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    Clinical Trial Results:
    Neuromuscular Changes In Small For Gestational Age (SGA) Children During Somatropin Therapy - A Prospective Randomized, Controlled, Open-Label Multicenter Trial (SGA-Power Study)

    Due to a system error, the data reported in v1 is not correct and has been removed from public view.
    Summary
    EudraCT number
    		 2006-004304-39
    Trial protocol
    		 DE  
    Global end of trial date
    14 Mar 2011

    Results information
    Results version number
    		 v2(current)
    This version publication date
    27 Apr 2016
    First version publication date
    01 Jul 2015
    Other versions
    		 v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    error resolution

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    A6281283
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00625872
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 1 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 1 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    06 Sep 2011
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Mar 2011
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Primary objective was to determine whether growth hormone therapy improved the motor- performance and coordinative skills in pre-pubertal individuals with SGA as defined by efficiency of muscular function.
    Protection of trial subjects
    This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of trial subjects.
    Background therapy
    		 -
    Evidence for comparator
    		 Treated versus untreated group during 6 month study period.
    Actual start date of recruitment
    01 Jul 2008
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 23
    Worldwide total number of subjects
    23
    EEA total number of subjects
    23
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    23
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Total 23 subjects were enrolled in 5 centres of Germany. Study started from 01 Jul 2008 and completed on 14 Mar 2011.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Somatropin
    Arm description
    		 Somatropin was administered for 12 months. Dose adjustments were made at 6 month intervals.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Somatropin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    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.

    Arm title
    		 Control
    Arm description
    		 No treatment for initial 6 months in control group. After 6 months, somatropin was administered for next 12 months.
    Arm type
    		 Control

    Investigational medicinal product name
    Somatropin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    No treatment for initial 6 months in control group. After 6 months, somatropin 0.067 mg/kg/day was administered s.c. according to exact body weight specific calculation, for the next 12 months.

    Number of subjects in period 1
    		Somatropin Control
    Started
    12
    11
    Treated
    12
    10
    Completed
    8
    5
    Not completed
    4
    6
         Consent withdrawn by subject
    1
    -
         Did not meet entrance criteria
    1
    -
         Randomized but not treated
    -
    1
         Study terminated by sponsor
    2
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Somatropin
    Reporting group description
    		 Somatropin was administered for 12 months. Dose adjustments were made at 6 month intervals.

    Reporting group title
    Control
    Reporting group description
    		 No treatment for initial 6 months in control group. After 6 months, somatropin was administered for next 12 months.

    Reporting group values
    		 Somatropin Control Total
    Number of subjects
    		 12 11 23
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 6.6 ± 1 7.6 ± 1.4 -
    Gender categorical
    Units: Subjects
        Female
    		 3 8 11
        Male
    		 9 3 12

    End points

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    End points reporting groups
    Reporting group title
    Somatropin
    Reporting group description
    		 Somatropin was administered for 12 months. Dose adjustments were made at 6 month intervals.

    Reporting group title
    Control
    Reporting group description
    		 No treatment for initial 6 months in control group. After 6 months, somatropin was administered for next 12 months.

    Primary: Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6

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    End point 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
    End point 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 subject performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the subject was to the reference population. Analysis was done on the full analysis set (FAS) population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Primary
    End point timeframe
    Baseline, Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    4 [1]
    8 [2]
    Units: Watt/kilogram (W/kg)
        least squares mean (standard error)
    -0.15 ± 1.01
    0.28 ± 0.51
    Notes
    [1] - Number of subjects analyzed (N) signifies the number of subjects evaluable for this outcome measure.
    [2] - N signifies the number of subjects evaluable for this outcome measure.
    Statistical analysis title
    		 Statistical Analysis at Month 6
    Statistical analysis description
    Analysis of covariance (ANCOVA) method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    12
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7232 [3]
    Method
    		 ANCOVA
    Parameter type
    		 Least squares (LS) mean difference
    Point estimate
    -0.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.93
         upper limit
    		 3.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.1
    Notes
    [3] - The statistical test was 2-sided and performed at the 5 percent significance level.

