Pharmacokinetics, Pharmacodynamics and Food-effect of Single Oral Dose of Tegoprazan (CJ-12420), a Novel Potassium-Competitive Acid Blocker (P-CAB) in Healthy Male Subjects

Background/Aaims Tegoprazan (CJ‐12420) is a novel P‐CAB for the treatment of acid‐related diseases. In the previous studies, most Proton Pump Inhibitors (PPIs) except dexlansoprazole are indicated to be taken before meal because Cmax and AUC decreased by half when administered after meals. This study aimed to investigate the food effect on the pharmacokinetics and pharmacodynamics of tegoprazan. Methods A phase I, randomized, 2‐period crossover clinical trial was conducted in 24 healthy subjects. Subjects were received a single dose of 200 mg tegoprazan under fasting or fed condition. The plasma concentrations were determined using validated LC‐MS/MS method. Pharmacokinetics were evaluated by noncompartmental method. A gastric pH was measured by a nasogastric pH monitoring system. Results On pharmacokinetic evaluation, the mean plasma tegoprazan concentration increased slowly and peak concentration was decreased under fed condition than under fasting condition. However, AUC and half‐life of tegoprazan were similar between fed and fasting conditions. The 90 % confidence intervals of the ratios of tegoprazan AUClast in the fed and fasting conditions were within the limits for bioequivalence (0.8687 ‐ 0.9358). On pharmacodynamic evaluation, mean percentage time for gastric pH > 4 (over 24 hours) under fed and fasting conditions were 86% and 74%. A single dose of tegoprazan 200 mg appeared to be safe and well tolerated. Conclusions In this study, Cmax of tegoprazan was decreased in fed state while AUC was in bioequivalence range showing similar trend in dexalansoprazole's food effect study. It is reported that efficacy of PPIs are dependent on AUC, and tegoprazan and PPI share same therapeutic target. Therefore, it is assumed that efficacy of tegoprazan is also correlated with AUC rather than Cmax. Based on the equivalent AUC and PD parameters between fasting and fed condition, efficacy of tegoprazan is supposed to be independent of food intake.