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Phase I study to evaluate of the gastric pH-dependent drug interaction between famitinib and the proton pump inhibitor omeprazole in healthy subjects

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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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All data generated or analyzed during this study are included in this published article.

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Acknowledgements

This work was supported by Jiangsu Hengrui Co. Ltd. The authors thank all the patients who participated in this study and their families, as well as all the investigators and site staff who made the study possible.

Funding

This project was also supported by the National Natural Science Foundation of China (No. 81503340), and the National Natural Science Foundation of Jiangsu Province (No. BK20150645), and the Project of scientific research plan for drug supervision, Grant/Award Number: 202106. We thank staff involved.

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Authors and Affiliations

  1. Office of Clinical Trial Institution, School of Medicine, Nanjing Zhongda Hospital, Southeast University, Nanjing, 210009, China

    Linlin Hu & Huiping Wang

  2. Department of Phase I Clinical Trial Unit, School of Medicine, Nanjing Zhongda Hospital, Southeast University, Nanjing, 210009, China

    Linlin Hu, Mingmin Cai, Wei Qian, Ting Dou, Qiuyue Sun, Lu Tang & Huiping Wang

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  1. Linlin Hu
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Contributions

Linlin Hu and Huiping 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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Correspondence to Linlin Hu or Huiping Wang.

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The authors declare no competing interests.

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Informed consent was obtained from all individual participants included in the study.

Research involving human participants and/or animals

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 (Nanjing, China).

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The authors declare no conflicts of interest. The author reports no conflicts of interest in this work.

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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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