Prevention of Growth Retardation by Early Treatment With Growth Hormone (GH) in Children With CJA Treated by Corticosteroid Therapy

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00174291
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arm: 1
• Duration (Months): 115
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

• To evaluate the effect of increasing the growth hormone dose on the statural response

• To assess the value of early treatment during the course of arthritic disease by comparing the height acquired in the medium term by children in the two groups: treated from the start, or 1 year to 15 months after the diagnosis of CJA, or treated for 4 years after the diagnosis

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

Detailed Description

This trial terminated on 10-Jun-2011 due to prolonged issues with drug accountability and data collection discrepancies. The decision to terminate was not based on any safety concerns.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prevention of Retarded Growth by Early Treatment With Recombinant Human Growth Factor Genotonorm (Registered) in Children With Systemic Forms of Chronic Juvenile Arthritis Receiving Long-term Corticosteroid Therapy. Extension of the Study Beyond Three Years
• Study Start Date: Mar 1, 2002
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Somatropin	Drug: Somatropin; Liquid, daily to final height Maximum Dosage: 50 µg/kg/day

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Annual Rate of Growth Standard Deviation Score (SDS) at Year 3 [Baseline, Year 3]

   Annual rate of growth SDS was obtained by measuring the annual growth rate, subtracting chronological age- and gender-appropriate mean annual growth rate and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population.

2. Change From Baseline in Annual Rate of Growth Standard Deviation Score (SDS) at Final Height [Baseline, final height (assessed up to Year 9.5)]

   Annual rate of growth SDS was obtained by measuring the annual growth rate, subtracting chronological age- and gender-appropriate mean annual growth rate and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population.

3. Change From Baseline in Height Standard Deviation Score (SDS) at Year 3 [Baseline, Year 3]

   Height was measured using a wall mounted device (example, Harpenden stadiometer). Height SDS was obtained by measuring the height, subtracting chronological age- and gender-appropriate mean height and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population.

4. Change From Baseline in Height Standard Deviation Score (SDS) at Final Height [Baseline, final height (assessed up to Year 9.5)]

   Height was measured using a wall mounted device (example, Harpenden stadiometer). Height SDS was obtained by measuring the height, subtracting chronological age- and gender-appropriate mean height and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population.

5. Change From Baseline in Predicted Height Standard Deviation Score (SDS) at Year 3 [Baseline, Year 3]

   Predicted height was calculated according to Greulich and Pyle using Bayley Pinneau method. Predicted height SDS was obtained by calculating the predicted height, subtracting chronological age- and gender-appropriate mean predicted height and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population.

6. Change From Baseline in Predicted Height Standard Deviation Score (SDS) at Final Height [Baseline, final height (assessed up to Year 9.5)]

   Predicted height was calculated according to Greulich and Pyle using Bayley Pinneau method. Predicted height SDS was obtained by calculating the predicted height, subtracting chronological age- and gender-appropriate mean predicted height and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population.

Secondary Outcome Measures

1. Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) Concentration at Year 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5 and 9 [Baseline, Year 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9]

2. Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGFBP3) Concentration at Year 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5 and 9 [Baseline, Year 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9]

3. Change From Baseline in Lean Mass and Fat Mass at Year 1, 2, 3, 4, 5, 6, 7, 8 and 9 [Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9]

   Lean mass and fat mass: measurements of body composition assessed using Dual Energy X-ray Absorptiometry (DEXA) scan.

4. Change From Baseline in Bone Mineralization at Year 1, 2, 3, 4, 5, 6, 7, 8 and 9 [Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9]

   Bone mineralization, an estimate of the amount of mineral (such as calcium) in the bone, was assessed using DEXA scan.

5. Change From Baseline in Weight Standard Deviation Score (SDS) at Year 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5 and 9 [Baseline, Year 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9]

   Body weight was measured using a balance scale. Weight SDS was obtained by measuring the weight, subtracting age- and gender- appropriate mean weight and dividing the result by standard deviation of that mean (as obtained from age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population.

