Effect of Pradigastat, a Diacylglycerol Acyltransferase 1 Inhibitor, on the Pharmacokinetics of a Combination Oral Contraceptive in Healthy Female Subjects

Objective: We evaluated the potential pharmacokinetic interaction between pradigastat, a potent and selective diacylglycerol acyltransferase 1 inhibitor, and Levora-28®, a combination oral contraceptive (COC) containing 30 μg ethinylestradiol (EE) and 150 μg levonorgestrel (LVG). Methods: A, in an open-label, single sequence, three-period (Period 1, single dose of COC; Period 2, pradigastat 100 mg x 3 days followed by 40 mg x 7 days; and Period 3, both pradigastat 40 mg and a single dose of COC) study involving 24 healthy female subjects of childbearing potential was conducted. Results: The pharmacokinetic parameters of EE were similar when administered alone or in combination with pradigastat, as the 90% confidence interval of geometric mean ratios for EE exposure (AUC and Cmax) were all within the range of 0.80 to 1.25. The AUCinf, AUClast, and Cmax of LVG were slightly increased in the presence of pradigastat, the geometric mean ratios (90% confidence interval) were 1.25 (1.16, 1.35), 1.24 (1.15, 1.34), and 1.16 (1.06, 1.27), respectively. Conclusions: Pradigastat did not elicit clinically relevant changes in Tthe magnitude of these changes Levora-28® exposurewas not considered clinically relevant. Therefore, dose adjustment is not required for Levora-28® when co-administered with pradigastat