Study Comparing Fexuprazan and Esomeprazole in Patients With Gastroesophageal Reflux Disease

NCT07326904 | Completed Phase 3 Results

• 1 other identifier: DW_DWP1401262001
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this clinical trial was to evaluate the effectiveness and safety of fexuprazan 40 mg for relieving symptoms of gastroesophageal reflux disease (GERD) in adults. The study also compared fexuprazan with esomeprazole 40 mg, a commonly used treatment for GERD. The main questions this study aimed to answer were:

• Did fexuprazan reduce GERD symptoms such as heartburn and acid regurgitation?
• Was fexuprazan safe and well tolerated compared with esomeprazole? Researchers compared fexuprazan with esomeprazole to determine whether fexuprazan provided similar symptom relief and safety. Participants in the study:
• Were randomly assigned to receive fexuprazan 40 mg or esomeprazole 40 mg once daily
• Took the study medication for 4 weeks, with treatment extended up to 8 weeks if symptoms did not improve
• Attended scheduled clinic visits for evaluations
• Completed symptom questionnaires and a daily symptom diary
• Were monitored for side effects and overall safety throughout the study

Conditions

Gastro Oesophageal Reflux Disease

Keywords

Gastroesophageal reflux disease (GERD); fexuprazan; esomeprazole; Potassium-competitive acid blockers (P-CABs); Proton pump inhibitors (PPIs); Randomized trial

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With Symptom Relief at Week 4 (GERD-Q Score <8)

  Symptom relief was assessed using the Gastroesophageal Reflux Disease Questionnaire (GERD-Q). The GERD-Q total score ranges from a minimum of 0 to a maximum of 18, where higher scores indicate a worse outcome (greater severity and higher likelihood of GERD). The primary outcome was defined as the proportion of participants with a GERD-Q total score \<8 at Week 4, indicating adequate relief of GERD symptoms.

  4 weeks

Secondary Outcomes (6)

• Proportion of Participants With Symptom Relief at Week 8 (GERD-Q Score <8)

  8 weeks

• Time to Complete Symptom Response After First Dose

  From first dose until achievement of complete response, up to 8 weeks

• Number of Participants Without Major GERD Symptoms

  Up to 8 weeks

• Percentage of Days Free of Major GERD Symptoms

  Up to 8 weeks

• Change From Baseline in GERD-Q Total Score

  Baseline up to 8 weeks (Evaluated at 7 days, 4 weeks, and 8 weeks)

Other Outcomes (3)

• Number of Participants With Relief From Chronic Cough

  Up to 8 weeks

• Number of Participants With Relief of Throat Irritation Sensation

  Up to 8 weeks

• Number of Participants Without Nocturnal GERD Symptoms

  Up to 8 weeks

Study Arms (2)

Fexuprazan 40 mg

EXPERIMENTAL

Participants assigned to this arm received fexuprazan 40 mg, a potassium-competitive acid blocker (P-CAB), administered orally once daily. The initial treatment period was 4 weeks. Participants who did not achieve adequate symptom relief after the initial treatment period continued treatment with fexuprazan 40 mg for an additional 4 weeks, for a maximum treatment duration of 8 weeks. Treatment adherence and safety were monitored throughout the study period according to the protocol.

Drug: Fexuprazan

Esomeprazole 40 mg

ACTIVE COMPARATOR

Participants assigned to this arm received esomeprazole 40 mg, a proton pump inhibitor, administered orally once daily. The initial treatment period was 4 weeks. Participants who did not achieve adequate symptom relief after the initial treatment period continued treatment with esomeprazole 40 mg for an additional 4 weeks, for a maximum treatment duration of 8 weeks. Treatment adherence and safety were monitored throughout the study period according to the protocol.

Drug: Esomeprazole

Interventions

Fexuprazan DRUG

Fexuprazan was administered orally at a dose of 40 mg once daily. Participants received treatment for an initial period of 4 weeks. Participants who did not achieve adequate symptom relief after the initial treatment period continued treatment with fexuprazan for an additional 4 weeks, for a maximum treatment duration of 8 weeks.