6. Change From Baseline in Corticosteroid Dose at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5 and 9 [Baseline, Year 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 14 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• This study will be proposed to all patients previously included in study CTN 97-8129-016

Exclusion Criteria:

• Discontinuation of corticosteroid therapy for more than a year during study CTN 97-8129-016

• Patients withdrawing from the study prematurely

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Paris		France	75019

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: NCT00174291
• Other Study ID Numbers: 307-MET-9002-052; A6281024
• First Posted: Sep 15, 2005
• Last Update Posted: Dec 4, 2012
• Last Verified: Oct 1, 2012

• Additional relevant MeSH terms: Endocrine System Diseases

Study Results

Participant Flow

Recruitment Details	Participants included in previous study CTN 97-8129-016 were eligible for this study.

Arm/Group Title	Somatropin (With Previous Somatropin Exposure)	Somatropin (Without Previous Somatropin Exposure)
Arm/Group Description	Participants who received low dose of somatropin (Genotonorm) for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 milligram per kilogram per week (mg/kg/week), equivalent to 1.8 international units/kg/week (IU/kg/week), divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 microgram/kg/day (mcg/kg/day), equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 centimeter (cm) per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.	Participants who received matching placebo for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 mg/kg/week, equivalent to 1.8 IU/kg/week, divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 mcg/kg/day, equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 cm per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.
Period Title: Overall Study
STARTED	11	10
COMPLETED	6	4
NOT COMPLETED	5	6

Baseline Characteristics

Arm/Group Title	Somatropin (With Previous Somatropin Exposure)	Somatropin (Without Previous Somatropin Exposure)	Total
Arm/Group Description	Participants who received low dose of somatropin (Genotonorm) for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 milligram per kilogram per week (mg/kg/week), equivalent to 1.8 international units/kg/week (IU/kg/week), divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 microgram/kg/day (mcg/kg/day), equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 centimeter (cm) per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.	Participants who received matching placebo for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 mg/kg/week, equivalent to 1.8 IU/kg/week, divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 mcg/kg/day, equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 cm per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.	Total of all reporting groups
Overall Participants	11	10	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.3 (2.6)	8.5 (3.3)	8.4 (2.9)
Sex: Female, Male (Count of Participants)
Female	6 54.5%	4 40%	10 47.6%
Male	5 45.5%	6 60%	11 52.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Annual Rate of Growth Standard Deviation Score (SDS) at Year 3
Description	Annual rate of growth SDS was obtained by measuring the annual growth rate, subtracting chronological age- and gender-appropriate mean annual growth rate and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population.
Time Frame	Baseline, Year 3

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants who received at least 1 dose of study treatment and had at least 1 post-baseline height measurement. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Somatropin (With Previous Somatropin Exposure)	Somatropin (Without Previous Somatropin Exposure)
Arm/Group Description	Participants who received low dose of somatropin (Genotonorm) for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 milligram per kilogram per week (mg/kg/week), equivalent to 1.8 international units/kg/week (IU/kg/week), divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 microgram/kg/day (mcg/kg/day), equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 centimeter (cm) per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.	Participants who received matching placebo for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 mg/kg/week, equivalent to 1.8 IU/kg/week, divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 mcg/kg/day, equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 cm per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.
Measure Participants	6	9
Baseline	-0.21	-2.96
Change at Year 3	1.34	3.52

2. Primary Outcome

Title	Change From Baseline in Annual Rate of Growth Standard Deviation Score (SDS) at Final Height
Description	Annual rate of growth SDS was obtained by measuring the annual growth rate, subtracting chronological age- and gender-appropriate mean annual growth rate and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population.
Time Frame	Baseline, final height (assessed up to Year 9.5)

Outcome Measure Data

Analysis Population Description

Data was not analyzed because of change in planned analysis after early termination of the study.

Arm/Group Title	Somatropin (With Previous Somatropin Exposure)	Somatropin (Without Previous Somatropin Exposure)
Arm/Group Description	Participants who received low dose of somatropin (Genotonorm) for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 milligram per kilogram per week (mg/kg/week), equivalent to 1.8 international units/kg/week (IU/kg/week), divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 microgram/kg/day (mcg/kg/day), equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 centimeter (cm) per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.	Participants who received matching placebo for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 mg/kg/week, equivalent to 1.8 IU/kg/week, divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 mcg/kg/day, equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 cm per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.
Measure Participants	0	0

3. Primary Outcome

Title	Change From Baseline in Height Standard Deviation Score (SDS) at Year 3
Description	Height was measured using a wall mounted device (example, Harpenden stadiometer). Height SDS was obtained by measuring the height, subtracting chronological age- and gender-appropriate mean height and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population.
Time Frame	Baseline, Year 3

