Effect of Food on the Pharmacokinetics, Pharmacodynamics, and Safety of Zastaprazan, a Potassium-Competitive Acid Blocker, in Healthy Participants.
- 1Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
- 2Department of Pediatric Surgery, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
- 3Onconic Therapeutics, Seoul, Korea.
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 (AUClast) increased (GMR, 1.3783; 90% CI, 1.2688-1.4973), accompanied by a delayed Tmax. 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).
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BibTeX
@article{lee2026effect,
title = {{Effect of Food on the Pharmacokinetics, Pharmacodynamics, and Safety of Zastaprazan, a Potassium-Competitive Acid Blocker, in Healthy Participants.}},
author = {Hyoeun Lee and Seok-Kyu Yoon and Soo-Min Jung and Moon Hee Lee and Shi-Hyang Lee and Eun Na Kim and John Kim and Hyunju Cha and Kyun-Seop Bae and Hyeong-Seok Lim},
journal = {Clinical and translational science},
year = {2026},
month = oct,
doi = {10.1111/cts.70757},
url = {https://europepmc.org/article/MED/42963322},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Effect of Food on the Pharmacokinetics, Pharmacodynamics, and Safety of Zastaprazan, a Potassium-Competitive Acid Blocker, in Healthy Participants.
AU - Hyoeun Lee
AU - Seok-Kyu Yoon
AU - Soo-Min Jung
AU - Moon Hee Lee
AU - Shi-Hyang Lee
AU - Eun Na Kim
AU - John Kim
AU - Hyunju Cha
AU - Kyun-Seop Bae
AU - Hyeong-Seok Lim
PY - 2026
DA - 2026/10/30
JO - Clinical and translational science
DO - 10.1111/cts.70757
UR - https://europepmc.org/article/MED/42963322
AB - 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 (AUClast) increased (GMR, 1.3783; 90% CI, 1.2688-1.4973), accompanied by a delayed Tmax. 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).
SN - 1752-8054
SN - 1752-8062
ER -