Effects of aprosulate, a novel synthetic glycosaminoglycan, on coagulationand platelet function parameters: A prospective, randomized phase I study

In a phase I clinical trial the effect of the highly sulfated polyanion "Ap rosulate" was studied in healthy volunteers using different coagulation and platelet function parameters. Eighteen healthy volunteers aged 21 to 30 ye ars received two single subcutaneous doses of aprosulate (0.5 mg/kg body we ight; 1.0 mg/kg body weight), or unfractionated heparin (Calciparin(R) 7,50 0 IU). The washout period between the different drugs/doses was at least 7 days. Coagulation and platelet function parameters (activated par tial thro mboplastin time, Heptest, fibrinogen, von Willebrand factor, ristocetin cof actor, platelet adhesion to siliconized glass, and platelet-induced thrombi n generation time [a new method fur measuring thrombin generation in platel et-rich plasma in the presence of platelets]) were assessed during 24 hours after each injection. Aprosulate led to a significant and dose-dependent p rolongation of activated partial thromboplastin time and Heptest. This effe ct lasted for 4, hours (activated partial thromboplastin time) to 8 hours ( Heptest). Activated partial thromboplastin time was not prolonged after the injection of unfractionated heparin (7,500 IU). Fibrinogen, von Willebrand factor, and ristocetin cofactor remained unchanged with both drugs. Platel et induced thrombin generation time was slightly prolonged and platelet adh esion was slightly diminished up to 2 hours using 0.5 mg/kg aprosulate, and up to 4 hours using 1.0 mg/kg aprosulate while the platelet induced thromb in generation time system was not influenced by the subcutaneous injection (7,500 IU) of unfractionated heparin. Both drugs and doses were well tolera ted. Plasma transaminase concentrations alanin aminotransferase and asparta te aminotransferase serum values were slightly in creased in some volunteer s but returned to normal during or after the study (<4 weeks). Further clin ical trials will have to establish whether aprosulate is an effective drug for the prophylaxis of deep venous thrombosis.