Phase I Double Blind, Placebo Controlled, Ascending Single Intravenous Dose Study with a Synthetic Direct Thrombin Inhibitor, TGN255

摘要

TGN255 is a potent (Ki = 7-22nM), reversible, low molecular weight, and highly selective synthetic direct thrombin inhibitorEighteen healthy male subjects were enrolled. Each dosage level included six subjects, five of whom received active compound and one received placebo. Three dose regimens were tested: 7 mg intravenous bolus over 30 sec followed by an infusion of 25 mg/h for 3 h, 10 mg bolus followed by an infusion of 40 mg/h for 3 h, and an infusion of 40 mg/h for 3 h. Blood samples were taken into 3.8% tri-sodium citrate. Plasma concentrations of TGN255 were evaluated through a LC-MS/ MS method. The dynamic activity of TGN255 was assessed through measurement of the thrombin clotting time (TT) and activated Partial Thromboplastin Time (aPTT).