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Torben Laursen

A novel oral preparation of human growth hormone (hGH) is absorbed and increases serum IGF-I levels after 7 days administration to GH-deficient adults

Research output: Contribution to book/anthology/report/proceedingConference abstract in proceedingsResearch

  • Torben Laursen
  • Linda Mindeholm, Novartis, Switzerland
  • Sibylle Haemmerle, Novartis, Switzerland
  • Alberto Ferreira, Novartis, Switzerland
  • Jens Otto Lunde Jørgensen
  • Moise Azria, Novartis, Switzerland
  • Jens Sandahl Christiansen, Denmark
  • Department of Pharmacology
  • The Department of Endocrinology and Diabetes
Growth hormone deficient (GHD) patients are currently effectively treated with daily subcutaneous (sc) injections of hGH in the evening, but alternative routes would be attractive. An oral formulationulation of hGH, using an amino-caprilic acid derivative (5-CNAC, Emisphere's eligen® technology) as carrier has recently been developed. The aim of this study was to determine if this oral formulation of hGH could be absorbed and be bioactive. Eight GHD men (mean age 50 years) receiving sc hGH therapy were withdrawn from therapy for 7 days and then treated for 7 days orally with tablets of HGH191 (Novartis). Each tablet contained 100 mg of hGH and 200 mg 5-CNAC. One tablet was given at 08 h and 17 h, and two tablets at 22 h to match nocturnal GH secretion. The patients were studied thrice for 24 hours: at day 7 of washout, at days 1 and 7 of treatment. GH peaks were recorded in all patients, although minor endogenous GH secretion interfered. Following the last dose (22 h) after 7 days of treatment, median Tmax was 0.75 h (range 0.37-3.98 h), and the geometric mean Cmax was 1.08 µg/L (range 0.23-17.46 µg/L). Absorption was most pronounced after the morning and bedtime dose. Serum IGF-I levels only changed slightly from end of the washout period (mean 118.2 µg/L, 95% CI [96.0, 140.3]) to day 1 of treatment (mean 126.0 µg/L, 95% CI [111.0, 140.9]). However, at day 7 IGF-I levels (mean 153.2 µg/L, 95% CI [126.2, 180.2]) were significantly increased (p=0.025) vs. end of washout. GH and IGF-I levels revealed pronounced between- and within-subject variation. No significant adverse reactions were seen.

In conclusion, this study shows, for the first time, absorption of an oral formulation of hGH. Bioactivity was demonstrated by increased serum IGF-I levels after 7 days treatment compared to the end of washout. Further studies should determine optimal formulation, dose and impact of meals, but the possibility of oral delivery of peptides opens new therapeutic perspectives.

Original languageEnglish
Title of host publicationClinical - Physiology & Pharmacology of the Growth Hormone Axis: New Treatment Modalities & Indications
PublisherUS Endocrine Society
Publication year2007
Publication statusPublished - 2007
EventUS Endocrine Society - Toronto, Canada
Duration: 2 Jun 20076 Jun 2007
Conference number: 89


ConferenceUS Endocrine Society

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