Gastroduodenal tolerability of lumiracoxib vs. placebo and naproxen: a pilot endoscopic study in healthy male subjects

Background: Lumiracoxib (Prexige(R)) is a cyclooxygenase-2 (COX-2) selective inhibitor. Aim: To compare the gastroduodenal tolerability of lumiracoxib with placebo and naproxen in a randomized, parallel-group, double-blind study. Methods: Sixty-five healthy male subjects were randomized to receive 8 days' dosing with lumiracoxib 200 mg twice daily (b.d.) (n = 21), placebo ( n = 22) or naproxen 500 mg b.d. ( n = 22). Endoscopic evaluations of gastric and duodenal mucosae were conducted at baseline and after 8 days' dosing. Serum was assayed for ex-vivo concentrations of thromboxane B-2 (TxB(2)) to determine cyclooxygenase-1 (COX-1) inhibitory activity. Results: Sixty subjects ( 20 per group) completed the study. No gastroduodenal erosions were observed in subjects receiving lumiracoxib. Thirteen subjects receiving naproxen developed duodenal erosions. At the gastric site, one subject in each of the naproxen and placebo groups had erosions; one subject receiving naproxen also developed a small asymptomatic gastric ulcer. Gastrointestinal adverse events accounted for 42.3% of all adverse events, occurring in 3/21, 4/22 and 6/22 of the lumiracoxib, placebo and naproxen groups, respectively. TxB(2) levels were similar for patients receiving placebo or lumiracoxib, but were reduced by > 95% in patients receiving naproxen, compared with placebo. Conclusions: Multiple doses of lumiracoxib resulted in gastroduodenal tolerability similar to placebo and superior to naproxen.