    Primary: Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6

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    End point title
    		 Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6
    End point 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 subject performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the subject was to the reference population. Analysis was done on the per protocol (PP) population- subjects who received the study medication for at least 22 weeks.
    End point type
    Primary
    End point timeframe
    Baseline, Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    2 [4]
    6 [5]
    Units: W/kg
        least squares mean (standard error)
    -1.02 ± 0.43
    0.59 ± 0.27
    Notes
    [4] - N signifies the number of subjects evaluable for this outcome measure.
    [5] - N signifies the number of subjects evaluable for this outcome measure.
    Statistical analysis title
    		 Statistical Analysis at Month 6
    Statistical analysis description
    ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1941 [6]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean difference
    Point estimate
    -1.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.04
         upper limit
    		 4.82
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.51
    Notes
    [6] - The statistical test was 2-sided and performed at the 5 percent significance level.

    Primary: Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6

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    End point 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 [7]
    End point description
    PJF was defined as the maximum of force of the ascending part of the jump which the subject 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 subject was to the reference population. Analysis was done on the FAS population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Primary
    End point timeframe
    Baseline, Month 6
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses
    End point values
    		 Somatropin Control
    Number of subjects analysed
    4 [8]
    8 [9]
    Units: Newtons
        least squares mean (standard error)
    -0.7 ± 0.62
    -0.55 ± 0.29
    Notes
    [8] - N signifies the number of subjects evaluable for this outcome measure.
    [9] - N signifies the number of subjects evaluable for this outcome measure.
    No statistical analyses for this end point

    Primary: Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6

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    End point title
    		 Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6 [10]
    End point description
    PJF was defined as the maximum of force of the ascending part of the jump which the subject 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 subject was to the reference population. Analysis was done on the PP population- subjects who received the study medication for at least 22 weeks.
    End point type
    Primary
    End point timeframe
    Baseline, Month 6
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses.
    End point values
    		 Somatropin Control
    Number of subjects analysed
    2 [11]
    6 [12]
    Units: Newtons
        least squares mean (standard error)
    -0.83 ± 1.27
    -0.85 ± 0.73
    Notes
    [11] - N signifies the number of subjects evaluable for this outcome measure.
    [12] - N signifies the number of subjects evaluable for this outcome measure.
    No statistical analyses for this end point

    Primary: Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6

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    End point title
    		 Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6 [13]
    End point description
    Vmax was measured by Leonardo Jumping Platform during two-leg jump. Analysis was done on the FAS population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Primary
    End point timeframe
    Baseline, Month 6
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses.
    End point values
    		 Somatropin Control
    Number of subjects analysed
    10 [14]
    11
    Units: Meter/second (m/s)
        least squares mean (standard error)
    0.01 ± 0.08
    0.12 ± 0.09
    Notes
    [14] - N signifies the number of subjects evaluable for this outcome measure.
    No statistical analyses for this end point

    Primary: Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Per Protocol (PP) Population at Month 6

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    End point title
    		 Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Per Protocol (PP) Population at Month 6 [15]
    End point description
    Vmax was measured by Leonardo Jumping Platform during two-leg jump. Analysis was done on the PP population- subjects who received the study medication for at least 22 weeks.
    End point type
    Primary
    End point timeframe
    Baseline, Month 6
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses
    End point values
    		 Somatropin Control
    Number of subjects analysed
    5 [16]
    9
    Units: m/s
        least squares mean (standard error)
    0.01 ± 0.05
    0.25 ± 0.06
    Notes
    [16] - N signifies the number of subjects evaluable for this outcome measure.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6

