A novel K+ competitive acid blocker, YH4808, sustains inhibition of gastric acid secretion with a faster onset than esomeprazole: randomised clinical study in healthy volunteers. Issue 3 (21st May 2017)

• Record Type: Journal Article
• Authors: Yi, S.; Lee, H.; Jang, S. B.; Byun, H. M.; Yoon, S. H.; Cho, J.‐Y.; Jang, I.‐J.; Yu, K.‐S.
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 46:Issue 3(2017)
• Page Start: 337
• Page End: 346
• Publication Date: 2017-05-21
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.14148
• Languages: English
• ISSNs: 0269-2813

Abstract

Summary: Background: YH4808, a K + ‐competitive acid blocker, is under clinical development for the treatment of acid‐related disorders, such as gastroesophageal reflux disease. Aims: To determine the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH4808, compared to placebo and esomeprazole. Methods: This double‐blind, randomised, placebo‐ and active comparator (esomeprazole)‐controlled study was conducted with 123 healthy male volunteers. We evaluated YH4808 (30‐800 mg) properties, administered in single (N=55) and multiple (N=24) oral doses, and recorded the effects on 24‐hour intragastric acidity. Results were compared to placebo (N=20) and esomeprazole 40 mg (N=24). Results: Plasma YH4808 exposure increased dose‐proportionally and declined in a multi‐phasic manner. YH4808 ≥200 mg/d maintained intragastric acidity at pH >4 for longer times than esomeprazole during both day and night (%Time at pH >4: >70% vs 58% of a 24‐hour period, respectively; and >50% vs 33% of a 9‐hour night respectively). A twice‐daily regimen of YH4808 more effectively controlled intragastric pH at night than a once‐daily regimen. In evaluating the mean areas under the intragastric pH‐time curves in 15‐minute intervals for 2 hours after dosing, we found that YH4808 had a faster onset than esomeprazole. Moreover, unlike esomeprazole, YH4808 PK and PD were not significantly affected by the CYP2C19 genotype of the subjects. YH4808 was well‐tolerated at all doses administered. Conclusion: This study showed that YH4808 produced a rapid, sustained suppression of gastric secretion with good tolerability. The results at YH4808 ≥200 mg/d provide a rationale for further clinical investigations in populations with acid‐related diseases.