Trial Outcomes & Findings for Neuromuscular Changes In Small For Gestational Age Children During Somatropin Therapy (NCT NCT00625872)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

23 participants

Primary outcome timeframe

Baseline and Month 6

Results posted on

2012-02-29

Participant Flow

Participant milestones

Participant milestones
Measure	Somatropin 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.	Control Arm 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.
Overall Study STARTED	12	11
Overall Study Treated	12	10
Overall Study COMPLETED	8	5
Overall Study NOT COMPLETED	4	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Somatropin 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.	Control Arm 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.
Overall Study Withdrawal by Subject	1	0
Overall Study Does not meet inclusion criteria	1	0
Overall Study Terminated by sponsor	2	5
Overall Study Randomized but not treated	0	1

Baseline Characteristics

Neuromuscular Changes In Small For Gestational Age Children During Somatropin Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Somatropin n=12 Participants 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.	Control Arm n=11 Participants 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 n=23 Participants Total of all reporting groups
Age Continuous	6.6 Years STANDARD_DEVIATION 1.0 • n=5 Participants	7.6 Years STANDARD_DEVIATION 1.4 • n=7 Participants	7.1 Years STANDARD_DEVIATION 1.3 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Month 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Somatropin n=4 Participants 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.	Control Arm n=8 Participants 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.
Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6	-0.15 Watt/kilogram (W/kg) Standard Error 1.01 • Interval to 3.07	0.28 Watt/kilogram (W/kg) Standard Error 0.51 • Interval to 1.91

PRIMARY outcome

Timeframe: Baseline and Month 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Somatropin n=2 Participants 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.	Control Arm n=6 Participants 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.
Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6	-1.02 W/kg Standard Error 0.43	0.59 W/kg Standard Error 0.27

PRIMARY outcome

Timeframe: Baseline and Month 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Somatropin n=4 Participants 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.	Control Arm n=8 Participants 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.
Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6	-0.70 Newtons Standard Error 0.62 • Interval to 1.29	-0.55 Newtons Standard Error 0.29 • Interval to 0.38

PRIMARY outcome

Timeframe: Baseline and Month 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Somatropin n=2 Participants 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.	Control Arm n=6 Participants 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.
Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6	-0.83 Newtons Standard Error 1.27	-0.85 Newtons Standard Error 0.73

PRIMARY outcome

Timeframe: Baseline and Month 6

Population: 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.

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

Outcome measures

Outcome measures
Measure	Somatropin n=10 Participants 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.	Control Arm n=11 Participants 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.
Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6	0.01 Meter/second (m/s) Standard Error 0.08 • Interval to 0.18	0.12 Meter/second (m/s) Standard Error 0.09 • Interval to 0.32

PRIMARY outcome

Timeframe: Baseline and Month 6

Population: 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.

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

Outcome measures

Outcome measures
Measure	Somatropin n=5 Participants 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.	Control Arm n=9 Participants 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.
Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Per Protocol (PP) Population at Month 6	0.01 m/s Standard Error 0.05	0.25 m/s Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline and Month 6

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

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 \[less than (\<) 69\].

Outcome measures

Outcome measures
Measure	Somatropin n=11 Participants 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.	Control Arm n=11 Participants 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.
Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 Baseline (Sequential Processing)	25.7 Units on a scale Standard Deviation 8.35	28.5 Units on a scale Standard Deviation 8.33
Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 Change at Month 6 (Sequential Processing)	2.6 Units on a scale Standard Deviation 5.82	-1.9 Units on a scale Standard Deviation 4.15
Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 Baseline (Simultaneous Processing)	45.7 Units on a scale Standard Deviation 7.20	49.8 Units on a scale Standard Deviation 12.74
Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 Change at Month 6 (Simultaneous Processing)	-0.1 Units on a scale Standard Deviation 4.53	1.5 Units on a scale Standard Deviation 4.30
Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 Baseline (Achievement)	300.7 Units on a scale Standard Deviation 66.83	341.8 Units on a scale Standard Deviation 76.88
Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 Change at Month 6 (Achievement)	32.1 Units on a scale Standard Deviation 48.79	16.7 Units on a scale Standard Deviation 27.52
Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 Baseline (Nonverbal)	46.2 Units on a scale Standard Deviation 8.65	49.8 Units on a scale Standard Deviation 13.21
Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 Change at Month 6 (Nonverbal)	-1.4 Units on a scale Standard Deviation 3.78	0.0 Units on a scale Standard Deviation 5.35
Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 Baseline (Mental Processing Composite)	70.0 Units on a scale Standard Deviation 12.38	78.1 Units on a scale Standard Deviation 19.95
Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6 Change at Month 6 (Mental Processing Composite)	1.4 Units on a scale Standard Deviation 6.39	-0.9 Units on a scale Standard Deviation 7.28

