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

Aliment Pharmacol Ther 2010; 32: 401–413

Summary

Background Gastroprotective co‐therapy may reduce the risk of nonsteroidal anti‐inflammatory 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 endoscopic 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).