SGA-POWER: Neuromuscular Changes In Small For Gestational Age Children During Somatropin Therapy

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00625872
• Collaborator: (none)
• Enrollment: 23
• Locations: 10
• Arms: 2
• Duration (Months): 32
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The planned study focuses on the effect of a one year Somatropin treatment (0.035 mg/kg/d or 0.067 mg/kg/d) in short children born SGA on neuromuscular function and cognitive performance.

Condition or Disease	Intervention/Treatment	Phase
Growth Hormone Therapy; Infant, Small for Gestational Age	Drug: Somatropin; Drug: Somatropin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Neuromuscular Changes In Small For Gestational Age (SGA) Children During Somatropin Therapy - A Prospective Randomized, Controlled, Open-Label Multicenter Trial
• Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Treatment Group Somatropin for 12 months	Drug: Somatropin; Patients will be randomized at baseline in a 1:1 ratio into treatment group or control group. After six months the control group will undergo GH therapy with a higher dose of 0.067 mg/kg/day, too. All patients are treated with growth hormone for 12 months.
Other: Control Group In the first 6 months no intervention, afterwards Somatropin for 12 months	Drug: Somatropin; Patients will be randomized at baseline in a 1:1 ratio into treatment group or control group. After six months the control group will undergo GH therapy with a higher dose of 0.067 mg/kg/day, too. All patients are treated with growth hormone for 12 months.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6 [Baseline and Month 6]

   Peak jump power (PJP) was defined as the peak of the calculated power (force multiplied by velocity). It was measured by Leonardo Jumping Platform during two-leg jump. The participant performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the participant was to the reference population.

2. Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6 [Baseline and Month 6]

   PJP was defined as the peak of the calculated power (force multiplied by velocity). It was measured by Leonardo Jumping Platform during two-leg jump. The participant performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the participant was to the reference population.

3. Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6 [Baseline and Month 6]

   PJF was defined as the maximum of force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms and as high as possible with the head and chest. It was measured by Leonardo Jumping Platform during two-leg jump. The SDS indicates how similar the participant was to the reference population.

4. Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6 [Baseline and Month 6]

   PJF was defined as the maximum of force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms and as high as possible with the head and chest. It was measured by Leonardo Jumping Platform during two-leg jump. The SDS indicates how similar the participant was to the reference population.

5. Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6 [Baseline and Month 6]

   Vmax was measured by Leonardo Jumping Platform during two-leg jump.

6. Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Per Protocol (PP) Population at Month 6 [Baseline and Month 6]

   Vmax was measured by Leonardo Jumping Platform during two-leg jump.

Secondary Outcome Measures

1. Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 [Baseline and Month 6]

   K-ABC was assessed in children between 2.5-12.5 years. Comprised of 16 subtests; 10 mental processing (intelligence) and 6 achievement subtests. Achievement subtests: expressive vocabulary, faces&places, arithmetic, riddles, reading/decoding, reading/comprehension. Sixteen subtests were weighted accordingly to form 5 global scales: sequential processing, simultaneous processing, achievement, non-verbal and mental processing composite. Scores were rated as upper extreme [greater than (>) 131], above average (116-130), average (85-115), below average (70-84), lower extreme [less than (<) 69].

2. Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Months 12 and 18 [Baseline, Month 12 and Month 18]

   K-ABC was assessed in children between 2.5-12.5 years. Comprised of 16 subtests; 10 mental processing (intelligence) and 6 achievement subtests. Achievement subtests: expressive vocabulary, faces&places, arithmetic, riddles, reading/decoding, reading/comprehension. Sixteen subtests were weighted accordingly to form 5 global scales: sequential processing, simultaneous processing, achievement, non-verbal and mental processing composite. Scores were rated as upper extreme [greater than (>) 131], above average (116-130), average (85-115), below average (70-84), lower extreme [less than (<) 69].

3. Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 [Baseline and Month 6]

   The KITAP is a computer aided standardized neuro-cognitive development test which allows examination of a wide range of attention and executive functions such as shift of attention (Distractibility); simple reaction time (Alertness); "Sustained Attention", change of reaction (Flexibility); "Divided Attention", controlled reaction disposition (Go/No go) and "Vigilance". It has been designed appropriately for children between the age of 6 to 10 years to allow optimal motivation during testing and to increase validity of results.

4. Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Months 12 and 18 [Baseline, Month 12 and Month 18]

   The KITAP is a computer aided standardized neuro-cognitive development test which allows examination of a wide range of attention and executive functions such as shift of attention (Distractibility); simple reaction time (Alertness); "Sustained Attention", change of reaction (Flexibility); "Divided Attention", controlled reaction disposition (Go/No go) and "Vigilance". It has been designed appropriately for children between the age of 6 to 10 years to allow optimal motivation during testing and to increase validity of results.

5. Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 [Baseline and Month 6]

   NVLT was assessed for visual memorization that was difficult to verbalize. Test recorded instability index, T-scores[sum of differences of correct {C} - incorrect {IC} "Yes" answers(1);sum of C "Yes" answers(2);sum of IC "Yes" answers(3);sum of differences of C-IC "Yes" answers with high associative items{ 87%-95%}(4);sum of differences of C-IC "Yes" answers with low associative items{ 54%-64%}(5); difference between difference values for high and low associative items(6)].Scores were rated as below average(<40), average(40-60), above average(>60) and working time ranging between 9-12 minutes.

6. Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Months 12 and 18 [Baseline, Month 12 and Month 18]

   NVLT was assessed for visual memorization that was difficult to verbalize. Test recorded instability index, T-scores[sum of differences of correct {C} - incorrect {IC} "Yes" answers(1);sum of C "Yes" answers(2);sum of IC "Yes" answers(3);sum of differences of C-IC "Yes" answers with high associative items{ 87%-95%}(4);sum of differences of C-IC "Yes" answers with low associative items{ 54%-64%}(5); difference between difference values for high and low associative items(6)].Scores were rated as below average(<40), average(40-60), above average(>60) and working time ranging between 9-12 minutes.