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 18

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

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 \[less than (\<) 69\].

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Somatropin n=9 Participants 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.	Control Arm n=11 Participants 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.
Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 Baseline (Distractibility)	554.3 Seconds Standard Deviation 201.08 • Interval 300.0 to 978.0	514.5 Seconds Standard Deviation 127.41 • Interval 321.0 to 709.0
Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 Change at 6 Month (Distractibility) (n= 7, 10)	5.6 Seconds Standard Deviation 230.95 • Interval -440.0 to 280.0	-11.4 Seconds Standard Deviation 139.52 • Interval -223.0 to 216.0
Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 Baseline (Alertness)	433.9 Seconds Standard Deviation 140.74 • Interval 250.0 to 626.0	384.6 Seconds Standard Deviation 124.94 • Interval 245.0 to 573.0
Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 Change at 6 Month (Alertness) (n= 8, 10)	-16.1 Seconds Standard Deviation 80.85 • Interval -150.0 to 119.0	4.0 Seconds Standard Deviation 107.42 • Interval -122.0 to 196.0
Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 Baseline (Flexibility)	1350.0 Seconds Standard Deviation 470.50 • Interval 728.0 to 2001.0	1313.0 Seconds Standard Deviation 477.19 • Interval 759.0 to 2140.0
Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 Change at 6 Month (Flexibility) (n= 8, 10)	-192.0 Seconds Standard Deviation 492.73 • Interval -704.0 to 875.0	-211.0 Seconds Standard Deviation 589.41 • Interval -1034.0 to 1189.0
Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 Baseline (Go/No Go)	539.8 Seconds Standard Deviation 106.73 • Interval 362.0 to 691.0	514.9 Seconds Standard Deviation 91.95 • Interval 399.0 to 730.0
Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 Change at 6 Month (Go/No Go) (n= 8, 9)	35.6 Seconds Standard Deviation 113.38 • Interval -95.0 to 208.0	-50.2 Seconds Standard Deviation 69.90 • Interval -133.0 to 45.0
Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 Baseline (Vigilance)	822.2 Seconds Standard Deviation 200.65 • Interval 569.0 to 1195.0	693.4 Seconds Standard Deviation 118.01 • Interval 525.0 to 967.0
Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6 Change at 6 Month (Vigilance) (n= 7, 10)	-146.0 Seconds Standard Deviation 278.60 • Interval -627.0 to 265.0	-31.2 Seconds Standard Deviation 107.62 • Interval -194.0 to 172.0

