title: 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.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Takeda Pharmaceutical Company Ltd., Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sakurai
authors.affiliation: Takeda Pharmaceutical Company Ltd., Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Takeda Pharmaceutical Company Ltd., Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Takeda Pharmaceutical Company Ltd., Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nishimura
authors.affiliation: Takeda Pharmaceutical Company Ltd., Osaka, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Komura
authors.affiliation: Takeda Pharmaceutical Company Ltd., Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Araki
authors.affiliation: Medical Co. LTA Hakata Clinic, Fukuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shiramoto
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D064098:Esomeprazole / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005744:Gastric Acid; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D064750:Rabeprazole / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: C552956:1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; D054328:Proton Pump Inhibitors; D011758:Pyrroles; D013449:Sulfonamides; D064750:Rabeprazole; D064098:Esomeprazole