Merck announced the completion of patient enrollment in the TRA 2°P-TIMI 50 clinical trial, a Phase III, randomized, double-blind, placebo-controlled, multinational study of SCH 530348, the company's investigational antiplatelet protease activated receptor-1 (PAR-1) inhibitor. The study, conducted by the Thrombolysis in Myocardial Infarction (TIMI) Study Group, reached its target of more than 26,000 patients.

"TIMI 50 is the largest and most rapidly enrolling trial in our 25-year history," commented Eugene Braunwald, M.D., Chairman of the TIMI Study Group. "We are very pleased with this achievement and look forward to completing this important clinical outcome trial," he added.

The trial will assess the ability of SCH 530348, a thrombin receptor antagonist, or PAR-1 inhibitor, to prevent major cardiovascular events when added to current antiplatelet regimens (aspirin or aspirin + ADP inhibitor) in patients who have previously experienced a heart attack or stroke or who have peripheral arterial disease.

SCH 530348 is also being studied in the treatment of patients with acute coronary syndrome (ACS) in the ongoing Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA-CER) trial, led by Duke Clinical Research Institute.

"The completion of enrollment in one of our two pivotal clinical outcome trials for this investigational medicine is a significant milestone achievement in the development of SCH 530348," said Luciano Rossetti, M.D., senior vice president and head, Global Scientific Strategy, Merck Research Laboratories. "Heart disease remains the leading cause of death worldwide, and we believe that this novel agent has the potential to address a significant unmet medical need," he added.

Approximately 7.2 million people worldwide die each year from coronary heart disease, the most common cause of death in Europe and the United States. In spite of advances in antiplatelet and other preventive treatments, there remains a residual risk for further cardiovascular events in patients with established vascular disease.

About SCH 530348

The investigational antiplatelet SCH 530348 is being developed by Merck for the prevention and treatment of atherothrombotic events in patients with acute coronary syndrome and in those with prior myocardial infarction or stroke, as well as in patients with existing peripheral arterial disease.

SCH 530348 binds selectively to the thrombin receptor on platelets (PAR-1), and is therefore a member of a potentially new class of drugs called PAR-1 inhibitors. Importantly, Merck's SCH 530348 is being investigated to determine whether it has the potential to provide clinical benefit through inhibition of this thrombin-mediated platelet activation without the liability of significantly increased major bleeding (when added to aspirin or aspirin plus an ADP inhibitor), a tendency associated with drugs that block thromboxane or ADP pathways. Specifically, this compound is being investigated as an oral antiplatelet agent for patients with established vascular disease, to evaluate whether it can provide incremental benefit when given with current standard antiplatelet (including aspirin and clopidogrel) and other antithrombotic therapies, without causing a significant increase in major bleeding.

The 1,030-patient TRA-PCI Phase II trial was published in the March 14, 2009 issue of The Lancet.

The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to the compound. Fast Track designation allows FDA to expedite review of drugs and biologics for serious or life-threatening conditions which demonstrate the potential to address unmet medical needs.

About the Phase III Trials

SCH 530348 is currently being evaluated in two large-scale multinational, randomized, double-blind, placebo-controlled Phase III clinical trials.

The Phase III Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2˚P-TIMI 50) trial, which has now completed full enrollment, is a randomized, double-blind, placebo-controlled study in patients with prior MI or stroke, as well as patients with existing peripheral arterial disease. Patients have been randomized to either placebo plus standard medical care (including aspirin and clopidogrel) or to SCH 530348 once daily plus standard medical care. This Phase III trial uses the 2.5 mg maintenance dose. The primary endpoint of the trial is the composite of cardiovascular death, MI, urgent coronary revascularization or stroke. The key secondary endpoint is the composite of cardiovascular death, MI or stroke. Patients will be followed for a minimum of one year. This Phase III trial is being conducted by the Thrombolysis in Myocardial Infarction (TIMI) Study Group. David Morrow, M.D. is the principal investigator.

The Phase III Thrombin Receptor Antagonist Clinical Event Reduction in acute coronary syndrome (TRA-CER) trial is a multinational, randomized, double-blind, placebo-controlled study in patients with non-ST-segment elevation acute coronary syndrome. Patients are being randomized to either placebo plus standard medical care (including aspirin or clopidogrel) or to SCH 530348 plus standard medical care. The Phase III TRA-CER trial uses the oral 40 mg loading dose and the 2.5 mg maintenance dose. The primary endpoint of the Phase III TRA-CER trial is the composite of cardiovascular death, MI, rehospitalization for ACS, urgent coronary revascularization or stroke. The key secondary endpoint is the composite of cardiovascular death, MI or stroke. Patients will be followed for a minimum of one year. This Phase III trial is being conducted by the Duke Clinical Research Institute, Durham, NC. .

Source
Merck