Abstract

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: An open-label, single-sequence three-period (period 1, single dose of COC; period 2, pradigastat 100 mg × 3 days followed by 40 mg × 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 (CI) of geometric mean ratios for EE exposure (AUC and C_max) were all within the range of 0.80 – 1.25. The AUC_∞, AUC_last, and C_max of LVG were slightly increased in the presence of pradigastat, the geometric mean ratios (90% CI) 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 the magnitude of Levora-28^® exposure. Therefore, dose adjustment is not required for Levora-28^® when co-administered with pradigastat.

Author Details

Authors

• Jin Chen¹
• Suraj Bhansali¹
• Srikanth Neelakantham²
• Craig Trusley³
• Tapan Majumdar¹
• Sam Rebello¹
• Gangadhar Sunkara¹
• Charles Meyers³

Departments

• ¹ Novartis Institutes for BioMedical Research, East Hanover, NJ, USA,
• ² Novartis Healthcare Private Ltd., Hyderabad, India, and
• ³ Novartis Institutes for BioMedical Research, Cambridge, MA, USA

Address

Jin Chen, PhD
Clinical PK/PD, Novartis Institutes for BioMedical Research
One Health Plaza, 438-3406, East Hanover, NJ 07936-1080, USA
Email: [email protected]

Citation