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    End point title
    		 Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6
    End point 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]. Analysis was done on the FAS population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    11
    11
    Units: Units on a scale
    arithmetic mean (standard deviation)
        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 ± 7.2
    49.8 ± 12.74
        Change at Month 6 (Simultaneous Processing)
    -0.1 ± 4.53
    1.5 ± 4.3
        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 ± 5.35
        Baseline (Mental Processing Composite)
    70 ± 12.38
    78.1 ± 19.95
        Change at Month 6 (Mental Processing Composite)
    1.4 ± 6.39
    -0.9 ± 7.28
    Statistical analysis title
    		 Statistical Analysis for Sequential Processing
    Statistical analysis description
    For K-ABC Test (Sequential Processing): Kruskal-Wallis Analysis of Variance (ANOVA) model was used to calculate p-value.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0532 [17]
    Method
    		 Kruskal-wallis
    Confidence interval
    Notes
    [17] - The statistical test was 2-sided and performed at the 5 percent significance level.
    Statistical analysis title
    		 Statistical Analysis for Simultaneous Processing
    Statistical analysis description
    For K-ABC Test (Simultaneous Processing): Kruskal-Wallis ANOVA model was used to calculate p-value.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3383 [18]
    Method
    		 Kruskal-wallis
    Confidence interval
    Notes
    [18] - The statistical test was 2-sided and performed at the 5 percent significance level.
    Statistical analysis title
    		 Statistical Analysis for Achievement
    Statistical analysis description
    For K-ABC Test (Achievement): Kruskal-Wallis ANOVA model was used to calculate p-value.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.683 [19]
    Method
    		 Kruskal-wallis
    Confidence interval
    Notes
    [19] - The statistical test was 2-sided and performed at the 5 percent significance level.
    Statistical analysis title
    		 Statistical Analysis for Non-Verbal
    Statistical analysis description
    For K-ABC Test (Non-Verbal): Kruskal-Wallis ANOVA model was used to calculate p-value.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4935 [20]
    Method
    		 Kruskal-wallis
    Confidence interval
    Notes
    [20] - The statistical test was 2-sided and performed at the 5 percent significance level.
    Statistical analysis title
    		 Statistical Analysis for Mental Processing
    Statistical analysis description
    For K-ABC Test (Mental Processing Composite): Kruskal-Wallis ANOVA model was used to calculate p-value.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3458 [21]
    Method
    		 Kruskal-wallis
    Confidence interval
    Notes
    [21] - The statistical test was 2-sided and performed at the 5 percent significance level.

    Secondary: Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Months 12 and 18

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    End point 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
    End point 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].
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [22]
    0 [23]
    Units: Units on a scale
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [22] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [23] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6

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    End point title
    		 Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6
    End point 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. Analysis was done on the FAS population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Here, 'n' signifies subjects who received the study drug and evaluated at the time point for each group respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    9 [24]
    11
    Units: Seconds
    arithmetic mean (standard deviation)
        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 ± 107.42
        Baseline (Flexibility)
    1350 ± 470
    1313 ± 477.19
        Change at 6 Month (Flexibility) (n= 8, 10)
    -192 ± 492.73
    -211 ± 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 ± 69.9
        Baseline (Vigilance)
    822.2 ± 200.65
    693.4 ± 118.01
        Change at 6 Month (Vigilance) (n= 7, 10)
    -146 ± 278.6
    -31.2 ± 107.62
    Notes
    [24] - N signifies the number of subjects evaluable for this outcome measure.
    Statistical analysis title
    		 Statistical Analysis for Distractibility
    Statistical analysis description
    For KITAP Test (Distractibility): Kruskal-Wallis ANOVA model was used to calculate p-value.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6256
    Method
    		 Kruskal-wallis
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis for Alertness
    Statistical analysis description
    For KITAP Test (Alertness): Kruskal-Wallis ANOVA model was used to calculate p-value.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.859
    Method
    		 Kruskal-wallis
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis for Flexibility
    Statistical analysis description
    For KITAP Test (Flexibility): Kruskal-Wallis ANOVA model was used to calculate p-value.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 1
    Method
    		 Kruskal-wallis
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis for Go/No Go
    Statistical analysis description
    For KITAP Test (Go/No Go): Kruskal-Wallis ANOVA model was used to calculate p-value.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1234
    Method
    		 Kruskal-wallis
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis for Vigilance
    Statistical analysis description
    For KITAP Test (Vigilance): Kruskal-Wallis ANOVA model was used to calculate p-value.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3291
    Method
    		 Kruskal-wallis
    Confidence interval

