Comparative pharmacokinetics and pharmacodynamics of a new sustained-release growth hormone (GH), LB03002, versus daily GH in adults with GH deficiency

J Clin Endocrinol Metab. 2006 Aug;91(8):2926-30. doi: 10.1210/jc.2006-0514. Epub 2006 May 23.

Abstract

Context: LB03002 is a novel sustained-release GH preparation administered once weekly.

Objective: Our objective was to examine the pharmacokinetics, pharmacodynamics, and safety of LB03002 vs. daily GH.

Design and setting: This open-label, crossover study compared the pharmacokinetics and pharmacodynamics of LB03002 and daily GH.

Patients and other participants: Six male and three female patients with adult GH deficiency participated in the single-center study.

Intervention: Subjects were on stable daily GH treatment before the study. After a 4-wk washout with no GH, five weekly doses of LB03002 were given.

Main outcome measure: GH and IGF-I concentrations were measured during the last dose of daily GH and during the first and fifth weekly doses of LB03002.

Results: The observed maximal serum GH concentration was approximately doubled after LB03002 (6.1 +/- 3.2 and 4.5 +/- 2.2 microg/liter at first and fifth doses) compared with daily GH (2.7 +/- 2.2 microg/liter). A sustained increase in GH concentration for more than 48 h was observed with LB03002, such that dose-normalized area under the curve (AUC) was not significantly different between daily GH and LB03002. Mean maximal serum IGF-I concentration was 34-41% greater with LB03002 than with daily GH, and AUC was 7-fold greater. However, normalized to GH dose, AUC for IGF-I was comparable. Adverse events and local reactions were acceptable, and there were no evident safety concerns with LB03002.

Conclusions: Multiple weekly doses of LB03002 appeared safe and well tolerated. Comparable GH bioavailability and sustained IGF-I elevations support the use of once-weekly LB03002 to replace daily GH therapy.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Biological Availability
  • Blood Glucose / analysis
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Fasting
  • Female
  • Growth Hormone / adverse effects
  • Growth Hormone / pharmacokinetics*
  • Growth Hormone / pharmacology*
  • Human Growth Hormone / deficiency*
  • Human Growth Hormone / pharmacokinetics
  • Human Growth Hormone / therapeutic use
  • Humans
  • Insulin-Like Growth Factor I / analysis
  • Kinetics
  • Male
  • Middle Aged

Substances

  • Blood Glucose
  • Delayed-Action Preparations
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Growth Hormone