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Therap Adv Gastroenterol. 2017 Jun;10(6):439-451. doi: 10.1177/1756283X17705329. Epub 2017 Apr 25.

A randomized, double-blind study to evaluate the acid-inhibitory effect of vonoprazan (20 mg and 40 mg) in patients with proton-pump inhibitor-resistant erosive esophagitis.

Author information

1
Department of Gastroenterology, Nippon Medical School Graduate School of Medicine, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8603, Japan.
2
Takeda Pharmaceutical Company Ltd., Osaka, Japan.
3
Department of Gastroenterology, Osaka University Graduate School of Medicine, Suita, Japan.
4
Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Japan.
5
Department of Gastroenterology, Rakuwakai Otowa Hospital, Kyoto, Japan.

Abstract

BACKGROUND:

Standard treatment for patients with erosive esophagitis (EE) is proton-pump inhibitors (PPIs), but some patients are resistant to PPIs. We aimed to evaluate the acid-inhibitory effects and efficacy of a novel potassium-competitive acid blocker (vonoprazan) in patients with PPI-resistant EE.

METHODS:

This randomized, double-blind, multicenter study of vonoprazan evaluated gastric and esophageal pH over a 24-hour period as the primary endpoint and EE healing rate as the secondary endpoint. Following a 7 to 14-day run-in period (lansoprazole 30 mg treatment), patients with endoscopically confirmed PPI-resistant EE received vonoprazan 20 mg or 40 mg for 8 weeks.

RESULTS:

Patients were randomized to receive vonoprazan 20 mg (n = 9) or 40 mg (n = 10). Over a 24-hour period; both groups showed a significant increase from baseline in the percentage of time gastric pH ≥ 4, referred to as pH 4 holding time ratio (HTR): an increase from 73.21% to 96.46% in the 20 mg group, and from 69.97% to 100.00% in the 40 mg group. Increases from baseline in esophageal pH 4 HTRs were not significant. The 40 mg group showed greater increases in gastric and esophageal pH 4 HTRs compared with the 20 mg group, but differences between groups were not significant. After 8 weeks' treatment, the healing rate in subjects with baseline EE grades A-D was 60.0% (3/5 patients) in the 20 mg group and 71.4% (5/7 patients) in the 40 mg group. Vonoprazan was generally well tolerated. One patient (40 mg group) experienced four treatment-emergent adverse events (TEAEs) (unrelated to study drug), leading to study discontinuation.

CONCLUSIONS:

Vonoprazan 20 mg and 40 mg effectively inhibited gastric acid secretion over a 24-hour period with significantly increased gastric pH 4 HTR, and resulted in an EE healing rate > 60.0% in this study. Vonoprazan treatment may be valuable for patients with PPI-resistant EE.

KEYWORDS:

TAK-438; erosive esophagitis; esophageal pH monitoring; gastroesophageal reflux; lansoprazole; potassium-competitive acid blocker; proton-pump inhibitors; vonoprazan

Conflict of interest statement

Conflict of interest statement: YS, MS, HO, KK, and AN are employees of Takeda Pharmaceutical Company Limited. KI, NH, EU, and KA are all paid consultants for Takeda Pharmaceutical Company Limited. Takeda Pharmaceutical Company Limited was involved in the study design, data collection, data analysis and preparation of the manuscript.

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