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

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.