Mucosal Healing Effectiveness and Safety of Anaprazole, a Novel PPI, vs. Rabeprazole in Patients With Duodenal Ulcers: A Randomized Double-Blinded Multicenter Phase II Clinical Trial

Abstract

Background: Proton pump inhibitors (PPIs) are validated gastric acid suppressors and have been widely used to treat patients with active duodenal ulcers. Although existing PPIs have shown great efficacy, many scientists are still devoted to developing more effective PPIs with better safety profile. Herein, we aimed to compare the safety and efficacy of anaprazole in duodenal mucosal healing, a novel PPI, to that of rabeprazole. Methods: In this multicenter, randomized, positive-controlled, double-blinded, parallel-group phase II clinical trial, a total of 150 qualified patients with endoscopically confirmed active duodenal ulcers were randomized (1:1:1) to receive rabeprazole 10 mg, anaprazole 20 mg or anaprazole 40 mg for 4 weeks. The ulcer healing rates after 4 weeks of treatment were compared between groups by independent central review and investigator review. In addition, symptoms and safety were evaluated. Results: Based on the independent central review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole and 40 mg anaprazole groups were 88.0, 85.1, and 87.5%, respectively, in the FAS population and 88.9, 86.0, and 90.9%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is -2.9% (95% CI, -16.5-10.7%), and -0.5% (95% CI, -13.5-12.5%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Based on the investigator review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole, and 40 mg anaprazole groups were 72.0, 70.2, and 77.1%, respectively, in the FAS population and 75.6, 72.1, and 79.5%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is -1.8% (95% CI, -19.8-16.3%), and 5.1% (95% CI, -12.2-22.3%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Most patients (>90%) eventually achieved complete symptom relief. The incidence rates of adverse events were of no significant differences among the treatment groups. Potential possible better liver tolerance was observed in two anaprazole dose groups than rabeprazole 10 mg group. Conclusion: Both at a dosage of 20 and 40 mg daily, anaprazole, is effective with good safety profile in the treatment of active duodenal ulcers in this Phase 2 study, which allows anaprazole to be advanced to a phase III clinical trial. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/results?cond=&term=NCT04503629&cntry=&state=&city=&dist=, Identifier: CTR20181464, NCT04503629.

Keywords: anaprazole; duodenal ulcer; peptic ulcer; proton pump inhibitors; rabeprazole.

Conflict of interest statement

YC and XD are employed by XuanzhuBiopharmaceutical Co., Ltd., Beijing. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest. The authors declare that this study received funding from Xuanzhu Biopharmaceutical Co., Ltd. The funder had the following involvement in the study: study design, data collection, and data analysis.

Copyright © 2021 Shu, Zhu, Fu, Zhang, Wang, Li, He, Fan, Liu, Zhang, Tang, Huang, Du, Wang, Xu, Du, Chen, Wang, Chen, Duan, Xie, Huo, Hou and Lu.

Figures

Figure 1

Flow diagram of the participants in this study. PPS, per-protocol set; FAS, full analysis set; SS, safety analysis set.

Figure 2

Cumulative percentages of patients with complete epigastric pain relief on days 7, 14, 21, and 28 of therapy with 10 mg rabeprazole (red line), 20 mg anaprazole (blue line), and 40 mg anaprazole (green line) in the FAS population.

Figure 3

Cumulative percentage of patients with complete nocturnal epigastric pain relief on days 7, 14, 21, and 28 of therapy with 10 mg rabeprazole (red line), 20 mg anaprazole (blue line) and 40 mg anaprazole (green line) in the FAS population.