Regular ArticleClinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Novel Factor Xa Inhibitor DY-807f in Healthy Volunteers

- A first-in-human study for a new oral factor Xa inhibitor DY-807f was conducted.
- Single doses of DY-807f were safe and well-tolerated up to 360 mg in healthy subjects.
- DY-807f has predictable and generally dose proportional Pharmacokinetic profiles.
- The effects of DY-807f on clotting times were correlated with plasma concentration.

IntroductionSince Vitamin K antagonists are associated with various limitations such as narrow therapeutic window, slow onset and offset of effect, and numerous interactions with food and drugs, new oral anticoagulants targeted to inhibit thrombin or factor Xa (FXa) have been developed. DY-807f is a highly selective, reversible and orally bioavailable FXa inhibitor.ObjectivesThis article describes a first-in-human study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending oral doses of the novel direct FXa inhibitor DY-807f in healthy males.Methodsa placebo-controlled, single-blinded, randomized, single ascending dose study with 84 subjects (10, 30, 60, 120, 240, and 360 mg). Effects of food and formulation (tablet vs solution) on bioavailability of 60 mg were also assessed as a crossover design.ResultsDY-807f doses were safe and well-tolerated with no dose-dependent increase in adverse events up to 360 mg. Pharmacokinetics profiles were consistent across doses with rapid absorption, biphasic elimination, and terminal elimination half-life of 10.5 to 12.4 hours. Coagulation parameters (Activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT)) were linearly correlated with plasma DY-807 (free base of DY-807f) concentrations (correlation coefficient: 0.786 for aPTT, 0.945 for PT).ConclusionsSingle doses of DY-807f are safe and well-tolerated up to 360 mg with predictable pharmacokinetic and pharmacodynamic profiles.