SCH 530348 (TRA), the novel investigational antiplatelet agent in development by Schering-Plough Corporation, was shown to be a potent inhibitor of platelet aggregation in a sub-analysis of the Thrombin Receptor Antagonist Percutaneous Coronary Intervention (TRA-PCI) trial presented at the American Heart Association Scientific Sessions.
The pharmacokinetic and pharmacodynamic analysis, conducted by the University of Tennessee Health Science Centre, Memphis, showed that SCH 530348 (TRA), a potent thrombin receptor antagonist, demonstrated sustained, dose- dependent, specific agonist-induced inhibition of platelet aggregation in blood samples from patients undergoing non-urgent percutaneous coronary intervention (PCI).
"The inhibition of platelet aggregation plays a critical role in reducing the formation of deleterious blood clots in patients undergoing PCI," said Lisa K Jennings, Ph.D., FAHA, Professor, Department of Medicine; Director, Vascular Biology Centre of Excellence, University of Tennessee Health Science Centre, Memphis, TN; and lead author. "TRA's potentially unique mechanism of action inhibits platelet aggregation through a different pathway from other antiplatelet agents currently available," added Jennings.
"Despite recent advances in cardiovascular care, current levels of morbidity and mortality make it clear that an unmet medical need exists for patients with acute coronary syndromes and those at risk of atherothrombosis. We believe these results add to the evidence indicating that TRA may be a promising therapeutic option for patients with unstable angina and non-ST elevation MI undergoing PCI," said Rick Veltri, MD, group vice president of global clinical research, Cardiovascular and Metabolic Disease, Schering- Plough Research Institute. "With our global phase III clinical development programme underway, we are continuing to evaluate the potential for TRA as a novel agent in reducing the incidence of cardiovascular events with no incremental bleeding when added to standard of care in the treatment of patients with acute coronary syndromes or established vascular disease," added Veltri.
The results were presented at the American Heart Association Scientific Sessions in Orlando, Florida, in a session titled "Thrombin Receptor Antagonist Is a Selective, Potent Inhibitor of PAR-1 Activity With Predictable Pharmacokinetics."
The phase II TRA-PCI trial was a multinational, randomized, double-blind, placebo-controlled dose-ranging trial assessing oral loading doses and maintenance doses of TRA. The trial enrolled 1,030 patients randomized to one of three oral loading doses of TRA (10 mg, 20 mg, 40 mg) plus standard of care (clopidogrel + aspirin) or placebo plus standard of care in a 3:1 ratio of active drug to placebo.