Dataset Information

The pharmacokinetic and pharmacodynamic properties and short-term outcome of a novel once-weekly PEGylated recombinant human growth hormone for children with growth hormone deficiency.

ABSTRACT:

Objectives

To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of Y-shape branched PEGylated recombinant human growth hormone (YPEG-rhGH) and evaluate its short-term efficacy and safety in children with growth hormone deficiency (GHD).

Methods

A total of 43 children with GHD from 12 sites in China were enrolled in this randomized, multicenter, active-controlled, double-blind (YPEG-rhGH doses) trial. Patients were randomized 1:1:1:1 to 100, 120, and 140 μg/kg/week of YPEG-rhGH groups and daily rhGH 35 μg/kg/day groups. The treatment lasted 12 weeks. The primary outcome was the area under the curve of the change of insulin-like growth factor-1 (IGF-1). The secondary outcome was the height velocity (HV) increment at week 12.

Results

A dose-dependent response of maximum plasma concentration (C_max) and area under the concentration-time curves from 0 to 168 hours (AUC_0-168h) were observed for YPEG-rhGH. The ratio of C_max and the ratio of AUC_0-168h from the first to the last dosing were 1.09~1.11 and 1.22~1.26 respectively. A YPEG-rhGH dose-dependent increase in area under effect curve (AUEC) of IGF-1 fold change was observed. Model-derived mean IGF-1 SDS was in the normal range for all three YPEG-rhGH doses. At week 12, HV was 7.07, 10.39, 12.27 cm/year, and 11.58 cm/year for YPEG-rhGH 100, 120, and 140 μg/kg/week and daily rhGH respectively. Adherence and safety were consistent with the profile of daily rhGH. No related serious adverse events were reported.

Conclusion

The PK/PD suggests that YPEG-rhGH is suitable for the once-weekly treatment of pediatric GHD. YPEG-rhGH 120 ~ 140 μg/kg/week provides the closest HV increment with similar safety and tolerability compared to daily rhGH 35 μg/kg/day in children with GHD.

Clinical trial registration

ClinicalTrials.gov, identifier [NCT04513171].

SUBMITTER: Liang Y

PROVIDER: S-EPMC9405430 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The pharmacokinetic and pharmacodynamic properties and short-term outcome of a novel once-weekly PEGylated recombinant human growth hormone for children with growth hormone deficiency.

Liang Yan Y Zhang Cai C Wei Haiyan H Du Hongwei H Zhang Gaixiu G Yang Yu Y Zhang Hua H Gong Haihong H Li Pin P Song Fuying F Xu Zhuangjian Z He Ruoyi R Zhou Weidong W Zheng Heng H Sun Li L Luo Xiaoping X

Frontiers in endocrinology 20220811

<h4>Objectives</h4>To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of Y-shape branched PEGylated recombinant human growth hormone (YPEG-rhGH) and evaluate its short-term efficacy and safety in children with growth hormone deficiency (GHD).<h4>Methods</h4>A total of 43 children with GHD from 12 sites in China were enrolled in this randomized, multicenter, active-controlled, double-blind (YPEG-rhGH doses) trial. Patients were randomized 1:1:1:1 to 100, 120, and 140 μg/kg/week of ...[more]

PMID: 36034448

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Dataset Information

The pharmacokinetic and pharmacodynamic properties and short-term outcome of a novel once-weekly PEGylated recombinant human growth hormone for children with growth hormone deficiency.

Objectives

Methods

Results

Conclusion

Clinical trial registration

Publications

The pharmacokinetic and pharmacodynamic properties and short-term outcome of a novel once-weekly PEGylated recombinant human growth hormone for children with growth hormone deficiency.

Similar Datasets

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