Randomized, Open-Label, Crossover Studies Evaluating the Effect of Food and Liquid Formulation on the Pharmacokinetics of the Novel Focal Adhesion Kinase (FAK) Inhibitor BI853520

BackgroundBI 853520 is a potent inhibitor of focal adhesion kinase and is currently under clinical development for the treatment of non-hematological malignancies.ObjectiveThe objective of this study was to evaluate the effect of food and liquid dispersion on the pharmacokinetics of BI853520 in two open-label, crossover substudies.Patients and MethodsSixteen patients with advanced solid tumors were enrolled in each substudy. The order of administration was randomized, and pharmacokinetic samples were collected for 48h after administration of a 200mg dose of BI853520. Lack of effect would be demonstrated if the 90% confidence interval (CI) of the ratio of the adjusted geometric mean (GMR) of the area under the plasma curve (area under the plasma concentration-time curve from time zero to the last quantifiable concentration at t(z) [AUC0-tz] and observed area under the plasma concentration-time curve extrapolated from time zero to infinity [AUC(0-,obs)]) and maximum plasma concentration (C-max) did not cross the 80-125% (bioequivalence) boundaries.ResultsAdjusted GMRs (90% CIs) for the fed versus fasted state were 92.46% (74.24-115.16), 98.17% (78.53-122.74), and 87.34% (71.04-107.38) for AUC0-tz, AUC(0-,obs), and C-max, respectively. Although the 90% CIs were not within bioequivalence limits for the food-effect study, the limited reductions in these pharmacokinetic parameters after administration with a high-fat meal are unlikely to be clinically relevant. Compared with a tablet, administration of BI853520 as a liquid dispersion did not strongly affect AUC0-tz, AUC(0-,obs), or C-max, resulting in adjusted GMRs (90% CIs) of 1.00 (0.92-1.09), 0.98 (0.90-1.07), and 0.93 (0.86-1.01), respectively.ConclusionsThese studies demonstrate that BI853520 can be given with no food restrictions, and as a liquid dispersion, without strongly impacting pharmacokinetics. These pharmacokinetic properties may help make BI853520 dosing more convenient and flexible, improving treatment compliance.Clinical trials registrationClinicalTrials.gov identifier: NCT01335269.