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.

Gastroduodenal injury and repair: novel targets for therapeutic intervention

“…Although anaprazole was effective at promoting ulcer healing, neither of the doses tested surpassed the clinical efficacy of rabeprazole [28 ▪▪ ]. However, in both dosage groups, there was a potential for better liver tolerance compared with rabeprazole, and therefore, the drug was advanced to phase III clinical trials [28 ▪▪ ]. The potassium competitive acid blocker (P-CAB), vonoprazan fumarate (Takeda Pharmaceutical Company, Tokyo, Japan), was also shown to be as effective at healing duodenal ulcers as the PPI lansoprazole in the setting of H. pylori infection [29 ▪ ], thus expanding available therapeutics for acid-induced duodenal ulceration.…”

“…For active duodenal ulcers, a novel PPI, anaprazole (Sihuan Pharmaceutical Holdings Group, China), was developed with the aim to provide better protection and a better safety profile compared with rabeprazole (AcipHex), which promotes ulcer healing and symptom relief, and has greater acid-blocking profile compared with other PPIs [28 ▪▪ ]. Although anaprazole was effective at promoting ulcer healing, neither of the doses tested surpassed the clinical efficacy of rabeprazole [28 ▪▪ ]. However, in both dosage groups, there was a potential for better liver tolerance compared with rabeprazole, and therefore, the drug was advanced to phase III clinical trials [28 ▪▪ ].…”

Effect and safety of anaprazole in the treatment of duodenal ulcers: a randomized, rabeprazole-controlled, phase III non-inferiority study

“…To reduce bias and control trial quality, the primary endpoint was evaluated by BICR as conducted in both phase II and phase III studies [11] . These phase III findings build on those of the phase II trial that assessed 4-week ulcer healing rates of anaprazole or rabeprazole treatment by BICR [11] . The difference in the ulcer healing rate (−2.8%; 95% CI: −7.7%, 2.2%) was similar to that of the phase II study (−2.9%), confirming the findings of the phase II study in a larger patient population.…”

“…In total, the contribution of 2C19 was only 3.5%. Preclinical and phase I studies have shown that anaprazole has an equivalent half-life and pharmacodynamic profile, and an improved safety profile, compared with rabeprazole [11,12] . Patients treated with 10 mg or 20 mg rabeprazole experience high rates of ulcer healing and clinical symptom relief [13,14] .…”

“…Patients treated with 10 mg or 20 mg rabeprazole experience high rates of ulcer healing and clinical symptom relief [13,14] . A phase II study reported similar duodenal ulcer healing rates of anaprazole and rabeprazole treatments [11] . Although these results are encouraging, a comparison of the efficacy and safety of anaprazole with rabeprazole in a larger patient population is needed.…”