A study of the pharmacokinetics and safety of recombinant activated factor VII in healthy Caucasian and Japanese subjects

In this randomized, placebo-controlled, double-blind, single-centre, dose escalation study, we report the first evaluation of the pharmacokinetics; and safety of recombinant activated factor VII (rFVIIa) in healthy Caucasian and Japanese subjects. Thirty-two healthy subjects were stratified according to sex and ethnic group to receive single bolus intravenous injections of three different doses of rFVIIa (40, 80, 160 mu g/kg rFVIIa) or placebo, each separated by a 7-day wash-out period. Blood samples were taken up to 24 h after dosing. The factor VII clotting activity appeared to be dose dependent, but independent of sex and ethnic group. Statistical analyses demonstrated no significant effect of dose, sex or ethnicity on the dose-normalized mean area under the plasma concentration -time curve AUC(o-t), indicating dose proportionality. No serious adverse events or thromboembolic events were reported. Analyses of coagulation parameters did not suggest induction of systemic coagulation when dosing rFVIIa up to 160 mu g/kg. In conclusion, the pharmacokinetics of rFVIIa in Caucasian and Japanese subjects are similar, and no safety issues were identified. (C) Lippincott Williams & Wilkins