Genotropin Treatment in Short Prepubertal Children With Intra-Uterine Growth Retardation

A Two Years Multicentre Study of Genotropin Treatment of Short Prepubertal Children With Intra-Uterine Growth Retardation

To evaluate the effect of continuous and intermittent administration of Genotonorm on stature in short prepubertal children with intra-uterine growth retardation

Study Overview

• Status: Completed
• Conditions: Growth Disorders; Intrauterine Growth Retardation
• Intervention / Treatment: Drug: Genotonorm; Drug: Genotonorm; Drug: Genotonorm

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80030
    • Pfizer Investigational Site
  • Angers cedex, France, 49933
    • Pfizer Investigational Site
  • Besancon Cedex, France, 25030
    • Pfizer Investigational Site
  • Bordeaux, France, 33000
    • Pfizer Investigational Site
  • Bordeaux Cedex, France, 33076
    • Pfizer Investigational Site
  • Boulogne, France, 92100
    • Pfizer Investigational Site
  • Brest, France, 29200
    • Pfizer Investigational Site
  • Bron Cedex, France, 69677
    • Pfizer Investigational Site
  • Clermont Ferrand, France, 63000
    • Pfizer Investigational Site
  • Dijon, France, 21034
    • Pfizer Investigational Site
  • Grenoble, France, 38043
    • Pfizer Investigational Site
  • Hyères, France, 83407
    • Pfizer Investigational Site
  • Lille, France, 59000
    • Pfizer Investigational Site
  • Lille, France, 59037
    • Pfizer Investigational Site
  • Marseille cedex 5, France, 13385
    • Pfizer Investigational Site
  • Montpellier, France, 34059
    • Pfizer Investigational Site
  • Nantes Cedex 1, France, 44093
    • Pfizer Investigational Site
  • Nice, France, 06202
    • Pfizer Investigational Site
  • Paris, France, 75019
    • Pfizer Investigational Site
  • Paris, France, 75571
    • Pfizer Investigational Site
  • Paris, France, 75674
    • Pfizer Investigational Site
  • Reims, France, 51092
    • Pfizer Investigational Site
  • Rennes, France, 35033
    • Pfizer Investigational Site
  • Rouen, France, 76000
    • Pfizer Investigational Site
  • Saint Priest en Jarez, France, 42277
    • Pfizer Investigational Site
  • Strasbourg Cedex 2, France, 67098
    • Pfizer Investigational Site
  • Tarbes, France
    • Pfizer Investigational Site
  • Toulouse Cedex, France, 31026
    • Pfizer Investigational Site
  • Tours, France, 37044
    • Pfizer Investigational Site
  • Vandoeuvre Les Nancy Cedex, France, 54511
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronological age (CA) between 3 and 10 for girls
• Chronological age between 3 and 12 for boys
• Height for CA below - 2 SD
• Birth length for CA below -2SD

Exclusion Criteria:

