Effect of pradigastat, a diacylglycerol acyltransferase 1 inhibitor, on the pharmacokinetics of a combination oral contraceptive in healthy female subjects (original) (raw)

2015, International Journal of Clinical Pharmacology and Therapeutics

Pradigastat, a novel diacylglycerol acyltransferase 1 inhibitor, has been studied in familial chylomicronemia syndrome. To evaluate the effects of supra-therapeutic concentrations of pradigastat on the QTc interval, two studies were conducted. The first study assessed the safety, tolerability and pharmacokinetics of single escalating intravenous doses of pradigastat (10, 30, 100 and 115mg over 60 minutes) in healthy adults. Single IV doses were safe, well tolerated, and at the higher doses resulted in supra-therapeutic pradigastat exposure. The second was a parallel, 3-arm thorough QTc study where healthy male subjects were randomized to pradigastat (115mg IV), moxifloxacin (400mg oral, positive control), or placebo. Following IV administration, pradigastat exposure peaked at 4 times the therapeutic concentration, and did not prolong the baseline adjusted and placebo corrected QTc interval. During the 60 minute pradigastat infusion, a number of infusion reactions and a small mean decrease in QTc were observed. Both effects disappeared when the infusion was stopped, suggesting that an infusate excipient may have been responsible. As expected, moxifloxacin This article is protected by copyright. All rights reserved. significantly increased the QTc interval at multiple time points, confirming the study's sensitivity to detect a true positive effect. Pradigastat is therefore unlikely to increase the risk of dysrhythmias associated with QTc prolongation in humans.