Korean J Gastroenterol.  2025 Jan;85(1):44-51. 10.4166/kjg.2024.124.

Efficacy and Safety of Dual Delayed-Release Formulation of Esomeprazole in Patients with Gastroesophageal Reflux Disease: A Multicenter, Prospective, Observational Study

• Lim H
• Park Mh

• KMID: 2565014
• DOI: http://doi.org/10.4166/kjg.2024.124

Abstract

Background/Aims
Gastroesophageal reflux disease (GERD) is a chronic and recurrent condition requiring constant dietary management and medication. This study evaluated the efficacy and safety of HIP1601, a dual delayed-release formulation of esomeprazole, in patients with GERD in a clinical setting.
Methods
This prospective, multicenter, observational study was conducted at 309 medical institutions in Korea between June 2021 and March 2023. HIP1601 was administered at daily doses of 40 mg or 20 mg to 5,407 patients requiring treatment or prevention of erosive esophagitis. The primary outcome was the improvement rate of GERD symptoms at four weeks. GERD-related symptoms and treatment-emergent adverse events were also analyzed.
Results
This study included 5,282 patients in the safety analysis set and 5,232 in the full analysis set. At four weeks, the improvement rate of GERD symptoms was 92.1% (95% confidence interval [CI]: 91.3–92.8%). By eight weeks, the improvement rate increased to 94.6% (95% CI: 94.0–95.3%). After HIP1601 administration, the severity scores for all four GERD symptoms decreased to less than 1, with statistically significant changes in the scores (p<0.001). HIP1601 was well-tolerated, with minimal adverse events reported (0.17%), and the treatment-emergent adverse events were mild to moderate in severity.
Conclusions
HIP1601 showed strong efficacy and safety in managing GERD symptoms, with high rates of symptom relief at four and eight weeks. Its extended action and improved symptom control make it a promising therapeutic option for GERD patients.

Keyword

Gastroesophageal reflux disease; Proton pump inhibitor; HIP1601; Esomeprazole

Figure

• 

  Fig. 1 Patient enrollment flow chart.

Reference

1. Jung HK, Tae CH, Song KH, et al. 2021; 2020 Seoul consensus on the diagnosis and management of gastroesophageal reflux disease. J Neurogastroenterol Motil. 27:453–481. DOI: 10.5056/jnm21077. PMID: 34642267. PMCID: PMC8521465.

2. Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. Global Consensus Group. 2006; The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 101:1900–1920. quiz 1943DOI: 10.1111/j.1572-0241.2006.00630.x. PMID: 16928254.

3. Kulig M, Leodolter A, Vieth M, et al. 2003; Quality of life in relation to symptoms in patients with gastro-oesophageal reflux disease--an analysis based on the ProGERD initiative. Aliment Pharmacol Ther. 18:767–776. DOI: 10.1046/j.1365-2036.2003.01770.x. PMID: 14535869.

4. Hongo M, Kinoshita Y, Shimozuma K, Kumagai Y, Sawada M, Nii M. 2007; Psychometric validation of the Japanese translation of the Quality of Life in Reflux and Dyspepsia questionnaire in patients with heartburn. J Gastroenterol. 42:807–815. DOI: 10.1007/s00535-007-2098-9. PMID: 17940833.

5. Iwakiri K, Fujiwara Y, Manabe N, et al. 2022; Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2021. J Gastroenterol. 57:267–285. DOI: 10.1007/s00535-022-01861-z. PMID: 35226174. PMCID: PMC8938399.

6. Yadlapati R, Gyawali CP, Pandolfino JE. CGIT GERD Consensus Conference Participants. 2022; AGA Clinical practice update on the personalized approach to the evaluation and management of GERD: Expert review. Clin Gastroenterol Hepatol. 20:984–994.e1. DOI: 10.1016/j.cgh.2022.01.025. PMID: 35123084. PMCID: PMC9838103.

7. Shin JM, Kim N. 2013; Pharmacokinetics and pharmacodynamics of the proton pump inhibitors. J Neurogastroenterol Motil. 19:25–35. DOI: 10.5056/jnm.2013.19.1.25. PMID: 23350044. PMCID: PMC3548122.

8. Dickman R, Maradey-Romero C, Gingold-Belfer R, Fass R. 2015; Unmet needs in the treatment of gastroesophageal reflux disease. J Neurogastroenterol Motil. 21:309–319. DOI: 10.5056/jnm15105. PMID: 26130628. PMCID: PMC4496897.

9. Hwang S, Hong SH, Jung J, Chung JY, Jang IJ, Lee S. 2023; Effect of food on the pharmacokinetics and pharmacodynamics of a novel dual delayed-release formulation of esomeprazole in healthy subjects. Clin Pharmacol Drug Dev. 12:839–844. DOI: 10.1002/cpdd.1237. PMID: 36929154.

10. Kim HC, Yang E, Ban MS, et al. 2023; Pharmacokinetics and pharmacodynamics of Esomezol DR, a new dual delayed-release formulation of esomeprazole 20 mg or 40 mg, in healthy subjects. Drug Des Devel Ther. 17:1115–1124. DOI: 10.2147/DDDT.S392533. PMID: 37077412. PMCID: PMC10106809.

11. Lim H, Park JK, Chung H, et al. 2023; Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study. BMC Gastroenterol. 23:447. DOI: 10.1186/s12876-023-03087-6. PMID: 38110901. PMCID: PMC10729464.

12. Yeom DH, Kim YS. 2023; History and pharmacological mechanism of gastric acid-suppressive drugs. Korean J Helicobacter Up Gastrointest Res. 23:159–166. DOI: 10.7704/kjhugr.2023.0040.

13. Kim YS, Kang DH, Park HC, Oh TH, Kim YS. 2023; Diagnosis and treatment of GastroEsophageal reflux disease at the primary health care clinics in Korea. Korean J Gastroenterol. 82:180–189. DOI: 10.4166/kjg.2023.032. PMID: 37876257.

14. Freedberg DE, Kim LS, Yang YX. 2017; The risks and benefits of long-term use of proton pump inhibitors: Expert review and best practice advice from the American Gastroenterological Association. Gastroenterology. 152:706–715. DOI: 10.1053/j.gastro.2017.01.031. PMID: 28257716.

15. Seo SI, Park CH, You SC, et al. 2021; Association between proton pump inhibitor use and gastric cancer: a population-based cohort study using two different types of nationwide databases in Korea. Gut. 70:2066–2075. DOI: 10.1136/gutjnl-2020-323845. PMID: 33975868.