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.
Administration, Oral
Adult
Aged
Aged, 80 and over
Area Under Curve
Capsules
Cross-Over Studies
Female
Focal Adhesion Kinase 1
/ antagonists & inhibitors
Food-Drug Interactions
Humans
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Metastasis
Neoplasms
/ drug therapy
Prognosis
Protein Kinase Inhibitors
/ pharmacokinetics
Tablets
/ administration & dosage
Therapeutic Equivalency
Tissue Distribution
Journal
Targeted oncology
ISSN: 1776-260X
Titre abrégé: Target Oncol
Pays: France
ID NLM: 101270595
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
pubmed:
12
2
2019
medline:
7
1
2020
entrez:
12
2
2019
Statut:
ppublish
Résumé
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 t 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 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.
Sections du résumé
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 t
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
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.
Identifiants
pubmed: 30742245
doi: 10.1007/s11523-018-00618-0
pii: 10.1007/s11523-018-00618-0
pmc: PMC6407750
doi:
Substances chimiques
Capsules
0
Protein Kinase Inhibitors
0
Tablets
0
Focal Adhesion Kinase 1
EC 2.7.10.2
PTK2 protein, human
EC 2.7.10.2
Banques de données
ClinicalTrials.gov
['NCT01335269']
Types de publication
Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
67-74Références
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