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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.
- Source :
-
Targeted oncology [Target Oncol] 2019 Feb; Vol. 14 (1), pp. 67-74. - Publication Year :
- 2019
-
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.<br />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.<br />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 t <subscript>z</subscript> [[Formula: see text]] and observed area under the plasma concentration-time curve extrapolated from time zero to infinity [AUC <subscript>0-∞,obs</subscript> ]) and maximum plasma concentration (C <subscript>max</subscript> ) did not cross the 80-125% (bioequivalence) boundaries.<br />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], AUC <subscript>0-∞,obs</subscript> , and C <subscript>max</subscript> , 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], AUC <subscript>0-∞,obs</subscript> , or C <subscript>max</subscript> , 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.<br />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.<br />Clinical Trials Registration: ClinicalTrials.gov identifier: NCT01335269.
- Subjects :
- Administration, Oral
Adult
Aged
Aged, 80 and over
Area Under Curve
Capsules
Cross-Over Studies
Female
Humans
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Metastasis
Neoplasms epidemiology
Neoplasms pathology
Prognosis
Therapeutic Equivalency
Tissue Distribution
Focal Adhesion Kinase 1 antagonists & inhibitors
Food-Drug Interactions
Neoplasms drug therapy
Protein Kinase Inhibitors pharmacokinetics
Protein Kinase Inhibitors therapeutic use
Tablets administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1776-260X
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Targeted oncology
- Publication Type :
- Academic Journal
- Accession number :
- 30742245
- Full Text :
- https://doi.org/10.1007/s11523-018-00618-0