Clinical trial: Endoscopic evaluation of naproxen etemesil, a naproxen prodrug, vs. naproxen - A proof-of-concept, randomized, double-blind, active-comparator study

Abstract

Background Nonsteroidal anti-inflammatory drugs are associated with upper gastrointestinal mucosal injury. Naproxen etemesil is a lipophilic, non-acidic, inactive prodrug of naproxen that is hydrolysed to pharmacologically active nap- roxen once absorbed. We hypothesized that with lesser topical exposure to naproxen from the prodrug, there would be reduced gastroduodenal muco- sal injury compared with naproxen. Aim To compare the degree of endoscopic mucosal damage of naproxen eteme- sil vs. naproxen. Methods This multicentre, randomized, double-blind, double-dummy trial compared oral naproxen etemesil 1200 mg twice daily (n = 61) with naproxen 500 mg twice daily (n = 59) for 7.5 days in 120 healthy subjects (45-70 years; mean 51 years; 58% female) with baseline total modified gastroduodenal Lanza score ≤2 (no erosions/ulcers) on endoscopy. The primary endpoint was mean total modified gastroduodenal Lanza score on day 7. A secondary endpoint was incidence of gastric ulcers. Results The day 7 mean total modified gastroduodenal Lanza score was 2.8 ± 1.7 for naproxen etemesil vs. 3.5 ± 2.0 for naproxen (P = 0.03), and signifi cantly fewer naproxen etemesil-treated subjects (3.3%) developed gastric ulcers compared with naproxen-treated subjects (15.8%) (P = 0.02). Conclusion In this first proof-of-concept study, naproxen etemesil was associated with significantly lower gastroduodenal mucosal injury compared with naproxen after 7 days of exposure (Clinical trial number: NCT00750243). © 2010 Blackwell Publishing Ltd.