Summary
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) × 109/l at Day 1, to 125 (± 47) × 109/l 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 (r2=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.
Keywords
Rafigrelide - platelet-lowering - thrombus formation - Badimon perfu-sion chamber
- thromboelastography
