClinicalTrials.gov/NCT02320409 PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200813 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Capsules) RN - 0 (Protein Kinase Inhibitors) SB - IM MH - Administration, Oral MH - Adolescent MH - Adult MH - Angiogenesis Inhibitors/*pharmacokinetics MH - Area Under Curve MH - Biological Availability MH - Capsules MH - Cross-Over Studies MH - Fasting MH - Female MH - *Food-Drug Interactions MH - Humans MH - Male MH - Middle Aged MH - Protein Kinase Inhibitors/*pharmacokinetics MH - Young Adult OTO - NOTNLM OT - food effects OT - pharmacokinetics OT - surufatinib OT - tolerability COIS- Disclosures This study was sponsored by Hutchison MediPharma Ltd. K. Li, Y. Sai, W.-G. Su are employees of Hutchison MediPharma Ltd. The authors have indicated that they have no other conflicts of interest regarding the content of this article. EDAT- 2020/08/18 06:00 MHDA- 2021/05/20 06:00 CRDT- 2020/08/18 06:00 PHST- 2020/05/15 00:00 [received] PHST- 2020/07/05 00:00 [revised] PHST- 2020/07/12 00:00 [accepted] PHST- 2020/08/18 06:00 [pubmed] PHST- 2021/05/20 06:00 [medline] PHST- 2020/08/18 06:00 [entrez] AID - S0149-2918(20)30344-1 [pii] AID - 10.1016/j.clinthera.2020.07.010 [doi] PST - ppublish SO - Clin Ther. 2020 Sep;42(9):1778-1786. doi: 10.1016/j.clinthera.2020.07.010. Epub 2020 Aug 13.