PA32540 cuts gastric acid faster than enteric-coated aspirin

The investigational compound PA32540 provides faster gastric protection than enteric-coated omeprazole 40 mg, researchers announced at Digestive Disease Week 2012. PA32540 is an investigational coordinated-delivery tablet of immediate-release (IR) omeprazole (40 mg), a proton pump inhibitor (PPI), layered around enteric-coated aspirin (325 mg). The product was developed to provide the cardiovascular benefits of aspirin in patients at risk for aspirin-associated ulcers. The data, from a phase I study, showed a significantly shorter mean time to first gastric pH >4 in subjects receiving PA32540 versus subjects receiving enteric-coated aspirin plus enteric-coated omeprazole 40 mg. "These findings confirm the optimal amount of immediate-release PPI needed for patients in the secondary cardiovascular prevention setting and demonstrate that patients may not need as much acid suppression as offered by currently prescribed formulations of omeprazole to achieve the protection needed," principal investigator Philip B. Miner, Jr., MD, President and Medical Director of the Oklahoma Foundation for Digestive Research in Oklahoma City, said in a news release. Study co-author John G. Fort, MD, Chief Medical Officer of POZEN, the Chapel Hill, North Carolina-based pharmaceutical company that developed PA32540, said: More than 50 million adults in the U.S. regularly take aspirin for cardiovascular disease prevention. However, aspirin use is associated with gastrointestinal (GI) adverse events, including ulceration and bleeding. In patients who require aspirin therapy and are at risk for GI events, PA32540 could provide a consistent and coordinated therapeutic approach to cardioprotection and reduced risk of GI injury." In the present study, 26 healthy, Helicobacter pylori-negative adult volunteers received 7 days' treatment with either once-daily PA32540 or once-daily enteric-coated aspirin 325 mg plus enteric-coated omeprazole 40 mg administered concurrently. After at least a 7-day washout, patients were crossed over to the alternative treatment. Gastric pH and pharmacokinetic measurements were obtained over 24 hours on day 7 of each treatment period. Results showed that the mean time to first gastric pH >4 was 17 minutes for PA32540 versus 36 minutes for enteric-coated aspirin 325 mg plus enteric-coated omeprazole 40 mg, P=0.011. PA32540 provided significantly faster gastric pH suppression than enteric-coated aspirin 325 mg plus enteric-coated omeprazole 40 mg (50.6% versus 57.6%, P=0.004). In addition, because of omeprazole's instability in the low pH of the stomach, exposure to omeprazole from PA32540 was 57% of the amount of exposure from enteric-coated omeprazole 40 mg even though both formulations contain the same amount of omeprazole. The phase I findings were recently replicated in a phase III study. The study was funded by POZEN.