Effect of Food on the Pharmacokinetics, Pharmacodynamics, and Safety of Zastaprazan, a Potassium‐Competitive Acid Blocker, in Healthy Participants

ABSTRACT Zastaprazan (JP‐1366) is a novel potassium‐competitive acid blocker characterized by rapid onset and sustained acid suppression. This study aimed to evaluate the effect of food on the pharmacokinetics (PK), pharmacodynamics (PD), and safety of zastaprazan in healthy participants. In this randomized, open‐label, two‐period crossover phase 1 study, 24 healthy participants received a single oral dose of zastaprazan 20 mg under fasted and fed conditions. PK parameters were evaluated using noncompartmental analysis, and PD effects were assessed through continuous intragastric pH monitoring. Under fed conditions, peak exposure (Cmax) decreased (geometric mean ratio [GMR], 0.6997; 90% confidence interval [CI], 0.6292–0.7781), whereas systemic exposure (AUC last ) increased (GMR, 1.3783; 90% CI, 1.2688–1.4973), accompanied by a delayed T max . Despite these PK differences, PD outcomes were comparable between fed and fasted conditions. The percentage of time with intragastric pH ≥ 4 over 24 h was similar under fed and fasted conditions (70.01% vs. 69.19%), with no meaningful differences observed in other pH‐based parameters. Zastaprazan was well tolerated, and no clinically significant safety concerns were identified. Food altered the rate and extent of zastaprazan absorption but did not affect its PD response. These findings indicate that food‐related PK changes do not meaningfully affect PD outcomes and support the administration of zastaprazan without regard to meals. This flexibility may enhance its clinical utility as an acid‐suppressive therapy. Trial Registration: The study was registered at ClinicalTrials.gov (NCT05712681)