SHR2285, the first selectively oral FXIa inhibitor in China: Safety, tolerability, pharmacokinetics and pharmacodynamics combined with aspirin, clopidogrel or ticagrelor

• DOI: 10.3389/fphar.2022.1027627
• Publication Date: 2022-10-19T04:38:11Z
• Authors: Tingting Ma; Yanli Dong; Lei Huang; Yuanxun Yang; Yan Geng; Fei Fei; Pinhao Xie; Yu Zhao; Hui Lin; Zeyu Yang; Yun Jin; Xitong Ju; Runbin Sun; Juan Li
• Keywords: Tolerability; Pharmacodynamics

Purpose: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR2285, first oral coagulation factor XIa (FXIa) inhibitor developed in China combination with aspirin, clopidogrel or ticagrelor healthy subjects. Methods: This study was a single-center, randomized, double-blind, placebo-controlled (only SHR2285) design (NCT04945616). A total 52 subjects, 29 male 23 female, were completed this study. The subjects divided into three groups: A, B C, 16 group [aspirin + placebo SHR2285 200 mg bid (1:3, 4 received 12 SHR2285)] 300 3 13 20 C (aspirin (2:3, 8 SHR2285)), respectively. All groups administered orally for six consecutive days. Safety, parameters assessed. Results: 1) well tolerated, all adverse events mild. There no evidence an increased risk bleeding. 2) After 6 days twice-daily administration, could reach steady state. mean half-life 13.9 h, 14.5 h 13.8 3) markedly inhibited FXI activity prolonged activated partial thromboplastin time (APTT). In maximum inhibition rate 84.8%, 89.3% 92.2% prolongation APTT 2.08-fold, 2.36-fold 2.26-fold, Conclusion: These data suggest that potential FXIa inhibitor, is expected to become novel, safe effective anticoagulant when combined ticagrelor.