Effect of Food on the Pharmacokinetics of the Investigational Aurora A Kinase Inhibitor Alisertib (MLN8237) in Patients with Advanced Solid Tumors
Objective This study was conducted to characterize the effects of food on single-dose pharmacokinetics (PK) of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in patients with advanced solid tumors. Methods Following overnight fasting for 10 h, a single 50 mg enteric-coated tablet...
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Veröffentlicht in: | Drugs in R&D 2016-03, Vol.16 (1), p.45-52 |
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Sprache: | eng |
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Zusammenfassung: | Objective
This study was conducted to characterize the effects of food on single-dose pharmacokinetics (PK) of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in patients with advanced solid tumors.
Methods
Following overnight fasting for 10 h, a single 50 mg enteric-coated tablet (ECT) of alisertib was administered under either fasted (alisertib with 240 mL of water) or fed (high-fat meal consumed 30 min before receiving alisertib with 240 mL of water) conditions using a two-cycle, two-way crossover design. Patients on both arms were not allowed food for 4 h post-dose. Water was allowed as desired, except for 1 h before and after alisertib administration.
Results
Twenty-four patients were enrolled and 14 patients were PK-evaluable (ten patients were not PK-evaluable due to insufficient data). Following a single oral dose of alisertib, median
t
max
was 6 h and 3 h under fed and fasted conditions, respectively. The geometric mean ratio of AUC
inf
(fed- vs. fasted-state dosing) was 0.94 [90 % confidence interval (CI) 0.68–1.32]. The geometric mean
C
max
under fed conditions was 84 % of that under fasted conditions (90 % CI 66–106). Alisertib was generally well-tolerated; most common drug-related grade 3/4 adverse events included neutropenia (50 %), leukopenia (38 %), and thrombocytopenia (21 %).
Conclusions
Systemic exposures achieved following a single 50 mg dose of alisertib administered as an ECT formulation after a high-fat meal are similar to those observed in the fasted state. Alisertib 50 mg ECT can be administered without regard for food.
ClinicalTrials.gov Identifier
NCT00962091. |
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ISSN: | 1174-5886 1179-6901 |
DOI: | 10.1007/s40268-015-0114-8 |