title: Effect of Food on the Pharmacokinetics of the Investigational Aurora A Kinase Inhibitor Alisertib (MLN8237) in Patients with Advanced Solid Tumors.
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.
  NCT00962091.
authors.affiliation: Sarah Cannon Research Institute at HealthONE, Denver, CO, USA.
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Falchook
authors.affiliation: Clinical Pharmacology, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, 35 Landsdowne Street, Cambridge, MA, 02139, USA. xiaofei.zhou@takeda.com.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Clinical Pharmacology, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, 35 Landsdowne Street, Cambridge, MA, 02139, USA.
authors.forename: Karthik
authors.initials: K
authors.lastname: Venkatakrishnan
authors.affiliation: The University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.affiliation: Institute for Drug Development, Cancer Therapy and Research Center at University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Devalingam
authors.initials: D
authors.lastname: Mahalingam
authors.affiliation: University of California, Los Angeles, Santa Monica, CA, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Goldman
authors.affiliation: Clinical Pharmacology, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, 35 Landsdowne Street, Cambridge, MA, 02139, USA.
authors.forename: JungAh
authors.initials: J
authors.lastname: Jung
authors.affiliation: Infinity Pharmaceuticals, Cambridge, MA, 02139, USA.
authors.forename: Claudio Dansky
authors.initials: CD
authors.lastname: Ullmann
authors.affiliation: Clinical Pharmacology, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, 35 Landsdowne Street, Cambridge, MA, 02139, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Milch
authors.affiliation: University of California, Los Angeles, Santa Monica, CA, USA.
authors.forename: Lee S
authors.initials: LS
authors.lastname: Rosen
authors.affiliation: Institute for Drug Development, Cancer Therapy and Research Center at University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: Sarantopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors*; D001381:Azepines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000970:Antineoplastic Agents; D001381:Azepines; C550258:MLN 8237; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D064096:Aurora Kinase A