title: First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica.
abstract: OBJECTIVE
  To evaluate the safety, tolerability, and pharmacokinetics of single doses of BG00010 (neublastin, artemin, enovin) in subjects with unilateral sciatica.
  
  
  METHODS
  This was a single-center, blinded, placebo-controlled, randomized Phase 1 sequential-cohort, dose-escalation study (ClinicalTrials.gov identifier NCT00961766; funded by Biogen Idec). Adults with unilateral sciatica were enrolled at The Royal Adelaide Hospital, Australia. Four subjects were assigned to each of eleven cohorts (intravenous BG00010 0.3, 1, 3, 10, 25, 50, 100, 200, 400, or 800 μg/kg, or subcutaneous BG00010 50 μg/kg) and were randomized 3:1 to receive a single dose of BG00010 or placebo. The primary safety and tolerability assessments were: adverse events; clinical laboratory parameters and vital signs; pain as measured by a Likert rating scale; intra-epidermal nerve fiber density; and longitudinal assessment of quantitative sensory test parameters. Blood, serum, and plasma samples were collected for pharmacokinetic and pharmacodynamic assessments. Subjects were blinded to treatment assignment throughout the study. The investigator was blinded to treatment assignment until the Data Safety Review Committee review of unblinded data, which occurred after day 28.
  
  
  RESULTS
  Beyond the planned enrollment of 44 subjects, four additional subjects were enrolled into to the intravenous BG00010 200 μg/kg cohort after one original subject experienced mild generalized pruritus. Therefore, a total of 48 subjects were enrolled between August 2009 and December 2011; all were included in the safety analyses. BG00010 was generally well tolerated: in primary analyses, the most common treatment-emergent adverse events were changes in temperature perception, pruritus, rash, or headache; no trends were observed in clinical laboratory parameters, vital signs, intra-epidermal nerve fiber density, or quantitative sensory testing. BG00010 was not associated with any clear, dose-dependent trends in Likert pain scores. BG00010 was rapidly distributed, with a prolonged terminal elimination phase.
  
  
  CONCLUSIONS
  These data support the development of BG00010 for the treatment of neuropathic pain.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00961766.
authors.affiliation: Clinical Pharmacology, School of Medical Sciences, University of Adelaide, Adelaide, Australia; Pain and Anaesthesia Research Clinic, Royal Adelaide Hospital, Adelaide, Australia; Pain Management Unit, Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Rolan
authors.affiliation: Biogen IDEC, Cambridge, MA, United States of America.
authors.forename: Gilmore
authors.initials: G
authors.lastname: O'Neill
authors.affiliation: Biogen IDEC, Cambridge, MA, United States of America.
authors.forename: Eve
authors.initials: E
authors.lastname: Versage
authors.affiliation: Biogen IDEC, Cambridge, MA, United States of America.
authors.forename: Jitesh
authors.initials: J
authors.lastname: Rana
authors.affiliation: Biogen IDEC, Cambridge, MA, United States of America.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Biogen IDEC, Cambridge, MA, United States of America.
authors.forename: Gerald
authors.initials: G
authors.lastname: Galluppi
authors.affiliation: Biogen IDEC, Cambridge, MA, United States of America.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Aycardi
mesh_terms: D000328:Adult; D000368:Aged; D004333:Drug Administration Routes; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000494:pharmacology* / Q000627:therapeutic use*; D010147:Pain Measurement; D012585:Sciatica / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009419:Nerve Tissue Proteins