7. Change From Baseline in Intellectual Performance of Children Using Child Behavior Checklist 4-18 Years (CBCL 4-18) at Months 6, 12 and 18 [Baseline, Month 6, Month 12 and Month 18]

   CBCL was standardized for children ages 4 to 18 years and measured child internalizing and externalizing behaviors and total problems. The 4-18 years' checklist contains 140 questions and responses were recorded on a Likert scale: 0 = Not True, 1 = Somewhat or Sometimes True, 2 = Very True or Often True. The range of possible values was 0-280 (0=good to 280=worst).

8. Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; One-leg-jump) at Months 6, 12 and 18 [Baseline, Month 6 , Month 12 and Month 18]

   PJP was defined as the peak of the calculated power (force multiplied by velocity). It was measured by Leonardo Jumping Platform during one leg jump. The participant performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the participant was to the reference population.

9. Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; One-leg-jump) at Months 6, 12 and 18 [Baseline, Month 6, Month 12 and Month 18]

   PJF was defined as the maximum of force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms and as high as possible with the head and chest. It was measured by Leonardo Jumping Platform during one leg jump. The SDS indicates how similar the participant was to the reference population.

10. Change From Baseline in Maximum Jump Velocity (Vmax; One-leg-jump) at Months 6, 12 and 18 [Baseline, Month 6, Month 12 and Month 18]

    Vmax was measured by Leonardo Jumping Platform during one leg jump.

11. Change From Baseline in Five-chair Rising Test- Peak Jump Power (PJP) at Month 6 [Baseline and Month 6]

    The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJP is defined as the peak of the calculated power (force multiplied by velocity).

12. Change From Baseline in Five-chair Rising Test-Peak Jump Power (PJP) at Months 12 and 18 [Baseline, Month 12 and Month 18]

    The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJP is defined as the peak of the calculated power (force multiplied by velocity).

13. Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Month 6 [Baseline and Month 6]

    The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJF is the maximum force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms as high as possible with the head and chest.

14. Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Months 12 and 18 [Baseline, Month 12 and Month 18]

    The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJF is the maximum force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms as high as possible with the head and chest.

15. Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Month 6 [Baseline and Month 6]

    The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). Vmax is defined as the maximum jump velocity.

16. Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Months 12 and 18 [Baseline, Month 12 and Month 18]

    The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). Vmax is defined as the maximum jump velocity.

17. Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 [Baseline and Month 6]

    Chair rising test is performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: 5 repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over chest (time to perform tasks, maximal PJP, maximal velocity and maximal PJF). Time to perform task includes: Average (avg) rise time which is avg time to perform 1 rise, avg time per test is the avg time to perform 1 test (rise and sitting down) and total time to perform 5 tests.

18. Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Months 12 and 18 [Baseline, Month 12 and Month 18]

    Chair rising test is performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: 5 repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over chest (time to perform tasks, maximal PJP, maximal velocity and maximal PJF). Time to perform task includes: Average (avg) rise time which is avg time to perform 1 rise, avg time per test is the avg time to perform 1 test (rise and sitting down) and total time to perform 5 tests.

19. Change From Baseline in One-chair Rising Test-Peak Jump Power (PJP) at Months 6, 12 and 18 [Baseline, Month 6 , Month 12 and Month 18]

    The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement to stand up. Test allows diagnostics of movement deficits using Leonardo jump plate. One stand up test: rising from a chair on the jump plate as quickly as possible with arms crossed over the chest (analysis of time, PJP, PJF and time of fastest rising). PJP is defined as the peak of the calculated power (force multiplied by velocity).

20. Change From Baseline in One-chair Rising Test-Peak Jump Force (PJF) at Months 6, 12 and 18 [Baseline, Month 6 , Month 12 and Month 18]

    The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement to stand up. Test allows diagnostics of movement deficits using Leonardo jump plate. One stand up test: rising from a chair on the jump plate as quickly as possible with arms crossed over the chest (analysis of time, PJP, PJF and time of fastest rising). PJF is the maximum force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms as high as possible with the head and chest.

21. Change From Baseline in One-chair Rising Test (Time to Perform the Tasks) at Months 6, 12 and 18 [Baseline, Month 6 , Month 12 and Month 18]

    The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement to stand up. Test allows diagnostics of movement deficits using Leonardo jump plate. One stand up test: rising from a chair on the jump plate as quickly as possible with arms crossed over the chest (analysis of time, PJP, PJF and time of fastest rising).

22. Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Month 6 [Baseline and Month 6]

    MIGF was assessed using standard adjustable Jamar dynamometer. MIGF (in Newtons) was calculated by multiplying the dynamometer reading (in kilograms) by a factor of 9.81. The SDS indicates how similar the participant was to the reference population.

23. Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Months 12 and 18 [Baseline, Month 12 and Month 18]

    MIGF was assessed using standard adjustable Jamar dynamometer. MIGF (in Newtons) was calculated by multiplying the dynamometer reading (in kilograms) by a factor of 9.81. The SDS indicates how similar the participant was to the reference population.

24. Mean Upper Arm Circumference [Baseline, Month 6, Month 12 and Month 18]

25. Mean Thigh Circumference [Baseline, Month 6, Month 12 and Month 18]

    Thigh measurements were taken as a mean of 3 consecutive measurements at upper thigh about an inch down from the crotch line.

26. Mean Calf Circumference [Baseline, Month 6, Month 12 and Month 18]

    Calf measurements were taken as a mean of 3 consecutive measurements at largest part of calf muscle, usually about 4 inches down from below the knee.

27. Mean Height at Month 6 [Month 6]

    Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer.

28. Mean Height at Months 12 and 18 [Month 12 and Month 18]

    Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer.

29. Mean Growth Velocity at Month 6 [Month 6]

    Growth velocity measures the annual rate of increase in height.

30. Mean Growth Velocity at Months 12 and 18 [Month 12 and Month 18]

    Growth velocity measures the annual rate of increase in height.

