title: The effect of food on the pharmacokinetics of tivozanib hydrochloride.
abstract: Tivozanib hydrochloride (tivozanib) is a potent, selective tyrosine kinase inhibitor of the vascular endothelial growth factor receptors 1, 2, and 3, with a long half-life. This Phase I study evaluated the effect of food on tivozanib pharmacokinetics (PK). A single oral dose of tivozanib was administered to healthy subjects in a fasted/fed and a fed/fasted state. Thirty subjects enrolled; 29 completed the study. Maximum concentration (Cmax ) in the fed state was lower than in the fasted state (geometric means, 14.1 and 18.1 ng/mL). The geometric mean ratio (90% confidence interval) (fed/fasted states) for Cmax was 77.5% (72.9-82.4%), indicating a food effect on Cmax . There was no difference in tivozanib area under the curve to infinity (AUC0-∞ ) between states (geometric means, 2,377 and 2,198 ng h/mL). Geometric mean ratios also indicated no food effect on tivozanib AUC0-∞ . Other PK parameters were similar between states. The most commonly reported adverse events affected the gastrointestinal system and were mild in intensity. There were no clinically significant changes in other safety measures. In conclusion, food does not have an impact on the AUC0-∞ of tivozanib but does decrease Cmax approximately 23%, suggesting that this agent can be dosed with or without food.
authors.affiliation: AVEO Oncology, Cambridge, MA, USA.
authors.forename: Monette M
authors.initials: MM
authors.lastname: Cotreau
authors.affiliation: AVEO Oncology, Cambridge, MA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Massmanian
authors.affiliation: AVEO Oncology, Cambridge, MA, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Strahs
authors.affiliation: AVEO Oncology, Cambridge, MA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Slichenmyer
authors.affiliation: AVEO Oncology, Cambridge, MA, USA.
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Vargo
keywords: food; pharmacokinetics; renal cell cancer; solid tumors; tivozanib hydrochloride