Also known as: Fexuclue, DWP14012

Fexuprazan 40 mg

Esomeprazole DRUG

Esomeprazole was administered orally at a dose of 40 mg once daily. Participants received treatment for an initial period of 4 weeks. Participants who did not achieve adequate symptom relief after the initial treatment period continued treatment with esomeprazole for an additional 4 weeks, for a maximum treatment duration of 8 weeks.

Also known as: Nexium

Esomeprazole 40 mg

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adults aged 18 to 60 years at the time of providing written informed consent
• Male or female participants
• History of gastroesophageal reflux disease (GERD) symptoms, including heartburn and/or acid regurgitation
• GERD symptoms confirmed by:
• GERD-Q score greater than 7, and
• Heartburn and/or acid regurgitation occurring on more than 3 days within the last 7 days
• Able to understand the study procedures and complete questionnaires and a daily symptom diary
• Willing and able to provide written informed consent

You may not qualify if:

• Gastrointestinal conditions:
• Diagnosis of inflammatory bowel disease (Crohn's disease, ulcerative colitis), primary esophageal motility disorders, or pancreatitis
• History of gastric or esophageal surgery affecting acid secretion (except appendectomy, cholecystectomy, or endoscopic polypectomy of benign polyps)
• Alarm symptoms suggestive of gastrointestinal malignancy (e.g., severe dysphagia, odynophagia, gastrointestinal bleeding, anemia, unexplained weight loss), unless malignancy was ruled out
• Medical history
• Clinically significant hepatic, renal, endocrine, hematologic, oncologic, or urinary system disease
• History of malignancy within the past 5 years (except non-digestive malignancies that were completely treated with no recurrence for ≥5 years)
• History of psychosis, substance abuse, or alcohol abuse
• Known HIV infection, active hepatitis B, or hepatitis C infection (HCV RNA-positive)
• Medication and treatment
• Use of prohibited concomitant medications within 2 weeks prior to enrollment or need for continuous prohibited medication during the study, including:
• Proton pump inhibitors, potassium-competitive acid blockers, H2-receptor antagonists, or other acid-suppressive agents
• Certain psychotropic drugs, anticholinergic drugs, antispasmodics, systemic steroids, or mucoprotective agents
• Use of another investigational product within 4 weeks prior to study drug administration
• Laboratory findings

Sponsors & Collaborators

• Indonesia University: lead
• Daewoong Pharmaceutical Co. LTD.: collaborator

Study Sites (3)

Menteng Mitra Afia Jakarta Hospital

Jakarta Pusat, DKI Jakarta, 10340, Indonesia

Location

RS Islam Jakarta Cempaka Putih

Jakarta Pusat, DKI Jakarta, 10510, Indonesia

Location

RS Universitas Indonesia

Depok, West Java, 16424, Indonesia

Location

Related Publications (26)

• Yang AY, Yoo H, Shin W, Lee YS, Lee H, Kim SE, Kim A. Size-reduced fexuprazan 20 mg demonstrated the optimal bioavailability and bioequivalence with the reference formulation. Transl Clin Pharmacol. 2023 Mar;31(1):40-48. doi: 10.12793/tcp.2023.31.e3. Epub 2023 Mar 22.

  PMID: 37034124 BACKGROUND

• Laine L, Sharma P, Mulford DJ, Hunt B, Leifke E, Smith N, Howden CW. Pharmacodynamics and Pharmacokinetics of the Potassium-Competitive Acid Blocker Vonoprazan and the Proton Pump Inhibitor Lansoprazole in US Subjects. Am J Gastroenterol. 2022 Jul 1;117(7):1158-1161. doi: 10.14309/ajg.0000000000001735. Epub 2022 Mar 16.

  PMID: 35294415 BACKGROUND

• Shin W, Yang AY, Park H, Lee H, Yoo H, Kim A. A Comparative Pharmacokinetic Study of Fexuprazan 10 mg: Demonstrating Bioequivalence with the Reference Formulation and Evaluating Steady State. Pharmaceuticals (Basel). 2023 Aug 11;16(8):1141. doi: 10.3390/ph16081141.

