Evaluation of safety and pharmacokinetics of bismuth-containing quadruple therapy with either vonoprazan or lansoprazole for Helicobacter pylori eradication.

Abstract

Aims Helicobacter pylori (Hp) eradication plays a key role in the treatment and prevention of peptic ulcer diseases. Increasing clarithromycin resistance in Hp necessitates more effective treatments for eradication, such as bismuth‐containing quadruple therapy. We aimed to compare the safety and pharmacokinetics (PK) of bismuth between vonoprazan‐ and lansoprazole‐containing quadruple therapy in Hp‐positive subjects.MethodsIn this randomised, double‐blind, parallel‐group study, Hp‐positive subjects were randomised to receive vonoprazan‐ or lansoprazole‐containing quadruple therapy. Each subject received vonoprazan 20 mg or lansoprazole 30 mg combined with bismuth 220 mg, clarithromycin 500 mg and amoxicillin 1000 mg twice daily for 14 days. Blood sampling and urine collection for bismuth PK were conducted predose and up to 12 hours postdose at steady‐state. The PK parameters of bismuth were derived using a noncompartmental method and compared between treatments. An exploratory breath test for Hp was conducted at screening and at the follow‐up visit on day 42. Safety was assessed by adverse event monitoring, physical examinations, vital signs, 12‐lead electrocardiograms and clinical laboratory tests.ResultsA total of 30 subjects were randomised and 26 subjects completed the study (12 in the vonoprazan group and 14 in the lansoprazole group). The systemic exposure of bismuth in the 2 treatments was comparable (~5% difference). All subjects turned negative for Hp at the follow‐up visit. No significant difference in safety profiles was noted between the 2 treatments.ConclusionThe systemic exposure of bismuth was similar between vonoprazan‐ and lansoprazole‐containing quadruple therapy. Vonoprazan‐containing quadruple therapy was safe and well tolerated.