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Effect of Food on the Pharmacokinetics of the Investigational Aurora A Kinase Inhibitor Alisertib (MLN8237) in Patients with Advanced Solid Tumors.

Authors :
Falchook, Gerald S
Falchook, Gerald S
Source :
Drugs in R&D; vol 16, iss 1, 45-52; 1174-5886
Publication Year :
2016

Abstract

ObjectiveThis 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.MethodsFollowing 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.ResultsTwenty-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 AUCinf (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%).ConclusionsSystemic 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 identifierNCT00962091.

Details

Database :
OAIster
Journal :
Drugs in R&D; vol 16, iss 1, 45-52; 1174-5886
Notes :
Falchook, Gerald S, Zhou, Xiaofei, Venkatakrishnan, Karthik, Kurzrock, Razelle, Mahalingam, Devalingam, Goldman, Jonathan W, Jung, JungAh, Ullmann, Claudio Dansky, Milch, Catherine, Rosen, Lee S, Sarantopoulos, John
Publication Type :
Electronic Resource
Accession number :
edsoai.on1367521919
Document Type :
Electronic Resource