Randomised Clinical Trial

Comparison of Tegoprazan and Placebo in Non-erosive Reflux Disease

Seung Han Kim; Kwang Bum Cho; Hoon Jai Chun; Sang Woo Lee; Joong Goo Kwon; Dong Ho Lee; Sang Gyun Kim; Hwoon-Yong Jung; Ji Won Kim; Joon Seong Lee; Hyojin Park; Suck Chei Choi; Sam Ryong Jee; Hyun-Soo Kim; Kwang Hyun Ko; Seun Ja Park; Yong Chan Lee; Soo Heon Park; Ah Rong Kim; Eun Ji Kim; Hyun Wook Park; Bong Tae Kim; Geun Seog Song

Disclosures

Aliment Pharmacol Ther. 2021;54(4):402-411. 

In This Article

Abstract and Introduction

Abstract

Background: Tegoprazan is a novel, fast- and long-acting potassium-competitive acid blocker that suppresses gastric acid secretion, which could benefit patients with non-erosive reflux disease (NERD), a type of gastroesophageal reflux disease.

Aim: To evaluate the efficacy and safety profiles of tegoprazan compared with those of a placebo in Korean patients with NERD.

Methods: In this phase 3, double-blind, placebo-controlled, multicentre study, 324 Korean patients with NERD were randomised into three treatment groups: tegoprazan 50 mg, tegoprazan 100 mg and placebo. These drugs were provided once daily for 4 weeks. The primary endpoint was the proportion of patients with complete resolution of major symptoms (both heartburn and regurgitation) for the last 7 days of the 4-week treatment period. Other outcomes related to efficacy, safety and tolerability were also evaluated.

Results: Among all, 42.5% (45/106), 48.5% (48/99) and 24.2% (24/99) of patients showed complete resolution of major symptoms at week 4 after receiving tegoprazan 50 mg, tegoprazan 100 mg, and placebo, respectively. Both doses of tegoprazan showed superior efficacy than the placebo (P = 0.0058 and P = 0.0004, respectively). The complete resolution rates of heartburn and proportions of heartburn-free days (as other efficacy outcomes) were significantly higher in both tegoprazan groups than in the placebo group (P < 0.05 for all). No significant difference in the incidence of treatment-emergent adverse events were noted.

Conclusions: Tegoprazan 50 and 100 mg showed superior therapeutic efficacy compared with the placebo, as well as a favourable safety profile in patients with NERD.

Registration number: ClinicalTrials.gov identifier NCT02556021.

Introduction

About 4.4%-14.0% of the adult population experience symptoms of gastroesophageal reflux disease (GERD), such as acid regurgitation and heartburn.[1–4] Among them, more than 50% exhibit normal oesophageal mucosa on upper endoscopy, diagnosed as non-erosive reflux disorder (NERD).[5–8] NERD, which significantly compromises the patient quality of life (QoL), is commonly and daily seen in the clinical setting.[5,6,8,9]

Proton pump inhibitors (PPIs) are currently used as a first-line therapy for NERD,[10,11] with the clinical goal of reducing reflux symptoms. However, previous studies showed that reflux symptoms were not completely resolved in approximately 30%-55% of patients with NERD.[12,13] Therefore, a new drug is needed to improve the clinical outcomes for patients with NERD.

Tegoprazan is a novel potassium-competitive acid blocker (P-CAB) that exhibits rapid and effective anti-secretory activity by reversibly binding to the H+/K+-ATPase on the parietal cell.[13,14] P-CAB inhibits the proton pump through a competitive interaction with the potassium site of the enzyme without acid activation.[14–17] P-CAB blocks the active and the inactive forms of the proton pump. Thus, P-CAB inhibits the gastric acid secretion rapidly and for longer time, which could also improve the clinical outcomes, such as heartburn and regurgitation, in patients with NERD. Animal studies and clinical pharmacology studies in healthy volunteers demonstrated that tegoprazan exhibited its maximum acid inhibitory effect rapidly and for a longer period than esomeprazole or revaprazan.[18–20] We assumed that these properties of tegoprazan would improve the clinical outcomes, such as heartburn and regurgitation, in patients with NERD.

Therefore, in this study, we evaluated the efficacy—in terms of the proportion of patients with complete resolution of symptoms including heartburn and regurgitation (primary objective)—and the safety (secondary objective) of tegoprazan in patients with NERD compared with those of a placebo. The recommended clinical dose of tegoprazan was also determined.

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