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of study treatment and had at least 1 post-baseline height measurement. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Somatropin (With Previous Somatropin Exposure)	Somatropin (Without Previous Somatropin Exposure)
Arm/Group Description	Participants who received low dose of somatropin (Genotonorm) for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 milligram per kilogram per week (mg/kg/week), equivalent to 1.8 international units/kg/week (IU/kg/week), divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 microgram/kg/day (mcg/kg/day), equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 centimeter (cm) per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.	Participants who received matching placebo for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 mg/kg/week, equivalent to 1.8 IU/kg/week, divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 mcg/kg/day, equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 cm per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.
Measure Participants	6	9
Baseline	-0.61	-2.34
Change at Year 3	0.73	1.21

4. Primary Outcome

Title	Change From Baseline in Height Standard Deviation Score (SDS) at Final Height
Description	Height was measured using a wall mounted device (example, Harpenden stadiometer). Height SDS was obtained by measuring the height, subtracting chronological age- and gender-appropriate mean height and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population.
Time Frame	Baseline, final height (assessed up to Year 9.5)

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of study treatment and had at least 1 post-baseline height measurement. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Somatropin (With Previous Somatropin Exposure)	Somatropin (Without Previous Somatropin Exposure)
Arm/Group Description	Participants who received low dose of somatropin (Genotonorm) for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 milligram per kilogram per week (mg/kg/week), equivalent to 1.8 international units/kg/week (IU/kg/week), divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 microgram/kg/day (mcg/kg/day), equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 centimeter (cm) per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.	Participants who received matching placebo for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 mg/kg/week, equivalent to 1.8 IU/kg/week, divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 mcg/kg/day, equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 cm per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.
Measure Participants	3	2
Baseline	0.96	-0.94
Change at Final Height	-0.43	0.08

5. Primary Outcome

Title	Change From Baseline in Predicted Height Standard Deviation Score (SDS) at Year 3
Description	Predicted height was calculated according to Greulich and Pyle using Bayley Pinneau method. Predicted height SDS was obtained by calculating the predicted height, subtracting chronological age- and gender-appropriate mean predicted height and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population.
Time Frame	Baseline, Year 3

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of study treatment and had at least 1 post-baseline height measurement. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Somatropin (With Previous Somatropin Exposure)	Somatropin (Without Previous Somatropin Exposure)
Arm/Group Description	Participants who received low dose of somatropin (Genotonorm) for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 milligram per kilogram per week (mg/kg/week), equivalent to 1.8 international units/kg/week (IU/kg/week), divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 microgram/kg/day (mcg/kg/day), equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 centimeter (cm) per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.	Participants who received matching placebo for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 mg/kg/week, equivalent to 1.8 IU/kg/week, divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 mcg/kg/day, equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 cm per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.
Measure Participants	4	3
Baseline	-0.76	-2.43
Change at Year 3	0.68	1.63

6. Primary Outcome

Title	Change From Baseline in Predicted Height Standard Deviation Score (SDS) at Final Height
Description	Predicted height was calculated according to Greulich and Pyle using Bayley Pinneau method. Predicted height SDS was obtained by calculating the predicted height, subtracting chronological age- and gender-appropriate mean predicted height and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population.
Time Frame	Baseline, final height (assessed up to Year 9.5)

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of study treatment and had at least 1 post-baseline height measurement. Here, N (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Somatropin (With Previous Somatropin Exposure)	Somatropin (Without Previous Somatropin Exposure)
Arm/Group Description	Participants who received low dose of somatropin (Genotonorm) for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 milligram per kilogram per week (mg/kg/week), equivalent to 1.8 international units/kg/week (IU/kg/week), divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 microgram/kg/day (mcg/kg/day), equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 centimeter (cm) per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.	Participants who received matching placebo for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 mg/kg/week, equivalent to 1.8 IU/kg/week, divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 mcg/kg/day, equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 cm per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.
Measure Participants	2	2
Baseline	-0.84	-1.74
Change at Final Height	-0.67	0.71

7. Secondary Outcome

Title	Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) Concentration at Year 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5 and 9
Time Frame	Baseline, Year 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of study treatment and had at least 1 post-baseline height measurement. Here, 'n' signifies those participants who were evaluable for this measure at given time points for each group respectively.

