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 (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.