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

Aliment Pharmacol Ther. 2015 Sep;42(6):719-30. doi: 10.1111/apt.13325. Epub 2015 Jul 21.


Background: Proton 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.

Aim: To 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.

Methods: In this randomised, open-label, two-period cross-over study, vonoprazan 20 mg and esomeprazole 20 mg (Study V vs. E) or rabeprazole 10 mg (Study V vs. R) were orally administered daily for 7 days. Primary pharmacodynamic endpoint was gastric pH over 24 h measured as percentage of time pH ≥3, ≥4 and ≥5 (pH holding time ratios; HTRs) and mean gastric pH.

Results: Acid-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.

Conclusions: This study demonstrated a more rapid and sustained acid-inhibitory effect of vonoprazan 20 mg vs. esomeprazole 20 mg or rabeprazole 10 mg. Therefore, vonoprazan may be a potentially new treatment for acid-related diseases.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cross-Over Studies
  • Esomeprazole / administration & dosage
  • Esomeprazole / adverse effects
  • Esomeprazole / therapeutic use*
  • Gastric Acid
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Middle Aged
  • Proton Pump Inhibitors / therapeutic use*
  • Pyrroles / administration & dosage
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*
  • Rabeprazole / administration & dosage
  • Rabeprazole / adverse effects
  • Rabeprazole / therapeutic use*
  • Research Design
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*


  • 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine
  • Proton Pump Inhibitors
  • Pyrroles
  • Sulfonamides
  • Rabeprazole
  • Esomeprazole