31. Mean Height-Standard Deviation Score (SDS) at Month 6 [Month 6]

    Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.

32. Mean Height-Standard Deviation Score (SDS) at Months 12 and 18 [Month 12 and Month 18]

    Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.

33. Mean Growth Velocity-Standard Deviation Score (SDS) at Month 6 [Month 6]

    Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the participant is to the reference population.

34. Mean Growth Velocity-Standard Deviation Score (SDS) at Months 12 and 18 [Month 12 and Month 18]

35. Change From Baseline in Height-Standard Deviation Score (SDS) at Month 6 [Baseline and Month 6]

    Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.

36. Change From Baseline in Height-Standard Deviation Score (SDS) at Months 12 and 18 [Baseline, Month 12 and Month 18]

    Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.

37. Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Month 6 [Baseline and Month 6]

    Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the participant is to the reference population.

38. Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Months 12 and 18 [Baseline, Month 12 and Month 18]

    Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the participant is to the reference population.

39. Sitting Height-Standard Deviation Score (SDS) [Baseline, Month 6, Month 12 and Month 18]

    Sitting height was measured using a stadiometer with a specialized chair. The SDS indicates how similar the participant was to the reference population.

40. Body Mass Index-Standard Deviation Score (BMI-SDS) [Baseline, Month 6, Month 12 and Month 18]

    The BMI was used to measure body fat based on height and weight. It was calculated by body weight (kg) divided by the height (m) squared. The SDS indicates how similar the participant was to the reference population.

41. Change From Baseline in Head Circumference at Months 6, 12 and 18 [Baseline, Month 6, Month 12 and Month 18]

    The maximum head circumference (usually horizontal just above the eyebrow ridges), was measured from just above the glabella area to the area near the top of the occipital bone (opisthocranion).

42. Change From Baseline in Head Circumference-Standard Deviation Score (SDS) at Months 6, 12 and 18 [Baseline, Month 6, Month 12 and Month 18]

    The maximum head circumference (usually horizontal just above the eyebrow ridges), was measured from just above the glabella area to the area near the top of the occipital bone (opisthocranion). The SDS indicates how similar the participant was to the reference population.

43. Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6 [Baseline and Month 6]

    Triceps, supra-iliac and subscapular skinfolds were measured on the right side of the body to the nearest 0.1 mm with a Holtain skinfold caliper. The measurement was performed at the left side of the participant. Triceps skinfold thickness was measured halfway down the left upper arm, while the arm was hanging relaxed at the participant's side. Suprascapular skinfold was measured laterally just below the angle of the left scapula. Suprailiac skinfold was measured just above the iliac crest in the middle-axillary line. SDS indicates how similar the participant was to the reference population.

44. Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Months 12 and 18 [Baseline, Month 12 and Month 18]

    Triceps, supra-iliac and subscapular skinfolds were measured on the right side of the body to the nearest 0.1 mm with a Holtain skinfold caliper. The measurement was performed at the left side of the participant. Triceps skinfold thickness was measured halfway down the left upper arm, while the arm was hanging relaxed at the participant's side. Suprascapular skinfold was measured laterally just below the angle of the left scapula. Suprailiac skinfold was measured just above the iliac crest in the middle-axillary line. SDS indicates how similar the participant was to the reference population.

Other Outcome Measures

1. Change From Baseline in Bone Density Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months [Baseline, Month 6, Month 12 and Month 18]

   Bone Mineral Density (BMD) was measured by pqCT. The Z-score measures the distance of the measured BMD value from the appropriate normal age matched population mean value in units of standard deviation of this population. More negative scores indicate less BMD compared to age matched population and more positive scores indicate higher BMD compared to age matched population.

2. Change From Baseline in Bone Structure Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months [Baseline, Month 6, Month 12 and Month 18]

   Bone structure was measured by pqCT.Parameters included:total area,cortical area,marrow area,cortical thickness,cortical density of the radius,bone strength,cross-sectional muscle and fat area,total bone density,bone mineral count,trabecular BMD,bone cross-sectional area.Baseline and post-baseline SDS values transformed to age and sex specific z-score([Ln(test result/M)]/S);Ln=natural logarithm;M=age-/height- and sex-specific mean value;S=age-/height- and sex-specific coefficient of variation).Positive values are above the average for participant's age and sex;negative values are below.

3. Change From Baseline in Bone Stability Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months [Baseline, Month 6, Month 12 and Month 18]

   Bone stability was measured by pqCT. Baseline and post-baseline SDS values transformed to age and sex specific z-score (Ln(test result/M)]/S); Ln=natural logarithm; M=age- (or height-) and sex-specific mean value; S=age-(or height-) and sex-specific coefficient of variation) then change from baseline is calculated. Positive values are above the average for participant's age and sex; negative values are below the average.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 10 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Pre-pubertal boys between 6 and 10 years of age or girls between 6 and 9 years of age.

• Birth length- and/or birth weight-SDS adjusted to gestational age < -2.0 (Voigt et al. 2002, Voigt et al. 2006 or Lawrence et al. 1989).

• Current height-SDS < -2.5 (Brandt/Reinken 1992) and parental adjusted height-SDS below -1 (Hermanussen and Cole 2003).

• Growth velocity SDS < 0 during the last year before inclusion (Brandt/Reinken 1988).

Exclusion Criteria:

• Severe SGA (birth weight or length < -4 SD) and clinically relevant dysmorphic features.

• Severe pre-maturity (GA < 32 weeks of gestation).

• Severe perinatal complications like asphyxia, sepsis, necrotizing enterocolitis (NEC), respiratory distress syndrome, if associated with long-term sequelae (like short bowel syndrome, bronchopulmonary dysplasia (BPD), cerebral palsy etc).

• Inability to perform one- or two leg jumps from a standing position.

