Nozaki, Sachiko, Meyers, Charles, Pal, Parasar, Joyson, Andrew, Lin, Tsu-Han, Majumdar, Tapan, Rebello, Sam, Sunkara, Gangadhar and Chen, Jin (2015) Effect of renal impairment on the pharmacokinetics of pradigastat, a novel diacylglycerol acyltransferase 1 (DGAT1) inhibitor. Clinical Pharmacokinetics, 54 (7). pp. 751-760. ISSN 0312-5963

Abstract

Background and objectives: Pradigastat, a diacylglycerol acytransferase 1 inhibitor, is being developed for the treatment of familial chylomicronemia syndrome. The primary objective of this clinical study is to evaluate the effect of renal impairment on the pharmacokinetics of pradigastat.
Methods: In an open-label, parallel-group study, the single-dose (40 mg) pharmacokinetics of pradigastat was evaluated in patients with mild (n=9), moderate (n=10) and severe renal impairment (n=9) compared with matched healthy subjects (n=28).. The protein binding and urinary excretion of pradigastat was also assessed in this study.
Results: In patients with mild and moderate renal impairment the geometric means Cmax and AUCinf of pradigastat were similar as compared to healthy subjects. In severe renal impairment patients, the geometric means of Cmax and AUCinf increased by 40% (90% CI: 0.92, 2.14) and 18% (90% CI: 0.68, 2.05), respectively. There was no significant correlation between renal function (measured by CLcr) and Cmax or AUCinf. Protein binding values were >99% and the urinary excretion of pradigastat was minimal in all subjects. There were no severe adverse events in the study and mild transient diarrhea was the most common adverse event. The safety profile was similar between patients with renal impairment and healthy subjects.
Conclusion: There is no change in the pharmacokinetics of pradigastat in patients with mild and moderate renal impairment. In patients with severe renal impairment, the mean exposure Cmax and AUCinf of pradigastat was increased by 40% and 18%, respectively.

Item Type:	Article
Keywords:	Pradigastat, renal impairment, pharmacokinetics, DGAT1, protein binding
Date Deposited:	14 Oct 2016 00:45
Last Modified:	14 Oct 2016 00:45
URI:	https://oak.novartis.com/id/eprint/22453