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

Gerald S. Falchook, Xiaofei Zhou, Karthik Venkatakrishnan, Razelle Kurzrock, Devalingam Mahalingam, Jonathan W. Goldman, Jung Ah Jung, Claudio Dansky Ullmann, Catherine Milch, Lee S. Rosen, John Sarantopoulos

Research output: Contribution to journalArticle

6 Scopus 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 tmax 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 Cmax 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.

Original languageEnglish (US)
Pages (from-to)45-52
Number of pages8
JournalDrugs in R and D
Volume16
Issue number1
DOIs
StatePublished - Mar 1 2016

ASJC Scopus subject areas

  • Pharmacology

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