KENILWORTH, N.J., Oct. 22 Schering-Plough Corporation(NYSE: SGP) today provided an update on the clinical development program forits novel oral thrombin receptor antagonist (TRA). Results from tworandomized, double-blind, placebo-controlled Phase II studies in patients withvascular disease showed that TRA does not increase the rate of major or minorbleeding in patients with acute coronary syndrome or prior ischemic strokewhen added to standard antiplatelet therapy. The trials were conducted inJapan as part of the global registration program for TRA.
"These findings confirm the results of the TRA-PCI Phase II trial, whichwere presented at the American College of Cardiology/i2 Summit earlier thisyear," said Rick Veltri, M.D., group vice president of global clinicalresearch, cardiovascular and metabolic disease, Schering-Plough ResearchInstitute. "We now have three Phase II trials involving a total of more than1,200 patients with vascular disease which consistently demonstrate that TRAis well-tolerated and not associated with an increased rate of bleedingcompared to patients who received standard of care therapy alone."
A secondary objective was to assess whether patients treated with TRA inaddition to standard of care therapy had fewer major adverse cardiovascularevents such as myocardial infarction (heart attack) compared to patientstreated with the standard of care alone. While not powered to establishefficacy, in the acute coronary syndrome study patients undergoingpercutaneous coronary intervention (PCI) treated with TRA had a statisticallysignificant reduction in myocardial infarctions during the periproceduralperiod compared to standard of care alone.
"The significant reduction in periprocedural myocardial infarctions, whichwas not expected given the small size of the study, if confirmed in the largerPhase III studies could demonstrate the potential for TRA as atransformational drug in the treatment of patients with acute coronarysyndrome," added Veltri.
Schering-Plough also announced that TRA has now begun dosing in patientsin the global Phase III development program. The Phase III developmentprogram includes two randomized, double-blind, placebo-controlled trialsenrolling nearly 30,000 patients with vascular disease. The first trial, insecondary prevention, involves approximately 19,500 patients with priormyocardial infarction or stroke, as well as patients with existing peripheralarterial disease. The second trial, in acute coronary syndrome, involvesapproximately 10,000 patients with non-ST segment elevation acute coronarysyndrome.
About the Phase II trials
The Phase II Japanese trial in acute coronary syndrome involved 120patients randomized 4 to 1 to TRA plus standard of care or standard of carealone, and treated for 60 days. Standard of care therapy in this studyincluded aspirin, ticlodipine, and heparin.
The Phase II Japanese trial in patients with prior ischemic strokeinvolved 90 patients randomized 2 to 1 to TRA plus standard of care therapy orstandard of care alone, and treated for 60 days. Standard of care therapyincluded aspirin and thienopyridine at the discretion of investigators.
Overall the incidence of adverse events in these trials was similar acrosstreatment arms.
Full data from the trials will be presented at a future medicalconference.
About the Phase III trials
The Phase III Thrombin Receptor Antagonist in Secondary Prevention ofAtherothrombotic Ischemic Events (TRA 2P-TIMI 50) trial is a multinational,randomized, double-blind, placebo-controlled study in approximately 19,500patients with prior MI or stroke, as well as patients with existingperipheral arterial disease. Patients will be randomized to either placeboplus standard medical care (including aspirin and clopidogrel) or to TRA oncedaily plus standard medical care. This Phase