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Somatropin n=9 Participants 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.	Control Arm n=11 Participants 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.
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Baseline (Instability Index)	0.3 Units on a scale Standard Deviation 0.15	0.2 Units on a scale Standard Deviation 0.21
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Change at Month 6 (Instability Index)	-0.1 Units on a scale Standard Deviation 0.11	-0.1 Units on a scale Standard Deviation 0.20
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Baseline (Working Time)	227.0 Units on a scale Standard Deviation 44.27	218.3 Units on a scale Standard Deviation 76.89
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Change at Month 6 (Working Time)	10.6 Units on a scale Standard Deviation 92.95	-11.1 Units on a scale Standard Deviation 34.86
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Baseline [T-scores (1)]	39.9 Units on a scale Standard Deviation 13.60	43.9 Units on a scale Standard Deviation 16.53
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Change at Month 6 [T-scores (1)]	4.4 Units on a scale Standard Deviation 11.64	6.7 Units on a scale Standard Deviation 12.12
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Baseline [T-scores (2)]	41.6 Units on a scale Standard Deviation 12.97	46.8 Units on a scale Standard Deviation 14.40
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Change at Month 6 [T-scores (2)]	5.0 Units on a scale Standard Deviation 10.72	-0.6 Units on a scale Standard Deviation 5.50
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Baseline [T-scores (3)]	45.9 Units on a scale Standard Deviation 14.89	48.1 Units on a scale Standard Deviation 18.20
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Change at Month 6 [T-scores (3)]	1.5 Units on a scale Standard Deviation 5.15	8.3 Units on a scale Standard Deviation 12.24
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Baseline [T-scores (4)]	39.3 Units on a scale Standard Deviation 16.97	46.4 Units on a scale Standard Deviation 16.03
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Change at Month 6 [T-scores (4)]	5.6 Units on a scale Standard Deviation 15.53	1.4 Units on a scale Standard Deviation 11.75
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Baseline [T-scores (5)]	43.3 Units on a scale Standard Deviation 11.12	43.6 Units on a scale Standard Deviation 15.13
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Change at Month 6 [T-scores (5)]	2.6 Units on a scale Standard Deviation 9.83	7.7 Units on a scale Standard Deviation 12.59
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Baseline [T-scores (6)]	44.9 Units on a scale Standard Deviation 15.83	52.9 Units on a scale Standard Deviation 19.96
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Change at Month 6 [T-scores (6)]	0.9 Units on a scale Standard Deviation 16.55	-7.4 Units on a scale Standard Deviation 14.88
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Baseline [Age-corrected T-scores (1)]	33.4 Units on a scale Standard Deviation 12.18	38.6 Units on a scale Standard Deviation 13.43
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Change at Month 6 [Age-corrected T-scores (1)]	6.0 Units on a scale Standard Deviation 10.21	5.2 Units on a scale Standard Deviation 11.26
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Baseline [Age-corrected T-scores (2)]	51.3 Units on a scale Standard Deviation 7.55	54.5 Units on a scale Standard Deviation 8.10
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Change at Month 6 [Age-corrected T-scores (2)]	3.1 Units on a scale Standard Deviation 5.59	-0.1 Units on a scale Standard Deviation 3.38
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Baseline [Age-corrected T-scores (3)]	40.0 Units on a scale Standard Deviation 13.86	41.1 Units on a scale Standard Deviation 16.38
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Change at Month 6 [Age-corrected T-scores (3)]	0.6 Units on a scale Standard Deviation 4.47	7.8 Units on a scale Standard Deviation 12.13
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Baseline [Age-corrected T-scores (4)]	37.4 Units on a scale Standard Deviation 17.01	45.0 Units on a scale Standard Deviation 15.21
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Change at Month 6 [Age-corrected T-scores (4)]	6.3 Units on a scale Standard Deviation 14.57	4.1 Units on a scale Standard Deviation 10.63
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Baseline [Age-corrected T-scores (5)]	35.0 Units on a scale Standard Deviation 11.88	37.3 Units on a scale Standard Deviation 13.48
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Change at Month 6 [Age-corrected T-scores (5)]	3.3 Units on a scale Standard Deviation 10.73	6.9 Units on a scale Standard Deviation 12.57
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Baseline [Age-corrected T-scores (6)]	50.0 Units on a scale Standard Deviation 16.49	55.5 Units on a scale Standard Deviation 16.64
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6 Change at Month 6 [Age-corrected T-scores (6)]	1.5 Units on a scale Standard Deviation 19.06	-4.1 Units on a scale Standard Deviation 13.77

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12 and Month 18

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

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 6 , Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12 and Month 18

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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Somatropin n=9 Participants 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.	Control Arm n=9 Participants 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.
Change From Baseline in Five-chair Rising Test- Peak Jump Power (PJP) at Month 6 Baseline	0.1 kilowatt (kW) Standard Deviation 0.07	0.1 kilowatt (kW) Standard Deviation 0.05
Change From Baseline in Five-chair Rising Test- Peak Jump Power (PJP) at Month 6 Change at Month 6	0.0 kilowatt (kW) Standard Deviation 0.07	0.0 kilowatt (kW) Standard Deviation 0.05

