Clinical trial: the incidence of NSAID-associated endoscopic gastric ulcers in patients treated with PN 400 (naproxen plus esomeprazole magnesium) vs. enteric-coated naproxen alone J. L. Goldstein*, M. C. Hochberg   , J. G. Fort à , Y. Zhang à , C. Hwang § & M. Sostek § *Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.   University of Maryland School of Medicine, Baltimore, MD, USA. à POZEN Inc., Chapel Hill, NC, USA. § AstraZeneca, Wilmington, DE, USA. Correspondence to: Dr. J. L. Goldstein, Department of Medicine, University of Illinois at Chicago, 840 South Wood Street (m ⁄ c787), Room 1020 – 10th Floor, Chicago, IL 60612, USA. E-mail: jlgoldst@uic.edu Publication data Submitted 31 March 2010 First decision 21 April 2010 Resubmitted 20 May 2010 Accepted 20 May 2010 Epub Accepted Article 22 May 2010 SUMMARY Background Gastroprotective co-therapy may reduce the risk of nonsteroidal anti-inflam- matory drug (NSAID)-associated gastric ulcers, but adherence is suboptimal. Aim To compare the incidence of gastric ulcers with PN 400 [enteric-coated (EC) naproxen 500 mg and immediate-release esomeprazole 20 mg], or EC naproxen. Methods Two randomized, double-blind, multicentre studies (PN400-301, PN400- 302). Patients [stratified by low-dose aspirin (£325 mg) use] aged ‡50 years or 18–49 years with a history of ulcer, received PN 400 BID (301, n = 218; 302, n = 210) or EC naproxen 500 mg BID (301, n = 216; 302, n = 210) for 6 months. The primary endpoint was the cumulative incidence of endo- scopic gastric ulcers. Results The cumulative incidence of gastric ulcers was significantly lower with PN 400 vs. EC naproxen (301: 4.1% vs. 23.1%, P < 0.001; 302: 7.1% vs. 24.3%, P < 0.001). PN 400 was associated with a lower combined incidence of gastric ulcers vs. EC naproxen in low-dose aspirin users (n = 201) (3.0% vs. 28.4%, P < 0.001) and non-users (n = 653) (6.4% vs. 22.2%, P < 0.001). The incidence of, and discontinuations due to, upper gastrointestinal (UGI) AEs was significantly lower with PN 400 relative to EC naproxen (P< 0.01, both studies). Conclusions PN 400 significantly reduces the incidence of gastric ulcers, regardless of low-dose aspirin use, in at-risk patients, and is associated with improved UGI tolerability relative to EC naproxen (ClinicalTrials.gov, NCT00527782). Aliment Pharmacol Ther 2010; 32: 401–413 ª 2010 Blackwell Publishing Ltd 401 doi:10.1111/j.1365-2036.2010.04378.x Alimentary Pharmacology and Therapeutics