In a phase I study, a 60 mg loading dose of the investigational antiplatelet compound prasugrel showed faster onset of activity and achieved greater inhibition of platelet aggregation than either the approved 300 mg loading dose of clopidogrel (Plavix) or a higher 600 mg clopidogrel dose, researchers with Daiichi Sankyo and Eli Lilly and company.
Thirty minutes after oral administration, the level of platelet inhibition with a prasugrel 60 mg dose was significantly higher than observed with either loading dose of clopidogrel. At one hour, the antiplatelet inhibition achieved with a prasugrel loading dose was greater than that seen at up to six hours following administration of the approved and high loading doses of clopidogrel.
"This data shows for the first time that as early as 30 minutes after dosing, a 60 mg prasugrel loading dose achieves greater platelet inhibition than both the approved loading dose and high-dose clopidogrel," said Kenneth Winters, MD, Lilly research cardiologist.
In an earlier phase I study with healthy volunteers, a 60 mg loading dose of prasugrel showed a lower rate of poor responders by platelet function testing compared with the approved 300 mg loading dose of clopidogrel. Poor responders are defined as those who fail to reach a specified level of platelet inhibition after receiving the drug. Findings showed poor antiplatelet response in 17 per cent to 43 per cent of those given the approved clopidogrel loading dose (depending on the definition of poor responder used) while no poor responders were observed with prasugrel.
Winters presented the new clinical data in an oral presentation at the cardiovascular research foundation's 18th annual transcatheter cardiovascular therapeutics meeting in Washington, DC Data from the other phase I study appeared in a poster presentation at the meeting.
Daiichi Sankyo and Lilly are currently studying prasugrel in the phase III head-to-head clinical trial Triton-Timi 38. The Triton-Timi 38 study will evaluate the safety and efficacy of prasugrel compared with clopidogrel in reducing ischemic events such as heart attacks, stroke and death in approximately 14,000 patients with acute coronary syndrome undergoing percutaneous coronary intervention, including coronary stenting. The study is expected to be complete in 2007, and, if successful, regulatory submissions will follow in the same year.