    Secondary: Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Months 12 and 18

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    End point title
    		 Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Months 12 and 18
    End point 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [25]
    0 [26]
    Units: Seconds
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [25] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [26] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6

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    End point title
    		 Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6
    End point 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. Analysis was done on the FAS population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    9 [27]
    11
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Baseline (Instability Index)
    0.3 ± 0.15
    0.2 ± 0.21
        Change at Month 6 (Instability Index)
    -0.1 ± 0.11
    -0.1 ± 0.2
        Baseline (Working Time)
    227 ± 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 ± 13.6
    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 ± 14.4
        Change at Month 6 [T-scores (2)]
    5 ± 10.72
    -0.6 ± 5.5
        Baseline [T-scores (3)]
    45.9 ± 14.89
    48.1 ± 18.2
        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 ± 10.21
    5.2 ± 11.26
        Baseline [Age-corrected T-scores (2)]
    51.3 ± 7.55
    54.5 ± 8.1
        Change at Month 6 [Age-corrected T-scores (2)]
    3.1 ± 5.59
    -0.1 ± 3.38
        Baseline [Age-corrected T-scores (3)]
    40 ± 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 ± 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 ± 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 ± 16.49
    55.5 ± 16.64
        Change at Month 6 [Age-corrected T-scores (6)]
    1.5 ± 19.06
    -4.1 ± 13.77
    Notes
    [27] - N signifies the number of subjects evaluable for this outcome measure.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Months 12 and 18

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    End point title
    		 Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Months 12 and 18
    End point 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [28]
    0 [29]
    Units: Units on a scale
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [28] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [29] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Intellectual Performance of Children Using Child Behavior Checklist 4-18 Years (CBCL 4-18) at Months 6, 12 and 18

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    End point 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
    End point 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).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [30]
    0 [31]
    Units: Units on a scale
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [30] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [31] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; One-leg-jump) at Months 6, 12 and 18

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    End point title
    		 Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; One-leg-jump) at Months 6, 12 and 18
    End point 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 subject performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the subject was to the reference population.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6 , Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [32]
    0 [33]
    Units: W/kg
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [32] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [33] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; One-leg-jump) at Months 6, 12 and 18

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    End point title
    		 Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; One-leg-jump) at Months 6, 12 and 18
    End point description
    PJF was defined as the maximum of force of the ascending part of the jump which the subject 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 subject was to the reference population.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [34]
    0 [35]
    Units: Newtons
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [34] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [35] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Maximum Jump Velocity (Vmax; One-leg-jump) at Months 6, 12 and 18

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    End point title
    		 Change From Baseline in Maximum Jump Velocity (Vmax; One-leg-jump) at Months 6, 12 and 18
    End point description
    Vmax was measured by Leonardo Jumping Platform during one leg jump.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [36]
    0 [37]
    Units: m/s
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [36] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [37] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Five-chair Rising Test- Peak Jump Power (PJP) at Month 6

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    End point title
    		 Change From Baseline in Five-chair Rising Test- Peak Jump Power (PJP) at Month 6
    End point 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). Analysis was done on the FAS population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    9 [38]
    9 [39]
    Units: kilowatt (kW)
    arithmetic mean (standard deviation)
        Baseline
    0.1 ± 0.07
    0.1 ± 0.05
        Change at Month 6
    0 ± 0.07
    0 ± 0.05
    Notes
    [38] - N signifies the number of subjects evaluable for this outcome measure.
    [39] - N signifies the number of subjects evaluable for this outcome measure.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Five-chair Rising Test-Peak Jump Power (PJP) at Months 12 and 18

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    End point title
    		 Change From Baseline in Five-chair Rising Test-Peak Jump Power (PJP) at Months 12 and 18
    End point 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).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [40]
    0 [41]
    Units: kW
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [40] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [41] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Month 6

