Randomized, Open-Label, Crossover Studies Evaluating the Effect of Food and Liquid Formulation on the Pharmacokinetics of the Novel Focal Adhesion Kinase (FAK) Inhibitor BI 853520

BI 853520 is a potent inhibitor of focal adhesion kinase and is currently under clinical development for the treatment of non-hematological malignancies. The objective of this study was to evaluate the effect of food and liquid dispersion on the pharmacokinetics of BI 853520 in two open-label, crossover substudies. Sixteen patients with advanced solid tumors were enrolled in each substudy. The order of administration was randomized, and pharmacokinetic samples were collected for 48 h after administration of a 200 mg dose of BI 853520. 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 tz [ $${\text{AUC}}_{{0{-}t_{\text{z}} }}$$ ] and observed area under the plasma concentration–time curve extrapolated from time zero to infinity [AUC0–∞,obs]) and maximum plasma concentration (Cmax) did not cross the 80–125% (bioequivalence) boundaries. Adjusted 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 $${\text{AUC}}_{{0{-}t_{\text{z}} }}$$ , AUC0–∞,obs, and Cmax, 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 BI 853520 as a liquid dispersion did not strongly affect $${\text{AUC}}_{{0{-}t_{\text{z}} }}$$ , AUC0–∞,obs, or Cmax, 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. These studies demonstrate that BI 853520 can be given with no food restrictions, and as a liquid dispersion, without strongly impacting pharmacokinetics. These pharmacokinetic properties may help make BI 853520 dosing more convenient and flexible, improving treatment compliance. ClinicalTrials.gov identifier: NCT01335269.

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