Arm/Group Title	Somatropin (With Previous Somatropin Exposure)	Somatropin (Without Previous Somatropin Exposure)
Arm/Group Description	Participants who received low dose of somatropin (Genotonorm) for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 milligram per kilogram per week (mg/kg/week), equivalent to 1.8 international units/kg/week (IU/kg/week), divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 microgram/kg/day (mcg/kg/day), equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 centimeter (cm) per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.	Participants who received matching placebo for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 mg/kg/week, equivalent to 1.8 IU/kg/week, divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 mcg/kg/day, equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 cm per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.
Measure Participants	11	10
Baseline (n = 11, 10)	0.0361	0.0165
Change at Year 0.5 (n = 9, 10)	0.0017	0.0255
Change at Year 1 (n = 11, 10)	0.0093	0.0329
Change at Year 1.5 (n = 11, 9)	0.0066	0.0406
Change at Year 2 (n = 10, 9)	0.0221	0.0223
Change at Year 2.5 (n = 8, 8)	0.0201	0.0366
Change at Year 3 (n = 7, 9)	0.0130	0.0445
Change at Year 3.5 (n = 7, 7)	0.0100	0.0396
Change at Year 4 (n = 6, 7)	0.0212	0.0453
Change at Year 4.5 (n = 5, 6)	0.0142	0.0431
Change at Year 5 (n = 5, 7)	0.0236	0.0369
Change at Year 5.5 (n = 4, 5)	0.0186	0.0448
Change at Year 6 (n = 4, 5)	0.0256	0.0454
Change at Year 6.5 (n = 2, 5)	0.0195	0.0593
Change at Year 7 (n = 1, 5)	0.0254	0.0424
Change at Year 7.5 (n = 0, 3)	NA	0.0529
Change at Year 8 (n = 0, 2)	NA	0.0576
Change at Year 8.5 (n = 0, 1)	NA	0.0280
Change at Year 9 (n = 2, 1)	0.0363	0.0403

8. Secondary Outcome

Title	Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGFBP3) Concentration at Year 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5 and 9
Time Frame	Baseline, Year 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9

Outcome Measure Data

Analysis Population Description

Data were collected and reported in individual participant listing but not statistically summarized due to early termination of the study.

Arm/Group Title	Somatropin (With Previous Somatropin Exposure)	Somatropin (Without Previous Somatropin Exposure)
Arm/Group Description	Participants who received low dose of somatropin (Genotonorm) for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 milligram per kilogram per week (mg/kg/week), equivalent to 1.8 international units/kg/week (IU/kg/week), divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 microgram/kg/day (mcg/kg/day), equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 centimeter (cm) per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.	Participants who received matching placebo for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 mg/kg/week, equivalent to 1.8 IU/kg/week, divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 mcg/kg/day, equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 cm per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.
Measure Participants	0	0

9. Secondary Outcome

Title	Change From Baseline in Lean Mass and Fat Mass at Year 1, 2, 3, 4, 5, 6, 7, 8 and 9
Description	Lean mass and fat mass: measurements of body composition assessed using Dual Energy X-ray Absorptiometry (DEXA) scan.
Time Frame	Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9

Outcome Measure Data

Analysis Population Description

Data were collected and reported in individual participant listing but not statistically summarized due to early termination of the study.

Arm/Group Title	Somatropin (With Previous Somatropin Exposure)	Somatropin (Without Previous Somatropin Exposure)
Arm/Group Description	Participants who received low dose of somatropin (Genotonorm) for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 milligram per kilogram per week (mg/kg/week), equivalent to 1.8 international units/kg/week (IU/kg/week), divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 microgram/kg/day (mcg/kg/day), equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 centimeter (cm) per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.	Participants who received matching placebo for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 mg/kg/week, equivalent to 1.8 IU/kg/week, divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 mcg/kg/day, equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 cm per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.
Measure Participants	0	0

10. Secondary Outcome

Title	Change From Baseline in Bone Mineralization at Year 1, 2, 3, 4, 5, 6, 7, 8 and 9
Description	Bone mineralization, an estimate of the amount of mineral (such as calcium) in the bone, was assessed using DEXA scan.
Time Frame	Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of study treatment and had at least 1 post-baseline height measurement. Here, 'n' signifies those participants who were evaluable for this measure at given time points for each group respectively.

