HONOLULU — A novel fixed-combination tablet comprising an immediate-release proton pump inhibitor plus an enteric-coated NSAID showed considerable promise for the prevention of upper GI mucosal injury in a pilot study, Dr. W. James Alexander reported at the American College of Gastroenterology's annual meeting.
Large clinical trials are being planned to evaluate the efficacy of the fixed-combination drug, which is designed to ensure adherence to gastroprotective therapy when recommended for NSAID users, explained Dr. Alexander, senior vice president of product development and chief medical officer at Pozen Inc., Chapel Hill, N.C.
Pozen has been issued a patent for the fixed-combination tablet, known for now as PN 100. Each tablet contains 15 mg of immediate-release lansoprazole surrounding a core of 500 mg of naproxen, which has a pH-sensitive enteric coating.
Dr. Alexander reported on 60 healthy volunteers randomized to 14 days of one of three treatment regimens: PN 100, twice daily; 500 mg of enteric-coated naproxen, twice daily; or 15 mg of delayed-release lansoprazole in the morning plus naproxen 500 mg, twice daily, which is the type of gastroprotective regimen most often used.
Endoscopy performed on day 14 by a gastroenterologist blinded to treatment status revealed 5 subjects in the PN 100 group had Lanza grade 3 or 4 mucosal lesions, compared with 15 subjects on twice-daily enteric naproxen and 14 on delayed-release lansoprazole plus naproxen twice daily. Two patients on enteric naproxen developed gastric ulcers, as did one on delayed-release lansoprazole plus naproxen. None of the PN 100-treated subjects developed gastric ulcers.
The mean cumulative number of erosions found at endoscopy on days 8 and 14 was 10 in the PN 100 group, 26 with enteric naproxen alone, and 19 with delayed-release lansoprazole plus naproxen. Twenty-four hour gastric pH monitoring indicated nocturnal acid suppression was better with PN 100 than with delayed-release lansoprazole plus naproxen.