• Prior GH treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Berlin		Germany	13353
2	Pfizer Investigational Site	Bonn		Germany	53113
3	Pfizer Investigational Site	Datteln		Germany	45711
4	Pfizer Investigational Site	Dresden		Germany	01307
5	Pfizer Investigational Site	Erlangen		Germany	91054
6	Pfizer Investigational Site	Essen		Germany	45122
7	Pfizer Investigational Site	Heidelberg		Germany	69120
8	Pfizer Investigational Site	Kiel		Germany	24105
9	Pfizer Investigational Site	Koeln		Germany	50937
10	Pfizer Investigational Site	Muenchen		Germany	80337

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: NCT00625872
• Other Study ID Numbers: A6281283
• First Posted: Feb 28, 2008
• Last Update Posted: Feb 29, 2012
• Last Verified: Jan 1, 2012

Study Results

Participant Flow

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 milligram/kilogram/day (mg/kg/day) was administered subcutaneously (s.c) according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Period Title: Overall Study
STARTED	12	11
Treated	12	10
COMPLETED	8	5
NOT COMPLETED	4	6

Baseline Characteristics

Arm/Group Title	Somatropin	Control Arm	Total
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.	Total of all reporting groups
Overall Participants	12	11	23
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	6.6 (1.0)	7.6 (1.4)	7.1 (1.3)
Sex: Female, Male (Count of Participants)
Female	3 25%	8 72.7%	11 47.8%
Male	9 75%	3 27.3%	12 52.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6
Description	Peak jump power (PJP) was defined as the peak of the calculated power (force multiplied by velocity). It was measured by Leonardo Jumping Platform during two-leg jump. The participant performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	4	8
Least Squares Mean (Standard Error) [Watt/kilogram (W/kg)]	-0.15 (1.01)	0.28 (0.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	Analysis of covariance (ANCOVA) method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7232
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares (LS) mean difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -3.93 to 3.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.10
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6
Description	PJP was defined as the peak of the calculated power (force multiplied by velocity). It was measured by Leonardo Jumping Platform during two-leg jump. The participant performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

PP population included participants who received the study medication for at least 22 weeks. Number of participants analyzed (N) signifies participants evaluable for the measure.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	2	6
Least Squares Mean (Standard Error) [W/kg]	-1.02 (0.43)	0.59 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1941
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	-1.61
	Confidence Interval	(2-Sided) 95%; -8.04 to 4.82
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.51
	Estimation Comments

3. Primary Outcome

Title	Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6
Description	PJF was defined as the maximum of force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms and as high as possible with the head and chest. It was measured by Leonardo Jumping Platform during two-leg jump. The SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	4	8
Least Squares Mean (Standard Error) [Newtons]	-0.70 (0.62)	-0.55 (0.29)

4. Secondary Outcome

Title	Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6
Description	K-ABC was assessed in children between 2.5-12.5 years. Comprised of 16 subtests; 10 mental processing (intelligence) and 6 achievement subtests. Achievement subtests: expressive vocabulary, faces&places, arithmetic, riddles, reading/decoding, reading/comprehension. Sixteen subtests were weighted accordingly to form 5 global scales: sequential processing, simultaneous processing, achievement, non-verbal and mental processing composite. Scores were rated as upper extreme [greater than (>) 131], above average (116-130), average (85-115), below average (70-84), lower extreme [less than (<) 69].
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	11	11
Baseline (Sequential Processing)	25.7 (8.35)	28.5 (8.33)
Change at Month 6 (Sequential Processing)	2.6 (5.82)	-1.9 (4.15)
Baseline (Simultaneous Processing)	45.7 (7.20)	49.8 (12.74)
Change at Month 6 (Simultaneous Processing)	-0.1 (4.53)	1.5 (4.30)
Baseline (Achievement)	300.7 (66.83)	341.8 (76.88)
Change at Month 6 (Achievement)	32.1 (48.79)	16.7 (27.52)
Baseline (Nonverbal)	46.2 (8.65)	49.8 (13.21)
Change at Month 6 (Nonverbal)	-1.4 (3.78)	0.0 (5.35)
Baseline (Mental Processing Composite)	70.0 (12.38)	78.1 (19.95)
Change at Month 6 (Mental Processing Composite)	1.4 (6.39)	-0.9 (7.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	For K-ABC Test (Sequential Processing): Kruskal-Wallis Analysis of Variance (ANOVA) model was used to calculate p-value.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0532
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	For K-ABC Test (Simultaneous Processing): Kruskal-Wallis ANOVA model was used to calculate p-value.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3383
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	For K-ABC Test (Achievement): Kruskal-Wallis ANOVA model was used to calculate p-value.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6830
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	For K-ABC Test (Non-Verbal): Kruskal-Wallis ANOVA model was used to calculate p-value.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4935
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	For K-ABC Test (Mental Processing Composite): Kruskal-Wallis ANOVA model was used to calculate p-value.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3458
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	Kruskal-Wallis
	Comments

5. Secondary Outcome

Title	Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Months 12 and 18
Description	K-ABC was assessed in children between 2.5-12.5 years. Comprised of 16 subtests; 10 mental processing (intelligence) and 6 achievement subtests. Achievement subtests: expressive vocabulary, faces&places, arithmetic, riddles, reading/decoding, reading/comprehension. Sixteen subtests were weighted accordingly to form 5 global scales: sequential processing, simultaneous processing, achievement, non-verbal and mental processing composite. Scores were rated as upper extreme [greater than (>) 131], above average (116-130), average (85-115), below average (70-84), lower extreme [less than (<) 69].
Time Frame	Baseline, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

