title: Randomised clinical trial: a dose-ranging study of vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the treatment of erosive oesophagitis.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Rakuwakai Otowa Hospital, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ashida
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: A
authors.initials: A
authors.lastname: Nishimura
authors.affiliation: Takeda Pharmaceutical Company Ltd., Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kudou
authors.affiliation: Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Hiramatsu
authors.affiliation: Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Umegaki
authors.affiliation: Nippon Medical School Graduate School of Medicine, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Iwakiri
authors.affiliation: Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004941:Esophagitis / Q000188:drug therapy*; D005260:Female; D005755:Gastrins / Q000097:blood; D006801:Humans; D064747:Lansoprazole / Q000627:therapeutic use*; D015141:Los Angeles; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: C552956:1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; D005755:Gastrins; D054328:Proton Pump Inhibitors; D011758:Pyrroles; D013449:Sulfonamides; D064747:Lansoprazole