Arm/Group Title	Somatropin (With Previous Somatropin Exposure)	Somatropin (Without Previous Somatropin Exposure)
Arm/Group Description	Participants who received low dose of somatropin (Genotonorm) for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 milligram per kilogram per week (mg/kg/week), equivalent to 1.8 international units/kg/week (IU/kg/week), divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 microgram/kg/day (mcg/kg/day), equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 centimeter (cm) per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.	Participants who received matching placebo for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 mg/kg/week, equivalent to 1.8 IU/kg/week, divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 mcg/kg/day, equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 cm per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.
Measure Participants	11	10
Baseline (n = 11, 10)	643.00	565.40
Change at Year 1 (n = 11, 10)	118.40	104.67
Change at Year 2 (n = 10, 9)	231.30	272.70
Change at Year 3 (n = 7, 8)	403.80	375.27
Change at Year 4 (n = 4, 3)	903.20	518.70
Change at Year 5 (n = 4, 7)	938.30	829.00
Change at Year 6 (n = 4, 5)	998.05	818.40
Change at Year 7 (n = 1, 5)	1408.50	1206.10
Change at Year 8 (n = 0, 2)	NA	1376.05
Change at Year 9 (n = 2, 1)	1210.15	1376.30

11. Secondary Outcome

Title	Change From Baseline in Weight Standard Deviation Score (SDS) at Year 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5 and 9
Description	Body weight was measured using a balance scale. Weight SDS was obtained by measuring the weight, subtracting age- and gender- appropriate mean weight and dividing the result by standard deviation of that mean (as obtained from age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population.
Time Frame	Baseline, Year 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of study treatment and had at least 1 post-baseline height measurement. Here, 'n' signifies those participants who were evaluable for this measure at given time points for each group respectively.

Arm/Group Title	Somatropin (With Previous Somatropin Exposure)	Somatropin (Without Previous Somatropin Exposure)
Arm/Group Description	Participants who received low dose of somatropin (Genotonorm) for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 milligram per kilogram per week (mg/kg/week), equivalent to 1.8 international units/kg/week (IU/kg/week), divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 microgram/kg/day (mcg/kg/day), equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 centimeter (cm) per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.	Participants who received matching placebo for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 mg/kg/week, equivalent to 1.8 IU/kg/week, divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 mcg/kg/day, equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 cm per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.
Measure Participants	11	10
Baseline (n = 11, 10)	0.04	-2.06
Change at Year 0.5 (n = 9, 10)	0.06	0.25
Change at Year 1 (n = 11, 10)	0.25	0.31
Change at Year 1.5 (n = 11, 9)	0.34	0.62
Change at Year 2 (n = 10, 9)	0.46	1.23
Change at Year 2.5 (n = 8, 8)	0.77	1.51
Change at Year 3 (n = 7, 9)	0.61	1.48
Change at Year 3.5 (n = 7, 7)	0.78	1.56
Change at Year 4 (n = 6, 7)	0.58	1.96
Change at Year 4.5 (n = 5, 6)	1.46	1.78
Change at Year 5 (n = 5, 7)	2.06	2.08
Change at Year 5.5 (n = 3, 5)	2.10	3.25
Change at Year 6 (n = 3, 5)	1.89	2.95
Change at Year 6.5 (n = 2, 5)	2.03	3.30
Change at Year 7 (n = 1, 5)	1.7	2.91
Change at Year 7.5 (n = 0, 3)	NA	1.49
Change at Year 8 (n = 0, 2)	NA	1.06
Change at Year 8.5 (n = 0, 1)	NA	0.7
Change at Year 9 (n = 1, 1)	2.0	1.4

12. Secondary Outcome

Title	Change From Baseline in Corticosteroid Dose at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5 and 9
Time Frame	Baseline, Year 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least 1 dose of study treatment and had at least 1 post-baseline height measurement. Here, 'n' signifies those participants who were evaluable for this measure at given time points for each group respectively.

