Study Comparing Fexuprazan and Esomeprazole in Patients With Gastroesophageal Reflux Disease

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.

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