6. Secondary Outcome

Title	Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6
Description	The KITAP is a computer aided standardized neuro-cognitive development test which allows examination of a wide range of attention and executive functions such as shift of attention (Distractibility); simple reaction time (Alertness); "Sustained Attention", change of reaction (Flexibility); "Divided Attention", controlled reaction disposition (Go/No go) and "Vigilance". It has been designed appropriately for children between the age of 6 to 10 years to allow optimal motivation during testing and to increase validity of results.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure and 'n' signifies participants who received the study drug and evaluated at the time point for each group respectively.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	9	11
Baseline (Distractibility)	554.3 (201.08)	514.5 (127.41)
Change at 6 Month (Distractibility) (n= 7, 10)	5.6 (230.95)	-11.4 (139.52)
Baseline (Alertness)	433.9 (140.74)	384.6 (124.94)
Change at 6 Month (Alertness) (n= 8, 10)	-16.1 (80.85)	4.0 (107.42)
Baseline (Flexibility)	1350.0 (470.50)	1313.0 (477.19)
Change at 6 Month (Flexibility) (n= 8, 10)	-192.0 (492.73)	-211.0 (589.41)
Baseline (Go/No Go)	539.8 (106.73)	514.9 (91.95)
Change at 6 Month (Go/No Go) (n= 8, 9)	35.6 (113.38)	-50.2 (69.90)
Baseline (Vigilance)	822.2 (200.65)	693.4 (118.01)
Change at 6 Month (Vigilance) (n= 7, 10)	-146.0 (278.60)	-31.2 (107.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	For KITAP Test (Distractibility): Kruskal-Wallis ANOVA model was used to calculate p-value.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6256
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	For KITAP Test (Alertness): Kruskal-Wallis ANOVA model was used to calculate p-value.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8590
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	For KITAP Test (Flexibility): Kruskal-Wallis ANOVA model was used to calculate p-value.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	For KITAP Test (Go/No Go): Kruskal-Wallis ANOVA model was used to calculate p-value.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1234
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	For KITAP Test (Vigilance): Kruskal-Wallis ANOVA model was used to calculate p-value.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3291
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	Kruskal-Wallis
	Comments

7. Secondary Outcome

Title	Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Months 12 and 18
Description	The KITAP is a computer aided standardized neuro-cognitive development test which allows examination of a wide range of attention and executive functions such as shift of attention (Distractibility); simple reaction time (Alertness); "Sustained Attention", change of reaction (Flexibility); "Divided Attention", controlled reaction disposition (Go/No go) and "Vigilance". It has been designed appropriately for children between the age of 6 to 10 years to allow optimal motivation during testing and to increase validity of results.
Time Frame	Baseline, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

8. Secondary Outcome

Title	Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6
Description	NVLT was assessed for visual memorization that was difficult to verbalize. Test recorded instability index, T-scores[sum of differences of correct {C} - incorrect {IC} "Yes" answers(1);sum of C "Yes" answers(2);sum of IC "Yes" answers(3);sum of differences of C-IC "Yes" answers with high associative items{ 87%-95%}(4);sum of differences of C-IC "Yes" answers with low associative items{ 54%-64%}(5); difference between difference values for high and low associative items(6)].Scores were rated as below average(<40), average(40-60), above average(>60) and working time ranging between 9-12 minutes.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	9	11
Baseline (Instability Index)	0.3 (0.15)	0.2 (0.21)
Change at Month 6 (Instability Index)	-0.1 (0.11)	-0.1 (0.20)
Baseline (Working Time)	227.0 (44.27)	218.3 (76.89)
Change at Month 6 (Working Time)	10.6 (92.95)	-11.1 (34.86)
Baseline [T-scores (1)]	39.9 (13.60)	43.9 (16.53)
Change at Month 6 [T-scores (1)]	4.4 (11.64)	6.7 (12.12)
Baseline [T-scores (2)]	41.6 (12.97)	46.8 (14.40)
Change at Month 6 [T-scores (2)]	5.0 (10.72)	-0.6 (5.50)
Baseline [T-scores (3)]	45.9 (14.89)	48.1 (18.20)
Change at Month 6 [T-scores (3)]	1.5 (5.15)	8.3 (12.24)
Baseline [T-scores (4)]	39.3 (16.97)	46.4 (16.03)
Change at Month 6 [T-scores (4)]	5.6 (15.53)	1.4 (11.75)
Baseline [T-scores (5)]	43.3 (11.12)	43.6 (15.13)
Change at Month 6 [T-scores (5)]	2.6 (9.83)	7.7 (12.59)
Baseline [T-scores (6)]	44.9 (15.83)	52.9 (19.96)
Change at Month 6 [T-scores (6)]	0.9 (16.55)	-7.4 (14.88)
Baseline [Age-corrected T-scores (1)]	33.4 (12.18)	38.6 (13.43)
Change at Month 6 [Age-corrected T-scores (1)]	6.0 (10.21)	5.2 (11.26)
Baseline [Age-corrected T-scores (2)]	51.3 (7.55)	54.5 (8.10)
Change at Month 6 [Age-corrected T-scores (2)]	3.1 (5.59)	-0.1 (3.38)
Baseline [Age-corrected T-scores (3)]	40.0 (13.86)	41.1 (16.38)
Change at Month 6 [Age-corrected T-scores (3)]	0.6 (4.47)	7.8 (12.13)
Baseline [Age-corrected T-scores (4)]	37.4 (17.01)	45.0 (15.21)
Change at Month 6 [Age-corrected T-scores (4)]	6.3 (14.57)	4.1 (10.63)
Baseline [Age-corrected T-scores (5)]	35.0 (11.88)	37.3 (13.48)
Change at Month 6 [Age-corrected T-scores (5)]	3.3 (10.73)	6.9 (12.57)
Baseline [Age-corrected T-scores (6)]	50.0 (16.49)	55.5 (16.64)
Change at Month 6 [Age-corrected T-scores (6)]	1.5 (19.06)	-4.1 (13.77)

9. Secondary Outcome

Title	Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Months 12 and 18
Description	NVLT was assessed for visual memorization that was difficult to verbalize. Test recorded instability index, T-scores[sum of differences of correct {C} - incorrect {IC} "Yes" answers(1);sum of C "Yes" answers(2);sum of IC "Yes" answers(3);sum of differences of C-IC "Yes" answers with high associative items{ 87%-95%}(4);sum of differences of C-IC "Yes" answers with low associative items{ 54%-64%}(5); difference between difference values for high and low associative items(6)].Scores were rated as below average(<40), average(40-60), above average(>60) and working time ranging between 9-12 minutes.
Time Frame	Baseline, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

