Effect of food on the single-dose pharmacokinetics and tolerability of savolitinib in Chinese healthy volunteers.

ABSTRACT

The aim of this study was to investigate the effect of a high-fat and high-calorie meal on the single-dose pharmacokinetics (PK) and tolerability of savolitinib. The study included two phases safety run-in phase and food effect assessment phase. In the safety run-in phase, 9 healthy male volunteers were divided into three groups to be administered a single oral dose of savolitinib tablets at 200, 400, and 600 mg. In the food effect assessment phase, 16 healthy male volunteers received a single 600 mg dose of savolitinib tablets following an overnight fast or a high-fat and high-calorie breakfast prior to dosing. Blood samples were collected at the designated time points for pharmacokinetic analysis. Safety and tolerability were assessed throughout the study by clinical assessments and adverse events (AEs). A total of 25 healthy male volunteers were enrolled in the study, including 9 in the safety run-in phase and 16 in the food effect assessment phase. In the food effect assessment phase, the geometric mean ratios (90% confidence interval) for savolitinib dosed under the fed condition compared with that dosed under the fasting condition were 102.7% (84.9%, 124.2%) and 117.1% (103.9%, 131.9%) for Cmax and AUC0-inf of savolitinib, respectively. The Tmax was delayed significantly (p = 0.023) under fed condition. The most common AEs possibly related to the study drug were dizziness, nausea, and emesis. The study indicated that a high-fat and high-calorie meal has no clinically relevant impact on the PK and bioavailability of savolitinib in healthy male volunteers.