Arm/Group Title	Somatropin (With Previous Somatropin Exposure)	Somatropin (Without Previous Somatropin Exposure)
Arm/Group Description	Participants who received low dose of somatropin (Genotonorm) for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 milligram per kilogram per week (mg/kg/week), equivalent to 1.8 international units/kg/week (IU/kg/week), divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 microgram/kg/day (mcg/kg/day), equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 centimeter (cm) per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.	Participants who received matching placebo for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 mg/kg/week, equivalent to 1.8 IU/kg/week, divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 mcg/kg/day, equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 cm per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.
Measure Participants	11	10
Baseline (n = 11, 10)	7.50	4.75
Change at Year 0.5 (n = 9, 10)	0.00	0.00
Change at Year 1 (n = 11, 9)	0.00	-0.67
Change at Year 1.5 (n = 11, 8)	0.00	0.50
Change at Year 2 (n = 10, 8)	0.00	-0.50
Change at Year 2.5 (n = 8, 7)	0.04	1.83
Change at Year 3 (n = 7, 7)	0.00	1.75
Change at Year 3.5 (n = 7, 6)	-0.75	1.83
Change at Year 4 (n = 6, 7)	-1.88	0.25
Change at Year 4.5 (n = 5, 6)	-3.40	0.23
Change at Year 5 (n = 5, 7)	-3.50	-2.00
Change at Year 5.5 (n = 4, 5)	-1.83	0.25
Change at Year 6 (n = 4, 5)	-1.83	-1.00
Change at Year 6.5 (n = 2, 5)	-2.46	-1.00
Change at Year 7 (n = 1, 5)	-2.50	-1.00
Change at Year 7.5 (n = 0, 3)	NA	-7.00
Change at Year 8 (n = 0, 2)	NA	-3.25
Change at Year 8.5 (n = 0, 1)	NA	0.50
Change at Year 9 (n = 2, 1)	-3.00	-7.00