10. Secondary Outcome

Title	Change From Baseline in Intellectual Performance of Children Using Child Behavior Checklist 4-18 Years (CBCL 4-18) at Months 6, 12 and 18
Description	CBCL was standardized for children ages 4 to 18 years and measured child internalizing and externalizing behaviors and total problems. The 4-18 years' checklist contains 140 questions and responses were recorded on a Likert scale: 0 = Not True, 1 = Somewhat or Sometimes True, 2 = Very True or Often True. The range of possible values was 0-280 (0=good to 280=worst).
Time Frame	Baseline, Month 6, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

11. Secondary Outcome

Title	Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; One-leg-jump) at Months 6, 12 and 18
Description	PJP was defined as the peak of the calculated power (force multiplied by velocity). It was measured by Leonardo Jumping Platform during one leg jump. The participant performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline, Month 6 , Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

12. Secondary Outcome

Title	Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; One-leg-jump) at Months 6, 12 and 18
Description	PJF was defined as the maximum of force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms and as high as possible with the head and chest. It was measured by Leonardo Jumping Platform during one leg jump. The SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline, Month 6, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

13. Secondary Outcome

Title	Change From Baseline in Maximum Jump Velocity (Vmax; One-leg-jump) at Months 6, 12 and 18
Description	Vmax was measured by Leonardo Jumping Platform during one leg jump.
Time Frame	Baseline, Month 6, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

14. Secondary Outcome

Title	Change From Baseline in Five-chair Rising Test- Peak Jump Power (PJP) at Month 6
Description	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJP is defined as the peak of the calculated power (force multiplied by velocity).
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	9	9
Baseline	0.1 (0.07)	0.1 (0.05)
Change at Month 6	0.0 (0.07)	0.0 (0.05)

15. Secondary Outcome

Title	Change From Baseline in Five-chair Rising Test-Peak Jump Power (PJP) at Months 12 and 18
Description	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJP is defined as the peak of the calculated power (force multiplied by velocity).
Time Frame	Baseline, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

16. Secondary Outcome

Title	Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Month 6
Description	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJF is the maximum force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms as high as possible with the head and chest.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	9	9
Baseline	0.4 (0.11)	0.4 (0.19)
Change at Month 6	-0.0 (0.23)	0.0 (0.20)

17. Secondary Outcome

Title	Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Months 12 and 18
Description	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJF is the maximum force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms as high as possible with the head and chest.
Time Frame	Baseline, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

18. Secondary Outcome

Title	Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Month 6
Description	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). Vmax is defined as the maximum jump velocity.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	9	9
Baseline	0.7 (0.22)	0.6 (0.16)
Change at Month 6	0.2 (0.29)	0.0 (0.18)

19. Secondary Outcome

Title	Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Months 12 and 18
Description	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). Vmax is defined as the maximum jump velocity.
Time Frame	Baseline, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

20. Secondary Outcome

Title	Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6
Description	Chair rising test is performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: 5 repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over chest (time to perform tasks, maximal PJP, maximal velocity and maximal PJF). Time to perform task includes: Average (avg) rise time which is avg time to perform 1 rise, avg time per test is the avg time to perform 1 test (rise and sitting down) and total time to perform 5 tests.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	9	9
Baseline (Average rise time)	1.2 (0.90)	0.7 (0.31)
Change at Month 6 (Average rise time)	-0.5 (1.15)	0.1 (0.27)
Baseline (Average time per test)	2.0 (0.70)	2.3 (0.60)
Change at Month 6 (Average time per test)	-0.2 (0.54)	-0.1 (0.87)
Baseline (Total time to perform 5 tests)	9.6 (3.91)	10.8 (2.24)
Change at Month 6 (Total time to perform 5 tests)	0.1 (3.04)	2.0 (8.48)

21. Secondary Outcome

Title	Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Months 12 and 18
Description	Chair rising test is performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: 5 repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over chest (time to perform tasks, maximal PJP, maximal velocity and maximal PJF). Time to perform task includes: Average (avg) rise time which is avg time to perform 1 rise, avg time per test is the avg time to perform 1 test (rise and sitting down) and total time to perform 5 tests.
Time Frame	Baseline, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

22. Secondary Outcome

Title	Change From Baseline in One-chair Rising Test-Peak Jump Power (PJP) at Months 6, 12 and 18
Description	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement to stand up. Test allows diagnostics of movement deficits using Leonardo jump plate. One stand up test: rising from a chair on the jump plate as quickly as possible with arms crossed over the chest (analysis of time, PJP, PJF and time of fastest rising). PJP is defined as the peak of the calculated power (force multiplied by velocity).
Time Frame	Baseline, Month 6 , Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

23. Secondary Outcome

Title	Change From Baseline in One-chair Rising Test-Peak Jump Force (PJF) at Months 6, 12 and 18
Description	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement to stand up. Test allows diagnostics of movement deficits using Leonardo jump plate. One stand up test: rising from a chair on the jump plate as quickly as possible with arms crossed over the chest (analysis of time, PJP, PJF and time of fastest rising). PJF is the maximum force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms as high as possible with the head and chest.
Time Frame	Baseline, Month 6 , Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

24. Secondary Outcome

Title	Change From Baseline in One-chair Rising Test (Time to Perform the Tasks) at Months 6, 12 and 18
Description	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement to stand up. Test allows diagnostics of movement deficits using Leonardo jump plate. One stand up test: rising from a chair on the jump plate as quickly as possible with arms crossed over the chest (analysis of time, PJP, PJF and time of fastest rising).
Time Frame	Baseline, Month 6 , Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

25. Secondary Outcome

Title	Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Month 6
Description	MIGF was assessed using standard adjustable Jamar dynamometer. MIGF (in Newtons) was calculated by multiplying the dynamometer reading (in kilograms) by a factor of 9.81. The SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	9	11
Least Squares Mean (Standard Error) [kg]	1.28 (1.69)	1.13 (1.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9560
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	0.14
	Confidence Interval	(2-Sided) 95%; -5.71 to 6.00
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.54
	Estimation Comments

