Growth Retardation In Children With Special Pathological Conditions Or Disease

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00163215
• Collaborator: (none)
• Enrollment: 46
• Locations: 18
• Arm: 1
• Duration (Months): 81
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

To show an increase in annual growth rate 3 years after Visit 2. Annual growth rate in standard deviation (SD) after 3 years will be compared to growth rate before the start of GH treatment.

Condition or Disease	Intervention/Treatment	Phase
Endocrine System Diseases	Drug: Somatropin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evolution Of Growth Rate In Children Suffering From A Disease Associated With Growth Retardation and Treated By Genotonorm. A Pilot Study.
• Study Start Date: Jan 1, 2005
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Somatropin	Drug: Somatropin; Adapted dosage based on IGF 1 level and weight Form: liquid; Dosage and Frequency: from 0.0033mg/kg/day to 0.0067 mg/kg/day; Duration: 3 years

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36 in Intent-to-Treat (ITT) Population [Baseline, Month 36]

   Change in annual growth rate (AGR) standard deviation score (SDS) for chronological age (CA) derived by subtracting AGR SDS CA at baseline from each time point (Yx) value. AGR at Yx= (height Yx-height Y[x-1])/([date of Yx-date of Y{x-1}]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25*12. SDS indicates how similar participant was to reference population.

2. Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36 in Per-Protocol (PP) Population [Baseline, Month 36]

   Change in annual growth rate (AGR) standard deviation score (SDS) for chronological age (CA) derived by subtracting AGR SDS CA at baseline from each time point (Yx) value. AGR at Yx= (height Yx-height Y[x-1])/([date of Yx-date of Y{x-1}]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25*12. SDS indicates how similar participant was to reference population.

Secondary Outcome Measures

1. Change From Baseline in Annual Growth Rate at Month 12, Month 24 and Month 36 in ITT Population [Baseline, Month 12, Month 24, Month 36]

   Change in AGR at Yx was derived by subtracting AGR at baseline from Yx value. Annual growth rate was calculated each year and rescaled to 1 year if the interval between Yx and Y[x-1] was not 365 days, as long as a participant remained in the study. AGR at Yx was calculated using the previous height measurements (Y[x-1]) and height recorded at Yx (AGR Yx = [height Yx-height Y{x-1}] / ([date of Yx - date of Y{x-1}] /365.25).

2. Change From Baseline in Annual Growth Rate at Month 12, Month 24, Month 36 in PP Population [Baseline, Month 12, Month 24, Month 36]

   Change in AGR at Yx was derived by subtracting AGR at baseline from Yx value. Annual growth rate was calculated each year and rescaled to 1 year if the interval between Yx and Y[x-1] was not 365 days, as long as a participant remained in the study. AGR at Yx was calculated using the previous height measurements (Y[x-1]) and height recorded at Yx (AGR Yx = [height Yx-height Y{x-1}] / ([date of Yx - date of Y{x-1}] /365.25).

3. Height [Baseline, Month 12, Month 24, Month 36]

   Height was measured using a wall mounted device (example, Harpenden stadiometer). The standing height of the participant was measured two times and the mean of these measurements was recorded.

4. Change From Baseline in Height at Month 12, Month 24 and Month 36 [Baseline, Month 12, Month 24, Month 36]

   Height was measured using a wall mounted device (example, Harpenden stadiometer). The standing height of the participant was measured two times and the mean of these measurements was recorded.

5. Mean Height Standard Deviation Score (SDS) for Chronological Age (CA) [Baseline, Month 12, Month 24, Month 36]

   Height was measured using a wall mounted device (example, Harpenden stadiometer). The standing height of the participant was measured two times and the mean of these measurements was recorded. Height SDS CA Yx = (height Yx - reference mean for CA Yx) / reference SD for CA Yx. Height in SDS was calculated using Sempe reference means and SD for height. CA calculated as integer (Date of height measurement-Date of birth)/365.25*12. SDS indicates how similar the participant was to the reference population.

6. Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12, Month 24 and Month 36 [Baseline, Month 12, Month 24, Month 36]

   Change in height SDS CA was derived by subtracting height SDS CA at baseline from Yx value. Height SDS CA (for both baseline and Yx) = (height - reference mean for CA)/reference SD for CA. Height in SDS was calculated using Sempe reference means and SD for height. CA calculated as integer (Date of height measurement - Date of birth)/365.25*12. SDS indicates how similar the participant was to the reference population.

7. Mean Height Standard Deviation Score (SDS) for Bone Age (BA) [Baseline, Month 12, Month 24, Month 36]

   Height SDS BA Yx = (height Yx - reference mean for BA Yx) / reference SD for BA Yx. Height in SDS was calculated using Sempe reference means and SD for height. BA was estimated locally using an X-ray from the left wrist and hand. SDS indicates how similar the participant was to the reference population.

8. Change From Baseline in Height Standard Deviation Score (SDS) for Bone Age (BA) at Month 12, Month 24 and Month 36 [Baseline, Month 12, Month 24, Month 36]

   Change in height SDS BA was derived by subtracting height SDS BA at baseline from Yx value. Height SDS BA (for both baseline and Yx) = (height-reference mean for BA)/reference SD for BA. Height in SDS was calculated using Sempe reference means and SD for height. BA was estimated locally using an X-ray from the left wrist and hand. SDS indicates how similar the participant was to the reference population.

9. Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12 and Month 24 in ITT Population [Baseline, Month 12, Month 24]

   Change in AGR SDS for CA derived by subtracting AGR SDS CA at baseline from Yx value. AGR at Yx= (height Yx-height Y[x-1])/([date of Yx-date of Y{x-1}]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25*12. SDS indicates how similar participant was to reference population.

10. Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12 and Month 24 in PP Population [Baseline, Month 12, Month 24]

    Change in annual growth rate (AGR) standard deviation score (SDS) for chronological age (CA) derived by subtracting AGR SDS CA at baseline from each time point (Yx) value. AGR at Yx= (height Yx-height Y[x-1])/([date of Yx-date of Y{x-1}]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25*12. SDS indicates how similar participant was to reference population.

11. Mean Growth Rate Standard Deviation Score (SDS) for Bone Age (BA) [Month 12, Month 24, Month 36]

    AGR at Yx was derived by subtracting AGR at baseline from Yx value. AGR was calculated each year and rescaled to 1 year if the interval between Yx and Y[x-1] was not 365 days, as long as a participant remained in the study. AGR at Yx = [height Yx-height Y{x-1}] / ([date of Yx - date of Y{x-1}] /365.25). GR in SDS was calculated using Sempe reference means and SD for growth. BA was estimated locally using an X-ray from the left wrist and hand. SDS indicates how similar the participant was to the reference population.

12. Body Mass Index (BMI) [Baseline, Month 12, Month 24, Month 36]

    BMI was used to measure body fat based on height and weight. It was calculated as body weight (kilogram) divided by the height (meter) squared.

13. Change From Baseline in Body Mass Index (BMI) at Month 12, Month 24 and Month 36 [Baseline, Month 12, Month 24, Month 36]

    BMI was used to measure body fat based on height and weight. It was calculated as body weight (kilogram) divided by the height (meter) squared.

14. Change From Baseline in Bone Age (BA) at Month 12, Month 24 and Month 36 [Baseline, Month 12, Month 24, Month 36]

    BA was estimated locally using an X-ray from the left wrist and hand.

15. Ratio of Bone Age (BA) to Chronological Age (CA) [Baseline, Month 12, Month 24, Month 36]

    BA was estimated locally using an X-ray from the left wrist and hand. CA at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA at each annual study visit was calculated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 11 Years to 13 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Bone age < 13 years for a boy and < 11 years for a girl

• Naive child: Measured Height < -2.5 SD for CA

• Child currently treated by GH

Exclusion Criteria:

• Idiopathic short stature

• Syndrome known to be associated with an increased risk of cancer e.g. family history of adenomatous polyposis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Annemasse Cedex		France	74107
2	Pfizer Investigational Site	Besancon		France	25030
3	Pfizer Investigational Site	Bordeaux		France	33000
4	Pfizer Investigational Site	Bordeaux		France	33076
5	Pfizer Investigational Site	Bron Cedex		France	69677
6	Pfizer Investigational Site	Dijon		France	21000
7	Pfizer Investigational Site	Grenoble Cedex		France	38043
8	Pfizer Investigational Site	Lorient		France	56100
9	Pfizer Investigational Site	Lyon Cedex 05		France	69322
10	Pfizer Investigational Site	Marseille		France	13385
11	Pfizer Investigational Site	Montpellier		France	34059
12	Pfizer Investigational Site	Paris		France	75015
13	Pfizer Investigational Site	Paris		France	75019
14	Pfizer Investigational Site	Paris		France	75571
15	Pfizer Investigational Site	Paris		France	75674 Cedex
16	Pfizer Investigational Site	PRINGY Cedex		France	74374
17	Pfizer Investigational Site	Toulouse Cedex		France	31026
18	Pfizer Investigational Site	Vandoeuvre Les Nancy Cedex		France	54511

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00163215
• Other Study ID Numbers: A6281269
• First Posted: Sep 13, 2005
• Last Update Posted: Dec 19, 2012
• Last Verified: Nov 1, 2012

• Additional relevant MeSH terms: Endocrine System Diseases

Study Results

Participant Flow

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Period Title: Overall Study
STARTED	46
COMPLETED	31
NOT COMPLETED	15

Baseline Characteristics

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Overall Participants	46
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.3 (3.6)
Sex: Female, Male (Count of Participants)
Female	12 26.1%
Male	34 73.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36 in Intent-to-Treat (ITT) Population
Description	Change in annual growth rate (AGR) standard deviation score (SDS) for chronological age (CA) derived by subtracting AGR SDS CA at baseline from each time point (Yx) value. AGR at Yx= (height Yx-height Y[x-1])/([date of Yx-date of Y{x-1}]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25*12. SDS indicates how similar participant was to reference population.
Time Frame	Baseline, Month 36

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies participants evaluated at that time point.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	42
Baseline (n = 42)	-1.29 (1.79)
Change at Month 36 (n = 26)	2.36 (1.98)

2. Primary Outcome

Title	Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36 in Per-Protocol (PP) Population
Description	Change in annual growth rate (AGR) standard deviation score (SDS) for chronological age (CA) derived by subtracting AGR SDS CA at baseline from each time point (Yx) value. AGR at Yx= (height Yx-height Y[x-1])/([date of Yx-date of Y{x-1}]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25*12. SDS indicates how similar participant was to reference population.
Time Frame	Baseline, Month 36

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) analysis set included all participants in the ITT set without a major protocol violation. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies participants evaluated at that time point.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	14
Baseline (n = 14)	-1.98 (1.06)
Change at Month 36 (n = 12)	2.70 (2.02)

3. Secondary Outcome

Title	Change From Baseline in Annual Growth Rate at Month 12, Month 24 and Month 36 in ITT Population
Description	Change in AGR at Yx was derived by subtracting AGR at baseline from Yx value. Annual growth rate was calculated each year and rescaled to 1 year if the interval between Yx and Y[x-1] was not 365 days, as long as a participant remained in the study. AGR at Yx was calculated using the previous height measurements (Y[x-1]) and height recorded at Yx (AGR Yx = [height Yx-height Y{x-1}] / ([date of Yx - date of Y{x-1}] /365.25).
Time Frame	Baseline, Month 12, Month 24, Month 36

Outcome Measure Data

Analysis Population Description

ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies participants evaluated at that time point.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	42
Baseline (n = 42)	4.5 (1.8)
Change at Month 12 (n = 36)	3.3 (2.9)
Change at Month 24 (n = 35)	2.5 (2.7)
Change at Month 36 (n = 26)	2.0 (2.0)

4. Secondary Outcome

Title	Change From Baseline in Annual Growth Rate at Month 12, Month 24, Month 36 in PP Population
Description	Change in AGR at Yx was derived by subtracting AGR at baseline from Yx value. Annual growth rate was calculated each year and rescaled to 1 year if the interval between Yx and Y[x-1] was not 365 days, as long as a participant remained in the study. AGR at Yx was calculated using the previous height measurements (Y[x-1]) and height recorded at Yx (AGR Yx = [height Yx-height Y{x-1}] / ([date of Yx - date of Y{x-1}] /365.25).
Time Frame	Baseline, Month 12, Month 24, Month 36

