Format

Send to

Choose Destination
Horm Res Paediatr. 2017;87(5):324-332. doi: 10.1159/000470842. Epub 2017 Apr 11.

Pharmacokinetic and Pharmacodynamic Modeling of MOD-4023, a Long-Acting Human Growth Hormone, in Growth Hormone Deficiency Children.

Author information

1
P Less Than, San Francisco, California, USA.
2
Stat5 Consulting, LLC, Los Altos, California, USA.
3
OPKO Biologics, Kiryat Gat, Israel.

Abstract

BACKGROUND/AIMS:

MOD-4023 is a long-acting human growth hormone (hGH) in clinical trials for the treatment of growth hormone deficiency (GHD). A key goal is maintenance of serum concentrations of insulin-like growth factor (IGF) 1 within normal range throughout GH dosing. The study aimed to develop a pharmacokinetic model for MOD-4023 and a pharmacodynamic model for the effect of MOD-4023 on IGF-1 to allow estimation of peak and mean IGF-1 and to identify the optimal IGF-1 sampling day.

METHODS:

MOD-4023 (0.25, 0.48, or 0.66 mg/kg) was administered weekly for 12 months to 41 GH-naive GHD children (age 3-11 years). The control group (n = 11, age 4-9 years) received daily recombinant human growth hormone (r-hGH; 34 µg/kg). Sparse samples (4/subject) were obtained to determine serum concentrations of MOD-4023 or r-hGH and IGF-1.

RESULTS:

A 2-compartment pharmacokinetic model with first-order absorption fit MOD-4023 data well; a 1-compartment model was appropriate for r-hGH. For both, weight-normalized systemic parameters were preferred over allometric scaling. For MOD-4023, an indirect model fit IGF-1 SDS data well; baseline IGF-1 increased over time. At steady state, samples obtained 4 days following dose administration predicted mean IGF-1 SDS during the dosing interval well.

CONCLUSION:

The IGF-1 profile is consistent with the weekly dosing interval. Sampling 4 days following dose administration allows estimation of mean IGF-1 SDS during the dosing interval in GHD patients.

KEYWORDS:

Growth hormone; Growth hormone deficiency; Growth hormone replacement; Growth in children; Insulin growth factor 1; Long-acting growth hormone; Pharmacokinetic/pharmacodynamic modeling; Weekly growth hormone

PMID:
28399519
PMCID:
PMC5637306
DOI:
10.1159/000470842
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for S. Karger AG, Basel, Switzerland Icon for PubMed Central
Loading ...
Support Center