A novel proprietary combination of aspirin and immediate-release omeprazole in a coordinated-delivery tablet resulted in markedly fewer gastric ulcers and treatment discontinuations than conventional enteric-coated aspirin in two pivotal phase III clinical trials reported at the annual scientific sessions of the American Heart Association.
The two double-blind, 6-month, multicenter, randomized phase III studies included 1,049 patients who had coronary heart disease and were taking aspirin for secondary cardiovascular prevention. Based upon the highly favorable results reported by Dr. David L. Whellan at the meeting as well as other evidence, the studies’ sponsor, Pozen, will seek regulatory approval of the coordinated-delivery product with an indication for use in secondary prevention of cardiovascular events in the roughly 15% of patients at risk for aspirin-induced upper-GI adverse events.
Study participants were randomized to once-daily conventional enteric-coated aspirin at 325 mg or to the investigational tablet, known for now as PA32540. The primary endpoint – the 6-month rate of endoscopically confirmed gastric ulcers – occurred in 3.8% of the PA32540 group, compared with 8.7% of controls, in one 524-patient study and in 2.7% of the PA32540 group, versus 8.5% of controls, in the 525-patient second study. This corresponds to relative risk reductions of 56% and 68%, respectively, according to Dr. Whellan of Thomas Jefferson University, Philadelphia.
A key secondary endpoint was the 6-month treatment discontinuation rate as a result of dyspepsia, erosive gastritis, and other upper-GI adverse events. The combined rate in the two trials was 1.5% in the PA32540 group and 8.2% in patients on enteric-coated aspirin, for an 82% relative risk reduction.
The rate of discontinuation for any adverse events was 6.7% with PA32540 and 11.2% in controls. Since patient adherence to aspirin therapy saves lives, these are clinically important outcomes, he noted.
The rate of acute MI and other major adverse cardiovascular events was 1.7% in the PA32540 group and 2.5% in controls, a nonsignificant difference. The study wasn’t of sufficient size or duration to provide definitive evidence regarding this endpoint.
PA32540 is a once-daily tablet containing 40 mg of immediate-release omeprazole layered around 325 mg of pH-sensitive aspirin. Pozen has announced that it is currently seeking strategic partners to help market the novel product on a wide scale at an affordable cost once PA32540 receives regulatory approval.
Dr. Whellan is a consultant to Pozen.