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    End point title
    		 Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Month 6
    End point 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 subject performed as a counter-movement jump with freely moving arms as high as possible with the head and chest. Analysis was done on the FAS population included- who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    9 [42]
    9 [43]
    Units: kilonewton (kN)
    arithmetic mean (standard deviation)
        Baseline
    0.4 ± 0.11
    0.4 ± 0.19
        Change at Month 6
    0 ± 0.23
    0 ± 0.2
    Notes
    [42] - N signifies the number of subjects evaluable for this outcome measure.
    [43] - N signifies the number of subjects evaluable for this outcome measure.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Months 12 and 18

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    End point title
    		 Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Months 12 and 18
    End point 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 subject performed as a counter-movement jump with freely moving arms as high as possible with the head and chest.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [44]
    0 [45]
    Units: kN
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [44] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [45] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Month 6

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    End point title
    		 Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Month 6
    End point 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. Analysis was done on the FAS population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    9 [46]
    9 [47]
    Units: m/s
    arithmetic mean (standard deviation)
        Baseline
    0.7 ± 0.22
    0.6 ± 0.16
        Change at Month 6
    0.2 ± 0.29
    0 ± 0.18
    Notes
    [46] - N signifies the number of subjects evaluable for this outcome measure.
    [47] - N signifies the number of subjects evaluable for this outcome measure.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Months 12 and 18

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    End point title
    		 Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Months 12 and 18
    End point 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12 and Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [48]
    0 [49]
    Units: m/s
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [48] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [49] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6

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    End point title
    		 Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6
    End point 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, average time per test is the average time to perform 1 test (rise and sitting down) and total time to perform 5 tests. Analysis was done on the FAS population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    9 [50]
    9 [51]
    Units: seconds
    arithmetic mean (standard deviation)
        Baseline (Average rise time)
    1.2 ± 0.9
    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 ± 0.7
    2.3 ± 0.6
        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 ± 8.48
    Notes
    [50] - N signifies subjects evaluable for the measure.
    [51] - N signifies subjects evaluable for the measure.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Months 12 and 18

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    End point title
    		 Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Months 12 and 18
    End point 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [52]
    0 [53]
    Units: seconds
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [52] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [53] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in One-chair Rising Test-Peak Jump Power (PJP) at Months 6, 12 and 18

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    End point title
    		 Change From Baseline in One-chair Rising Test-Peak Jump Power (PJP) at Months 6, 12 and 18
    End point 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).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6 , Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [54]
    0 [55]
    Units: kW
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [54] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [55] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in One-chair Rising Test-Peak Jump Force (PJF) at Months 6, 12 and 18

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    End point title
    		 Change From Baseline in One-chair Rising Test-Peak Jump Force (PJF) at Months 6, 12 and 18
    End point 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 subject performed as a counter-movement jump with freely moving arms as high as possible with the head and chest.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6 , Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [56]
    0 [57]
    Units: kN
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [56] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [57] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in One-chair Rising Test (Time to Perform the Tasks) at Months 6, 12 and 18

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    End point title
    		 Change From Baseline in One-chair Rising Test (Time to Perform the Tasks) at Months 6, 12 and 18
    End point 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).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6 , Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [58]
    0 [59]
    Units: seconds
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [58] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [59] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Month 6

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    End point title
    		 Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Month 6
    End point 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 subject was to the reference population. Analysis was done on the FAS population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    9 [60]
    11
    Units: kg
        least squares mean (standard error)
    1.28 ± 1.69
    1.13 ± 1.64
    Notes
    [60] - N signifies the number of subjects evaluable for this outcome measure.
    Statistical analysis title
    		 Statistical Analysis at Month 6
    Statistical analysis description
    ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.956 [61]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean difference
    Point estimate
    0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.71
         upper limit
    		 6
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.54
    Notes
    [61] - The statistical test was 2-sided and performed at the 5 percent significance level.

