Pharmacokinetics, pharmacodynamics, and safety of frunexian in healthy Chinese volunteer adults: A randomized dose-escalation phase I study

Clin Transl Sci. 2024 Apr;17(4):e13787. doi: 10.1111/cts.13787.


The purpose of this study was to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of frunexian (formerly known as EP-7041 and HSK36273) injection, a small molecule inhibitor of activated coagulation factor XI (FXIa), in healthy Chinese adult volunteers. This study was a randomized, placebo- and positive-controlled, sequential, ascending-dose (0.3/0.6/1.0/1.5/2.25 mg/kg/h) study of 5-day continuous intravenous infusions of frunexian. Frunexian administration exhibited an acceptable safety profile with no bleeding events. Steady state was rapidly reached with a median time ranging from 1.02 to 1.50 h. The mean half-life ranged from 1.15 to 1.43 h. Frunexian plasma concentration at a steady state and area under the concentration-time curve exhibited dose-proportional increases. The dose-escalation study of frunexian demonstrated its progressively enhanced capacities to prolong activated partial thromboplastin time (aPTT) and inhibit FXIa activity. The correlations between PK and PD biomarkers (aPTT/baseline and FXI clotting activity/baseline) were described by the two Emax models, with the EC50 values of 8940 and 1300 ng/mL, respectively. Frunexian exhibits good safety and PK/PD properties, suggesting it is a promising candidate for anticoagulant drug.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticoagulants*
  • Blood Coagulation*
  • China
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Healthy Volunteers
  • Humans
  • Partial Thromboplastin Time


  • Anticoagulants