Lee Hae Won, Kang Woo Youl, Park Ji Seo, Lee Jae Hwa, Park Jin Ju, Gwon Mi-Ri, Yoon Young-Ran, Seong Sook Jin
School of Medicine, Kyungpook National University and Department of Clinical Pharmacology and Therapeutics, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea.
Clinical Trial Dossier Evaluation Team, Innovative Products Support Department, National Institute of Food and Drug Safety Evaluation, Cheongju, 28159, Republic of Korea.
Drug Des Devel Ther. 2025 Jan 8;19:97-110. doi: 10.2147/DDDT.S500253. eCollection 2025.
YYD601 is a new dual delayed-release formulation of esomeprazole, developed to enhance plasma exposure and prolong the duration of acid suppression.
This study aimed to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of YYD601 20 mg following single and multiple oral administrations in healthy, fasting adult Koreans, and to compare these outcomes to those of the conventional esomeprazole 20 mg capsule.
A randomized, open-label, two-period crossover study was conducted in 28 participants, who were divided into two treatment groups: one group received YYD601 20 mg, and the other received conventional esomeprazole 20 mg, once daily for five consecutive days. Blood samples for PK analysis were collected pre-dose and up to 24 hours post-dose. The primary PK parameters (AUC and AUC) were evaluated. PD endpoints included integrated gastric acidity, percentage of time with intragastric pH > 4 over 24-hour and nighttime intervals, and percent change in serum gastrin levels after multiple dosing.
A total of 22 participants completed the study. YYD601 displayed more prolonged plasma concentration-time profiles than the conventional formulation, although the extent of the systemic exposure (AUC values) showed no statistically significant difference between the two formulations. With regard to the 24-hour gastric acid inhibition, YYD601 was comparable to the conventional formulation. The YYD601 showed a greater tendency for acid inhibition at night, as indicated by the percentage change of time with nocturnal acid breakthrough and other PD parameters. Both treatments were well tolerated, with no serious adverse events reported.
Through extended systemic exposure of esomeprazole, YYD601 produces gastric acid suppression that is comparable to that of the conventional esomeprazole formulation, with a greater tendency to suppress acid at night. YYD601 20 mg was safe and well tolerated following single and multiple oral administrations, supporting its use as an effective alternative to conventional esomeprazole therapy.
http://clinicaltrials.gov, NCT03985319 (Date of registration: May 29, 2019; Study period: between July 2019 and March 2020).
YYD601是一种新的埃索美拉唑双延迟释放制剂，旨在提高血浆暴露量并延长抑酸持续时间。
本研究旨在评估在健康、空腹的成年韩国人中单次和多次口服YYD601 20 mg后的安全性、药代动力学（PK）和药效学（PD）特征，并将这些结果与传统埃索美拉唑20 mg胶囊的结果进行比较。
对28名参与者进行了一项随机、开放标签、两期交叉研究，将他们分为两个治疗组：一组接受YYD601 20 mg，另一组接受传统埃索美拉唑20 mg，连续五天每天一次。在给药前和给药后长达24小时采集用于PK分析的血样。评估主要PK参数（AUC和AUC）。PD终点包括综合胃酸度、24小时和夜间胃内pH>4的时间百分比，以及多次给药后血清胃泌素水平的变化百分比。
共有22名参与者完成了研究。YYD601的血浆浓度-时间曲线比传统制剂更持久，尽管两种制剂的全身暴露程度（AUC值）在统计学上没有显著差异。关于24小时胃酸抑制，YYD601与传统制剂相当。夜间酸突破时间百分比和其他PD参数的变化表明，YYD601在夜间显示出更大的酸抑制趋势。两种治疗耐受性良好，未报告严重不良事件。
通过延长埃索美拉唑的全身暴露，YYD601产生的胃酸抑制作用与传统埃索美拉唑制剂相当，且在夜间有更大的酸抑制趋势。单次和多次口服YYD601 20 mg安全且耐受性良好，支持其作为传统埃索美拉唑治疗的有效替代药物使用。
http://clinicaltrials.gov，NCT03985319（注册日期：2019年5月29日；研究期间：2019年7月至2020年3月）。