    Secondary: Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Months 12 and 18

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    End point title
    		 Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Months 12 and 18
    End point 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 subject was to the reference population.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [62]
    0 [63]
    Units: kg
        least squares mean (standard error)
    ±
    ±
    Notes
    [62] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [63] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Mean Upper Arm Circumference

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    End point title
    		 Mean Upper Arm Circumference
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [64]
    0 [65]
    Units: centimeter (cm)]
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [64] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [65] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Mean Thigh Circumference

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    End point title
    		 Mean Thigh Circumference
    End point description
    Thigh measurements were taken as a mean of 3 consecutive measurements at upper thigh about an inch down from the crotch line.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [66]
    0 [67]
    Units: cm
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [66] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [67] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Mean Calf Circumference

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    End point title
    		 Mean Calf Circumference
    End point 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, Month 12 and Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [68]
    0 [69]
    Units: cm
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [68] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [69] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Mean Height at Month 6

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    End point title
    		 Mean Height at Month 6
    End point description
    Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. Analysis was done on the FAS population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    11
    11
    Units: cm
        arithmetic mean (standard deviation)
    112.8 ± 5.13
    115 ± 7.93
    No statistical analyses for this end point

    Secondary: Mean Height at Months 12 and 18

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    End point title
    		 Mean Height at Months 12 and 18
    End point description
    Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer.
    End point type
    Secondary
    End point timeframe
    Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [70]
    0 [71]
    Units: cm
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [70] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [71] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Mean Growth Velocity at Month 6

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    End point title
    		 Mean Growth Velocity at Month 6
    End point description
    Growth velocity measures the annual rate of increase in height. Analysis was done on the FAS population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    11
    11
    Units: cm/year
        arithmetic mean (standard deviation)
    8.2 ± 1.93
    4.6 ± 1.44
    No statistical analyses for this end point

    Secondary: Mean Growth Velocity at Months 12 and 18

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    End point title
    		 Mean Growth Velocity at Months 12 and 18
    End point description
    Growth velocity measures the annual rate of increase in height.
    End point type
    Secondary
    End point timeframe
    Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [72]
    0 [73]
    Units: cm/year
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [72] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [73] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Mean Height-Standard Deviation Score (SDS) at Month 6

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    End point title
    		 Mean Height-Standard Deviation Score (SDS) at Month 6
    End point description
    Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the subject was to the reference population. Analysis was done on the FAS population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    11
    11
    Units: cm
        arithmetic mean (standard deviation)
    -3.1 ± 0.86
    -3.7 ± 0.77
    No statistical analyses for this end point

    Secondary: Mean Height-Standard Deviation Score (SDS) at Months 12 and 18

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    End point title
    		 Mean Height-Standard Deviation Score (SDS) at Months 12 and 18
    End point description
    Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the subject was to the reference population.
    End point type
    Secondary
    End point timeframe
    Month 12 and Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [74]
    0 [75]
    Units: cm
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [74] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [75] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Mean Growth Velocity-Standard Deviation Score (SDS) at Month 6

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    End point title
    		 Mean Growth Velocity-Standard Deviation Score (SDS) at Month 6
    End point description
    Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the subject was to the reference population. Analysis was done on the FAS population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    11
    11
    Units: cm/year
        arithmetic mean (standard deviation)
    3.4 ± 2.62
    -1.1 ± 1.43
    No statistical analyses for this end point

    Secondary: Mean Growth Velocity-Standard Deviation Score (SDS) at Months 12 and 18

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    End point title
    		 Mean Growth Velocity-Standard Deviation Score (SDS) at Months 12 and 18
    End point description
    End point type
    Secondary
    End point timeframe
    Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [76]
    0 [77]
    Units: cm/year
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [76] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [77] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Height-Standard Deviation Score (SDS) at Month 6

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    End point title
    		 Change From Baseline in Height-Standard Deviation Score (SDS) at Month 6
    End point description
    Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the subject was to the reference population. Analysis was done on the FAS population included subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    11
    11
    Units: cm
        least squares mean (standard error)
    0.33 ± 0.21
    -0.22 ± 0.25
    Statistical analysis title
    		 Statistical Analysis at Month 6
    Statistical analysis description
    ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1107 [78]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean difference
    Point estimate
    0.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 1.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.31
    Notes
    [78] - The statistical test was 2-sided and performed at the 5 percent significance level.

