title: Long-acting pegylated human GH in children with GH deficiency: a single-dose, dose-escalation trial investigating safety, tolerability, pharmacokinetics and pharmacodynamics.
abstract: OBJECTIVE
  GH replacement therapy currently requires daily injections, which may be inconvenient and distressing for young patients. This study determined the safety, tolerability, pharmacokinetics and pharmacodynamics of escalating single doses of a pegylated GH (NNC126-0083) developed for once-weekly administration, in children with GH deficiency (GHD).
  
  
  METHODS
  Thirty children (age ≥6 and ≤12 years, weight ≥16 kg) were randomised to NNC126-0083 or daily GH treatment. The subjects discontinued their daily GH treatment 7-9 days before receiving NNC126-0083 at 0.01, 0.02, 0.04 or 0.06 mg protein/kg (n=22) or seven once-daily doses of GH at 0.035 mg protein/kg (n=8).
  
  
  RESULTS
  NNC126-0083 was well tolerated, and no short-term safety or local tolerability issues were identified. After NNC126-0083 treatment, dose-dependent IGF1 increases were evident for maximum concentration (C(max)), but not area under the curve (AUC(0)(-)(168 h)). Mean values for IGF1 AUC(0)(-)(168 h)/168 h and C(max) were higher for GH than for NNC126-0083, although the difference was not statistically significant for cohort's 0.06 mg protein/kg. At 0.06 mg protein/kg, the resulting IGF1 response began subsiding at ∼3 days post-dose.
  
  
  CONCLUSIONS
  Single doses of long-acting NNC126-0083 were safe and well tolerated in children with GHD. Increased IGF1 levels were observed in all NNC126-0083 dose groups; however, a satisfactory once-weekly IGF1 profile was not reached within the NNC126-0083 dose levels administered.
authors: UZ Brussel, Department of Pediatrics Laarbeeklaan 101, 1090 Brussels, Belgium.
authors: Jean
authors: J
authors: de Schepper
authors: Michael Højby
authors: MH
authors: Rasmussen
authors: Zoran
authors: Z
authors: Gucev
authors: Alon
authors: A
authors: Eliakim
authors: Tadej
authors: T
authors: Battelino
mesh_terms: D019540:Area Under Curve; D002648:Child; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019382:Human Growth Hormone / Q000172:deficiency* / Q000031:analogs & derivatives; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D019382:Human Growth Hormone; D011092:Polyethylene Glycols; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C558310:NNC126-0083