Acid-inhibitory effects of vonoprazan 20mg compared with esomeprazole 20mg or rabeprazole 10mg in healthy adult male subjects - a randomised open-label cross-over study

BackgroundProton pump inhibitors (PPIs) are widely used for the treatment of acid-related diseases. Vonoprazan is a member of a new class of acid suppressants; potassium-competitive acid blockers. Vonoprazan may thus be an alternative to PPIs. AimTo evaluate efficacy, rapidity and duration of acid-inhibitory effects of vonoprazan vs. two control PPIs, esomeprazole and rabeprazole, in 20 healthy Japanese adult male volunteers with CYP2C19 extensive metaboliser genotype. MethodsIn this randomised, open-label, two-period cross-over study, vonoprazan 20mg and esomeprazole 20mg (Study V vs. E) or rabeprazole 10mg (Study V vs. R) were orally administered daily for 7days. Primary pharmacodynamic endpoint was gastric pH over 24h measured as percentage of time pH 3, 4 and 5 (pH holding time ratios; HTRs) and mean gastric pH. ResultsAcid-inhibitory effect (pH4 HTR) of vonoprazan was significantly greater than that of esomeprazole or rabeprazole on both Days 1 and 7; Day 7 difference in pH4 HTR for vonoprazan vs. esomeprazole was 24.6% [95% confidence interval (CI): 16.2-33.1] and for vonoprazan vs. rabeprazole 28.8% [95% CI: 17.2-40.4]. The Day 1 to Day 7 ratio of 24-h pH4 HTRs was >0.8 for vonoprazan, compared with 0.370 for esomeprazole and 0.393 for rabeprazole. Vonoprazan was generally well tolerated. One vonoprazan subject withdrew due to a rash which resolved after discontinuation. ConclusionsThis study demonstrated a more rapid and sustained acid-inhibitory effect of vonoprazan 20mg vs. esomeprazole 20mg or rabeprazole 10mg. Therefore, vonoprazan may be a potentially new treatment for acid-related diseases.