DALLAS, Nov. 15 /PRNewswire-FirstCall/ -- New Phase IIb data from the DISPERSE2 Study(1) presented today at the American Heart Association's Scientific Sessions, assessed the safety and tolerability of the AstraZeneca investigational drug AZD6140 plus aspirin compared with clopidogrel plus aspirin in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). The primary end point of the study was the incidence of total (major plus minor) bleeding events seen in patients taking AZD6140 or clopidogrel, which overall was 10.2% for the AZD6140 90 mg twice daily (BID) group, 10.2% for the AZD6140 180 mg BID group, and 9.2% for the clopidogrel 75 mg once daily (QD) group. Within these figures, those adjudicated as major bleeds totaled 7.8% (AZD6140 90 mg BID group), 6.2% (AZD6140 180 mg BID group) versus 8.0% (clopidogrel 75 mg QD group).
AZD6140 is being studied as an oral reversible adenosine diphosphate (ADP) receptor antagonist for acute coronary syndrome. It is proposed to selectively inhibit the P2Y12 receptor, a key target receptor for ADP on platelets.
"The hypothesis is that a new antiplatelet therapy that can offer a higher level of inhibition of platelet aggregation could have an even greater clinical benefit. This would need to be tested in a large clinical trial, but the data today are an important step: precisely because there has been concern in the past that with a higher level of inhibition one might expect to see an increased risk of bleeding. In the current study, this was not the case with AZD6140," said Dr. Christopher Cannon, TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, and DISPERSE2 lead investigator.
The DISPERSE2 results also showed the incidence of total (major plus minor) bleeding events for patients taking AZD6140 or clopidogrel was 9.6% for the AZD6140 90 mg BID group, 7.7% for the AZD6140 180 mg BID group, and 8.0% for the clopidogrel 75 mg QD group at the four week time point.
Discontinuation rates due to adverse events for the DISPERSE2 trial were 6% for the AZD6140 90 mg BID group, 7% for the AZD6140 180 mg BID group and 6% for the clopidogrel 75 mg QD group.
This is the second Phase II study of AZD6140 to be presented at a major medical meeting. The first study, DISPERSE, which was presented earlier this year at the European Society of Cardiology (ESC) meeting in Stockholm, compared the ability of AZD6140 to inhibit platelet aggregation with clopidogrel.
AZD6140
AZD6140 is an investigational antiplatelet agent being studied for the prevention of thrombotic events in patients with ACS. AZD6140 is proposed to work by inhibiting the aggregation of platelets in the blood, which may reduce the risk of clot formation. AZD6140 is being studied as a reversible oral ADP receptor antagonist. It is proposed to selectively inhibit the P2Y12 receptor, a key target receptor for ADP on platelets. AZD6140 is currently in phase II development.
The DISPERSE2 Study
The Dose confirmatIon Study assessing anti-Platelet Effects of AZD6140 vs clopidogRel in NSTEMI was a double-blind, double-dummy, parallel group, randomized dose confirmation and feasibility study of AZD6140 plus ASA compared with clopidogrel plus ASA in 990 patients with non-ST elevation acute coronary syndromes. Subjects received daily aspirin up to 325 mg first dose, then 75 to 100 mg, and heparin/LMWH and/or GP IIb/IIIa inhibition per local physician. They were randomized to receive one of two doses of AZD6140 (90 mg or 180 mg twice daily) or clopidogrel 75 mg once daily for up to 12 weeks. Half of the AZD6140 patients were subrandomized to receive a loading dose of 270 mg while the other half started therapy with the maintenance dose. Patients randomized to clopidogrel received a 300 mg loading dose unless they had been on previous clopidogrel therapy with the option to give an additional double-blind clopidogrel 300 mg dose pre-PCI (total 600 mg dose). The primary end point studied was adjudicated total bleeding events (major plus minor) within the first four treatment weeks and overall.
Acute coronary syndrome (ACS)
ACS is an umbrella term for conditions that cause chest pain due to insufficient blood supply to the heart muscle (acute myocardial ischemia). ACS includes two conditions - unstable angina (chest pain with ECG changes compatible with ischemia) and heart attack (non ST-elevation myocardial infarction). ACS represents a major medical and economic burden on society, accounting for approximately 2.5 million hospitalizations and 500,000 deaths in the United States alone, each year.(2) Patients with ACS are at increased risk for strokes and heart attacks.
AstraZeneca
AstraZeneca is a major international health care business engaged in the research, development, manufacture, and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world's leading pharmaceutical companies with health care sales of over $21.4 billion and leading positions in sales of gastrointestinal, oncology, cardiovascular, neuroscience, and respiratory products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index. AstraZeneca has more than 40 years experience in cardiovascular medicine and aims to increase lifespan and improve quality of life by reducing the risk, prevalence, and impact of cardiovascular disease. AstraZeneca has a comprehensive cardiovascular portfolio.
This press release contains forward-looking statements with respect to the AstraZeneca business. By their nature, forward-looking statements and forecasts involve risks and uncertainties because they relate to events and depend on circumstances that will occur in the future. There are a number of factors that could cause actual results and developments to differ materially. For a discussion of those risks and uncertainties, please see the company's Annual Report/Form 20-F for 2004.
References 1. Cannon CP, Husted S, Storey RF, Harrington RA, Watkins C, Hill S, Price D, Sanders N, Emanuelsson H, and Peters G. Safety, Tolerability and Preliminary Efficacy of AZD6140, the First Oral Reversible ADP Receptor Antagonist Compared with Clopidogrel in Patients with Non-ST Segment Elevation Acute Coronary Syndrome (The DISPERSE2 Study). Presented at American Heart Association (AHA), Dallas, 15 November, 2005. 2. Parmley W. Trials of Glycoprotein IIb-IIIa Inhibitors in Non-ST-Segment Elevation Acute Coronary Syndromes: Applicability to the Practice of Medicine in the United States Clin. Cardiol. Vol. 22, (Suppl. VI) VI-1 (1999).
AstraZenecaCONTACT: Kellie Caldwell, AstraZeneca, +1-302-885-1435
Web site: http://www.astrazeneca-us.com/
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