Faculty Collaboration Database

Effect of Food on the Pharmacokinetics of the Investigational Aurora A Kinase Inhibitor Alisertib (MLN8237) in Patients with Advanced Solid Tumors. Drugs R D 2016 Mar;16(1):45-52

Date

12/23/2015

Pubmed ID

26689566

Pubmed Central ID

PMC4767718

DOI

10.1007/s40268-015-0114-8

Scopus ID

2-s2.0-84959233070 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

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 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%).

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.

Author List

Falchook GS, Zhou X, Venkatakrishnan K, Kurzrock R, Mahalingam D, Goldman JW, Jung J, Ullmann CD, Milch C, Rosen LS, Sarantopoulos J

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antineoplastic Agents
Aurora Kinase A
Azepines
Cross-Over Studies
Dose-Response Relationship, Drug
Female
Food-Drug Interactions
Humans
Male
Maximum Tolerated Dose
Middle Aged
Neoplasms
Protein Kinase Inhibitors
Pyrimidines