Randomized clinical trial: A double‐blind, proof‐of‐concept, phase 2 study evaluating the efficacy and safety of vonoprazan 20 or 40 mg versus esomeprazole 40 mg in patients with symptomatic gastro‐esophageal reflux disease and partial response to a healing dose of a proton‐pump inhibitor
Jan Tack, Borislav Vladimirov, Ivo Horný, Chui Fung Chong, J Eisner, Richard Czerniak, Yohei Takanami
Abstract
Abstract Background Proton‐pump inhibitors (PPIs) are cornerstone treatments for gastro‐esophageal reflux disease (GERD); however, evidence suggests that most patients exhibit partial response to PPIs, suggesting the need for novel therapies that can provide an improved and sustained increase in gastric pH. Aims This study aimed to determine the effect of vonoprazan, a novel, orally active small‐molecule potassium‐competitive acid blocker, versus esomeprazole, a PPI, in preventing heartburn symptoms over a 4‐week treatment period in patients with GERD and a partial response to esomeprazole treatment. Methods This randomized, double‐blind, proof‐of‐concept, phase 2 clinical trial was conducted between 2016 and 2018 at 39 sites across Europe and designed to evaluate the efficacy and safety of vonoprazan 20 mg once daily (q.d.) and 40 mg q.d. versus esomeprazole 40 mg q.d. after 1:1:1 randomization of symptomatic patients with GERD and a partial response to a healing dose of esomeprazole. Results Overall, 256 eligible patients (female, 59.4%; mean age, 52.6 years) received vonoprazan 20 mg ( n = 85), vonoprazan 40 mg ( n = 85), or esomeprazole 40 mg ( n = 86); mean ( SD ) percentages of heartburn‐free 24‐h periods during double‐blind treatment were 36.7% (33.4%), 36.5% (35.6%), and 38.4% (34.8%), respectively, with no intergroup statistical significance. Vonoprazan exposure increased proportionally from the 20‐mg to 40‐mg dose (mean C max : 23.3 ng/ml to 47.1 ng/ml, respectively). Most treatment‐emergent adverse events were mild, with no deaths reported. Conclusions No statistically significant difference in efficacy and safety was observed among treatment groups, and vonoprazan was well tolerated. The trial is registered with the National Board of Health (EudraCT: 2015–001154‐14) database.