Pharmacokinetics, Safety, and Tolerability of Vonoprazan‐ or Esomeprazole‐Based Bismuth‐Containing Quadruple Therapy: A Phase 1, Double‐Blind, Parallel‐Group Study in Adults with Helicobacter pylori Infection in China

Abstract

Quadruple therapy comprising 2 antibiotics, a proton pump inhibitor, and bismuth, is recommended for Helicobacter pylori eradication in China. This Phase 1, double‐blind, parallel‐group study aimed to evaluate the pharmacokinetics, safety, and tolerability of bismuth‐containing vonoprazan‐ or esomeprazole‐based quadruple therapy in H. pylori–positive healthy subjects at a single site in China. Quadruple therapy comprising vonoprazan 20 mg or esomeprazole 20 mg with bismuth potassium citrate 600 mg (equivalent to bismuth 220 mg), clarithromycin 500 mg, and amoxicillin 1000 mg was administered twice daily for 2 weeks. Forty‐four subjects were enrolled, 22 each in the vonoprazan (mean age, 34.5 years; men, 63.6%) and esomeprazole (mean age, 31.6 years; men, 59.1%) groups. Day 14 bismuth plasma pharmacokinetic parameters area under the plasma concentration–time curve during a dosing interval (geometric mean ratio, 1.07 [90% confidence interval, 0.82–1.40]) and maximum observed plasma concentration (geometric mean ratio, 1.30 [90% confidence interval, 0.94–1.81]) were similar between the treatment groups. At Day 42 follow‐up, 100% and 94.4% of subjects were H. pylori negative in the vonoprazan and esomeprazole groups, respectively. The incidence of treatment‐emergent adverse events was similar between the groups, with no serious adverse events. No new safety concerns were identified. In conclusion, vonoprazan had no significant effect on plasma bismuth exposure compared with esomeprazole.

Vonoprazan‐based therapies versus PPI‐based therapies in patients with H. pylori infection: Systematic review and meta‐analyses of randomized controlled trials

“…Finally, 27 studies were included in this metaanalysis. [19][20][21][22][23][24] Seventeen studies were two-arm RCTs, eight were three-arm RCTs, and two were four-arm RCTs. Fifteen studies were conducted in China, four in Japan, two in Thailand, two in Pakistan, one in China mainland, South Korea, and Taiwan, one in Korea, one in Singapore, and one in the United States and Europe.…”

“…Moreover, studies with vonoprazan-based quadruple therapy have been published only recently and thus were not included in the currently published meta-analyses. [19][20][21][22][23][24] Hence, a comprehensive comparative analyses of the efficacy and safety of VA dual therapy, VAC triple therapy, and vonoprazan-based bismuthcontaining quadruple therapy (QBQT), and vonoprazan-based versus PPI-based therapies with the consideration of amoxicillin dosing frequency and duration of therapy is needed to guide the treatment of patients with H. pylori infection.…”