Keverprazan, a novel potassium-competitive acid blocker: Single ascending dose safety, tolerability, pharmacokinetics, pharmacodynamics and food effect in healthy subjects

• DOI: 10.1016/j.ejps.2023.106578
• Publication Date: 2023-09-04T04:58:25Z
• Authors: Sufeng Zhou; Lijun Xie; Chen Zhou; Yuqing Zhao; Lu Wang; Sijia Ding; Juan Chen; Bei Zhu; Mei Su; Feng Shao
• Keywords: Pharmacodynamics; Tolerability

Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related diseases. To evaluate safety, pharmacokinetics, pharmacodynamics, and food effect single oral doses keverprazan in healthy Chinese subjects. In dose-escalated phase Ia trial, first 8 subjects received 5 mg, others successively entered 10 20 40 60 mg groups were randomized to receive (n=8), lansoprazole (LSZ) 30 (n=2) or placebo each dose group. The Ib study randomly enrolled fasting-fed (n=7) fed-fasting evaluating keverprazan. Twenty (35.71%) adverse events (AEs) occurred Ia, including 13 (32.50%), 3 (37.50%), 4 (50.00%) AEs keverprazan, placebo, LSZ groups, respectively. Four (28.57%) Phase Ib. Tmax was 1.25-1.75 h. Cmax AUC increased with dose, t1/2, CL/F 6.00-7.17 h, 88.8-198 L/h, intragastric pH >5 holding-time ratio (HTR) but reached ceiling at mg. 5-60 HTRs during 24 h 57.1%±26.4%, 7.9%±8.1%, 26.2%±22.8%, 80.2%±8.8%, 88.1%±8.6%, 93.0%±1.7%, geometric mean ratios (90% CI) AUC0-∞ plasma under fed vs. fasting state 126.8% (109.0%-147.5%) 134.9% (123.8%-146.9%). tolerable, provides significant stable lasting inhibition efficacy acidity