Clinical trial: evaluation of gastric acid suppression with three doses of immediate-release esomeprazole in the fixed-dose combination of PN 400 (naproxen/esomeprazole magnesium) compared with naproxen 500 mg and enteric-coated esomeprazole 20 mg: a randomized, open-label, Phase I study in healthy volunteers.

摘要

BACKGROUND: PN 400 is a fixed-dose combination formulated to provide sequential delivery of immediate-release (IR) esomeprazole and enteric-coated (EC) naproxen. AIM: To evaluate gastric acid suppression with three doses of esomeprazole in PN 400 compared with EC esomeprazole 20 mg. METHODS: In this Phase I, randomized, open-label study, 28 healthy adults received PN 400 b.d. (naproxen 500 mg plus esomeprazole 10, 20 and 30 mg) and non-EC naproxen 500 mg b.d. plus EC esomeprazole 20 mg o.d., each for 9 days in a crossover fashion. The primary endpoint was percentage of time on day 9 that intragastric pH was >4.0; secondary endpoints included pharmacokinetics and safety. RESULTS: Day 9 percentage of time where intragastric pH was >4.0 was 76.5%, 71.4%, 40.9% and 59.9% for PN 400 containing 30, 20 and 10 mg esomeprazole, and naproxen plus esomeprazole 20 mg respectively. This was significantly greater for PN 400 containing 30 and 20 mg esomeprazole vs. naproxen plus esomeprazole 20 mg (95% CI: 13.0-26.0 and 7.8-20.7 respectively). The pharmacokinetics of PN 400 were consistent with its formulation. No serious adverse events occurred. CONCLUSION: PN 400 containing 20 mg esomeprazole was the lowest dose to achieve gastric acid suppression comparable to EC esomeprazole 20 mg and was selected for further evaluation.