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 18

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

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Somatropin n=9 Participants 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.	Control Arm n=9 Participants 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.
Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Month 6 Baseline	0.4 kilonewton (kN) Standard Deviation 0.11	0.4 kilonewton (kN) Standard Deviation 0.19
Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Month 6 Change at Month 6	-0.0 kilonewton (kN) Standard Deviation 0.23	0.0 kilonewton (kN) Standard Deviation 0.20

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Somatropin n=9 Participants 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.	Control Arm n=9 Participants 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.
Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Month 6 Baseline	0.7 m/s Standard Deviation 0.22	0.6 m/s Standard Deviation 0.16
Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Month 6 Change at Month 6	0.2 m/s Standard Deviation 0.29	0.0 m/s Standard Deviation 0.18

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Somatropin n=9 Participants 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.	Control Arm n=9 Participants 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.
Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 Baseline (Average rise time)	1.2 seconds Standard Deviation 0.90	0.7 seconds Standard Deviation 0.31
Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 Change at Month 6 (Average rise time)	-0.5 seconds Standard Deviation 1.15	0.1 seconds Standard Deviation 0.27
Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 Baseline (Average time per test)	2.0 seconds Standard Deviation 0.70	2.3 seconds Standard Deviation 0.60
Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 Change at Month 6 (Average time per test)	-0.2 seconds Standard Deviation 0.54	-0.1 seconds Standard Deviation 0.87
Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 Baseline (Total time to perform 5 tests)	9.6 seconds Standard Deviation 3.91	10.8 seconds Standard Deviation 2.24
Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6 Change at Month 6 (Total time to perform 5 tests)	0.1 seconds Standard Deviation 3.04	2.0 seconds Standard Deviation 8.48

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 6 , Month 12 and Month 18

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

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 6 , Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 6 , Month 12 and Month 18

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

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Somatropin n=9 Participants 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.	Control Arm n=11 Participants 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.
Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Month 6	1.28 kg Standard Error 1.69	1.13 kg Standard Error 1.64

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12 and Month 18

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12 and Month 18

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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 6

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

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

Outcome measures

Outcome measures
Measure	Somatropin n=11 Participants 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.	Control Arm n=11 Participants 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.
Mean Height at Month 6	112.8 cm Standard Deviation 5.13	115.0 cm Standard Deviation 7.93

SECONDARY outcome

Timeframe: Month 12 and Month 18

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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 6

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

Growth velocity measures the annual rate of increase in height.

Outcome measures

Outcome measures
Measure	Somatropin n=11 Participants 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.	Control Arm n=11 Participants 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.
Mean Growth Velocity at Month 6	8.2 cm/year Standard Deviation 1.93	4.6 cm/year Standard Deviation 1.44

SECONDARY outcome

Timeframe: Month 12 and Month 18

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

Growth velocity measures the annual rate of increase in height.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 6

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

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.

Outcome measures

Outcome measures
Measure	Somatropin n=11 Participants 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.	Control Arm n=11 Participants 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.
Mean Height-Standard Deviation Score (SDS) at Month 6	-3.1 cm Standard Deviation 0.86	-3.7 cm Standard Deviation 0.77

SECONDARY outcome

Timeframe: Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 6

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

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

Outcome measures

Outcome measures
Measure	Somatropin n=11 Participants 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.	Control Arm n=11 Participants 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.
Mean Growth Velocity-Standard Deviation Score (SDS) at Month 6	3.4 cm/year Standard Deviation 2.62	-1.1 cm/year Standard Deviation 1.43

SECONDARY outcome

Timeframe: Month 12 and Month 18

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Month 6

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

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.

Outcome measures

Outcome measures
Measure	Somatropin n=11 Participants 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.	Control Arm n=11 Participants 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.
Change From Baseline in Height-Standard Deviation Score (SDS) at Month 6	0.33 cm Standard Error 0.21	-0.22 cm Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: 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.

