title: Effect of Food on the Pharmacokinetics of Olaparib after Oral Dosing of the Capsule Formulation in Patients with Advanced Solid Tumors.
abstract: BACKGROUND
  The oral, potent poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, is well tolerated at doses of ≤400 mg twice daily (BID) (administered as capsules), and has shown efficacy in patients with advanced BRCA-mutated ovarian and breast cancer.
  
  
  METHODS
  This Phase I, open-label, randomized trial investigates the effect of food on the pharmacokinetics of olaparib in patients with refractory/resistant advanced solid tumors. In Part A, a three-period crossover study, patients received a single oral dose of olaparib 400 mg (8 × 50 mg capsules) in three prandial states: fasted, a high-fat meal or a standard meal (with a 5-14 day washout). Blood samples for pharmacokinetic (PK) assessments were taken pre-dose and up to 72 h post-dose. After completing Part A, patients could enter Part B, where they would receive olaparib 400 mg BID.
  
  
  RESULTS
  32 patients were randomized; 31 contributed to the PK statistical analysis and entered Part B. The presence of food slowed the rate of absorption (time to maximal plasma concentration [t max] was delayed by ~2 h). Maximum plasma concentration (C max) was increased by 10% following a standard meal and was unchanged with a high-fat meal (ratio of geometric means [90% confidence interval (CI)]: 1.10 [1.02-1.20] for standard and 1.00 [0.92-1.09] for high-fat meal). The extent of olaparib absorption (AUC) was increased by ~20% in the fed state (ratio of geometric means: 1.21 [1.10-1.33] for standard and 1.19 [1.08-1.31] for high-fat meal).
  
  
  CONCLUSIONS
  The presence of food decreased the rate and increased the extent of absorption of olaparib following oral dosing of the capsule formulation. However, the effects of food on olaparib PK were not deemed clinically important, according to predefined criteria. Safety data were consistent with the known safety profile of olaparib.
  
  
  BACKGROUND
  AstraZeneca.
authors.affiliation: Phase I, Early Clinical Trials Unit, Department of Oncology, University Hospital Antwerp, Wijlrijkstraat 10, 2650, Edegem, Belgium, christian.rolfo@uza.be.
authors.forename: Christian
authors.initials: C
authors.lastname: Rolfo
authors.forename: Helen
authors.initials: H
authors.lastname: Swaisland
authors.forename: Karin
authors.initials: K
authors.lastname: Leunen
authors.forename: Annemie
authors.initials: A
authors.lastname: Rutten
authors.forename: Patricia
authors.initials: P
authors.lastname: Soetekouw
authors.forename: Sarah
authors.initials: S
authors.lastname: Slater
authors.forename: Henk M W
authors.initials: HM
authors.lastname: Verheul
authors.forename: Anitra
authors.initials: A
authors.lastname: Fielding
authors.forename: Karen
authors.initials: K
authors.lastname: So
authors.forename: Wendy
authors.initials: W
authors.lastname: Bannister
authors.forename: Emma
authors.initials: E
authors.lastname: Dean
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018592:Cross-Over Studies; D005260:Female; D018565:Food-Drug Interactions; D065569:Gastrointestinal Absorption; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010793:Phthalazines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010879:Piperazines / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D010793:Phthalazines; D010879:Piperazines; C531550:olaparib