26. Secondary Outcome

Title	Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Months 12 and 18
Description	MIGF was assessed using standard adjustable Jamar dynamometer. MIGF (in Newtons) was calculated by multiplying the dynamometer reading (in kilograms) by a factor of 9.81. The SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

27. Other Pre-specified Outcome

Title	Change From Baseline in Bone Density Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months
Description	Bone Mineral Density (BMD) was measured by pqCT. The Z-score measures the distance of the measured BMD value from the appropriate normal age matched population mean value in units of standard deviation of this population. More negative scores indicate less BMD compared to age matched population and more positive scores indicate higher BMD compared to age matched population.
Time Frame	Baseline, Month 6, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

28. Other Pre-specified Outcome

Title	Change From Baseline in Bone Structure Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months
Description	Bone structure was measured by pqCT.Parameters included:total area,cortical area,marrow area,cortical thickness,cortical density of the radius,bone strength,cross-sectional muscle and fat area,total bone density,bone mineral count,trabecular BMD,bone cross-sectional area.Baseline and post-baseline SDS values transformed to age and sex specific z-score([Ln(test result/M)]/S);Ln=natural logarithm;M=age-/height- and sex-specific mean value;S=age-/height- and sex-specific coefficient of variation).Positive values are above the average for participant's age and sex;negative values are below.
Time Frame	Baseline, Month 6, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

29. Other Pre-specified Outcome

Title	Change From Baseline in Bone Stability Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months
Description	Bone stability was measured by pqCT. Baseline and post-baseline SDS values transformed to age and sex specific z-score (Ln(test result/M)]/S); Ln=natural logarithm; M=age- (or height-) and sex-specific mean value; S=age-(or height-) and sex-specific coefficient of variation) then change from baseline is calculated. Positive values are above the average for participant's age and sex; negative values are below the average.
Time Frame	Baseline, Month 6, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

30. Secondary Outcome

Title	Mean Upper Arm Circumference
Time Frame	Baseline, Month 6, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

31. Secondary Outcome

Title	Mean Thigh Circumference
Description	Thigh measurements were taken as a mean of 3 consecutive measurements at upper thigh about an inch down from the crotch line.
Time Frame	Baseline, Month 6, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

32. Secondary Outcome

Title	Mean Calf Circumference
Description	Calf measurements were taken as a mean of 3 consecutive measurements at largest part of calf muscle, usually about 4 inches down from below the knee.
Time Frame	Baseline, Month 6, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

33. Secondary Outcome

Title	Mean Height at Month 6
Description	Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	11	11
Mean (Standard Deviation) [cm]	112.8 (5.13)	115.0 (7.93)

34. Secondary Outcome

Title	Mean Height at Months 12 and 18
Description	Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer.
Time Frame	Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

35. Secondary Outcome

Title	Mean Growth Velocity at Month 6
Description	Growth velocity measures the annual rate of increase in height.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	11	11
Mean (Standard Deviation) [cm/year]	8.2 (1.93)	4.6 (1.44)

36. Secondary Outcome

Title	Mean Growth Velocity at Months 12 and 18
Description	Growth velocity measures the annual rate of increase in height.
Time Frame	Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

37. Secondary Outcome

Title	Mean Height-Standard Deviation Score (SDS) at Month 6
Description	Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	11	11
Mean (Standard Deviation) [cm]	-3.1 (0.86)	-3.7 (0.77)

38. Secondary Outcome

Title	Mean Height-Standard Deviation Score (SDS) at Months 12 and 18
Description	Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.
Time Frame	Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

39. Secondary Outcome

Title	Mean Growth Velocity-Standard Deviation Score (SDS) at Month 6
Description	Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the participant is to the reference population.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	11	11
Mean (Standard Deviation) [cm/year]	3.4 (2.62)	-1.1 (1.43)

40. Secondary Outcome

Title	Mean Growth Velocity-Standard Deviation Score (SDS) at Months 12 and 18
Time Frame	Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

41. Secondary Outcome

Title	Change From Baseline in Height-Standard Deviation Score (SDS) at Month 6
Description	Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	11	11
Least Squares Mean (Standard Error) [cm]	0.33 (0.21)	-0.22 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1107
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; -0.15 to 1.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.31
	Estimation Comments

42. Secondary Outcome

Title	Change From Baseline in Height-Standard Deviation Score (SDS) at Months 12 and 18
Description	Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

43. Secondary Outcome

Title	Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Month 6
Description	Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the participant is to the reference population.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	9	9
Least Squares Mean (Standard Error) [cm/year]	3.89 (1.02)	-0.77 (1.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0161
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	4.67
	Confidence Interval	(2-Sided) 95%; 1.13 to 8.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.54
	Estimation Comments

44. Secondary Outcome

Title	Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Months 12 and 18
Description	Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the participant is to the reference population.
Time Frame	Baseline, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

45. Primary Outcome

Title	Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6
Description	PJF was defined as the maximum of force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms and as high as possible with the head and chest. It was measured by Leonardo Jumping Platform during two-leg jump. The SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

PP population included participants who received the study medication for at least 22 weeks. Number of participants analyzed (N) signifies participants evaluable for the measure.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	2	6
Least Squares Mean (Standard Error) [Newtons]	-0.83 (1.27)	-0.85 (0.73)

46. Primary Outcome

Title	Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6
Description	Vmax was measured by Leonardo Jumping Platform during two-leg jump.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	10	11
Least Squares Mean (Standard Error) [Meter/second (m/s)]	0.01 (0.08)	0.12 (0.09)

47. Primary Outcome

Title	Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Per Protocol (PP) Population at Month 6
Description	Vmax was measured by Leonardo Jumping Platform during two-leg jump.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

