title: Pharmacokinetic and pharmacodynamic profile of a new sustained-release GH formulation, LB03002, in children with GH deficiency.
abstract: OBJECTIVE
  LB03002 is a novel, sustained-release recombinant human GH, developed for once-a-week s.c. injection. To evaluate the suitability for long-term GH replacement therapy in children with GH deficiency (GHD), the present study assessed the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of LB03002 at three doses.
  
  
  METHODS
  The randomised, comparator-controlled, assessor-blinded, phase II study assessed 37 (24 boys, 13 girls) pre-pubertal, GH-naïve children with GHD, in 11 European centres, for PK and PD analyses. GH, IGF1 and IGFBP3 concentrations were measured following the last daily GH dose and the first and 13th once-a-week administration of LB03002 at doses of 0.2, 0.5 or 0.7 mg/kg.
  
  
  RESULTS
  GH C(max) values after the three doses of LB03002 were increased up to fourfold, with a clear dose proportionality. For each LB03002 dose, GH area under the concentration versus time curve did not increase from the first to 13th (month 3) administration, indicating no accumulation of circulating GH. IGF1 C(max) showed a progressive increase during LB03002 administration. Conversely, IGFBP3 showed a rapid increase in C(max). IGF1 SDS were fully normalised after 3 months of treatment, whereas IGFBP3 SDS were already in the normal range for all the three LB03002 dosages after 1 week.
  
  
  CONCLUSIONS
  At the doses used, LB03002 has a suitable profile for long-term treatment to promote growth in children with GHD. The quantitative changes in IGF1 and IGFBP3 indicate adequate stimulation of the IGF system by LB03002 and the pattern of increase is comparable with that seen in GHD children in a standard IGF1 generation test using daily GH.
authors.affiliation: Buda Children's Hospital, Budapest, Hungary BioPartners GmbH, Baar, Switzerland.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Peter
authors.forename: Conrad
authors.initials: C
authors.lastname: Savoy
authors.forename: Hyi-Jeong
authors.initials: HJ
authors.lastname: Ji
authors.forename: Mihaly
authors.initials: M
authors.lastname: Juhasz
authors.forename: Martin
authors.initials: M
authors.lastname: Bidlingmaier
authors.forename: Paul
authors.initials: P
authors.lastname: Saenger
mesh_terms: D002648:Child; D002675:Child, Preschool; D003692:Delayed-Action Preparations; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy*; D019382:Human Growth Hormone / Q000172:deficiency* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male
chemical_list: D003692:Delayed-Action Preparations; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I