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New Cardiovascular Drugs for Patients at Risk of Aspirin-Induced Ulcers

NDA submitted for omeprazole/aspirin combo tablets (Mar. 27)

A new drug application (NDA) has been submitted to the FDA for marketing approval of PA32540 and PA8140 (Pozen, Inc.). Both products are a tablet combining immediate-release omeprazole 40 mg — a proton pump inhibitor — layered around a pH-sensitive coating of an aspirin core. Pending regulatory approval, an indication is sought for use of the tablets for the secondary prevention of cardiovascular disease in patients at risk of aspirin-induced gastric ulcers.

The NDA submission was based on data from a clinical trials program that included two pivotal phase III studies (PA32540–301 and PA32540–302) for PA32540, which met their primary and secondary endpoints, as well as phase 1 studies for both PA32540 and PA8140. In the 301 and 302 trials, significantly fewer subjects taking PA32540 experienced endoscopically confirmed gastric ulcers compared with subjects receiving enteric-coated aspirin alone (Study 301: 3.8% vs. 8.7%, respectively; P = 0.02; Study 302: 2.7% vs. 8.5%, respectively; P = 0.005).

The two phase III, double-blind, randomized trials enrolled a total of 1,049 subjects who had been prescribed daily aspirin (325 mg) for 3 months or longer for secondary prevention of cardiovascular events. The primary endpoint was the cumulative observed incidence of gastric ulcers over 6 months. Secondary endpoints included the cumulative incidence of gastric and duodenal ulcers, discontinuation due to prespecified upper gastrointestinal (UGI) adverse events, and heartburn resolution. The subjects were randomly assigned to once-daily treatment with PA32540 or 325 mg of enteric-coated aspirin. Endoscopic assessments were performed at screening and at 1, 3, and 6 months.

Each study achieved its individual primary endpoint and met all secondary endpoints. Results from the combined data from the two studies demonstrated that patients treated with PA32540, compared with those on enteric-coated aspirin (325 mg), were able to stay on therapy longer because of fewer discontinuations due to an adverse event (6.7% vs. 11.2%, respectively). The rates of discontinuations due to prespecified UGI events were lower in subjects taking PA32540 compared with subjects taking enteric-coated aspirin (1.5% vs. 8.2% respectively, P < 0.001).

In combined data from the two trials, 85.1% of subjects receiving enteric-coated aspirin (325 mg) reported adverse events compared with 71.8% of subjects treated with PA32540. The most commonly reported adverse events with PA32540 and enteric-coated aspirin (325 mg) involved the GI tract and included dyspepsia (11.3% vs. 30.2%, respectively), erosive gastritis (11.5% vs. 26.3%), and gastritis (17.5% vs. 16.0%).

Source: Pozen, Inc.; March 27, 2013.

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