PMID- 21461891
OWN - NLM
STAT- MEDLINE
DCOM- 20120111
LR  - 20150325
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 68
IP  - 6
DP  - 2011 Dec
TI  - 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.
PG  - 1377-85
LID - 10.1007/s00280-011-1603-2 [doi]
AB  - 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.
FAU - LoRusso, Patricia
AU  - LoRusso P
AD  - Karmanos Cancer Institute, 4100 John R, Detroit, MI 48201, USA. 
      lorussop@karmanos.org
FAU - Shapiro, Geoffrey I
AU  - Shapiro GI
FAU - Hurwitz, Herbert
AU  - Hurwitz H
FAU - Pilat, Mary Jo
AU  - Pilat MJ
FAU - Chemidlin, Janice
AU  - Chemidlin J
FAU - Kollia, Georgia
AU  - Kollia G
FAU - Syed, Shariq
AU  - Syed S
FAU - Fischer, Bruce
AU  - Fischer B
FAU - Masson, Eric
AU  - Masson E
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20110403
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Triazines)
RN  - DDU33B674I (brivanib)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alanine/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - Antineoplastic Agents/*pharmacokinetics
MH  - Cross-Over Studies
MH  - Female
MH  - Food
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasms/*drug therapy
MH  - Triazines/administration & dosage/adverse effects/*pharmacokinetics
EDAT- 2011/04/05 06:00
MHDA- 2012/01/12 06:00
CRDT- 2011/04/05 06:00
PHST- 2010/11/12 00:00 [received]
PHST- 2011/03/01 00:00 [accepted]
PHST- 2011/04/05 06:00 [entrez]
PHST- 2011/04/05 06:00 [pubmed]
PHST- 2012/01/12 06:00 [medline]
AID - 10.1007/s00280-011-1603-2 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2011 Dec;68(6):1377-85. doi: 
      10.1007/s00280-011-1603-2. Epub 2011 Apr 3.