Randomised clinical trial: a dose-ranging study of vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the treatment of erosive oesophagitis

Aliment Pharmacol Ther. 2015 Sep;42(6):685-95. doi: 10.1111/apt.13331. Epub 2015 Jul 22.

Abstract

Background: The potassium-competitive acid blocker vonoprazan (VPZ) has potent acid-inhibitory effects and may offer clinical advantages over conventional therapy for acid-related disorders.

Aim: To investigate the efficacy and safety of VPZ in patients with erosive oesophagitis (EO).

Methods: In this multicentre, randomised, double-blind, parallel-group, dose-ranging study, patients ≥20 years with endoscopically confirmed EO [Los Angeles (LA) grades A-D] received VPZ 5, 10, 20 or 40 mg, or lansoprazole (LPZ) 30 mg once daily for 8 weeks. The primary endpoint was the proportion of healed EO subjects as shown by endoscopy at week 4.

Results: A total of 732 subjects received VPZ or LPZ. The proportion of healed EO subjects at week 4 was 92.3%, 92.5%, 94.4%, 97.0% and 93.2%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. All VPZ doses were non-inferior to LPZ when adjusted for baseline LA grades A/B and C/D. Among those with LA grades C/D, the proportions of healed EO subjects were 87.3%, 86.4%, 100%, 96.0% and 87.0%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. The incidence of adverse events was similar across the groups.

Conclusions: Vonoprazan was effective and non-inferior to LPZ in healing EO. VPZ 20 mg or higher was highly efficacious for severe EO (LA grades C/D). VPZ was associated with no safety concern during this 8-week study, while there was a dose-dependent increase in serum gastrin. Once-daily VPZ 20 mg is the recommended clinical dose for treating EO.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Esophagitis / drug therapy*
  • Female
  • Gastrins / blood
  • Humans
  • Lansoprazole / therapeutic use*
  • Los Angeles
  • Male
  • Middle Aged
  • Proton Pump Inhibitors / therapeutic use*
  • Pyrroles / administration & dosage
  • Pyrroles / therapeutic use*
  • Sulfonamides / administration & dosage
  • Sulfonamides / therapeutic use*

Substances

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