title: Ascending dose-controlled trial of beloranib, a novel obesity treatment for safety, tolerability, and weight loss in obese women.
abstract: OBJECTIVE
  Evaluate the safety and tolerability of beloranib, a fumagillin-class methionine aminopetidase-2 (MetAP2) inhibitor, in obese women over 4 weeks.
  
  
  METHODS
  Thirty-one obese (mean BMI 38 kg/m2) women were randomized to intravenous 0.1, 0.3, or 0.9 mg/m2 beloranib or placebo twice weekly for 4 weeks (N = 7, 6, 9, and 9).
  
  
  RESULTS
  The most frequent AEs were headache, infusion site injury, nausea, and diarrhea. Nausea and infusion site injury occurred more with beloranib than placebo. The most common reason for discontinuation was loss of venous access. There were no clinically significant abnormal laboratory findings. In subjects completing 4 weeks, median weight loss with 0.9 mg/m2 beloranib was -3.8 kg (95% CI -5.1, -0.9; N = 8) versus -0.6 kg with placebo (-4.5, -0.1; N = 6). Weight change for 0.1 and 0.3 mg/m2 beloranib was similar to placebo. Beloranib (0.9 mg/m2) was associated with a significant 42 and 18% reduction in triglycerides and LDL-cholesterol, as well as improvement in C-reactive protein and reduced sense of hunger. Changes in β-hydroxybutyrate, adiponectin, leptin, and fibroblast growth factor-21 were consistent with the putative mechanism of MetAP2 inhibition. Glucose and blood pressure were unchanged.
  
  
  CONCLUSIONS
  Beloranib treatment was well tolerated and associated with rapid weight loss and improvements in lipids, C-reactive protein, and adiponectin.
authors.affiliation: Zafgen, Inc., Cambridge, MA, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: Hughes
authors.forename: D D
authors.initials: DD
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Marjason
authors.forename: J
authors.initials: J
authors.lastname: Proietto
authors.forename: J P
authors.initials: JP
authors.lastname: Whitehead
authors.forename: J E
authors.initials: JE
authors.lastname: Vath
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D052242:Adiponectin / Q000097:blood*; D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001230:Aspergillus / Q000737:chemistry; D001688:Biological Products / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D003510:Cyclohexanes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005231:Fatty Acids, Unsaturated / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D006801:Humans; D006815:Hunger / Q000187:drug effects; D007262:Infusions, Intravenous; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood*; D063208:Methionyl Aminopeptidases; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000188:drug therapy*; D012717:Sesquiterpenes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D052242:Adiponectin; D019440:Anti-Obesity Agents; D001688:Biological Products; D001786:Blood Glucose; D008078:Cholesterol, LDL; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D006023:Glycoproteins; D020738:Leptin; D008055:Lipids; D012717:Sesquiterpenes; D014280:Triglycerides; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; C026211:fumagillin; D002097:C-Reactive Protein; D000626:Aminopeptidases; C081311:METAP2 protein, human; D063208:Methionyl Aminopeptidases; D020155:3-Hydroxybutyric Acid