Xiaodong Wang
Tesaro, Inc, USA
Title: Relative bioavailability of rolapitant tablets compared with rolapitant capsules and the effect of food on rolapitant pharmacokinetics in healthy subjects
Biography
Biography: Xiaodong Wang
Abstract
Rolapitant (VARUBI®/VARUBY®), a selective and long-acting neurokinin-1 receptor antagonist, is approved in oral tablet formulation for the prevention of delayed chemotherapy-induced nausea and vomiting in adults in the US and EU. These studies assessed the relative bioavailability of rolapitant tablet formulations compared with rolapitant capsules used in Phase 3 studies and the effect of food on rolapitant tablet pharmacokinetics (PK) in healthy subjects. An open-label, single-dose, parallel-group study was conducted in 84 healthy subjects to evaluate the relative bioavailability of two test formulations of rolapitant (high shear tablets and fluid bed tablets; each 2 x 90 mg) versus the reference capsules (4 x 45 mg). A second open-label, single-dose, parallel-group study was conducted in 80 healthy subjects to assess the effect of a high-fat meal on rolapitant PK (2 x 90 mg the intended commercial formulation of high shear tablets).
Bioavailability was similar for the test tablets verses capsules. For tablets versus the capsules, the 90% confidence intervals (CI) for the geometric mean Cmax and AUC ratios were contained within the equivalence limits of 0.80 to 1.25. For the food effect assessment, the 90% CIs for the geometric mean AUC ratios (fed/fasted) were within 0.8 to 1.25.
These data suggested that the bioavailability of rolapitant following administration as 2 x 90 mg high shear tablets and 2 x 90 mg fluid bed tablets was comparable to that following administration of 4 x 45 mg of the reference capsules. In addition, rolapitant can be taken without regard to meals