title: Gadobutrol in the central nervous system at three doses: results from a phase II, randomized, multicenter trial.
abstract: OBJECTIVE
  To investigate the efficacy and safety of three doses of gadobutrol and determine the minimum effective dose for contrast-enhanced MRI of the central nervous system (CNS).
  
  
  METHODS
  This was a Phase II, multicenter, double-blind, parallel-group controlled study in subjects referred for contrast-enhanced MRI of the CNS. Subjects were randomized to receive gadobutrol 0.03, 0.1, or 0.3 mmol/kg body weight, and underwent unenhanced, gadobutrol-enhanced, and comparator-enhanced MRI scans. Three blinded readers assessed the images. Primary efficacy variables were number of lesions detected, border delineation, contrast enhancement, and internal morphology.
  
  
  RESULTS
  Of the 229 randomized subjects, 173 were evaluated for efficacy. Clinically meaningful improvements in lesion border delineation, contrast enhancement, and internal morphology were observed for 0.1 mmol/kg gadobutrol. Pair-wise comparisons of a composite score of the four primary variables showed the 0.1 mmol/kg dose to be statistically superior to the 0.03 mmol/kg dose (P = 0.003). The 0.3 mmol/kg dose showed no statistically significant difference with the 0.1 mmol/kg dose. Twenty-two (9.8%) subjects reported at least one treatment-emergent adverse event (TEAE). No TEAE was reported at an incidence >3.5%.
  
  
  CONCLUSIONS
  The 0.1 mmol/kg dose of gadobutrol was effective and well tolerated for contrast-enhanced MRI of the CNS.
authors.affiliation: Bayer Healthcare Pharmaceuticals, Berlin, Germany.
authors.forename: Josy
authors.initials: J
authors.lastname: Breuer
authors.forename: Juan
authors.initials: J
authors.lastname: Gutierrez
authors.forename: Richard
authors.initials: R
authors.lastname: Latchaw
authors.forename: Robert
authors.initials: R
authors.lastname: Lehr
authors.forename: A Gregory
authors.initials: AG
authors.lastname: Sorensen
mesh_terms: D001932:Brain Neoplasms / Q000473:pathology*; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014481:United States
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; C090600:gadobutrol
keywords: central nervous system; contrast-enhanced magnetic resonance imaging; gadobutrol