title: Evaluation of the Efficacy and Safety of Vonoprazan in Patients with Nonerosive Gastroesophageal Reflux Disease: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study.
abstract: BACKGROUND
  For many patients, current treatments do not adequately resolve heartburn in nonerosive reflux disease (NERD).
  
  
  OBJECTIVE
  To compare vonoprazan and placebo with respect to the frequency and severity of heartburn in patients with NERD.
  
  
  METHODS
  This Phase III, double-blind, placebo-controlled, parallel-group, multicenter study included patients in Japan aged ≥20 years with Grade N or M NERD and recurrent acid reflux symptoms. Patients were blinded and randomized 1:1:1 to receive placebo or vonoprazan 10 mg or 20 mg. The primary efficacy outcome was the proportion of days without heartburn measured by patient scores during the 4-week treatment period.
  
  
  RESULTS
  Eight hundred twenty-seven patients were randomized (placebo: n = 278, vonoprazan 10 mg: n = 278, and vonoprazan 20 mg: n = 271). Median proportion of days without heartburn was 7.4% (placebo), 10.3% (vonoprazan 10 mg), and 12.0% (vonoprazan 20 mg). Proportion of days without heartburn was not statistically significant between the vonoprazan and placebo groups (P= 0.2310 [10 mg] andP= 0.0504 [20 mg]). Mean severity of heartburn was significantly higher with placebo (median score = 1.070) than with vonoprazan 10 mg (median score = 0.990;P= 0.0440) and 20 mg (median score = 0.960;P= 0.0139). Patients whose symptoms improved at Week 2 experienced significantly increased proportion of days without heartburn and reduced mean severity of heartburn at Week 4 with vonoprazan compared with placebo (proportion of days without heartburn:P= 0.0004 [10 mg] andP= 0.0001 [20 mg] and mean severity:P< 0.0001 [10 mg] andP< 0.0001 [20 mg]). A significant difference in median proportion of days without heartburn was observed for vonoprazan 20 mg compared with placebo in patients with Grade M NERD. Incidence of treatment-emergent adverse events was 32.7% (placebo), 27.7% (vonoprazan 10 mg), and 28.0% (vonoprazan 20 mg).
  
  
  CONCLUSIONS
  Vonoprazan at doses of 10 mg and 20 mg are not superior to placebo with respect to proportion of days without heartburn, whereas the mean severity of heartburn is lower with vonoprazan compared with placebo in patients with NERD. ClinicalTrials.gov identifier: NCT01474369.
authors.affiliation: Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Izumo, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
authors.affiliation: Takeda Development Center Japan, Takeda Pharmaceutical Company Ltd, Osaka, Japan.
authors.forename: Yuuichi
authors.initials: Y
authors.lastname: Sakurai
authors.affiliation: Takeda Development Center Japan, Takeda Pharmaceutical Company Ltd, Osaka, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Shiino
authors.affiliation: Takeda Development Center Japan, Takeda Pharmaceutical Company Ltd, Osaka, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kudou
authors.affiliation: Takeda Development Center Japan, Takeda Pharmaceutical Company Ltd, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nishimura
authors.affiliation: Department of Gastroenterology and Hepatology, Yao Municipal Hospital, Yao, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyagi
authors.affiliation: Department of Gastroenterology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Iwakiri
authors.affiliation: Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Umegaki
authors.affiliation: Department of Gastroenterology, Rakuwakai Otowa Hospital, Kyoto, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ashida
keywords: NERD; gastroesophageal reflux; heartburn; nonerosive gastroesophageal reflux disease; potassium-competitive acid blockers; vonoprazan