PP population included participants who received the study medication for at least 22 weeks. Number of participants analyzed (N) signifies participants evaluable for the measure.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	5	9
Least Squares Mean (Standard Error) [m/s]	0.01 (0.05)	0.25 (0.06)

48. Secondary Outcome

Title	Sitting Height-Standard Deviation Score (SDS)
Description	Sitting height was measured using a stadiometer with a specialized chair. The SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline, Month 6, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

49. Secondary Outcome

Title	Body Mass Index-Standard Deviation Score (BMI-SDS)
Description	The BMI was used to measure body fat based on height and weight. It was calculated by body weight (kg) divided by the height (m) squared. The SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline, Month 6, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

50. Secondary Outcome

Title	Change From Baseline in Head Circumference at Months 6, 12 and 18
Description	The maximum head circumference (usually horizontal just above the eyebrow ridges), was measured from just above the glabella area to the area near the top of the occipital bone (opisthocranion).
Time Frame	Baseline, Month 6, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

51. Secondary Outcome

Title	Change From Baseline in Head Circumference-Standard Deviation Score (SDS) at Months 6, 12 and 18
Description	The maximum head circumference (usually horizontal just above the eyebrow ridges), was measured from just above the glabella area to the area near the top of the occipital bone (opisthocranion). The SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline, Month 6, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

52. Secondary Outcome

Title	Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6
Description	Triceps, supra-iliac and subscapular skinfolds were measured on the right side of the body to the nearest 0.1 mm with a Holtain skinfold caliper. The measurement was performed at the left side of the participant. Triceps skinfold thickness was measured halfway down the left upper arm, while the arm was hanging relaxed at the participant's side. Suprascapular skinfold was measured laterally just below the angle of the left scapula. Suprailiac skinfold was measured just above the iliac crest in the middle-axillary line. SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	11	11
Change at Month 6 (Triceps SDS)	-0.41 (0.16)	-0.06 (0.18)
Change at Month 6 (Subscapular SDS)	-0.30 (0.10)	-0.16 (0.13)
Change at Month 6 (Suprailiac SDS)	-0.60 (0.07)	-0.33 (0.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	Triceps SDS: ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1870
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 95%; -0.89 to 0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.25
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	Subscapular SDS: ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3494
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.49 to 0.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Control Arm
	Comments	Suprailiac SDS: ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0458
	Comments	The statistical test was 2-sided and performed at the 5 percent significance level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 95%; -0.54 to -0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

53. Secondary Outcome

Title	Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Months 12 and 18
Description	Triceps, supra-iliac and subscapular skinfolds were measured on the right side of the body to the nearest 0.1 mm with a Holtain skinfold caliper. The measurement was performed at the left side of the participant. Triceps skinfold thickness was measured halfway down the left upper arm, while the arm was hanging relaxed at the participant's side. Suprascapular skinfold was measured laterally just below the angle of the left scapula. Suprailiac skinfold was measured just above the iliac crest in the middle-axillary line. SDS indicates how similar the participant was to the reference population.
Time Frame	Baseline, Month 12 and Month 18

Outcome Measure Data

Analysis Population Description

Data were not analyzed as study was prematurely terminated due to insufficient number of participants.

Arm/Group Title	Somatropin	Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.	No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
Measure Participants	0	0

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		Control Arm
Arm/Group Description	Somatropin 0.035 mg/kg/day was administered s.c according to exact body weight specific calculation for 12 months. Dose adjustments were made at 6 month intervals.		No treatment for initial 6 months in control group, after 6 months, somatropin 0.067 mg/kg/day administered s.c. according to exact body weight specific calculation for 12 months.
All Cause Mortality
	Somatropin		Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Somatropin		Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Somatropin		Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/12 (83.3%)		7/11 (63.6%)
Congenital, familial and genetic disorders
Cryptorchism	1/12 (8.3%)		0/11 (0%)
Endocrine disorders
Hypothyroidism	1/12 (8.3%)		0/11 (0%)
Eye disorders
Conjunctivitis	0/12 (0%)		1/11 (9.1%)
Eyelid oedema	1/12 (8.3%)		0/11 (0%)
Gastrointestinal disorders
Abdominal pain	1/12 (8.3%)		0/11 (0%)
Constipation	0/12 (0%)		1/11 (9.1%)
Diarrhoea	1/12 (8.3%)		0/11 (0%)
Infections and infestations
Acute tonsillitis	0/12 (0%)		1/11 (9.1%)
Bronchitis	0/12 (0%)		1/11 (9.1%)
Gastroenteritis	0/12 (0%)		1/11 (9.1%)
Herpes zoster	1/12 (8.3%)		0/11 (0%)
Lice infestation	1/12 (8.3%)		0/11 (0%)
Otitis media	1/12 (8.3%)		1/11 (9.1%)
Respiratory tract infection	2/12 (16.7%)		0/11 (0%)
Rhinitis	0/12 (0%)		1/11 (9.1%)
Scarlet fever	1/12 (8.3%)		0/11 (0%)
Tonsillitis	0/12 (0%)		1/11 (9.1%)
Tooth infection	1/12 (8.3%)		0/11 (0%)
Upper respiratory tract infection	1/12 (8.3%)		1/11 (9.1%)
Urinary tract infection	0/12 (0%)		1/11 (9.1%)
Injury, poisoning and procedural complications
Concussion	0/12 (0%)		1/11 (9.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/12 (0%)		1/11 (9.1%)
Lordosis	1/12 (8.3%)		0/11 (0%)
Pain in extremity	1/12 (8.3%)		0/11 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma	0/12 (0%)		1/11 (9.1%)
Nervous system disorders
Headache	2/12 (16.7%)		2/11 (18.2%)
Renal and urinary disorders
Enuresis	1/12 (8.3%)		0/11 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/12 (8.3%)		1/11 (9.1%)
Skin and subcutaneous tissue disorders
Eczema	0/12 (0%)		1/11 (9.1%)
Rash	1/12 (8.3%)		0/11 (0%)

Limitations/Caveats

The study was prematurely discontinued, therefore not all data was powered.

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.