Randomised trial of acid inhibition by vonoprazan 10/20 mg once daily vs rabeprazole 10/20 mg twice daily in healthy Japanese volunteers (SAMURAI pH study).

Abstract

Vonoprazan (V), a potassium-competitive acid blocker, has a more durable acid-inhibitory effect as compared with standard-dose proton pump inhibitors (PPIs) but has not been compared with 2-4 times higher daily PPI doses administered in two divided doses. To evaluate the acid-inhibitory effect of V 10/20mg once-daily (OD; V10/V20) vs rabeprazole (R) 10/20mg twice-daily (BID; R20/R40) in healthy Japanese volunteers. This multicentre, randomised, open-label, two-period, crossover study compared V10 or V20 vs R20, or V20 vs R40 using three cohorts of 10 healthy Japanese adults. Within each cohort, subjects were randomised to receive V or R for 7days and, following a washout period≥7days, the other treatment for 7days. On day 6 of each period, 24-hours multichannel gastric impedance-pH monitoring was performed. Percent times pH≥3, ≥4 and≥5 (pH 3, 4 and 5 holding time ratios [HTRs]) in 24hours were evaluated as primary pharmacodynamic endpoints. Acid-inhibitory effect (24-hours pH 3 HTR) of V20 was greater than those of R20 (91.0% vs 65.3%; P=.0049) and R40 (98.5% vs 85.9%; P=.0073). Similar results were obtained for 24-hours pH 4 and 5 HTRs. V20 also achieved greater nocturnal pH 4 (91.5% vs 73.2%; P=.0319) and 5 HTRs (78.8% vs 62.2%; P=.0325) as compared with R40. One subject (20%) developed diarrhoea while receiving R40 which was considered treatment-related. Compared with 2-4 times the standard daily dose of R, V20 exerts a more potent and durable acid-inhibitory effect. Trial identifier: UMIN000022198 (www.umin.ac.jp/ctr/index.htm).