Evaluation of food effect on the oral bioavailability of pradigastat, a diacylglycerol acyltransferase 1 inhibitor.

Abstract

Pradigastat, a diacylglycerol acyltransferase 1 inhibitor, is being developed for the treatment of familial chylomicronemia syndrome. The results of two studies that evaluated the effect of food on the oral bioavailability of pradigastat using randomized, open-label, parallel group designs in healthy subjects (n=24/treatment/study) are presented. In study 1, a single dose of 20 mg pradigastat was administered under the fasted condition or with a high-fat meal. In study 2, a single dose of 40 mg pradigastat was administered under the fasted condition or with a low- or high-fat meal. At the 20 mg dose, the pradigastat Cmax and AUClast increased by 38% and 41%, respectively, with a high-fat meal. When 40 mg pradigastat was administered with a low-fat meal, the Cmax and AUClast increased by 8% and 18%, respectively, whereas with a high-fat meal the increase was 20% and 18%, respectively. The population pharmacokinetic analysis with the pooled data from 13 studies indicated that administration of pradigastat with a meal resulted in an increase of 30% in both the Cmax and AUC parameters. Based on these results, food overall increased pradigastat exposure in the range of less than 40%, which is not considered clinically significant. Both 20 and 40 mg doses of pradigastat were well tolerated under fasted or fed conditions.

DOI: 10.1002/bdd.1958

Cite this paper

@article{Ayalasomayajula2015EvaluationOF, title={Evaluation of food effect on the oral bioavailability of pradigastat, a diacylglycerol acyltransferase 1 inhibitor.}, author={Surya Ayalasomayajula and C. D. Meyers and Jing Yu and Mark Kagan and Ralph Matott and Parasar Pal and Tapan K Majumdar and Zhenzhong Su and Anne Crissey and Sam Rebello and Gangadhar Sunkara and Jin Chen}, journal={Biopharmaceutics & drug disposition}, year={2015}, volume={36 7}, pages={452-61} }