Tu1059 A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of TAK-438 (20 mg Once-Daily) Compared to Lansoprazole (30 mg Once-Daily) in Patients With Erosive Esophagitis

Abstract

Introduction: Vonoprazan fumarate (TAK-438), a novel class of acid suppressant referred to as a potassium-competitive acid blocker (P-CAB), has been shown in animal models to exert more potent and sustained acid-inhibitory effects than PPIs. In addition, in a phase 2, dose-ranging study in Japanese patients with erosive esophagitis (EE), the non-inferiority of all TAK-438 doses (5, 10, 20 and 40 mg) to lansoprazole (LPZ) 30 mg was confirmed, and 20 mg was recommended as the clinical dose (DDW2013). Aims: To confirm the efficacy of TAK-438 in patients with EE of Los Angeles Classification (LA Classification) Grades A to D by verifying the non-inferiority of TAK-438 to LPZ. Methods: This was a phase 3, randomized, double-blind, parallel-group, multicenter study to verify the non-inferiority of TAK-438 (20 mg once-daily) to LPZ (30 mg once-daily) in patients with EE. This study consisted of 2 periods; an observation period of 3 to 7 days and a double-blind treatment period of 8 weeks. The subjects' LA Classification Grades at the start of the observation period were used as stratification factors (Grade A/B or C/D). The subjects with endoscopically confirmed healing of EE 2, 4, or 8 weeks after the start of the treatment were regarded as having completed the study. Results: A total of 409 subjects were randomized. The primary endpoint, EE healing rate after 8 weeks of treatment was 99.0% in the TAK-438 group and 95.5% in the LPZ group. In addition to the non-inferiority, the superiority of TAK-438 to LPZ was verified. The EE healing rate after 2 weeks of treatment in the TAK-438 group (90.7%) was also superior to that observed in the LPZ group (81.9%). Furthermore, the EE healing rate after 4 weeks of treatment with TAK-438 (96.6%) was non-inferior to that after 8 weeks of treatment with LPZ (95.5%). Notably, in subjects with baseline LA Classification Grade C or D, the EE healing rate after 8 weeks of treatment was higher in the TAK-438 group compared with the LPZ group (98.7% vs 87.5%, respectively). The incidences of treatment-emergent adverse events (TEAE) were similar between the groups; 22.2% in the TAK-438 group, 22.3% in the LPZ group. The most common TEAE was nasopharyngitis (3.4% in the TAK-438 group and 4.0% in the LPZ group). Conclusion: The superiority of TAK-438 20 mg compared with LPZ 30 mg was verified for the primary endpoint, EE healing rate after 8 weeks of treatment. Furthermore, the non-inferiority of 4 weeks treatment with TAK-438 20 mg compared with 8 weeks treatment with LPZ 30 mg was confirmed. Even for subjects with severe baseline Grade C or D, treatment with TAK-438 was highly effective. These results demonstrate the rapid and potent therapeutic effect of TAK-438 20 mg, once daily, for the treatment of EE. The safety profile of TAK-438 was similar to that of LPZ and TAK-438 was safe and well tolerated in patients with EE.