Efficacy and Safety Profile of Z-215 (Azeloprazole Sodium), a Proton Pump Inhibitor, Compared with Rabeprazole Sodium in Patients with Reflux Esophagitis: A Phase II, Multicenter, Randomized, Double-Blind, Comparative Study

Yoshikazu Kinoshita; Motoyasu Kusano; Katsuhiko Iwakiri; Mitsuhiro Fujishiro; Naoto Tachikawa; Ken Haruma

doi:10.1016/j.curtheres.2018.03.004

Efficacy and Safety Profile of Z-215 (Azeloprazole Sodium), a Proton Pump Inhibitor, Compared with Rabeprazole Sodium in Patients with Reflux Esophagitis: A Phase II, Multicenter, Randomized, Double-Blind, Comparative Study

Curr Ther Res Clin Exp. 2018 Mar 22:88:26-34. doi: 10.1016/j.curtheres.2018.03.004. eCollection 2018.

Authors

Yoshikazu Kinoshita¹, Motoyasu Kusano², Katsuhiko Iwakiri³, Mitsuhiro Fujishiro⁴, Naoto Tachikawa⁵, Ken Haruma⁶

Affiliations

¹ Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Shimane, Japan.
² Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Gunma, Japan.
³ Department of Gastroenterology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan.
⁴ Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁵ Clinical Research, Research & Development, Zeria Pharmaceutical Co Ltd, Tokyo, Japan.
⁶ Department of General Internal Medicine 2, General Medical Center, Kawasaki Medical School, Okayama, Japan.

Abstract

Background: The metabolism of many proton pump inhibitors is influenced by CYP2C19 genotype, which is a limitation of their use.

Objectives: To determine the efficacy and safety profile of Z-215 (azeloprazole sodium) as initial treatment for reflux esophagitis (RE), dose response, and optimal dose compared with rabeprazole sodium (RPZ).

Methods: We conducted an exploratory, multicenter, randomized, double-blind, parallel-group study in Japan. Patients with RE aged ≥20 years were enrolled and randomly assigned to receive 10, 20, or 40 mg Z-215 or 10 mg RPZ (1:1:1:1), and orally administered the respective drug for 8 weeks. The primary efficacy end point was the endoscopic healing rate after 8 weeks of treatment (at Week 8). We also assessed the effects of CYP2C19 genotype. Safety end points were the incidence of adverse events and adverse drug reactions.

Results: Five hundred three patients received the study drugs (10 mg Z-215: 125 patients, 20 mg Z-215: 126 patients, 40 mg Z-215: 126 patients, and 10 mg RPZ: 126 patients). The endoscopic healing rate at Week 8 was above 95% in all groups (10 mg Z-215: 95.2%, 20 mg Z-215: 96.8%, 40 mg Z-215: 95.2%, and 10 mg RPZ: 96.8%). The endoscopic healing rate and serum gastrin levels of the Z-215 groups were not influenced by CYP2C19 genotype. In patients with Grade C/D, the endoscopic healing rate at Week 4 was slightly higher in the 40-mg Z-215 group compared with the other groups. Incidences of adverse events/adverse drug reactions did not markedly differ between the Z-215 and 10-mg RPZ groups.

Conclusions: Z-215 was as effective and well tolerated as 10 mg RPZ in the treatment of RE in this selected population. CYP2C19 genotype status may not influence the efficacy and safety of Z-215. There were no clear dose-response effects between Z-215 doses in the endoscopic healing of RE. These findings suggest that Z-215 may be 1 option for the initial treatment of RE. ClinicalTrials.gov identifier: NCT 02463643.

Keywords: CYP2C19; GERD; azeloprazole; proton pump inhibitors; rabeprazole; reflux esophagitis.