Schering-Plough Presents Data on Oral Thrombin Receptor Antagonist

Schering-Plough presented results of a Phase II trial of its novel oral thrombin receptor antagonist (TRA), SCH 530348, at the American College of Cardiology's meeting in New Orleans. The trial met its primary endpoint of demonstrating no increase in major and minor bleeding, according to the Thrombolysis in Myocardial Infarction (TIMI) bleeding scale, when this investigational antiplatelet compound was added to standard antiplatelet therapy (including aspirin and clopidogrel) among patients undergoing percutaneous coronary intervention.

The 1,030-patient trial was designed to evaluate the safety and tolerability of TRA in patients undergoing percutaneous coronary intervention. A secondary objective was to assess whether patients treated with the compound in addition to standard-of-care therapies had fewer cardiovascular events such as heart attack, need for urgent coronary revascularization or death at 60 days compared with patients treated with the standard of care alone. While not powered to establish efficacy, the study did report a non-statistically significant 46 percent reduction in cardiovascular events at the highest TRA dose tested compared with standard of care.

The study was a multinational, randomized, double-blind, placebo-controlled, dose-ranging trial assessing both oral loading doses as well as maintenance doses of TRA. The trial enrolled 1,030 patients randomized to one of three oral loading doses of TRA (10, 20 or 40 mg) or placebo in a 3-1 ratio of active drug to placebo. The loading doses were increased in a sequential fashion based on a blinded review by an independent safety review committee. Those patients who subsequently underwent percutaneous coronary intervention were randomized to one of three oral daily maintenance doses of TRA (0.5, 1 or 2.5 mg) for those who had received a TRA loading dose, or randomized to standard of care for those who had received a placebo loading dose. The total duration of treatment was 60 days, and patients were followed for an additional 60 days.

In the primary cohort, the incidence of TIMI major and minor bleeding in the collective TRA treatment arms was 2.8 percent compared with 3.3 percent in the standard care alone arm. Non-TIMI bleeding was also not significantly increased with TRA compared with standard care alone. Overall, TRA was well-tolerated, with discontinuations due to any adverse events of 6 percent compared with 5 percent with placebo.