Crossover Study to Assess the Safety and Pharmacokinetic of Pegylated Somatropin(PEG Somatropin) in GHD Children

Study Overview
=================
Brief Summary
-----------------
The purpose of the phase 1 study is to assess the safety and pharmacokinetics of PEG somatropin, which administered once per week, compared with the daily used somatropin, and to evaluate the safety and possibility to replace daily used somatropin.

Official Title
-----------------
A Phase 1, Open-Label, Single and Multiple Dose Study to Assess the Safety and Pharmacokinetics of Pegylated Somatropin(PEG Somatropin) in GHD Children

Conditions
-----------------
Growth Hormone Deficiency

Intervention / Treatment
-----------------
* Drug: somatropin AQ
* Drug: pegylated somatropin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: have a height less than two standard deviations (SD) below the median height for individuals of the same age or height, a growth velocity (GV) ≤4 cm/yr, a GH peak concentration <7 ng/ml in two different provocative tests, a bone age (BA; ≤9 years in girls and ≤10 years in boys) at least 2 years less than his/her chronological age (CA);be in preadolescence (Tanner stage 1) and have a CA >3 years;have a height value recorded 3 months before the start of GH treatment to calculate pre-treatment GV; receive no prior GH treatment or stop the GH treatment for more than 4 weeks;sign informed consent Exclusion Criteria: Patients with Liver and kidney dysfunction (ALT> upper limit of normal 2 times, Cr> upper limit of normal), hepatitis B virus detection, antigen-HBc, HBsAg and HBeAg are positive patients with known to a highly allergic constitution or allergic to the drug of this study Patients with diabetes, serious cardiopulmonary, blood system, malignant tumor and other diseases or systemic infection in immunocompromised and mental diseases Patients with other growth disorders, such as Turner syndrome, constitutional delay of growth and puberty, Laron syndrome, GH receptor deficiency, girls with growth delay have not ruled out chromosomal abnormalities Participated in clinical trials of other drugs in 3 months Other cases that the researchers considered unsuitable for this clinical trial

Ages Eligible for Study
-----------------
Minimum Age: 4 Years
Maximum Age: 10 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: somatropin AQ|somatropin injection 0.2mg/kg/w once per day, inject for 7 continuous days 4 weeks for cleaning period|
|Drug: pegylated somatropin|Pegylated somatropin 0.2mg/kg/w once per week, for continuous 6 weeks Subcutaneous injection|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetics parameter | Cmax, AUC during the time interval for the first dose and last dose, Half-Life(t1/2), Apparent body clearance(CL), Mean residence time(MRT),steady-state volume of distribution(Vss) | Somatropin AQ: predose(0),1,2,3,4,6,8,10,12,16,20,24 hours post-dose. PEG somatropin: predose (0),2,4,8,12,18,24,36,48,72,96,120,144,168 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IGF-1, IGFBP-3 |  | Day I to Day 7 in each treatment period (33 time points) for daily used somatropin, Day I to Day 42 in each treatment period (35 time points) for PEG somatropin | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pegylated Somatropin, PEG-GH, Phase 1 study, Pharmacokinetics