title: One-Year Data from a Long-Term Phase IV Study of Recombinant Human Growth Hormone in Short Children Born Small for Gestational Age.
abstract: BACKGROUND
  This prospective, open-label, non-comparative, multicentre, long-term phase IV study is examining the efficacy and safety of somatropin [recombinant human growth hormone (rhGH)] in short children born small for gestational age (SGA) and its impact on the incidence of diabetes. This report is the first interim analysis of patients who have completed 1 year of treatment.
  
  
  METHODS
  A total of 278 pre-pubertal patients were enrolled. Key eligibility criteria included height standard deviation score (HSDS) <-2.5; parental adjusted SDS <-1; birth weight and/or length <-2 SD and failure to show catch-up growth by ≥4 years of age. Patients were treated with rhGH 0.035 mg/kg/day. The primary objective was to evaluate the long-term effect of rhGH on carbohydrate metabolism [including fasting glucose, stimulated glucose (2-h oral glucose tolerance test, OGTT) and glycated haemoglobin (HbA1c)]. Secondary objectives included evaluation of height parameters [body height, HSDS, height velocity (HV), HVSDS]; insulin-like growth factor 1 (IGF-I) and insulin-like growth factor-binding protein 3 (IGFBP-3) serum levels during treatment; and incidence and severity of adverse events (AEs).
  
  
  RESULTS
  None of the children developed diabetes mellitus within the first year of treatment. Mean levels of fasting glucose, HbA1c and 2-h OGTT values remained stable during the study period. Treatment with rhGH was effective, as documented by all height parameters. Mean HSDS improved from -3.39 at baseline to -2.57 at Year 1. Mean HV increased markedly from 4.25 cm/year at baseline to 8.99 cm/year during the first year. Similarly, mean peak-centred HVSDS increased from -2.13 at baseline to +4.16 at Year 1. Mean IGF-I SDS and IGFBP-3 SDS also increased within the first year (by +1.80 and +0.41, respectively). 13 patients (4.7%) did not respond adequately to treatment (HVSDS <1); they were withdrawn from the study. In total, 192 children (69.3%) experienced treatment-emergent AEs; most (98.7%) were mild-to-moderate, and the majority (96.5%) were unrelated to study treatment.
  
  
  CONCLUSIONS
  This interim analysis shows that short children born SGA can be effectively and safely treated with rhGH and that rhGH treatment has no major impact on carbohydrate metabolism after the first year of treatment.
authors.affiliation: Department of Endocrinology, von Haunersches Kinderspital, University Hospital Munich, Munich, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Schwarz
authors.affiliation: Medical University, Gdansk, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Birkholz-Walerzak
authors.affiliation: Department of Endocrinology, Children's Health Research Institute, Warsaw, Poland.
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Szalecki
authors.affiliation: Department of Paediatric Endocrinology and Diabetology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Walczak
authors.affiliation: Department of Endocrinology, University of Medicine and Pharmacy "Gr.T.Popa", Iasi, Romania.
authors.forename: Corina
authors.initials: C
authors.lastname: Galesanu
authors.affiliation: Department of Endocrinology, Tblisi State Medical University, Tblisi, Georgia.
authors.forename: David
authors.initials: D
authors.lastname: Metreveli
authors.affiliation: Sandoz Biopharmaceuticals, HEXAL AG, Industriestr. 25, 83607, Holzkirchen, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Khan-Boluki
authors.affiliation: Sandoz Biopharmaceuticals, HEXAL AG, Industriestr. 25, 83607, Holzkirchen, Germany. ellen.schuck@sandoz.com.
authors.forename: Ellen
authors.initials: E
authors.lastname: Schuck
keywords: Endocrinology; Omnitrope; Recombinant human growth hormone; Small for gestational age; Somatropin