• Endocrine disease except well-substituted hypothyroidism
• Sever chronic disease
• Skeletal dysplasia
• Known chromosomal aberration
• Ongoing treatment with steroids
• Known intrauterine infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Genotonorm A; Continuous 0.7 IU/kg/week or 0.03 mg/kg/day	Drug: Genotonorm; 0.7 IU/kg/week or 0.03 mg/kg/day, daily subcutaneous injection; Drug: Genotonorm; 1.4 IU/kg/week or 0.06 mg/kg/day, daily subcutaneous injection; Drug: Genotonorm; 1.4 IU/kg/week or 0.06 mg/kg/day, daily subcutaneous injection Intermittent treatment (6 months with treatment and 6 months without)
Active Comparator: Genotonorm B; Continuous, 1.4 IU/kg/week or 0.06 mg/kg/day	Drug: Genotonorm; 0.7 IU/kg/week or 0.03 mg/kg/day, daily subcutaneous injection; Drug: Genotonorm; 1.4 IU/kg/week or 0.06 mg/kg/day, daily subcutaneous injection; Drug: Genotonorm; 1.4 IU/kg/week or 0.06 mg/kg/day, daily subcutaneous injection Intermittent treatment (6 months with treatment and 6 months without)
Active Comparator: Genotonorm C; Intermittent, 1.4 IU/kg/week or 0.06 mg/kg/day	Drug: Genotonorm; 0.7 IU/kg/week or 0.03 mg/kg/day, daily subcutaneous injection; Drug: Genotonorm; 1.4 IU/kg/week or 0.06 mg/kg/day, daily subcutaneous injection; Drug: Genotonorm; 1.4 IU/kg/week or 0.06 mg/kg/day, daily subcutaneous injection Intermittent treatment (6 months with treatment and 6 months without)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Annual Growth Rate Measured at 2 Years Following Treatment With Genotonorm	Annual growth rate was expressed as height velocity (centimeter [cm]/year). This was derived by substracting annual growth rate at Baseline from 2-year value. (Annual growth rate was calculated each year and rescaled to 1 year if the interval between x and x-1 was not 365 days, as long as a subject remains in the study): ANGRYx = (Height Yx - Height Y{x-1}) / {(Date of Yx - Date of Y{x-1}) /365.25}	Baseline, 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual Growth Rate Standard Deviation Score (SDS)	Calculated using Sempe reference means and standard deviations for growth rate according to age and sex. Standardization was performed for chronological age.	Baseline, 1 to 6 years
Change From Baseline in Annual Growth Rate SDS	Calculated corresponding to the gender and chronological age by substracting annual growth rate SDS at Baseline from annual growth rate SDS at each year.	Baseline, 1 to 3 years
Height (cm)	Performed by use of a wallmounted device (eg, Harpenden Stadiometer). Each subject was measured 3 times and the mean of these measurements was recorded as the present height. Final Height: Children are defined as reaching their final height when annual Growth Rate is less than 2 cm in the previous year and bone age is equal to or greater than 17 years in boys and equal to or greater than 15 years in girls.	Baseline, 1 to 6 years, final height
Change From Baseline in Height (cm)	Calculated by substracting height at Baseline from height at each year. Final Height: Children are defined as reaching their final height when annual Growth Rate is less than 2 cm in the previous year and bone age is equal to or greater than 17 years in boys and equal to or greater than 15 years in girls.	Baseline, 1 to 6 years, final height
Height (SDS)	Calculated using Sempe reference means and standard deviations for height. Final Height: Children are defined as reaching their final height when annual Growth Rate is less than 2 cm in the previous year and bone age is equal to or greater than 17 years in boys and equal to or greater than 15 years in girls.	Baseline, 1 to 6 years, final height
Change From Baseline in Height (SDS)	Calculated by substracting height SDS at Baseline from height SDS at each year. Final Height: Children are defined as reaching their final height when annual Growth Rate is less than 2 cm in the previous year and bone age is equal to or greater than 17 years in boys and equal to or greater than 15 years in girls.	Baseline, 1 to 6 years, final height
Body Mass Index (BMI)	BMI was calculated by weight divided by height squared.	Baseline, 1 to 6 years
Weight		Baseline, 1 to 6 years
Change From Baseline in Bone Age	Bone age was determined by the Greulich-Pyle method. Calculated by substracting bone age at Baseline from bone age at each year	Baseline, 1 to 3 years
Change From Baseline in Bone Age/Change From Baseline in Chronological Age Ratio	Bone age was determined by the Greulich-Pyle method. Chronological Age (years) was calculated as: (Date minus Date of Birth) divided by 365.25. Chronological Age used was the age at the date that the corresponding Bone Age X-ray was performed. Ratio was calculated by change from Baseline in bone age divided by change from Baseline in chronological age.	1 to 3 years
Chronological Age at Onset of Puberty	Chronological age (years) at first study visit with onset of puberty = (Date of study visit minus Date of Birth) divided by 365.25.	Onset of puberty
Number of Subjects Reaching Puberty	The defined criteria for reaching puberty were: boy=if right or left testes volume ≥4 ml; girl=if breast development ≥2. Tanner Adolescent Pubertal Staging Questionnaire documents the stage of development of secondary sexual characteristics rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size). Onset of puberty was defined as the visit where the data recorded first met the above criteria for starting puberty.	Baseline, 1 to 6 years

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: July 1, 1993
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: February 22, 2010
• First Submitted That Met QC Criteria: February 22, 2010
• First Posted (Estimate): February 23, 2010

Study Record Updates

• Last Update Posted (Estimate): November 18, 2010
• Last Update Submitted That Met QC Criteria: November 8, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: Short height; intra-uterine growth retardation; Genotonorm; continuous treatment; intermittent treatment
• Additional Relevant MeSH Terms: Pathologic Processes; Fetal Diseases; Pregnancy Complications; Fetal Growth Retardation; Growth Disorders
• Other Study ID Numbers: 93-8122-001; A6281186, CTN 93-8122-001