  PMID: 37631056 BACKGROUND

• Kim GH, Choi MG, Kim JI, Lee ST, Chun HJ, Lee KL, Choi SC, Jang JY, Lee YC, Kim JG, Kim KB, Shim KN, Sohn CI, Kim SK, Kim SG, Jang JS, Kim N, Jung HY, Park H, Huh KC, Lee KJ, Hong SJ, Baek S, Han JJ, Lee OY. Efficacy and Safety of Fexuprazan in Patients with Acute or Chronic Gastritis. Gut Liver. 2023 Nov 15;17(6):884-893. doi: 10.5009/gnl220457. Epub 2023 Feb 15.

  PMID: 36789577 BACKGROUND

• Kim SI, Lee YC, Cha W, Jung AR, Jang JY, Choi JS, Lee DK, Lee HH, Kwon MS, Lee YS, Eun YG. Efficacy and safety of fexuprazan in patients with symptoms and signs of laryngopharyngeal reflux disease: a randomized clinical trial. Eur Arch Otorhinolaryngol. 2024 Nov;281(11):5873-5883. doi: 10.1007/s00405-024-08877-6. Epub 2024 Aug 8.

  PMID: 39115573 BACKGROUND

• Zhuang Q, Liao A, He Q, Liu C, Zheng C, Li X, Liu Y, Wang B, Liu S, Zhang Y, Lin R, Chen H, Deng M, Tang Y, He C, Dai W, Tang H, Gong L, Li L, Xu B, Yang C, Zhou B, Su D, Guo Q, Li B, Zhou Y, Wang X, Fei S, Wu H, Wei S, Peng Z, Wang J, Li Y, Wang H, Deng T, Ding S, Li F, Chen M, Xiao Y. The efficacy and safety of fexuprazan in treating erosive esophagitis: a phase III, randomized, double-blind, multicenter study. J Gastroenterol Hepatol. 2024 Apr;39(4):658-666. doi: 10.1111/jgh.16471. Epub 2024 Jan 22.

  PMID: 38251791 BACKGROUND

• Kang N, Kang MG, Lee SE, Kang SY, Jo EJ, Lee JH, Kim SH, Bahn JW, Lee BJ, Song WJ. Efficacy and Safety of Fexuprazan Versus Esomeprazole for Gastroesophageal Reflux Disease-Related Chronic Cough: A Randomized, Double-Blind, Active-Controlled Exploratory Trial. Lung. 2025 Apr 29;203(1):59. doi: 10.1007/s00408-025-00815-5.

  PMID: 40299084 BACKGROUND

• Won H, Kim E, Chae J, Lee H, Cho JY, Jang IJ, Chung JY, Kim MG, Lee S. Pharmacokinetic interactions between fexuprazan, a potassium-competitive acid blocker, and nonsteroidal anti-inflammatory drugs in healthy males. Clin Transl Sci. 2024 May;17(5):e13798. doi: 10.1111/cts.13798.

  PMID: 38700290 BACKGROUND

• Oh J, Yang E, Jang IJ, Lee H, Yoo H, Chung JY, Lee S, Oh J. Pharmacodynamic and Pharmacokinetic Drug Interactions between Fexuprazan, a Novel Potassium-Competitive Inhibitor, and Aspirin, in Healthy Subjects. Pharmaceutics. 2023 Feb 7;15(2):549. doi: 10.3390/pharmaceutics15020549.

  PMID: 36839870 BACKGROUND

• Hwang JG, Jeon I, Park SA, Lee A, Yu KS, Jang IJ, Lee S. Pharmacodynamics and pharmacokinetics of DWP14012 (fexuprazan) in healthy subjects with different ethnicities. Aliment Pharmacol Ther. 2020 Dec;52(11-12):1648-1657. doi: 10.1111/apt.16131. Epub 2020 Oct 27.

  PMID: 33111337 BACKGROUND

• Sunwoo J, Oh J, Moon SJ, Ji SC, Lee SH, Yu KS, Kim HS, Lee A, Jang IJ. Safety, tolerability, pharmacodynamics and pharmacokinetics of DWP14012, a novel potassium-competitive acid blocker, in healthy male subjects. Aliment Pharmacol Ther. 2018 Jul;48(2):206-218. doi: 10.1111/apt.14818. Epub 2018 Jun 4.

