Summary

The pharmacokinetics, pharmacodynamics and safety of the directfactor Xa inhibitor, otamixaban, with and without concomitantacetylsalicylic acid (ASA) were investigated in healthy volunteers.The study was a double-blind, placebo-controlled 3-waycrossover study. Sixty-eight male volunteers in total were randomisedto otamixaban, ASA, or otamixaban with ASA. ASA(300 mg once a day) was started 2 days before and continued onthe day of the otamixaban 6-hour IV infusion (0.3 and 0.5 mg/kg).Pharmacokinetic and pharmacodynamic parameters (coagulationmarkers, platelet function tests and skin bleeding time)were determined.Drug interaction was assessed by the ratios ofgeometric means and 90% confidence intervals (90% CI)of theparameter estimates. Pharmacokinetic parameters of otamixaban remain ed unchangedwithASA.Ratios of geometric means (90% CI) were forC_eoi 96.54 (91.21–102.19) and 95.04 (90.10–100.24) and forAUC 98.0 (93.92–102.25) and 95.90 (92.61–99.31), for 0.3 and0.5 mg/kg, respectively. No drug interaction was observed betweenotamixaban andASA on the coagulation and platelet functionparameters. Neither otamixaban nor ASA had an effect onskin bleeding time; their co-administration led to a slight prolongationof skin bleeding time above the normal range without anyclinically relevant bleeding.This study demonstrated that the desiredeffects of otamixaban and ASA, namely anticoagulation andplatelet inhibition, respectively, are maintained during co-administrationof both drugs.