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Safety and Tolerability of Tecarfarin (ATI-5923) in Healthy Chinese Volunteers: Multiple Oral Dose-Escalation Phase I Trial

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Abstract

Background

Tecarfarin (ATI-5923), a structural analog of warfarin, was designed to provide more uniform and stable anticoagulation.

Objective

We aimed to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profile of tecarfarin when administered in multiple ascending doses (MADs) to healthy Chinese volunteers.

Methods

Forty healthy Chinese volunteers were enrolled into four sequential cohorts (10, 20, 30, and 40 mg), with 10 subjects in each cohort. Participants in the MAD study for each sequential cohort were dose-titrated to achieve the target international normalized ratio (INR 1.7–2.0) for 14 days. Safety and tolerability were assessed throughout the study.

Results

The pharmacokinetic and pharmacodynamic profile of tecarfarin was investigated in a healthy Chinese population. Dose titration of tecarfarin was necessary to keep the INR in the target range in all subjects in the 20, 30 and 40 mg cohorts and a few subjects (n = 3) in the 10 mg cohort. Tecarfarin was well tolerated without serious adverse events. Only one treatment-related adverse event (hematochezia) resulted in early withdrawal from the MAD 40 mg cohort.

Conclusion

Tecarfarin was well-tolerated by Chinese volunteers. Dose titration was needed for tecarfarin doses larger than 20 mg to keep the INR in the target range.

Registration

ClinicalTrials.gov identifier: NCT04627116.

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Author notes

  1. Qiang Zhou and Zhiqiang Wang contributed equally as co-first authors.

Authors and Affiliations

  1. Department of Laboratory Medicine, The Second Hospital of Anhui Medical University, Hefei, China

    Qiang Zhou, Heming Wang & Zhidong Chen

  2. Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, China

    Zhiqiang Wang, Renpeng Zhou & Wei Hu

  3. Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China

    Zhiqiang Wang

  4. The Zhaoke Pharmaceutical Co., Ltd, Guangzhou, China

    **aoyi Li, **angrong Dai, Yong Zhang & **aohui Yu

Authors
  1. Qiang Zhou
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Corresponding authors

Correspondence to Renpeng Zhou or Wei Hu.

Ethics declarations

Conflicts of interest/competing interest

**aoyi Li, **angrong Dai, Yong Zhang and **aohui Yu are employed by Zhaoke Pharmaceutical Co., Ltd, Guangzhou, China. Qiang Zhou, Zhiqiang Wang, Heming Wang, Zhidong Chen, Renpeng Zhou and Wei Hu have no relevant financial or non-financial competing interests to report.

Funding

This study was supported by the National Major Scientific and Technological Special Project (2020ZX09201014). NCT04627116 was sponsored by Lee’s Pharmaceutical Limited.

Author contributions

Qiang Zhou, Zhiqiang Wang, Renpeng Zhou and Wei Hu contributed to the study conception and design. Renpeng Zhou and Wei Hu performed the clinical trials. Heming Wang, Zhidong Chen, **aoyi Li and Xaingrong Dai conducted the biosample analysis. Zhiqiang Wang, Yong Zhang and Xaiohui Yu performed the statistical analysis and interpretation of the data. Qiang Zhou and Zhiqiang Wang drafted the manuscript. All authors were involved in revising the paper critically for intellectual content, and approved the final version to be published.

Ethical approval

This study was approved by the Ethics Committee of the Second Affiliated Hospital of Anhui Medical University (Hefei, China).

Consent to participate

Not applicable.

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Not applicable.

Data availability

The data that support the findings of this study are available from the corresponding author (Wei Hu) upon reasonable request.

Code availability

Not applicable.

Supplementary Information

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Supplementary file1 (PDF 1503 kb)

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Zhou, Q., Wang, Z., Wang, H. et al. Safety and Tolerability of Tecarfarin (ATI-5923) in Healthy Chinese Volunteers: Multiple Oral Dose-Escalation Phase I Trial. Am J Cardiovasc Drugs 23, 101–112 (2023). https://doi.org/10.1007/s40256-022-00562-5

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  • DOI: https://doi.org/10.1007/s40256-022-00562-5

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