Summary
To evaluate the potential gastric pH-dependent drug-drug interaction (DDI), safety and tolerability of famitinib co-administered with omeprazole in healthy subjects. Twenty healthy subjects were enrolled in a single-center, single-arm, open-label, fixed-sequence study. Famitinib was administered as a single oral 25 mg under a fasting condition on day 1, omeprazole (40 mg once daily) was given on days 10–14, concomitantly with famitinib on day 15, and for the follow-up 7 additional days (days 16–22). Blood samples were collected for the pharmacokinetic analysis of famitinib and its metabolite SHR116637 following each famitinib dose. Safety and tolerability were assessed during the whole progress via clinical laboratory tests. The least-squares geometric mean ratios (GMRs) (90% CI) of Cmax, AUC0-t and AUC0-∞ for famitinib combined with omeprazole to famitinib alone were 0.989 (0.953, 1.027), 0.956 (0.907, 1.007) and 0.953(0.905, 1.005) respectively. For the metabolite SHR116637, their GMRs (90% CI) of the above parameters were 0.851 (0.786, 0.920), 0.890 (0.838, 0.946)and 0.887 (0.835, 0.943), indicating the absence of significant differences in the parameters. During the treatment period, 9(45%) subjects reported 16 treatment emergent adverse events (TEAE), among which 6 subjects (30%) reported 9 TEAEs and 1 subject (5%) reported 1 TEAE during famitinib or omeprazole administered alone respectively, 5 subjects (25.0%) reported 6 TEAEs during in the combined administration phase. Omeprazole did not have a significant influence on the pharmacokinetics (PK) of famitinib and SHR116637, and the safety profile was good upon co-administration. ClinicalTrials.gov identifier NCT 05,041,920.
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Contributions
Linlin Hu and Hui** Wang contributed to the study conception and design. Material preparation, data collection and analysis were performed by Linlin Hu, Mingmin Cai, Wei Qian, Lu Tang, Qiuyue Sun and Ting Dou. The first draft of the manuscript was written by Linlin Hu and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Informed consent was obtained from all individual participants included in the study.
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This study was performed in line with the principles of the Declaration of Helsinki. The study protocol was approved (approval number, 2021ZDSYLL195-P01) by the Ethics Committee of the Zhongda Hospital, Medical School, Southeast University (Nan**g, China).
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Hu, L., Cai, M., Qian, W. et al. Phase I study to evaluate of the gastric pH-dependent drug interaction between famitinib and the proton pump inhibitor omeprazole in healthy subjects. Invest New Drugs 40, 1274–1281 (2022). https://doi.org/10.1007/s10637-022-01299-3
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DOI: https://doi.org/10.1007/s10637-022-01299-3