title: A long-acting human growth hormone with delayed clearance (VRS-317): results of a double-blind, placebo-controlled, single ascending dose study in growth hormone-deficient adults.
abstract: BACKGROUND
  Administration of daily recombinant human GH (rhGH) poses a considerable challenge to patient compliance. Reduced dosing frequency may improve treatment adherence and potentially overall treatment outcomes.
  
  
  OBJECTIVE
  This study assessed the safety and tolerability and the potential for achieving IGF-I levels within the target range in adults with GH deficiency after a single dose of the long-acting rhGH analog, VRS-317.
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled, single ascending dose study.
  
  
  METHODS
  Fifty adults with growth hormone deficiency (mean age, 45 years) were studied in 5 treatment groups of 10 subjects each (8 active drug and 2 placebo).
  
  
  METHODS
  The study was conducted in 17 adult endocrinology centers in North America and Europe.
  
  
  METHODS
  Adverse events, laboratory safety assessments, and VRS-317 pharmacokinetics and pharmacodynamics (IGF-I and IGF binding protein-3) were analyzed.
  
  
  RESULTS
  At 0.80 mg/kg, VRS-317 had a mean terminal elimination half-life of 131 hours. Single VRS-317 doses of 0.05, 0.10, 0.20, 0.40, and 0.80 mg/kg (approximately equivalent to daily rhGH doses of 0.3-5.0 μg/kg over 30 d) safely increased the amplitude and duration of IGF-I responses in a dose-dependent manner. After a single 0.80 mg/kg dose, serum IGF-I was maintained in the normal range between -1.5 and 1.5 SD values for a mean of 3 weeks. No unexpected or serious adverse events were observed.
  
  
  CONCLUSIONS
  The elimination half-life for VRS-317 is 30- to 60-fold longer and stimulates more durable IGF-I responses than previously studied rhGH products. Prolonged IGF-I responses do not come at the expense of overexposure to high IGF-I levels. The pharmacokinetics and pharmacodynamics combined with the observed safety profile indicate the potential for safe and effective monthly dosing.
authors.affiliation: Endocrinology, Diabetes and Clinical Nutrition, Oregon Health and Science University, Portland, Oregon 97239, USA.
authors.forename: Kevin C J
authors.initials: KC
authors.lastname: Yuen
authors.forename: Gerard S
authors.initials: GS
authors.lastname: Conway
authors.forename: Vera
authors.initials: V
authors.lastname: Popovic
authors.forename: George R
authors.initials: GR
authors.lastname: Merriam
authors.forename: Timothy
authors.initials: T
authors.lastname: Bailey
authors.forename: Amir H
authors.initials: AH
authors.lastname: Hamrahian
authors.forename: Beverly M K
authors.initials: BM
authors.lastname: Biller
authors.forename: Mark
authors.initials: M
authors.lastname: Kipnes
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Moore
authors.forename: Eric
authors.initials: E
authors.lastname: Humphriss
authors.forename: George M
authors.initials: GM
authors.lastname: Bright
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Cleland
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000009:adverse effects / Q000172:deficiency* / Q000493:pharmacokinetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I