    Secondary: Change From Baseline in Height-Standard Deviation Score (SDS) at Months 12 and 18

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    End point title
    		 Change From Baseline in Height-Standard Deviation Score (SDS) at Months 12 and 18
    End point description
    Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the subject was to the reference population.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [79]
    0 [80]
    Units: cm
        least squares mean (standard error)
    ±
    ±
    Notes
    [79] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [80] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Month 6

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    End point title
    		 Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Month 6
    End point description
    Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the subject was to the reference population. Analysis was done on the FAS population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    9 [81]
    9 [82]
    Units: cm/year
        least squares mean (standard error)
    3.89 ± 1.02
    -0.77 ± 1.4
    Notes
    [81] - N signifies subjects evaluable for the measure.
    [82] - N signifies subjects evaluable for the measure.
    Statistical analysis title
    		 Statistical Analysis at Month 6
    Statistical analysis description
    ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0161 [83]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean difference
    Point estimate
    4.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.13
         upper limit
    		 8.21
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.54
    Notes
    [83] - The statistical test was 2-sided and performed at the 5 percent significance level.

    Secondary: Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Months 12 and 18

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    End point title
    		 Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Months 12 and 18
    End point description
    Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the subject was to the reference population.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [84]
    0 [85]
    Units: cm/year
        least squares mean (standard error)
    ±
    ±
    Notes
    [84] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [85] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Sitting Height-Standard Deviation Score (SDS)

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    End point title
    		 Sitting Height-Standard Deviation Score (SDS)
    End point description
    Sitting height was measured using a stadiometer with a specialized chair. The SDS indicates how similar the subject was to the reference population.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [86]
    0 [87]
    Units: cm
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [86] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [87] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Body Mass Index-Standard Deviation Score (BMI-SDS)

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    End point title
    		 Body Mass Index-Standard Deviation Score (BMI-SDS)
    End point 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 subject was to the reference population.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [88]
    0 [89]
    Units: Kilogram per square meter (kg/m^2)
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [88] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [89] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Head Circumference at Months 6, 12 and 18

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    End point title
    		 Change From Baseline in Head Circumference at Months 6, 12 and 18
    End point 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).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [90]
    0 [91]
    Units: cm
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [90] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [91] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Head Circumference-Standard Deviation Score (SDS) at Months 6, 12 and 18

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    End point title
    		 Change From Baseline in Head Circumference-Standard Deviation Score (SDS) at Months 6, 12 and 18
    End point 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 subject was to the reference population.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [92]
    0 [93]
    Units: cm
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [92] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [93] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6

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    End point title
    		 Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6
    End point 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 subject. Triceps skinfold thickness was measured halfway down the left upper arm, while the arm was hanging relaxed at the subject'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 subject was to the reference population. Analysis was done on the FAS population- subjects who received at least 1 dose of study medication and had at least one post baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6
    End point values
    		 Somatropin Control
    Number of subjects analysed
    11
    11
    Units: Millimeter (mm)
    least squares mean (standard error)
        Change at Month 6 (Triceps SDS)
    -0.41 ± 0.16
    -0.06 ± 0.18
        Change at Month 6 (Subscapular SDS)
    -0.3 ± 0.1
    -0.16 ± 0.13
        Change at Month 6 (Suprailiac SDS)
    -0.6 ± 0.07
    -0.33 ± 0.12
    Statistical analysis title
    		 Statistical Analysis for Triceps SDS
    Statistical analysis description
    ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.187 [94]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean difference
    Point estimate
    -0.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.89
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.25
    Notes
    [94] - The statistical test was 2-sided and performed at the 5 percent significance level.
    Statistical analysis title
    		 Statistical Analysis for Subscapular SDS
    Statistical analysis description
    ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3494 [95]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean difference
    Point estimate
    -0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.49
         upper limit
    		 0.19
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.15
    Notes
    [95] - The statistical test was 2-sided and performed at the 5 percent significance level.
    Statistical analysis title
    		 Statistical Analysis for Suprailiac SDS
    Statistical analysis description
    ANCOVA method was used to calculate p-value with treatment, baseline value, study duration and site as covariates.
    Comparison groups
    Somatropin v Control
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0458 [96]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean difference
    Point estimate
    -0.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.54
         upper limit
    		 -0.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Notes
    [96] - The statistical test was 2-sided and performed at the 5 percent significance level.

