Phase 3 Trial Update of PA32540 for Secondary Prevention of Cardiovascular Disease

Pozen announced positive results from two pivotal Phase 3 clinical trials of the investigational product, PA32540, being assessed for the secondary prevention of cardiovascular disease in patients at risk for aspirin-induced ulcers. PA32540 is a coordinated-delivery tablet combining immediate-release omeprazole (40mg), a proton pump inhibitor, layered around pH-sensitive aspirin.

The two Phase 3, double-blind, randomized, multicenter studies enrolled 1,049 subjects who were prescribed daily aspirin (325mg) for greater than or equal to three months for secondary prevention of cardiovascular events. The primary endpoint was the cumulative observed incidence of gastric ulcers over six months. Secondary endpoints included cumulative incidence of gastric and duodenal ulcers, discontinuation due to pre-specified UGI adverse events and heartburn resolution. Subjects were randomly assigned to once-daily treatment with PA32540 or 325mg of enteric-coated aspirin. Endoscopic assessments were performed at screening and at one, three and six months.

Data for the primary endpoint are shown below:

Primary Endpoint: Endoscopically-Confirmed Gastric Ulcer


PA32540

EC-ASA

(325mg)

P-value

Relative

Reduction

Study 301

3.8%

8.7%

0.02

56%

Study 302

2.7%

8.5%

0.005

68%

A summary of discontinuation rates of the combined data are shown below:

Discontinuation Due To Pre-Specified UGI Events:



PA32540


EC-ASA

(325mg)


P-value


Relative

Reduction

Studies 301 & 302


1.5%


8.2%


< 0.001


82%

In addition, the results from the combined data from the two studies demonstrated that patients on PA32540, compared to those on enteric-coated aspirin (325mg), were able to stay on therapy longer due to fewer discontinuations to any adverse events (6.7% vs. 11.2%). In the combined data from the two trials, 85.1% of subjects on enteric-coated aspirin (325mg) reported adverse events compared to 71.8% of subjects on PA32540. The most commonly reported adverse events with PA32540 and enteric-coated aspirin (325mg) were of the GI tract and include dyspepsia (11.3% vs. 30.2%), erosive gastritis (11.5% vs. 26.3%), and gastritis (17.5% vs. 16%) respectively. The incidence and nature of adjudicated Major Adverse Cardiac Events (MACE) such as heart attacks was similar between the 2 treatment arms: 9 subjects (1.7%) on PA32540 experienced adjudicated MACE compared to 13 subjects (2.5%) on aspirin (325mg).

PA32540 is a coordinated-delivery tablet combining immediate-release omeprazole (40mg), a proton pump inhibitor, layered around pH-sensitive aspirin.

For more information call (919) 913-1030 or visit www.pozen.com.