Keverprazan, a novel potassium‐competitive acid blocker: Multiple oral doses safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy subjects

Abstract

Keverprazan, a novel potassium‐competitive acid blocker, was approved for treating acid‐related diseases. This study aimed to analyze the safety, pharmacokinetics (PKs) and pharmacodynamics (PDs) of multiple doses of keverprazan. This was a randomized, positive‐/placebo‐controlled, phase Ic trial. Twenty‐six healthy adults were randomized to receive 20 mg/day keverprazan (n = 8), 40 mg/day keverprazan (n = 8), placebo (n = 6), or 20 mg/day vonoprazan (n = 4) for 7 days. Safety, PK and PD assessments were conducted. In the keverprazan, vonoprazan, and placebo groups, adverse events (AEs) were reported in nine (56.25%), two (50.00%), and three (50.00%) subjects, respectively. AEs were mild except a moderate abdominal pain leading to withdraw. No serious AEs occurred. The plasma concentration‐time profiles of keverprazan showed rapid absorption (median time to maximum plasma concentration of 1.25–3.0 h). The terminal half‐life was 6.23 and 7.01 h for keverprazan 20 and 40 mg groups on day 7. The maximum plasma concentration was 43.1 and 93.2 ng/mL, respectively. There was no apparent accumulation of keverprazan and the major metabolite after 7‐day administration. The intragastric pH greater than 5 holding time ratios (HTRs) over 24 h postdose increased from 79.1%, 84.4%, and 84.5% on day 1 to 99.0%, 97.4%, and 100.0% on day 7 in the vonoprazan 20 mg and keverprazan 20 and 40 mg groups, respectively. The intragastric pH greater than 5 HTR of keverprazan reached a plateau at 20 mg. Keverprazan is well‐tolerable. A steady‐state in exposure was generally reached after 7 days of treatment. A dose of 20 mg/day keverprazan can elicit a significant, stable, and long‐lasting gastric acid inhibition effect.

Potassium-competitive acid blockers and proton-pump inhibitors for healing of erosive esophagitis: a systematic review and network meta-analysis

“…It was designed based on the structure of Vonoprazan and has a high distribution in the stomach, providing better control of stomach acid. 73 A published clinical trial (ChiCTR2100050136) indicated that the percentages of time of intragastric pH greater than 4 [pH >4 holding-time ratio (HTR)] in Placebo, 20 mg Vonoprazan, and 20 mg Keverprazan groups were 5.6 ± 2.4%, 82.2 ± 12.6%, and 85.0 ± 3.0% on day 1, respectively, and the corresponding night-time HTR values were 3.9 ± 4.7%, 87.9 ± 15.7%, and 99.9 ± 0.0%, respectively. 67 Another phase I study showed that starting 4 h after administration, the pH levels in the 20–60 mg dose groups of Keverprazan were consistently higher than those in the 30 mg Lansoprazole group.…”

Comparative Efficacy and Safety of Potassium-Competitive Acid Blockers vs. Proton Pump Inhibitors for Peptic Ulcer with or without Helicobacter pylori Infection: A Systematic Review and Network Meta-Analysis

“…Keverprazan was approved in China in February 2023 [ 16 ]. Based on the structure of vonoprazan, keverprazan changes the pyridine into a benzene ring with an ether chain, altering its lipid solubility, enhancing its water solubility, and thereby changing its tissue distribution, particularly increasing its distribution in the target organ [ 78 ]. Consequently, it also achieves a good acid inhibition effect.…”