Effects of Tegoprazan Versus Esomeprazole on Nighttime Heartburn and Sleep Quality in Gastroesophageal Reflux Disease: A Multicenter Double-blind Randomized Controlled Trial.

Background/Aims: Patients with gastroesophageal reflux disease (GERD) frequently experience nighttime heartburn and sleep disturbance. Tegoprazan is a new potassium-competitive acid blocker that can rapidly block acid secretion. This study aims to evaluate the efficacy of tegoprazan compared with esomeprazole in relieving nighttime heartburn and sleep disturbances. Methods: Patients with erosive esophagitis, nighttime heartburn, and sleep disturbances were randomized to receive tegoprazan 50 mg or esomeprazole 40 mg for 2 weeks. The primary endpoint was time to first nighttime heartburn-free interval. The percentage of nighttime heartburn-free days was also compared between the 2 groups. Results: A total of 46 patients were enrolled in this study. Time to the first nighttime heartburn-free interval was shorter with tegoprazan than with esomeprazole but the difference was not statistically significant (1.5 days vs 3 days, P = 0.151). The percentage of nighttime heartburn-free days was higher in the tegoprazan group but the difference was insignificant (57.8% vs 43.1%, P = 0.107). Adverse events occurred in 2 patients. They were mild in severity. Conclusions: Tegoprazan may induce faster relief of nighttime heartburn symptoms and may improve sleep disorders associated with nighttime heartburn. Further large-scale studies are required to validate our findings.

Randomised clinical trial: comparison of tegoprazan and placebo in non-erosive reflux disease.

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.

Effects of Tegoprazan, a Novel Potassium-Competitive Acid Blocker, on Rat Models of Gastric Acid-Related Disease.

Tegoprazan, a novel potassium-competitive acid blocker (P-CAB), is a next-generation therapeutics developed for the treatment of acid-related gastrointestinal diseases such as gastroesophageal reflux disease (GERD) and peptic ulcers. In the present study, the in vitro and in vivo pharmacological properties of tegoprazan were compared with those of esomeprazole, a representative proton pump inhibitor. In vitro enzyme assays were performed using ion-leaky vesicles containing gastric H+/K+-ATPases isolated from pigs. The in vivo efficacies of tegoprazan were evaluated in rat models of GERD and peptic ulcer. Tegoprazan inhibited the activity of porcine H+/K+-ATPase with an IC50 value of 0.53 µM in a reversible manner, whereas esomeprazole showed weak and irreversible inhibition with an IC50 value of 42.52 µM. In a GERD model, tegoprazan showed dose-dependent efficacy in inhibiting esophageal injury and gastric acid secretion with an ED50 of 2.0 mg/kg, which was 15-fold more potent than that of esomeprazole. In peptic ulcer models, tegoprazan exhibited superior antiulcer activity compared with esomeprazole. The ED50 of tegoprazan in the naproxen-, ethanol-, and water-immersion restraint stress-induced peptic ulcer models were 0.1, 1.4, and 0.1 mg/kg, respectively. In the acetic acid-induced peptic ulcer model, the curative ratio of tegoprazan at 10 mg/kg was higher than that of esomeprazole at 30 mg/kg (44.2% vs. 32.7%, respectively), after 5 days of repeated oral administration. Thus, tegoprazan is a novel P-CAB that shows potent and reversible inhibition of gastric H+/K+-ATPase and may provide stronger efficacy compared with previous proton pump inhibitors.

Randomised phase 3 trial: tegoprazan, a novel potassium-competitive acid blocker, vs. esomeprazole in patients with erosive oesophagitis.

BACKGROUND: Tegoprazan is a novel potassium-competitive acid blocker that has a fast onset of action and can control gastric pH for a prolonged period, which could offer clinical benefit in acid-related disorders. AIM: To confirm the non-inferiority of tegoprazan to esomeprazole in patients with erosive oesophagitis (EE). METHODS: In this multicentre, randomised, double-blind, parallel-group comparison study, 302 Korean patients with endoscopically confirmed EE (Los Angeles Classification Grades A-D) were randomly allocated to either tegoprazan (50 or 100 mg) or esomeprazole (40 mg) treatment groups for 4 or 8 weeks. The primary endpoint was the cumulative proportion of patients with healed EE confirmed by endoscopy up to 8 weeks from treatment initiation. Symptoms, safety and tolerability were also assessed. RESULTS: The cumulative healing rates at week 8 were 98.9% (91/92), 98.9% (90/91) and 98.9% (87/88) for tegoprazan 50 mg, tegoprazan 100 mg and esomeprazole 40 mg, respectively. Both doses of tegoprazan were non-inferior to esomeprazole 40 mg. The incidence of adverse events was comparable among the groups, and tegoprazan was well-tolerated. CONCLUSION: Once daily administration of tegoprazan 50 or 100 mg showed non-inferior efficacy in healing EE and tolerability to that of esomeprazole 40 mg.