Tu1056 A Phase 3, Double-Blind Study of a Triple Therapy With TAK-438, Amoxicillin, and Clarithromycin As First Line Eradication of H. pylori and a Triple Therapy With TAK-438, Amoxicillin, and Metronidazole As Second Line Eradication of H. pylori

Introduction: TAK-438 is a novel class of acid suppressants, referred to as a potassiumcompetitive acid blocker. Since the acid-inhibitory effect of TAK-438 was much more potent than that of lansoprazole (LPZ), it was expected to have comparable efficacy to LPZ in H. pylori eradication therapy. Aims: To verify the non-inferiority of the efficacy and safety of the triple therapy with TAK-438/amoxicillin (AMPC)/clarithromycin (CAM) (first line therapy with TAK-438) to the triple therapy with LPZ/AMPC/CAM (first line therapy with LPZ) in H. pylori-positive patients with cicatrized gastric or duodenal ulcer (GU or DU), and also to evaluate the efficacy and safety of the triple therapy with TAK-438/AMPC/metronidazole (MNDZ) (second line therapy with TAK-438). Methods: This was a phase 3, randomized, double-blind, double dummy, multicenter, parallel group comparison study. Eligible subjects were randomly allocated to receive one of four 7-day courses in the first line therapy; TAK438 (20 mg b.i.d.), AMPC (750 mg b.i.d.) and CAM (200 mg b.i.d. or 400 mg b.i.d.), or LPZ (30 mg b.i.d.), AMPC (750 mg b.i.d.) and CAM (200 mg b.i.d. or 400 mg b.i.d.). TAK438 group and LPZ group were compared regardless of CAM dose. Fifty of 101 subjects for whom the first line eradication had failed in this study received 7-day course of TAK438 (20 mg b.i.d.), AMPC (750 mg b.i.d.) and MNDZ (250 mg b.i.d.) as the second line therapy. Eradication was evaluated by 13C urea breath test more than 4 weeks after the therapy. Results: A total of 650 subjects were randomized. The first line H. pylori eradication rate was 92.6% in the TAK-438 group and 75.9% in the LPZ group. The superiority of TAK-438 to LPZ was verified in the first line therapy. Notably in the subjects with CAM resistance, the H. pylori eradication rate was significantly higher in the TAK-438 group than in the LPZ group (82.0% and 40.0%, respectively). In the second line therapy with TAK438, eradication rate was 98.0%. In the first line therapy with TAK-438 and LPZ, the overall incidence of drug-related treatment-emergent adverse events (TEAEs) was 20.4% in the TAK-438 group and 24.6% in the LPZ group. Most of the TEAEs were mild in intensity. In the second line therapy with TAK-438, the overall incidence of drug-related TEAEs was 16.0%. Most of the TEAEs were mild in intensity. Conclusion: The superiority of TAK-438 to LPZ was verified in the first line therapy, and also the significant difference was observed between in the TAK-438 group and in the LPZ group especially in the subjects with CAM resistance. TAK-438-based second line triple therapy was also effective. Both triple therapies with TAK-438 were safe, and well tolerated in this study.