A novel K plus competitive acid blocker, YH4808, sustains inhibition of gastric acid secretion with a faster onset than esomeprazole: randomised clinical study in healthy volunteers

作者：Yi S; Lee H; Jang S B; Byun H M; Yoon S H; Cho J Y; Jang I J; Yu K S^*

来源：Alimentary Pharmacology and Therapeutics, 2017, 46(3): 337-346.

DOI：10.1111/apt.14148

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.

• 出版日期2017-8