Lack of food effect on single-dose pharmacokinetics of brivanib, and safety and efficacy following multiple doses in subjects with advanced or metastatic solid tumors.

Published

Journal Article

PURPOSE: Brivanib alaninate, an orally available prodrug of brivanib, is currently under evaluation for the treatment of several malignancies. This study aimed to (1) investigate effects of a high-fat meal on single-dose pharmacokinetics of brivanib in subjects with advanced/metastatic solid tumors and (2) assess the safety and preliminary efficacy of single and multiple doses of brivanib alaninate in this population. METHODS: A two-part study was conducted consisting of a single-dose phase (Part A) and a multiple-dose phase (Part B). In Part A, subjects received a single dose of brivanib alaninate (800 mg) either in a fasting state or following ingestion of a high-fat meal (approximately 951 kcal [15% protein, 33% carbohydrate, 52% fat]); serial blood samples were collected for pharmacokinetic analysis up to 48 h post-dosing. In Part B, subjects received brivanib alaninate (800 mg) once daily until discontinuation. Throughout both phases, subjects were evaluated for adverse events (AEs) and best clinical response. RESULTS: No clinically significant differences in brivanib exposure were observed between fed and fasting subjects in Part A; C (max) was unchanged and AUC(INF) decreased marginally when administered in a fed versus fasted state. In Part A, the incidence of treatment-emergent AEs was broadly similar in a fed or fasted state. Brivanib alaninate was generally well tolerated throughout the study and showed preliminary evidence of antitumor activity. CONCLUSIONS: Consumption of a high-fat meal had no significant effect on brivanib pharmacokinetics. The study further demonstrates the acceptable safety/tolerability profile and antitumor potential of brivanib in patients with advanced malignancies.

Full Text

Duke Authors

Cited Authors

  • LoRusso, P; Shapiro, GI; Hurwitz, H; Pilat, MJ; Chemidlin, J; Kollia, G; Syed, S; Fischer, B; Masson, E

Published Date

  • December 2011

Published In

Volume / Issue

  • 68 / 6

Start / End Page

  • 1377 - 1385

PubMed ID

  • 21461891

Pubmed Central ID

  • 21461891

Electronic International Standard Serial Number (EISSN)

  • 1432-0843

Digital Object Identifier (DOI)

  • 10.1007/s00280-011-1603-2

Language

  • eng

Conference Location

  • Germany