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	Somatropin (With Previous Somatropin Exposure)		Somatropin (Without Previous Somatropin Exposure)
Arm/Group Description	Participants who received low dose of somatropin (Genotonorm) for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 milligram per kilogram per week (mg/kg/week), equivalent to 1.8 international units/kg/week (IU/kg/week), divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 microgram/kg/day (mcg/kg/day), equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 centimeter (cm) per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.		Participants who received matching placebo for 3 years during previous study CTN 97-8129-016, received somatropin (Genotonorm) up to 0.6 mg/kg/week, equivalent to 1.8 IU/kg/week, divided in 7 daily doses subcutaneously initially for first 3 years and then somatropin (Genotonorm) 0.46 mg/kg/week, equivalent to 1.4 IU/kg/week, divided in 7 daily doses subcutaneously until the additional study drug dose evaluation visit and thereafter received somatropin (Genotonorm) 50 mcg/kg/day, equivalent to 0.35 mg/kg/week or 1.05 IU/kg/week, subcutaneously until the final height was reached or up to Year 8.5. Final height was confirmed to have been achieved if the growth velocity was less than or equal to 1.5 cm per year during the preceding 12 months and bone age was greater than or equal to 17 years for boys and 15 years for girls.
All Cause Mortality
	Somatropin (With Previous Somatropin Exposure)		Somatropin (Without Previous Somatropin Exposure)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Somatropin (With Previous Somatropin Exposure)		Somatropin (Without Previous Somatropin Exposure)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/11 (54.5%)		2/10 (20%)
Blood and lymphatic system disorders
Lymphadenitis	0/11 (0%)		1/10 (10%)
Congenital, familial and genetic disorders
Hip dysplasia	1/11 (9.1%)		0/10 (0%)
General disorders
Pyrexia	1/11 (9.1%)		1/10 (10%)
Immune system disorders
Drug hypersensitivity	1/11 (9.1%)		0/10 (0%)
Infections and infestations
Leishmaniasis	1/11 (9.1%)		0/10 (0%)
Lung infection	0/11 (0%)		1/10 (10%)
Relapsing fever	1/11 (9.1%)		0/10 (0%)
Sinusitis	0/11 (0%)		1/10 (10%)
Musculoskeletal and connective tissue disorders
Juvenile arthritis	2/11 (18.2%)		0/10 (0%)
Osteochondritis	1/11 (9.1%)		0/10 (0%)
Pain in extremity	0/11 (0%)		1/10 (10%)
Scoliosis	1/11 (9.1%)		0/10 (0%)
Tendon disorder	1/11 (9.1%)		0/10 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Histiocytosis haematophagic	1/11 (9.1%)		0/10 (0%)
Melanocytic naevus	0/11 (0%)		1/10 (10%)
Nervous system disorders
Headache	0/11 (0%)		1/10 (10%)
Renal and urinary disorders
Glomerulonephritis	1/11 (9.1%)		0/10 (0%)
Nephrotic syndrome	0/11 (0%)		1/10 (10%)
Renal colic	1/11 (9.1%)		0/10 (0%)
Renal failure acute	0/11 (0%)		1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Lung disorder	1/11 (9.1%)		1/10 (10%)
Pleural effusion	1/11 (9.1%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Lipoatrophy	1/11 (9.1%)		0/10 (0%)
Surgical and medical procedures
Gastrostomy closure	1/11 (9.1%)		0/10 (0%)
Hip arthroplasty	1/11 (9.1%)		0/10 (0%)
Tooth extraction	1/11 (9.1%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Somatropin (With Previous Somatropin Exposure)		Somatropin (Without Previous Somatropin Exposure)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/11 (100%)		9/10 (90%)
Blood and lymphatic system disorders
Anaemia	0/11 (0%)		1/10 (10%)
Blood disorder	1/11 (9.1%)		0/10 (0%)
Iron deficiency anaemia	0/11 (0%)		1/10 (10%)
Lymphadenopathy	1/11 (9.1%)		1/10 (10%)
Congenital, familial and genetic disorders
Congenital scoliosis	1/11 (9.1%)		0/10 (0%)
Endocrine disorders
Hyperparathyroidism	0/11 (0%)		1/10 (10%)
Eye disorders
Cataract	2/11 (18.2%)		0/10 (0%)
Conjunctivitis	0/11 (0%)		1/10 (10%)
Visual acuity reduced	1/11 (9.1%)		0/10 (0%)
Gastrointestinal disorders
Abdominal pain	1/11 (9.1%)		1/10 (10%)
Aphthous stomatitis	0/11 (0%)		1/10 (10%)
Diarrhoea	1/11 (9.1%)		0/10 (0%)
Functional gastrointestinal disorder	0/11 (0%)		1/10 (10%)
Gastritis	0/11 (0%)		2/10 (20%)
