Abstract 5496: Antiplatelet Effects and Bleeding Risk of DZ-697b, a Novel, Oral Antiplatelet Agent, versus Clopidogrel: Results of a Phase-I Study
INTRODUCTION: DZ-697b is a new orally active antiplatelet agent that inhibits collagen and ristocetin-mediated platelet aggregation. It does not require metabolization for the generation of its active compound and has a safer profile than clopidogrel in pre-clinical studies. The aim of this study was to investigate the platelet inhibitory effects and the bleeding risk of 3 doses of DZ-697b compared to 300mg clopidogrel.
METHODS: In a 4-treatment, 3-period, crossover design, 20 healthy subjects (31±7 years, 85% male) were randomized to a single oral dose of DZ-697b 60mg, 120mg and 360mg, and clopidogrel 300mg (n=15 in each treatment). Antiplatelet effects were assessed by measuring changes from pre-dose to 6 hours post-dose in platelet-thrombus size at high- and low-flow rates in the Badimon chamber, and platelet adhesion at high- and low-shear rates using Diamed Impact-R platelet function assay. Bleeding risk was assessed using surgicutt bleeding time procedure, measured at predose and 6 hours postdose.
RESULTS: DZ-697b caused dose-dependent reductions in thrombus size and platelet adhesion (Table⇓). Antiplatelet effects of DZ-697b 120mg were closest to clopidogrel 300mg. Bleeding times with all DZ-697b doses were significantly shorter than clopidogrel.
CONCLUSIONS: The oral agent DZ-697b shows potent, dose-dependent, antiplatelet properties. Bleeding time prolongations with even the highest tested dose of DZ-697b is significantly shorter than 300mg clopidogrel. Further studies are warranted.