Outcome Measure Data

Analysis Population Description

PP analysis set included all participants in the ITT set without a major protocol violation. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies participants evaluated at that time point.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	14
Baseline (n = 14)	4.0 (1.0)
Change at Month 12 (n = 14)	4.0 (1.0)
Change at Month 24 (n = 14)	2.5 (1.3)
Change at Month 36 (n = 12)	1.8 (1.1)

5. Secondary Outcome

Title	Height
Description	Height was measured using a wall mounted device (example, Harpenden stadiometer). The standing height of the participant was measured two times and the mean of these measurements was recorded.
Time Frame	Baseline, Month 12, Month 24, Month 36

Outcome Measure Data

Analysis Population Description

ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here "n" signifies those participants evaluated at that time point.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	44
Baseline (n = 44)	123.9 (17.3)
Month 12 (n = 39)	130.3 (17.5)
Month 24 (n = 39)	137.8 (16.9)
Month 36 (n = 27)	143.5 (15.8)

6. Secondary Outcome

Title	Change From Baseline in Height at Month 12, Month 24 and Month 36
Description	Height was measured using a wall mounted device (example, Harpenden stadiometer). The standing height of the participant was measured two times and the mean of these measurements was recorded.
Time Frame	Baseline, Month 12, Month 24, Month 36

Outcome Measure Data

Analysis Population Description

ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies participants evaluated at that time point.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	39
Change at Month 12 (n = 39)	7.7 (2.1)
Change at Month 24 (n = 39)	14.9 (3.4)
Change at Month 36 (n = 27)	22.3 (3.7)

7. Secondary Outcome

Title	Mean Height Standard Deviation Score (SDS) for Chronological Age (CA)
Description	Height was measured using a wall mounted device (example, Harpenden stadiometer). The standing height of the participant was measured two times and the mean of these measurements was recorded. Height SDS CA Yx = (height Yx - reference mean for CA Yx) / reference SD for CA Yx. Height in SDS was calculated using Sempe reference means and SD for height. CA calculated as integer (Date of height measurement-Date of birth)/365.25*12. SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline, Month 12, Month 24, Month 36

Outcome Measure Data

Analysis Population Description

ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here "n" signifies those participants evaluated at that time point.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	44
Baseline (n = 44)	-2.84 (0.91)
Month 12 (n = 39)	-2.42 (0.98)
Month 24 (n = 39)	-2.09 (1.08)
Month 36 (n = 27)	-1.72 (0.96)

8. Secondary Outcome

Title	Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12, Month 24 and Month 36
Description	Change in height SDS CA was derived by subtracting height SDS CA at baseline from Yx value. Height SDS CA (for both baseline and Yx) = (height - reference mean for CA)/reference SD for CA. Height in SDS was calculated using Sempe reference means and SD for height. CA calculated as integer (Date of height measurement - Date of birth)/365.25*12. SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline, Month 12, Month 24, Month 36

Outcome Measure Data

Analysis Population Description

ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies participants evaluated at that time point.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	39
Change at Month 12 (n = 39)	0.41 (0.42)
Change at Month 24 (n = 39)	0.81 (0.60)
Change at Month 36 (n = 27)	1.03 (0.62)

9. Secondary Outcome

Title	Mean Height Standard Deviation Score (SDS) for Bone Age (BA)
Description	Height SDS BA Yx = (height Yx - reference mean for BA Yx) / reference SD for BA Yx. Height in SDS was calculated using Sempe reference means and SD for height. BA was estimated locally using an X-ray from the left wrist and hand. SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline, Month 12, Month 24, Month 36

Outcome Measure Data

Analysis Population Description

ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies participants evaluated at that time point.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	35
Baseline (n = 35)	-0.71 (1.52)
Month 12 (n = 32)	-0.55 (1.68)
Month 24 (n = 32)	-0.49 (1.77)
Month 36 (n = 20)	-0.30 (1.46)

