Gastro Oesophageal Reflux Disease
Conditions
Keywords
Gastroesophageal reflux disease (GERD), fexuprazan, esomeprazole, Potassium-competitive acid blockers (P-CABs), Proton pump inhibitors (PPIs), Randomized trial
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
Detailed description
This multicenter, randomized, open-label, active-controlled clinical study was conducted to evaluate the efficacy and safety of fexuprazan 40 mg, a potassium-competitive acid blocker (P-CAB), compared with esomeprazole 40 mg, a proton pump inhibitor (PPI), in adult patients with gastroesophageal reflux disease (GERD). GERD is a chronic condition characterized by reflux-related symptoms such as heartburn and acid regurgitation, which can significantly impair quality of life. Although PPIs are widely used as first-line therapy, limitations including delayed onset of action and insufficient control of nocturnal symptoms have been reported. Fexuprazan, a novel P-CAB, inhibits gastric acid secretion through reversible and potassium-competitive inhibition of the H⁺/K⁺-ATPase and has demonstrated rapid onset and sustained acid suppression in prior clinical studies. Eligible participants were randomized in a 1:1 ratio to receive either fexuprazan 40 mg or esomeprazole 40 mg administered orally once daily. The initial treatment period was 4 weeks. Participants who did not achieve adequate symptom relief after the initial treatment period were eligible to continue the assigned treatment for an additional 4 weeks, for a total treatment duration of up to 8 weeks. Efficacy was assessed primarily through patient-reported symptom evaluation using validated questionnaires and daily symptom diaries. Safety assessments included monitoring of adverse events, vital signs, physical examinations, and laboratory evaluations throughout the study and during follow-up. The study was conducted in accordance with the principles of the Declaration of Helsinki, International Council for Harmonisation Good Clinical Practice (ICH-GCP), and applicable local regulatory requirements. Written informed consent was obtained from all participants prior to the performance of any study-related procedures.
Interventions
DRUGFexuprazan
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.
DRUGEsomeprazole
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.
Sponsors
Indonesia University
Daewoong Pharmaceutical Co. LTD.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
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 * Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin ≥2 times the upper limit of normal * Serum creatinine or blood urea nitrogen ≥2 times the upper limit of normal Reproductive status * Pregnant or breastfeeding women * Women of childbearing potential or male participants who were unwilling to use appropriate contraception during the study Other * Known hypersensitivity to the investigational product or comparator drug * Any condition that, in the opinion of the investigator, made the participant unsuitable for study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Symptom Relief at Week 4 (GERD-Q Score <8) | 4 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Symptom Relief at Week 8 (GERD-Q Score <8) | 8 weeks | The proportion of participants who achieved symptom relief at Week 8, defined as a total score of less than 8 on 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 symptom severity). This assessment applied only to participants who continued treatment beyond the initial 4-week period. |
| Time to Complete Symptom Response After First Dose | From first dose until achievement of complete response, up to 8 weeks | Complete response was defined as the absence of heartburn and/or acid regurgitation symptoms for 7 consecutive days based on patient diaries. Time to complete response was measured in days from the first dose to the first day of the 7-day symptom-free period. Analysis included all subjects using time-to-event methods. |
| Number of Participants Without Major GERD Symptoms | Up to 8 weeks | The number of participants without major GERD symptoms (heartburn and/or acid regurgitation) during predefined periods, including the first 7 days, 4 weeks, and 8 weeks after initiation of treatment, as recorded in participant diaries. |
| Percentage of Days Free of Major GERD Symptoms | Up to 8 weeks | The percentage of days without heartburn and/or acid regurgitation per participant during the first 7 days, 4 weeks, and 8 weeks after treatment initiation. This includes daytime, nighttime, and combined daytime/nighttime periods based on participant diary entries, analyzed and reported as the mean percentage of symptom-free days |
| Change From Baseline in GERD-Q Total Score | Baseline up to 8 weeks (Evaluated at 7 days, 4 weeks, and 8 weeks) | Change from baseline in the Gastroesophageal Reflux Disease Questionnaire (GERD-Q) total score. The GERD-Q is a 6-item scale used to evaluate the frequency of GERD symptoms. Total scores range from a minimum of 0 to a maximum of 18, where higher scores indicate greater symptom severity (a worse outcome). |
| Change From Baseline in GERD-Health-Related Quality of Life (GERD-HRQL) Total Score | Baseline to up to 8 weeks | Change from baseline in the Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) total score. The GERD-HRQL is a 10-item instrument used to assess the impact of symptoms on daily life. Total scores range from a minimum of 0 to a maximum of 50, where higher scores indicate worse health-related quality of life (a worse outcome). |
Countries
Indonesia
Contacts
STUDY_CHAIRAri Fahrial Syam, MD, PhD
RS Islam Jakarta Cempaka Putih
Participant flow
Recruitment details
Participants were recruited at three hospital-based outpatient clinics in Indonesia (University of Indonesia Hospital, Islam Cempaka Putih Hospital, and Menteng Mitra Afia Hospital). Recruitment began on 23 September 2024 following institutional review board approval. The last participant was enrolled on 10 October 2024. Eligible adult patients with gastroesophageal reflux disease were identified during routine clinical visits and screened according to protocol-defined criteria.
Pre-assignment details
After enrollment and informed consent, participants underwent a screening and washout period of up to 2 weeks, during which prohibited acid-suppressive or concomitant medications were discontinued. Eligibility was reassessed prior to randomization, and participants who did not meet protocol-defined inclusion or exclusion criteria or withdrew consent were not assigned to a treatment arm.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized Age, year | 29.5 Years |
| Body Mass Index (BMI) | 26.30 kg/m^2 STANDARD_DEVIATION 5.49 |
| Drinking History Alcoholic | 0 Participants |
| Drinking History Non-alcoholic | 67 Participants |
| Race and Ethnicity Not Collected | 0 Participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 43 Participants |
| Smoking History Non-smoker | 57 Participants |
| Smoking History Smoker | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 0 / 67 |
| other Total, other adverse events | 42 / 67 | 38 / 67 |
| serious Total, serious adverse events | 0 / 67 | 0 / 67 |
Outcome results
None listed