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

Outcome measures

Outcome measures
Measure	Somatropin n=9 Participants 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.	Control Arm n=9 Participants 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.
Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Month 6	3.89 cm/year Standard Error 1.02	-0.77 cm/year Standard Error 1.40

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 18

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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12 and Month 18

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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12 and Month 18

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

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Month 6

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

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.

Outcome measures

Outcome measures
Measure	Somatropin n=11 Participants 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.	Control Arm n=11 Participants 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.
Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6 Change at Month 6 (Triceps SDS)	-0.41 Millimeter (mm) Standard Error 0.16	-0.06 Millimeter (mm) Standard Error 0.18
Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6 Change at Month 6 (Subscapular SDS)	-0.30 Millimeter (mm) Standard Error 0.10	-0.16 Millimeter (mm) Standard Error 0.13
Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6 Change at Month 6 (Suprailiac SDS)	-0.60 Millimeter (mm) Standard Error 0.07	-0.33 Millimeter (mm) Standard Error 0.12

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Month 6, Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Month 6, Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Month 6, Month 12 and Month 18

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

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.

Outcome measures

Outcome data not reported

Adverse Events

Control Arm

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Somatropin

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Control Arm n=11 participants at risk 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.	Somatropin n=12 participants at risk 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.
Congenital, familial and genetic disorders Cryptorchism	0.00% 0/11 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.	8.3% 1/12 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.
Endocrine disorders Hypothyroidism	0.00% 0/11 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.	8.3% 1/12 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.
Eye disorders Conjunctivitis	9.1% 1/11 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.	0.00% 0/12 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.
Eye disorders Eyelid oedema	0.00% 0/11 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.	8.3% 1/12 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.
Gastrointestinal disorders Abdominal pain	0.00% 0/11 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.	8.3% 1/12 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.
Gastrointestinal disorders Constipation	9.1% 1/11 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.	0.00% 0/12 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.
Gastrointestinal disorders Diarrhoea	0.00% 0/11 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.	8.3% 1/12 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.
Infections and infestations Acute tonsillitis	9.1% 1/11 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.	0.00% 0/12 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.
Infections and infestations Bronchitis	9.1% 1/11 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.	0.00% 0/12 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.
Infections and infestations Gastroenteritis	9.1% 1/11 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.	0.00% 0/12 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.
Infections and infestations Herpes zoster	0.00% 0/11 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.	8.3% 1/12 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.
Infections and infestations Lice infestation	0.00% 0/11 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.	8.3% 1/12 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.
Infections and infestations Otitis media	9.1% 1/11 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.	8.3% 1/12 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.
Infections and infestations Respiratory tract infection	0.00% 0/11 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.	16.7% 2/12 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.
Infections and infestations Rhinitis	9.1% 1/11 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.	0.00% 0/12 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.
Infections and infestations Scarlet fever	0.00% 0/11 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.	8.3% 1/12 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.
Infections and infestations Tonsillitis	9.1% 1/11 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.	0.00% 0/12 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.
Infections and infestations Tooth infection	0.00% 0/11 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.	8.3% 1/12 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.
Infections and infestations Upper respiratory tract infection	9.1% 1/11 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.	8.3% 1/12 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.
Infections and infestations Urinary tract infection	9.1% 1/11 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.	0.00% 0/12 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.
Injury, poisoning and procedural complications Concussion	9.1% 1/11 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.	0.00% 0/12 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.
Musculoskeletal and connective tissue disorders Arthralgia	9.1% 1/11 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.	0.00% 0/12 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.
Musculoskeletal and connective tissue disorders Lordosis	0.00% 0/11 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.	8.3% 1/12 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.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/11 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.	8.3% 1/12 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	9.1% 1/11 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.	0.00% 0/12 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.
Nervous system disorders Headache	18.2% 2/11 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.	16.7% 2/12 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.
Renal and urinary disorders Enuresis	0.00% 0/11 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.	8.3% 1/12 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.
Respiratory, thoracic and mediastinal disorders Cough	9.1% 1/11 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.	8.3% 1/12 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.
Skin and subcutaneous tissue disorders Eczema	9.1% 1/11 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.	0.00% 0/12 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.
Skin and subcutaneous tissue disorders Rash	0.00% 0/11 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.	8.3% 1/12 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.