Pilot Evaulation of a Novel Combination Tablet (PN 100) Containing a Proton Pump Inhibitor and a Nonsteroidal Anti-Inflammatory Drug in Prevention of Upper Gastrointestinal Mucosal Injury

Abstract

Purpose: To compare the incidence of gastric and duodenal mucosal injury with twice-daily administration of PN100, twice-daily enteric-coated naproxen, and twice-daily naproxen with delayed-release lansoprazole once daily. Methods: A single-center, randomized, parallel-group study enrolled 60 male and female volunteers aged 40–65 years. After normal baseline endoscopy (EGD), subjects received 14 days' treatment with either: (a) twice-daily PN100 (immediate-release lansoprazole 15mg and enteric-coated (EC) naproxen 500mg in a combination tablet), (b) twice-daily EC naproxen 500mg, or (c) delayed-release lansoprazole 15mg capsule each morning and twice-daily naproxen 500mg. The endoscopist was blinded to treatment assignment. EGD was performed at baseline and on days 8 and 14. Gastric pH monitoring (24 hour) and pharmacokinetic sampling were performed on days 1 and 7. Mucosal injury was assessed by the Lanza scale and enumeration of erosions and/or ulcers. Results: After two weeks, no ulcers were present in subjects receiving PN100 whereas 11% of subjects receiving EC naproxen had gastric ulcers. Subjects who received naproxen twice-daily with delayed-release lansoprazole each morning had an ulcer rate of 5%. The cumulative median numbers of gastric erosions at days 8 and 14 were: 5 for PN100; 14 for naproxen and lansoprazole; and 21 for EC naproxen (p = 0.02, Kruskal-Wallis test among 3 treatment groups). No mucosal lesions meeting criteria for Lanza Grade 4 were present at day 14 in subjects receiving PN100, whereas 53% of subjects receiving EC naproxen and 30% of subjects receiving naproxen and lansoprazole met criteria for Lanza Grade 4 injury (≥25 erosions or hemorrhages or any ulcer). Gastric pH monitoring suggested the possibility of better nocturnal acid suppression with use of twice-daily PN100 than with once-daily delayed-release lansoprazole and twice-daily naproxen. Conclusions: A combination tablet containing lansoprazole and EC naproxen was associated with the lowest incidence of upper gastrointestinal mucosal injury when compared with either EC naproxen alone or with naproxen administered with a morning dose of delayed-release lansoprazole. If these results are confirmed, clinical use of this novel formulation would ensure adherence with gastroprotective therapy when recommended for use with an NSAID.