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FFR-rFVIIa is an antithrombotic agent, which has also proven to have antirestenotic properties in animal models. FFR-rFVIIa is a modified recombinant FVIIa in which the catalytic site is irreversibly inactivated by a synthetic tripeptide covalently bound with the FVIIa molecule. The modified rFVIIa retains its tissue factor (TF) binding capacity but is otherwise enzymatically inactive. A double-blind, placebo-controlled, randomized dose escalation trial was conducted to investigate eight single i.v. doses of FFR-rFVIIa (0.01, 0.02, 0.05, 0.08, 0.12, 0.18, 0.27, or 0.40 mg/kg body weight) in healthy male volunteers (n = 62). Safety, pharmacokinetics, and pharmacodynamics of FFR-rFVIIa were assessed. Mean (SB)AUC(0-∞) ranged from 0.35 (0.11) to 28.8 (3.5) g·h/ml, and mean Cmax ranged from 0.078 (0.019) to 4.8 (0.7) g/ml. The mean elimination half-life ranged from 3.8 to 5.8 hours. Mean AUC(0-∞) increased with increasing dose levels. Cmax appeared to be proportional to the dose level, with the exception of the lowest dose level. A dose-dependent prolongation of the prothrombin time was found, demonstrating that FFR-rFVIIa inhibited coagulation via the TF-dependent pathway. FFR-rFVIIa was generally well tolerated at all dose levels studied.