  PMID: 29863280 BACKGROUND

• Lee SP, Sung IK, Lee OY, Choi MG, Huh KC, Jang JY, Chun HJ, Kwon JG, Kim GH, Kim N, Rhee PL, Kim SG, Jung HY, Lee JS, Lee YC, Jung HK, Kim JG, Kim SK, Sohn CI. Randomized Multicenter Study to Evaluate the Efficacy and Safety of Fexuprazan According to the Timing of Dosing in Patients With Erosive Esophagitis. J Neurogastroenterol Motil. 2025 Jan 31;31(1):86-94. doi: 10.5056/jnm24032. Epub 2024 Dec 13.

  PMID: 39667898 BACKGROUND

• Hafiz RA, Wong C, Paynter S, David M, Peeters G. The Risk of Community-Acquired Enteric Infection in Proton Pump Inhibitor Therapy: Systematic Review and Meta-analysis. Ann Pharmacother. 2018 Jul;52(7):613-622. doi: 10.1177/1060028018760569. Epub 2018 Feb 18.

  PMID: 29457492 BACKGROUND

• Strand DS, Kim D, Peura DA. 25 Years of Proton Pump Inhibitors: A Comprehensive Review. Gut Liver. 2017 Jan 15;11(1):27-37. doi: 10.5009/gnl15502.

  PMID: 27840364 BACKGROUND

• Rettura F, Bronzini F, Campigotto M, Lambiase C, Pancetti A, Berti G, Marchi S, de Bortoli N, Zerbib F, Savarino E, Bellini M. Refractory Gastroesophageal Reflux Disease: A Management Update. Front Med (Lausanne). 2021 Nov 1;8:765061. doi: 10.3389/fmed.2021.765061. eCollection 2021.

  PMID: 34790683 BACKGROUND

• Kim SE, Kim N, Oh S, Kim HM, Park MI, Lee DH, Jung HC. Predictive factors of response to proton pump inhibitors in korean patients with gastroesophageal reflux disease. J Neurogastroenterol Motil. 2015 Jan 1;21(1):69-77. doi: 10.5056/jnm14078.

  PMID: 25537676 BACKGROUND

• Weijenborg PW, Cremonini F, Smout AJ, Bredenoord AJ. PPI therapy is equally effective in well-defined non-erosive reflux disease and in reflux esophagitis: a meta-analysis. Neurogastroenterol Motil. 2012 Aug;24(8):747-57, e350. doi: 10.1111/j.1365-2982.2012.01888.x. Epub 2012 Feb 6.

  PMID: 22309489 BACKGROUND

• Yadlapati R, Gyawali CP, Pandolfino JE; CGIT GERD Consensus Conference Participants. AGA Clinical Practice Update on the Personalized Approach to the Evaluation and Management of GERD: Expert Review. Clin Gastroenterol Hepatol. 2022 May;20(5):984-994.e1. doi: 10.1016/j.cgh.2022.01.025. Epub 2022 Feb 2.

  PMID: 35123084 BACKGROUND

• ASGE Standards of Practice Committee; Desai M, Ruan W, Thosani NC, Amaris M, Scott JS, Saeed A, Abu Dayyeh B, Canto MI, Abidi W, Alipour O, Amateau SK, Cosgrove N, Elhanafi SE, Forbes N, Kohli DR, Kwon RS, Fujii-Lau LL, Machicado JD, Marya NB, Ngamruengphong S, Pawa S, Sheth SG, Thiruvengadam NR, Qumseya BJ; ASGE Standards of Practice Committee Chair. American Society for Gastrointestinal Endoscopy guideline on the diagnosis and management of GERD: summary and recommendations. Gastrointest Endosc. 2025 Feb;101(2):267-284. doi: 10.1016/j.gie.2024.10.008. Epub 2024 Dec 17.

  PMID: 39692638 BACKGROUND

• Zhang D, Liu S, Li Z, Wang R. Global, regional and national burden of gastroesophageal reflux disease, 1990-2019: update from the GBD 2019 study. Ann Med. 2022 Dec;54(1):1372-1384. doi: 10.1080/07853890.2022.2074535.

  PMID: 35579516 BACKGROUND

• Shaqran TM, Ismaeel MM, Alnuaman AA, Al Ahmad FA, Albalawi GA, Almubarak JN, AlHarbi RS, Alaqidi RS, AlAli YA, Alfawaz KS, Daghriri AA. Epidemiology, Causes, and Management of Gastro-esophageal Reflux Disease: A Systematic Review. Cureus. 2023 Oct 21;15(10):e47420. doi: 10.7759/cureus.47420. eCollection 2023 Oct.

