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Antithrombotic properties of rafigrelide: a phase 1, open-label, non-randomised, single-sequence, crossover study

Lookup NU author(s): Dr Karthik Balasubramaniam, Dr Girish Viswanathan, Professor Azfar Zaman

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Abstract

Platelets play a central role in atherothrombotic events. We investigated the effect of a novel platelet-lowering agent, rafigrelide, on thrombus formation and characteristics. In this phase 1, open-label, non-randomised, single-sequence, crossover study, healthy male volunteers received rafigrelide for 14 days (Period 1). Following a >= 6-week washout period, they then received rafigrelide + acetylsalicylic acid (ASA) for 14 days (Period 2). Thrombus formation was assessed ex vivo using the Badimon perfusion chamber, and thrombus characteristics were assessed using thromboelastography. A total of 15 volunteers were enrolled in the study and were assigned to Panel A or Panel B, which had different schedules of assessments. In Panel A, after treatment with rafigrelide alone (Period 1), mean (+/- standard deviation) platelet count was reduced from 283 (+/- 17) x 10(9)/I at Day 1, to 125 (+/- 47) x 10(9)/I at Day 14 (n=6) and thrombus area reduced under high and low shear conditions. Reductions in thrombus area under high shear conditions correlated with reductions in platelet count (r(2)=0.11, p=0.022; n=12). Rafigrelide treatment prolonged clot formation time and reduced clot strength. The addition of ASA to rafigrelide (Period 2) had no additional effect on platelet count or thrombus area under high or low shear conditions. Similar results were seen in Panel B for all parameters. The most common adverse events (>= 3 participants per period) were thrombocytopenia and headache. While confirming the platelet-lowering effects of rafigrelide, this early phase study also indicates that rafigrelide has antithrombotic properties under both high and low shear conditions.

Publication metadata

Author(s): Balasubramaniam K, Viswanathan G, Dragone J, Grose-Hodge R, Martin P, Troy S, Preston P, Zaman AG

Publication type: Article

Publication status: Published

Journal: Thrombosis and Haemostasis

Year: 2014

Volume: 112

Issue: 1

Pages: 205-215

Print publication date: 20/02/2014

ISSN (print): 0340-6245

Publisher: Schattauer GmbH

URL: http://dx.doi.org/10.1160/TH13-08-0681

DOI: 10.1160/TH13-08-0681

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