Sigmoiditis	1/11 (9.1%)		0/10 (0%)
General disorders
Fatigue	0/11 (0%)		2/10 (20%)
Ill-defined disorder	2/11 (18.2%)		1/10 (10%)
Inflammation	0/11 (0%)		1/10 (10%)
Influenza like illness	1/11 (9.1%)		0/10 (0%)
Injection site haemorrhage	0/11 (0%)		1/10 (10%)
Nodule	0/11 (0%)		1/10 (10%)
Oedema	1/11 (9.1%)		0/10 (0%)
Pyrexia	1/11 (9.1%)		1/10 (10%)
Hepatobiliary disorders
Hepatomegaly	1/11 (9.1%)		0/10 (0%)
Infections and infestations
Bronchitis	1/11 (9.1%)		3/10 (30%)
Ear infection	1/11 (9.1%)		2/10 (20%)
Gastroenteritis	2/11 (18.2%)		1/10 (10%)
Herpes simplex	0/11 (0%)		1/10 (10%)
Herpes virus infection	0/11 (0%)		1/10 (10%)
Herpes zoster	0/11 (0%)		2/10 (20%)
Infectious mononucleosis	0/11 (0%)		1/10 (10%)
Influenza	1/11 (9.1%)		0/10 (0%)
Laryngitis	1/11 (9.1%)		1/10 (10%)
Nail candida	0/11 (0%)		2/10 (20%)
Nasopharyngitis	2/11 (18.2%)		2/10 (20%)
Oral herpes	1/11 (9.1%)		0/10 (0%)
Otitis externa	1/11 (9.1%)		0/10 (0%)
Otitis media	0/11 (0%)		1/10 (10%)
Pharyngitis	0/11 (0%)		1/10 (10%)
Sinusitis	1/11 (9.1%)		1/10 (10%)
Tracheitis	0/11 (0%)		1/10 (10%)
Varicella	0/11 (0%)		1/10 (10%)
Viral infection	2/11 (18.2%)		1/10 (10%)
Injury, poisoning and procedural complications
Humerus fracture	1/11 (9.1%)		0/10 (0%)
Joint injury	1/11 (9.1%)		0/10 (0%)
Ligament sprain	1/11 (9.1%)		2/10 (20%)
Procedural vomiting	0/11 (0%)		1/10 (10%)
Investigations
Blood corticotrophin decreased	2/11 (18.2%)		0/10 (0%)
Blood glucose decreased	1/11 (9.1%)		0/10 (0%)
Blood urine present	0/11 (0%)		1/10 (10%)
Glucose tolerance test	1/11 (9.1%)		0/10 (0%)
Glycosylated haemoglobin increased	0/11 (0%)		2/10 (20%)
Insulin-like growth factor increased	8/11 (72.7%)		6/10 (60%)
Weight decreased	1/11 (9.1%)		0/10 (0%)
Metabolism and nutrition disorders
Glucose tolerance impaired	5/11 (45.5%)		0/10 (0%)
Hyperinsulinaemia	0/11 (0%)		1/10 (10%)
Insulin resistance	6/11 (54.5%)		5/10 (50%)
Musculoskeletal and connective tissue disorders
Amyotrophy	1/11 (9.1%)		1/10 (10%)
Arthralgia	1/11 (9.1%)		2/10 (20%)
Arthritis	1/11 (9.1%)		1/10 (10%)
Back pain	1/11 (9.1%)		0/10 (0%)
Joint effusion	2/11 (18.2%)		1/10 (10%)
Joint range of motion decreased	0/11 (0%)		1/10 (10%)
Juvenile arthritis	4/11 (36.4%)		4/10 (40%)
Osteonecrosis	0/11 (0%)		1/10 (10%)
Synovial cyst	0/11 (0%)		1/10 (10%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus	0/11 (0%)		1/10 (10%)
Nervous system disorders
Headache	0/11 (0%)		1/10 (10%)
Hyporeflexia	1/11 (9.1%)		0/10 (0%)
Hypotonia	1/11 (9.1%)		0/10 (0%)
Loss of consciousness	1/11 (9.1%)		0/10 (0%)
Visual field defect	1/11 (9.1%)		0/10 (0%)
Psychiatric disorders
Depression	1/11 (9.1%)		0/10 (0%)
Insomnia	1/11 (9.1%)		0/10 (0%)
Nightmare	1/11 (9.1%)		0/10 (0%)
Sleep disorder	1/11 (9.1%)		2/10 (20%)
Renal and urinary disorders
Enuresis	0/11 (0%)		2/10 (20%)
Hypercalciuria	1/11 (9.1%)		0/10 (0%)
Nephrolithiasis	0/11 (0%)		1/10 (10%)
Renal colic	2/11 (18.2%)		0/10 (0%)
Reproductive system and breast disorders
Gynaecomastia	0/11 (0%)		1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Cough	0/11 (0%)		1/10 (10%)
Epistaxis	0/11 (0%)		1/10 (10%)
Lung disorder	0/11 (0%)		1/10 (10%)
Productive cough	0/11 (0%)		1/10 (10%)
Skin and subcutaneous tissue disorders
Acanthosis nigricans	1/11 (9.1%)		1/10 (10%)
Acne	1/11 (9.1%)		1/10 (10%)
Ecchymosis	0/11 (0%)		1/10 (10%)
Erythema	0/11 (0%)		1/10 (10%)
Hyperhidrosis	0/11 (0%)		1/10 (10%)
Lividity	0/11 (0%)		1/10 (10%)
Pruritus	1/11 (9.1%)		0/10 (0%)
Pruritus generalised	1/11 (9.1%)		0/10 (0%)
Rash	1/11 (9.1%)		0/10 (0%)
Skin atrophy	1/11 (9.1%)		0/10 (0%)
Social circumstances
Walking disability	1/11 (9.1%)		0/10 (0%)
Surgical and medical procedures
Knee operation	0/11 (0%)		1/10 (10%)
Vascular disorders
Hypertension	1/11 (9.1%)		1/10 (10%)
Poor peripheral circulation	0/11 (0%)		1/10 (10%)

Limitations/Caveats

Data for bone mineral density (BMD), bone mineral content (BMC) and IGFBP3 were not analyzed because of change in planned analysis after the study was prematurely terminated due to Good Clinical Practice (GCP) non-compliance issues.

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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.