2. Academic Validation
  3. 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

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

  • Target Oncol. 2019 Feb;14(1):67-74. doi: 10.1007/s11523-018-00618-0.
Remy B Verheijen 1,  Diane A J van der Biessen 2,  Sebastien J Hotte 3,  Lillian L Siu 4,  Anna Spreafico 4,  Maja J A de Jonge 5,  Linda C Pronk 6,  Filip Y F L De Vos 7,  David Schnell 8,  Hal W Hirte 3,  Neeltje Steeghs 1,  Martijn P Lolkema 9 10
Affiliations

Affiliations

  • 1 Department of Medical Oncology and Clinical Pharmacology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
  • 2 Department of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
  • 3 Division of Medical Oncology, Juravinski Cancer Centre, 699 Concession Street, Hamilton, ON, L8V 5C2, Canada.
  • 4 Division of Medical Oncology and Haematology, Princess Margaret Cancer Centre, 700 University Avenue, 7th Floor, Toronto, ON, M5G 1Z5, Canada.
  • 5 Department of Internal Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
  • 6 Clinical Development Oncology, Boehringer Ingelheim España S.A., Parque Empresarial Alvento, Via de los Poblados, 1 planta baja-Edif. B ofic. A y C, 28033, Madrid, Spain.
  • 7 Department of Medical Oncology, University Medical Center Utrecht Cancer Center, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
  • 8 Department of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH and Co. KG, Birkendorfer Str. 65, 88397, Biberach, Germany.
  • 9 Department of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands. m.lolkema@erasmusmc.nl.
  • 10 Department of Internal Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands. m.lolkema@erasmusmc.nl.
PMID: 30742245 DOI: 10.1007/s11523-018-00618-0
Abstract

Background: BI 853520 is a potent inhibitor of focal adhesion kinase and is currently under clinical development for the treatment of non-hematological malignancies.

Objective: 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.

Patients and methods: 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 [[Formula: see text]] 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.

Results: 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 [Formula: see text], 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 [Formula: see text], 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.

Conclusions: 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.

Clinical trials registration: ClinicalTrials.gov identifier: NCT01335269.

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