Randomized Multicenter Study to Evaluate the Efficacy and Safety of Fexuprazan According to the Timing of Dosing in Patients With Erosive Esophagitis

Abstract

Background/aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing.

Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs).

Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, -0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, -0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively.

Conclusions: Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Keywords: Esophagitis; Gastroesophageal reflux; Potassium-competitive acid blocker; Proton pumps.

Figure 1

Study schema. V, visit; ◆, upper endoscopy.

Figure 2

Flowchart showing the selection of study patients. ^*Reasons for exclusion may overlap. SS, safety set; FAS, full analysis set; PPS, per-protocol set.

Figure 3

Non-inferiority in erosive esophagitis (EE) healing rate at weeks 2 and 4 in the full analysis set and per-protocol set. The light gray vertical line represents the non-inferiority margin (–15.00%). The dark gray horizontal line is the confidence interval (CI) of study results. The diamond shape in the middle means risk difference. In all analyses, CIs (horizontal line) did not include the non-inferiority margin (vertical line). Thus, non-inferiorities were proven.