Summary
Background
Tegoprazan (CJ‐12420) is a potassium‐competitive acid blocker (P‐CAB) with therapeutic potential for gastro‐oesophageal reflux disease (GERD) by reversibly suppressing gastric H+/K+‐ATPase.
Aims
To investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of tegoprazan
Methods
A phase I, randomised, double‐blind and placebo‐controlled clinical trial was conducted in 56 healthy male subjects without Helicobacter pylori infection. In the single ascending dose study, 50, 100, 200 and 400 mg tegoprazan were administered to 32 subjects. In the multiple ascending dose study, 100 and 200 mg tegoprazan were administered every 24 hours to each of the eight subjects for 7 days. In the comparative pharmacodynamics study, 40 mg esomeprazole was administered to eight subjects every 24 hours for 7 days. The assessment included safety, tolerability, pharmacodynamics through monitoring of 24‐hour gastric pH and pharmacokinetics of tegoprazan in plasma and urine.
Results
Tegoprazan was generally well tolerated. Most adverse events reported in the study were mild in intensity and resolved without any sequelae. Exposure to tegoprazan increased in a dose‐proportional manner. Multiple dosing with tegoprazan showed no accumulation in plasma on day 7. The pharmacodynamic analysis revealed that tegoprazan showed rapid, dose‐dependent gastric acid suppression.
Conclusions
Tegoprazan was well tolerated and showed rapid and potent gastric acid suppression. This supports the further development of tegoprazan as a treatment for acid‐related disorders.
Summary
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.
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Aims
Nocturnal acid breakthrough has been considered an unmet need of proton‐pump inhibitors. Tegoprazan, a novel potassium‐competitive acid blocker, is expected to show improved properties for this unmet need. This study was aimed to compare night‐time acid suppression by tegoprazan with that by vonoprazan or esomeprazole, and to explore the effect of CYP2C19 phenotypes on acid‐suppressive effects.
Methods
A randomized, open‐label, 3‐period, 6‐sequence crossover study was conducted. A single oral dose of tegoprazan 50 mg, vonoprazan 20 mg or esomeprazole 40 mg was administered at night in each period. Continuous intragastric pH was monitored at baseline and after each dosing.
Results
Sixteen healthy subjects (6 CYP2C19 extensive metabolizers, 5 intermediate metabolizers, 5 poor metabolizers) completed the study. After a single dose of tegoprazan, intragastric pH increased more rapidly to over 4 at approximately 1 hour compared to the other treatments, and elevated intragastric pH was maintained stably at night. Tegoprazan exhibited night‐time acid suppression for slightly but not significantly longer than vonoprazan, and greater than esomeprazole; % time at pH ≥ 4 at night was 66.0%, 60.5% and 36.1% for tegoprazan, vonoprazan and esomeprazole, respectively. Night‐time acid suppression by tegoprazan and vonoprazan was not dependent on CYP2C19 phenotypes, while that by esomeprazole tended to be influenced by CYP2C19 phenotypes.
Conclusion
Tegoprazan produced more rapid, potent and well sustained night‐time acid suppression vs. vonoprazan or esomeprazole when administered at night. Furthermore, tegoprazan showed no CYP2C19 phenotype dependency in acid suppression. It suggests the potential of tegoprazan, especially in preventing nocturnal acid breakthrough.
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