10. Secondary Outcome

Title	Change From Baseline in Height Standard Deviation Score (SDS) for Bone Age (BA) at Month 12, Month 24 and Month 36
Description	Change in height SDS BA was derived by subtracting height SDS BA at baseline from Yx value. Height SDS BA (for both baseline and Yx) = (height-reference mean for BA)/reference SD for BA. Height in SDS was calculated using Sempe reference means and SD for height. BA was estimated locally using an X-ray from the left wrist and hand. SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline, Month 12, Month 24, Month 36

Outcome Measure Data

Analysis Population Description

ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies participants evaluated at that time point.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	28
Change at Month 12 (n = 28)	-0.05 (1.04)
Change at Month 24 (n = 27)	0.06 (1.36)
Change at Month 36 (n = 17)	0.05 (1.32)

11. Secondary Outcome

Title	Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12 and Month 24 in ITT Population
Description	Change in AGR SDS for CA derived by subtracting AGR SDS CA at baseline from Yx value. AGR at Yx= (height Yx-height Y[x-1])/([date of Yx-date of Y{x-1}]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25*12. SDS indicates how similar participant was to reference population.
Time Frame	Baseline, Month 12, Month 24

Outcome Measure Data

Analysis Population Description

ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	36
Change at Month 12 (n = 36)	3.23 (2.66)
Change at Month 24 (n = 35)	2.62 (2.05)

12. Secondary Outcome

Title	Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12 and Month 24 in PP Population
Description	Change in annual growth rate (AGR) standard deviation score (SDS) for chronological age (CA) derived by subtracting AGR SDS CA at baseline from each time point (Yx) value. AGR at Yx= (height Yx-height Y[x-1])/([date of Yx-date of Y{x-1}]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25*12. SDS indicates how similar participant was to reference population.
Time Frame	Baseline, Month 12, Month 24

Outcome Measure Data

Analysis Population Description

PP analysis set included all participants in the ITT set without a major protocol violation. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	14
Change at Month 12 (n = 14)	4.40 (2.12)
Change at Month 24 (n = 14)	2.97 (1.68)

13. Secondary Outcome

Title	Mean Growth Rate Standard Deviation Score (SDS) for Bone Age (BA)
Description	AGR at Yx was derived by subtracting AGR at baseline from Yx value. AGR was calculated each year and rescaled to 1 year if the interval between Yx and Y[x-1] was not 365 days, as long as a participant remained in the study. AGR at Yx = [height Yx-height Y{x-1}] / ([date of Yx - date of Y{x-1}] /365.25). GR in SDS was calculated using Sempe reference means and SD for growth. BA was estimated locally using an X-ray from the left wrist and hand. SDS indicates how similar the participant was to the reference population.
Time Frame	Month 12, Month 24, Month 36

Outcome Measure Data

Analysis Population Description

ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies participants evaluated at that time point.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	28
Month 12 (n = 28)	1.06 (1.57)
Month 24 (n = 25)	0.46 (1.15)
Month 36 (n = 19)	-0.01 (1.19)

14. Secondary Outcome

Title	Body Mass Index (BMI)
Description	BMI was used to measure body fat based on height and weight. It was calculated as body weight (kilogram) divided by the height (meter) squared.
Time Frame	Baseline, Month 12, Month 24, Month 36

Outcome Measure Data

Analysis Population Description

ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here "n" signifies those participants evaluated at that time point.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	44
Baseline (n = 44)	16.57 (2.37)
Month 12 (n = 39)	16.96 (2.64)
Month 24 (n = 39)	17.59 (2.69)
Month 36 (n = 27)	17.67 (2.08)

15. Secondary Outcome

Title	Change From Baseline in Body Mass Index (BMI) at Month 12, Month 24 and Month 36
Description	BMI was used to measure body fat based on height and weight. It was calculated as body weight (kilogram) divided by the height (meter) squared.
Time Frame	Baseline, Month 12, Month 24, Month 36

Outcome Measure Data

Analysis Population Description

ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies participants evaluated at that time point.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	39
Change at Month 12 (n = 39)	0.52 (1.01)
Change at Month 24 (n = 39)	1.30 (1.35)
Change at Month 36 (n = 27)	1.89 (1.61)

