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- Title
Safety and Tolerability of Tecarfarin (ATI-5923) in Healthy Chinese Volunteers: Multiple Oral Dose-Escalation Phase I Trial.
- Authors
Zhou, Qiang; Wang, Zhiqiang; Wang, Heming; Chen, Zhidong; Li, Xiaoyi; Dai, Xiangrong; Zhang, Yong; Yu, Xiaohui; Zhou, Renpeng; Hu, Wei
- 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.
- Subjects
DRUG tolerance; GASTROINTESTINAL hemorrhage; WARFARIN; ANTICOAGULANTS; DOSE-effect relationship in pharmacology; BLIND experiment; RESEARCH funding; INTERNATIONAL normalized ratio; PATIENT safety; PHARMACODYNAMICS
- Publication
American Journal of Cardiovascular Drugs, 2023, Vol 23, Issue 1, p101
- ISSN
1175-3277
- Publication type
Article
- DOI
10.1007/s40256-022-00562-5