RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROLLED PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ZASTAPRAZAN COMPARED WITH ESOMEPRAZOLE IN EROSIVE ESOPHAGITIS [ZASTAPRAN EROSIVE REFLUX OESOPHAGITIS-1 STUDY (ZERO-1)]

Introduction: Zastaprazan is a novel potassium-competitive acid blocker (P-CAB) with fast onset and prolonged duration. This study aims to assess the efficacy and safety of zastaprazan compared to esomeprazole in patient with erosive esophagitis.


Aims & Methods: A phase 3, multicenter, randomized, double-blind, active-controlled clinical study was conducted with 300 subjects with confirmed erosive esophagitis (Los Angeles classification grades A to D). Subjects were randomized to receive zastaprazan 20 mg or esomeprazole 40 mg once daily up to 8 weeks. The primary endpoint was the cumulative proportion of subject with healed erosive esophagitis confirmed by endoscopy up to week 8. The secondary endpoints included the healing rate at week 4, symptom response and quality of life. Safety profiles and serum gastrin levels were also assessed. [ClinicalTrials.gov: NCT04282954]


Results: The cumulative healing rate at week 8 and week 4 are shown in Table 1. For the primary variable (healing rate at week 8, PPS) shows that zastaprazan is non-inferior to esomeprazole. The cumulative healing rate at week 4 was 95.1% for zastaprazan and 87.7% for esomeprazole (FAS) with a statistically significant difference of 7.44% (p <0.05). The incidence of adverse events was comparable between groups, and zastaprazan was well-tolerated. Serum gastrin levels significantly increased during the treatment and declined after the treatment.


Conclusion: An 8-week therapy of zastaprazan 20 mg is non-inferior to esomeprazole 40 mg in subjects with erosive esophagitis. The healing rate at week 4 appears to be higher for zastaprazan than esomeprazole at week 4. These findings suggest that zastaprazan would be a promising alternative to proton pump inhibitors for the treatment of erosive esophagitis.