A randomized, crossover phase 1 study to assess the effects of formulation (capsule vs tablet) and meal consumption on the bioavailability of dovitinib (TKI258)

Jeffrey R. Infante, Ramesh K. Ramanathan, Daniel George, Eugene Tan, Michelle Quinlan, Angela Liu, Jeffrey W. Scott, Sunil Sharma

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Purpose: 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.

Original languageEnglish (US)
Pages (from-to)729-737
Number of pages9
JournalCancer chemotherapy and pharmacology
Volume75
Issue number4
DOIs
StatePublished - Apr 2015

Keywords

  • Bioavailability
  • Dovitinib
  • Fibroblast growth factor receptor
  • Food effect
  • Pharmacokinetics
  • TKI258

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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