title: 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.
abstract: OBJECTIVE
  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.
authors: Karmanos Cancer Institute, 4100 John R, Detroit, MI 48201, USA. lorussop@karmanos.org
authors: Patricia
authors: P
authors: LoRusso
authors: Geoffrey I
authors: GI
authors: Shapiro
authors: Herbert
authors: H
authors: Hurwitz
authors: Mary Jo
authors: MJ
authors: Pilat
authors: Janice
authors: J
authors: Chemidlin
authors: Georgia
authors: G
authors: Kollia
authors: Shariq
authors: S
authors: Syed
authors: Bruce
authors: B
authors: Fischer
authors: Eric
authors: E
authors: Masson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D005502:Food; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy*; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000970:Antineoplastic Agents; D014227:Triazines; C509922:brivanib; D000409:Alanine