16. Secondary Outcome

Title	Change From Baseline in Bone Age (BA) at Month 12, Month 24 and Month 36
Description	BA was estimated locally using an X-ray from the left wrist and hand.
Time Frame	Baseline, Month 12, Month 24, Month 36

Outcome Measure Data

Analysis Population Description

ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies participants evaluated at that time point.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	40
Baseline (n = 40)	8.70 (3.28)
Change at Month 12 (n = 28)	1.69 (0.90)
Change at Month 24 (n = 28)	2.60 (0.97)
Change at Month 36 (n = 21)	4.04 (1.09)

17. Secondary Outcome

Title	Ratio of Bone Age (BA) to Chronological Age (CA)
Description	BA was estimated locally using an X-ray from the left wrist and hand. CA at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA at each annual study visit was calculated.
Time Frame	Baseline, Month 12, Month 24, Month 36

Outcome Measure Data

Analysis Population Description

ITT set included all participants who received at least 1 dose of study medication and had at least 1 evaluation of height after start of study medication. Here 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure and "n" signifies those participants evaluated at that time point.

Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
Measure Participants	40
Baseline (n = 40)	0.79 (0.15)
Month 12 (n = 30)	0.83 (0.15)
Month 24 (n = 32)	0.85 (0.12)
Month 36 (n = 23)	0.89 (0.14)

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Genotonorm
Arm/Group Description	Genotonorm (recombinant somatropin) up to maximum of 50 microgram/kilogram/day (mcg/kg/day) subcutaneously as decided by the investigator, divided in 7 daily doses for up to 3 years.
All Cause Mortality
	Genotonorm
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Genotonorm
	Affected / at Risk (%)	# Events
Total	4/46 (8.7%)
Congenital, familial and genetic disorders
Cryptorchism	1/46 (2.2%)
Infections and infestations
Laryngitis	1/46 (2.2%)
Staphylococcal infection	1/46 (2.2%)
Staphylococcal sepsis	1/46 (2.2%)
Viral infection	1/46 (2.2%)
Injury, poisoning and procedural complications
Head injury	1/46 (2.2%)
Investigations
Weight decreased	1/46 (2.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Histiocytosis haematophagic	1/46 (2.2%)
Other (Not Including Serious) Adverse Events
	Genotonorm
	Affected / at Risk (%)	# Events
Total	21/46 (45.7%)
Gastrointestinal disorders
Diarrhoea	2/46 (4.3%)
Infections and infestations
Bronchopulmonary aspergillosis allergic	1/46 (2.2%)
Influenza	1/46 (2.2%)
Laryngitis	1/46 (2.2%)
Nasopharyngitis	1/46 (2.2%)
Oral herpes	2/46 (4.3%)
Tracheitis	1/46 (2.2%)
Injury, poisoning and procedural complications
Joint injury	1/46 (2.2%)
Ligament sprain	1/46 (2.2%)
Investigations
Ammonia increased	1/46 (2.2%)
Metabolism and nutrition disorders
Glucose tolerance impaired	1/46 (2.2%)
Insulin resistance	1/46 (2.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/46 (2.2%)
Back pain	1/46 (2.2%)
Bone pain	1/46 (2.2%)
Knee deformity	1/46 (2.2%)
Muscle spasms	1/46 (2.2%)
Rickets	1/46 (2.2%)
Scoliosis	1/46 (2.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus	1/46 (2.2%)
Nervous system disorders
Headache	5/46 (10.9%)
Loss of consciousness	1/46 (2.2%)
Psychiatric disorders
Abnormal behaviour	1/46 (2.2%)
Encopresis	1/46 (2.2%)
Renal and urinary disorders
Enuresis	1/46 (2.2%)
Renal failure	1/46 (2.2%)
Respiratory, thoracic and mediastinal disorders
Cough	1/46 (2.2%)
Rhinitis allergic	1/46 (2.2%)
Sleep apnoea syndrome	1/46 (2.2%)
Skin and subcutaneous tissue disorders
Nail disorder	1/46 (2.2%)
Seborrhoeic dermatitis	1/46 (2.2%)
Skin irritation	1/46 (2.2%)
Surgical and medical procedures
Ear tube insertion	1/46 (2.2%)
Vascular disorders
Haematoma	1/46 (2.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.