title: Oral administration of the growth hormone secretagogue NN703 in adult patients with growth hormone deficiency.
abstract: OBJECTIVE
  Little is known of the usefulness of GH secretagogues (GHSs) in GH-deficient (GHD) adults. The objective of this study was to determine the number of responders to treatment with NN703 in GHD adults.
  
  
  METHODS
  A multicentre, randomized, double-blind, and placebo-controlled study.
  
  
  METHODS
  Ninety-seven GHD adults were included.
  
  
  METHODS
  The GH response before and after 1 week of oral treatment with NN703 (n = 83) or placebo (n = 14) was determined. The first and last dose of NN703 was 3 mg/kg, whereas the dose of NN703 was 1.5 mg/kg/day during the 6 days between the first and last doses. Furthermore, all 97 patients received 1 micro g/kg GH-releasing hormone (GHRH) 3 weeks after the last dose of NN703.
  
  
  RESULTS
  Serum GH peak and area under curve (AUC) values after the first NN703 administration were greater than those after placebo administration (P < 0.05). However, after correction for the lower body mass index (BMI) in the NN703 group, this difference lost statistical significance. After 1 week of therapy, GH peak and AUC values were similar following the final doses of NN703 and placebo. Serum peak and AUC values of other anterior pituitary hormones were similar between the NN703 and placebo groups both after the first and last administration of study drug. Nine of the 83 patients (11%) responded with a serum peak GH concentration >or= 5 micro g/l after the first and/or last NN703 administration, whereas no patient responded after placebo administration. Serum IGF-I was unaffected by 1-week NN703 treatment, whereas serum IGFBP-3 was increased (P < 0.05 vs. placebo) also after correction for BMI. Mean serum peak GH concentration after GHRH administration was 2.1 micro g/l (+/-0.3, SEM), which was higher than that after the first NN703 administration (1.32 +/- 0.3, P < 0.05).
  
  
  CONCLUSIONS
  NN703 administration was generally well tolerated. Eleven per cent of the GHD adult patients responded with a peak GH response >or= 5 micro g/l after the first and/or last administration of oral NN703. Although a majority of GHD adults will not respond to NN703, the present results suggest that oral NN703 treatment could be useful in some adult patients with moderately severe GHD. These patients may be identified by a test dose of GHS.
authors.affiliation: Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Göteborg, Sweden. Johan.Svensson@medic.gu.se
authors.forename: J
authors.initials: J
authors.lastname: Svensson
authors.forename: J P
authors.initials: JP
authors.lastname: Monson
authors.forename: T
authors.initials: T
authors.lastname: Vetter
authors.forename: T K
authors.initials: TK
authors.lastname: Hansen
authors.forename: R
authors.initials: R
authors.lastname: Savine
authors.forename: P
authors.initials: P
authors.lastname: Kann
authors.forename: M
authors.initials: M
authors.lastname: Bex
authors.forename: M
authors.initials: M
authors.lastname: Reincke
authors.forename: C
authors.initials: C
authors.lastname: Hagen
authors.forename: A
authors.initials: A
authors.lastname: Beckers
authors.forename: M M
authors.initials: MM
authors.lastname: Ilondo
authors.forename: M
authors.initials: M
authors.lastname: Zdravkovic
authors.forename: B-A
authors.initials: BA
authors.lastname: Bengtsson
authors.forename: M
authors.initials: M
authors.lastname: Korbonits
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001794:Blood Pressure / Q000502:physiology; D004151:Dipeptides / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010901:Pituitary Function Tests; D010907:Pituitary Hormones / Q000097:blood
chemical_list: D004151:Dipeptides; D005230:Fatty Acids, Nonesterified; D018972:Insulin-Like Growth Factor Binding Protein 3; D010907:Pituitary Hormones; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C120631:tabimorelin