493P - Pharmacokinetic profile of MGCD265, an oral tyrosine kinase inhibitor, with or without food in healthy volunteers

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Drug Development
Presenter Eric Sicard
Authors E. Sicard1, M. Juretic2, M. Drouin2, G. Reid2, J. Wang2, W. Hunt2, C. Maroun2, J. Besterman2
  • 1Clinical Research, Algorithme Pharma, Laval/CA
  • 2Clinical Affairs, Methylgene, Inc, Montreal/CA



MGCD265 is a novel targeted cancer therapeutic, currently in phase I/II clinical trials, that inhibits Met and VEGF receptor tyrosine kinases. The abnormal activation of Met is involved in tumor development and metastasis, and VEGF kinase is responsible for inappropriate angiogenesis that nourishes the tumor. MGCD265 has demonstrated a favorable safety profile in patients with advanced malignancies and can safely be combined with other cancer therapeutics such as docetaxel and erlotinib. The objective of this Phase I study was to assess the bioavailability of MGCD265 under fasting and fed conditions in healthy volunteers.


This was a randomized, laboratory-blinded, 2-period, crossover study. MGCD265 was administered as a single dose (100 mg) after a 10-hr overnight fast. For the fasting condition, fasting was continued for at least 4 hrs following drug administration. For the fed condition, subjects received a standardized meal 30 mins before drug administration. Blood samplings for the pharmacokinetic (PK) evaluation were done from pre-dose to up to 96 hrs post-dose. Safety was evaluated through the assessment of adverse events (AEs), laboratory tests, vital signs and 12-lead ECG.


Fourteen subjects were recruited [M/F: 8/6; median age: 51 years old (range 41-65); median BMI: 25 kg/m2 (range: 19-29)]. One female subject discontinued early due to a fall (unrelated to MGCD265). Using nominal timepoints, on average, the fed condition was associated with an ∼3 fold increase in Cmax, AUCT, and AUCinf. The half-life of MGCD265 was found to be ∼34 hrs. Tmax was calculated to be 7 hrs and 10 hrs under fasting and fed conditions, respectively. MGCD265 related AEs were mostly mild and included dry mouth in 3 subjects, somnolence in 1 subject and moderate diarrhea in 1 subject. There were no clinically significant changes in vital signs, ECG or laboratory values.


Exposure of MGCD265 increased significantly in the presence of a meal, with no added toxicity. The prolonged sampling time used in this study provided a more accurate estimation of MGCD265 half-life (∼34 hrs) compared to the estimate found in patients with advanced malignancies (∼23 hrs).


E. Sicard: Research funding from Methylgene, Inc.

M. Juretic: Employee of Methylgene, Inc.

M. Drouin: Employee of Methylgene, Inc.

G. Reid: Employee of Methylgene, Inc.

J. Wang: Employee of Methylgene, Inc.

W. Hunt: Employee of Methylgene, Inc.

C. Maroun: Employee of Methylgene, Inc.

J. Besterman: Employee of Methylgene, Inc.