Key result
Single oral doses of edoxaban 30, 60, or 120 mg caused rapid and sustained inhibition of coagulation up to 24 hours in the shed blood model, significantly greater than fondaparinux.
Why the study?
Does single-dose edoxaban reduce markers of coagulation in shed and venous blood in healthy male subjects compared to fondaparinux or placebo?
RCT (n=100)
Does single-dose edoxaban reduce markers of coagulation in shed and venous blood in healthy male subjects compared to fondaparinux or placebo?
Single oral doses of edoxaban provide rapid and sustained inhibition of coagulation up to 24 hours in a shed blood model, demonstrating greater inhibition than prophylactic fondaparinux.
Edoxaban's PD profile supports dosing evaluation in patients; extends comparative data versus fondaparinux.
Edoxaban, an oral direct factor Xa (FXa) inhibitor, is in phase III clinical development for stroke prevention in atrial fibrillation and treatment of venous thromboembolism. The shed blood model allows for study of activated coagulation at a site of standardised tissue injury due to local release of tissue factor. The objective of this study was to evaluate the effect of three doses of edoxaban on markers of coagulation in shed and venous blood versus placebo and a standard prophylactic dose of fondaparinux. A total of 100 healthy male subjects were randomised to receive single doses of one of five treatments: subcutaneously administered fondaparinux 2.5 mg; orally administered edoxaban 30, 60, or 120 mg; or placebo. The primary objective was measurement of blood coagulation markers prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin (TAT) complex, and platelet activation marker β-thromboglobulin (β-TG), in venous and shed blood. Secondary objectives included pharmacokinetics, shed blood volume, and safety of edoxaban. Single doses of edoxaban caused rapid and significant decreases of F1+2, TAT, and β-TG in the shed blood model, indicating inhibition of thrombin generation and platelet activation. Inhibition was significantly less for fondaparinux versus edoxaban. Baseline-corrected F1+2, TAT, and β-TG values demonstrated sustained inhibition up to 24 hours for shed blood in the edoxaban groups but no significant inhibition in venous blood. Overall, edoxaban treatments were well tolerated. In conclusion, single oral doses of edoxaban 30, 60, or 120 mg caused rapid and sustained inhibition of coagulation up to 24 hours in the shed blood model.
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A 2011 study conducted an RCT in Healthy subjects (n=100). Edoxaban vs. Fondaparinux 2.5 mg subcutaneously or placebo was evaluated on Measurement of blood coagulation markers prothrombin fragment 1+2 (F1+2), thrombin-antithrombin (TAT) complex, and β-thromboglobulin (β-TG) in venous and shed blood. Single oral doses of edoxaban 30, 60, or 120 mg caused rapid and sustained inhibition of coagulation up to 24 hours in the shed blood model, significantly greater than fondaparinux.
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