title: A randomized, crossover phase 1 study to assess the effects of formulation (capsule vs tablet) and meal consumption on the bioavailability of dovitinib (TKI258).
abstract: OBJECTIVE
  This 2-arm crossover study compared the relative bioavailability of two dovitinib (TKI258) formulations [anhydrate clinical service form (CSF) capsule and monohydrate final market image (FMI) tablet; Arm 1] and determined the effect of food on dovitinib exposure (Arm 2).
  
  
  METHODS
  Patients with advanced solid tumors, excluding breast cancer, were enrolled in 1 of the 2 arms of the study. Patients in Arm 1 were randomized to a single 500-mg dose of CSF capsule or FMI tablet followed by 7 days of rest and 500 mg of the other formulation. Patients in Arm 2 received 300 mg of FMI tablet daily and were randomized to follow 1 of 6 meal sequences, each with 3 prandial conditions: low fat (LF), high fat (HF), or no meal (NM).
  
  
  RESULTS
  In Arm 1 (n = 21), 17 patients were evaluable. FMI tablet compared with CSF capsule showed only slight reductions in the adjusted geometric means for area under the plasma concentration-time curve (AUClast; 3%) and maximum plasma concentration (C max; 1%). In Arm 2 (n = 42), 19 patients were evaluable. HF meal versus NM showed a 9% decrease in the adjusted geometric mean for AUClast and an 18% decrease for C max. Comparison of LF meal versus NM showed a 1% decrease for AUClast and a 10% decrease for C max. Common adverse events suspected to be study drug related included vomiting, diarrhea, nausea, and fatigue.
  
  
  CONCLUSIONS
  Dovitinib FMI tablet had similar systemic exposure to the CSF capsule and was not affected by food.
authors: Sarah Cannon Research Institute, Nashville, TN, USA.
authors: Jeffrey R
authors: JR
authors: Infante
authors: Ramesh K
authors: RK
authors: Ramanathan
authors: Daniel
authors: D
authors: George
authors: Eugene
authors: E
authors: Tan
authors: Michelle
authors: M
authors: Quinlan
authors: Angela
authors: A
authors: Liu
authors: Jeffrey W
authors: JW
authors: Scott
authors: Sunil
authors: S
authors: Sharma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D002214:Capsules; D018592:Cross-Over Studies; D018572:Disease-Free Survival; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015363:Quinolones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013607:Tablets
chemical_list: C500007:4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D002214:Capsules; D015363:Quinolones; D013607:Tablets; D011505:Protein-Tyrosine Kinases