Pharmacokinetics, pharmacodynamics, and safety of frunexian in healthy Chinese volunteer adults: A randomized dose-escalation phase I study.
Clin Transl Sci
; 17(4): e13787, 2024 04.
Article
in En
| MEDLINE
| ID: mdl-38558535
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Blood Coagulation
/
Anticoagulants
Limits:
Adult
/
Humans
Country/Region as subject:
Asia
Language:
En
Journal:
Clin Transl Sci
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Estados Unidos