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A Phase I, Single-sequence, Open-label Study to Evaluate the Drug-Drug Interaction Between Hetrombopag and Cyclosporine in Healthy Chinese Subjects.
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  • Fengshan Li,
  • Hongda Lin,
  • Qin Yu,
  • Kai Shen,
  • Lingli Zhang,
  • Sheng Feng,
  • Yiwen Wu,
  • Shiyin Feng,
  • Xiaohong Liu,
  • Linrui Cai,
  • Zhuo Chen,
  • Qin Zou,
  • Xu Su
Fengshan Li
Sichuan University West China Second University Hospital

Corresponding Author:lifengshan@scu.edu.cn

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Hongda Lin
Jiangsu Hengrui Medicine Co Ltd
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Qin Yu
Sichuan University West China Second University Hospital
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Kai Shen
Jiangsu Hengrui Medicine Co Ltd
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Lingli Zhang
Sichuan University West China Second University Hospital
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Sheng Feng
Jiangsu Hengrui Medicine Co Ltd
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Yiwen Wu
Jiangsu Hengrui Medicine Co Ltd
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Shiyin Feng
Sichuan University West China Second University Hospital
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Xiaohong Liu
Sichuan University West China Second University Hospital
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Linrui Cai
West China Women's and Children's Hospital
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Zhuo Chen
West China Women's and Children's Hospital
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Qin Zou
West China Women's and Children's Hospital
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Xu Su
West China Women's and Children's Hospital
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Abstract

Aims: This study aims to evaluate the drug-drug interaction(DDI) between hetrombopag and cyclosporine in healthy Chinese subjects. Methods: Twenty-six eligible subjects enrolled in this single-center, single-sequence, open-label, DDI study with three treatment periods, receiving 5 mg hetrombopag once on day 1, 100 mg cyclosporine twice daily from day 11 to day 15, and 5 mg hetrombopag + 100 mg cyclosporine on day 16. Serial blood samples were collected for pharmacokinetic evaluation. Adverse events were monitored throughout the study. Results: The plasma hetrombopag geometric mean ratios (GMRs) (90% CI) of Cmax, AUC0-t and AUC0-∞ of co-administration of hetrombopag with cyclosporine vs hetrombopag alone are 95.97% (70.08%, 131.43%), 105.75% (75.04%, 149.04%) and 104.19% (74.71%, 145.32%), respectively, indicating multiple doses of cyclosporine had minimal effects on hetrombopag exposure. The GMRs (90% CI) of Cmax and AUCss,tau for blood cyclosporine of co-administration vs cyclosporine alone were 100.49% (91.89%, 109.89%) and 100.81% (107.88%, 103.82%), respectively, suggesting a single dose of hetormbopag had no impact on the exposure of cyclosporine. Co-administration of hetormbopag with cyclosporine was generally well tolerated. Conclusion: No clinically significant DDI was observed when co-administration of hetrombopag with cyclosporine. No additional dose adjustment is warranted for this combination.
14 Sep 2022Submitted to British Journal of Clinical Pharmacology
15 Sep 2022Submission Checks Completed
15 Sep 2022Assigned to Editor
15 Sep 2022Reviewer(s) Assigned
25 Oct 2022Review(s) Completed, Editorial Evaluation Pending
31 Oct 2022Editorial Decision: Revise Major
12 Dec 20221st Revision Received
13 Dec 2022Submission Checks Completed
13 Dec 2022Assigned to Editor
13 Dec 2022Review(s) Completed, Editorial Evaluation Pending
13 Dec 2022Reviewer(s) Assigned
01 Jan 2023Editorial Decision: Accept