  PMID: 38022211 BACKGROUND

• Nirwan JS, Hasan SS, Babar ZU, Conway BR, Ghori MU. Global Prevalence and Risk Factors of Gastro-oesophageal Reflux Disease (GORD): Systematic Review with Meta-analysis. Sci Rep. 2020 Apr 2;10(1):5814. doi: 10.1038/s41598-020-62795-1.

  PMID: 32242117 BACKGROUND

• Lee KN, Lee OY, Chun HJ, Kim JI, Kim SK, Lee SW, Park KS, Lee KL, Choi SC, Jang JY, Kim GH, Sung IK, Park MI, Kwon JG, Kim N, Kim JJ, Lee ST, Kim HS, Kim KB, Lee YC, Choi MG, Lee JS, Jung HY, Lee KJ, Kim JH, Chung H. Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis. World J Gastroenterol. 2022 Nov 28;28(44):6294-6309. doi: 10.3748/wjg.v28.i44.6294.

  PMID: 36504556 BACKGROUND

• Maret-Ouda J, Markar SR, Lagergren J. Gastroesophageal Reflux Disease: A Review. JAMA. 2020 Dec 22;324(24):2536-2547. doi: 10.1001/jama.2020.21360.

  PMID: 33351048 BACKGROUND

• Eusebi LH, Ratnakumaran R, Yuan Y, Solaymani-Dodaran M, Bazzoli F, Ford AC. Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis. Gut. 2018 Mar;67(3):430-440. doi: 10.1136/gutjnl-2016-313589. Epub 2017 Feb 23.

  PMID: 28232473 BACKGROUND

• Hojo M, Nagahara A, Hahm KB, Iwakiri R, Watanabe T, Rani AA, Zhu Q, Chan FKL, Sollano JD, Kamiya T, Yamaguchi S, Motoya S, Fock KM, Fukudo S, Kachintorn U, Suzuki H, Murakami K; The International Gastroenterology Consensus Symposium Study Group. Management of Gastroesophageal Reflux Disease in Asian Countries: Results of a Questionnaire Survey. Digestion. 2020;101(1):66-79. doi: 10.1159/000504749. Epub 2019 Dec 4.

  PMID: 31801133 BACKGROUND

MeSH Terms

Conditions

Gastroesophageal Reflux

Interventions

fexuprazan; Esomeprazole

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Omeprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Open-label design may introduce reporting bias for subjective symptoms. As an investigator-initiated trial, the scope was narrower than large registration trials. Use of Last Observation Carried Forward (LOCF) for missing efficacy data might not accurately reflect outcomes post-dropout. Finally, results from the specific geographic setting (Indonesia) may have limited generalizability to broader global populations.

Results Point of Contact

• Title: Prof Dr. dr. Ari Fahrial Syam, SpPD, K-GEH, MMB, FACP, FACG, FINASIM
• Organization: RS Islam Jakarta Cempaka Putih

arisyam91@yahoo.com

+62 818-706-199

Study Officials

• Ari Fahrial Syam, MD, PhD

  RS Islam Jakarta Cempaka Putih

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Gastroenterologist, Department of Internal Medicine

Model Details: This study used a parallel-group interventional design. Eligible participants were randomized in a 1:1 ratio to receive either fexuprazan 40 mg or esomeprazole 40 mg. Each participant remained in the assigned treatment group throughout the study duration. All participants received their assigned intervention for an initial treatment period of 4 weeks. Participants who did not achieve adequate symptom relief after the initial treatment period continued treatment with the same assigned intervention for an additional 4 weeks, for a maximum treatment duration of 8 weeks. No crossover between treatment groups occurred at any time during the study. Efficacy and safety outcomes were evaluated in parallel between the two treatment groups over the course of the study.

Study Record Dates

• First Submitted: December 17, 2025
• First Posted: January 8, 2026
• Study Start: August 28, 2024
• Primary Completion: November 12, 2024
• Study Completion: December 13, 2024
• Last Updated: August 24, 2026
• Results First Posted: August 24, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

ID (3)