A new oral antiplatelet agent with potent antithrombotic properties: Comparison of DZ-697b with clopidogrel in a randomised phase I study

Urooj M. Zafar; Borja Ibáñez; Brian G. Choi; David A. Vorchheimer; Antonio Piñero; Xiaoping Jin; Raman K. Sharma; Juan J. Badimon

doi:10.1160/TH09-06-0378

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 103(01): 205-212
DOI: 10.1160/TH09-06-0378

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

A new oral antiplatelet agent with potent antithrombotic properties: Comparison of DZ-697b with clopidogrel in a randomised phase I study

Authors

Urooj M. Zafar

¹Mount Sinai School of Medicine, New York, New York, USA
Borja Ibáñez

¹Mount Sinai School of Medicine, New York, New York, USA
Brian G. Choi

¹Mount Sinai School of Medicine, New York, New York, USA
David A. Vorchheimer

¹Mount Sinai School of Medicine, New York, New York, USA
Antonio Piñero

¹Mount Sinai School of Medicine, New York, New York, USA
Xiaoping Jin

²Daiichi-Sankyo Pharma Development, Edison, New Jersey, USA
Raman K. Sharma

¹Mount Sinai School of Medicine, New York, New York, USA
Juan J. Badimon

¹Mount Sinai School of Medicine, New York, New York, USA

Abstract

Summary

DZ-697b is a new orally active antiplatelet agent that inhibits collagen and ristocetin-mediated platelet activation. It does not require meta-bolisation to generate its active compound and has a safer profile than clopidogrel in pre-clinical studies. We compared the antithrombotic effects and bleeding time prolongations of three DZ-697b doses with clopidogrel 300 mg. In a four-treatment, three-period, crossover-design, 20 healthy subjects (31 ± 7 years, 85% males) were randomised to single oral doses of DZ-697b (60, 120 and 360 mg), and clopidogrel (300 mg) (n=15 in each treatment with crossing-over). Antithrombotic effects were assessed by measuring six-hour post-dose changes from baseline in thrombus size in the Badimon chamber and platelet adhesion using Diamed Impact-R platelet function assay. Bleeding times were also measured pre-dose and at six hours post-dose. DZ-697b caused dose-dependent reductions in thrombus size at both high- and low-shear rates (mean reductions at 60, 120 and 360 mg doses of: 13.0%, 18.7%, 26.4% and 11.4%, 12.7%, 22.1% respectively, p<0.05 for all). Effect of clopidogrel (reductions of 18.7% and 11.0% respectively, p<0.05 for both) was closest to DZ-697b 120 mg. Reductions in platelet adhesion were also dose-dependent. Bleeding time ratio from baseline were shorter with DZ-697b versus clopidogrel (1.3, 1.4 and 1.5 versus 1.9, p<0.05 for all). The oral agent DZ-697b shows potent, dose-dependent, antithrombotic effects that are comparable to 300 mg clopidogrel at the 120 mg dose. Despite having equal or greater anti-platelet potency than 300 mg clopidogrel, bleeding time prolongations are significantly shorter with DZ-697b.

Keywords

Antiplatelet agents - thrombosis - clinical studies - antiplatelet drugs

Full Text

References

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