    Secondary: Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Months 12 and 18

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    End point title
    		 Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Months 12 and 18
    End point 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 subject. Triceps skinfold thickness was measured halfway down the left upper arm, while the arm was hanging relaxed at the subject'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 subject was to the reference population.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [97]
    0 [98]
    Units: mm
        least squares mean (standard error)
    ±
    ±
    Notes
    [97] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [98] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Other pre-specified: Change From Baseline in Bone Density Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months

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    End point title
    		 Change From Baseline in Bone Density Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months
    End point 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.
    End point type
    Other pre-specified
    End point timeframe
    Baseline, Month 6, Month 12 and Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [99]
    0 [100]
    Units: z-score
        least squares mean (standard error)
    ±
    ±
    Notes
    [99] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [100] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Other pre-specified: Change From Baseline in Bone Structure Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months

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    End point title
    		 Change From Baseline in Bone Structure Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months
    End point 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 subject’s age and sex; negative values are below.
    End point type
    Other pre-specified
    End point timeframe
    Baseline, Month 6, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [101]
    0 [102]
    Units: z-score
        least squares mean (standard error)
    ±
    ±
    Notes
    [101] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [102] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Other pre-specified: Change From Baseline in Bone Stability Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months

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    End point title
    		 Change From Baseline in Bone Stability Using Peripheral Quantitative Computed Tomography (pqCT) at 6 or 12 or 18 Months
    End point 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 subject’s age and sex; negative values are below the average.
    End point type
    Other pre-specified
    End point timeframe
    Baseline, Month 6, Month 12, Month 18
    End point values
    		 Somatropin Control
    Number of subjects analysed
    0 [103]
    0 [104]
    Units: z-score
        least squares mean (standard error)
    ±
    ±
    Notes
    [103] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    [104] - Data were not analyzed, study was prematurely terminated due to insufficient number of subjects.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment emergent adverse events were reported from time of first dose of study treatment up to 28 days after last dose of study treatment.
    Adverse event reporting additional description
    EU BR specific adverse event tables were generated separately as per EU format using latest coding.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Control
    Reporting group description
    		 No treatment for initial 6 months in control group. After 6 months, somatropin was administered for next 12 months.

    Reporting group title
    Somatropin
    Reporting group description
    		 Somatropin was administered for 12 months. Dose adjustments were made at 6 month intervals.

    Serious adverse events
    		 Control Somatropin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 12 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Control Somatropin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 11 (63.64%)
    10 / 12 (83.33%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lipoma
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    Injury, poisoning and procedural complications
    Concussion
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Congenital, familial and genetic disorders
    Cryptorchism
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 11 (18.18%)
    2 / 12 (16.67%)
         occurrences all number
    2
    3
    Eye disorders
    Eyelid oedema
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Conjunctivitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Abdominal pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Diarrhoea
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Eczema
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Enuresis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Lordosis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Arthralgia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Acute tonsillitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Bronchitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Herpes zoster
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Lice infestation
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Otitis media
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Respiratory tract infection
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    3
    Tonsillitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Scarlet fever
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Rhinitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Tooth infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 12 (8.33%)
         occurrences all number
    1
    6
    Urinary tract infection
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Jan 2008
    Changes were requested by the Ethics Committee and the Competent Authorities. Determination of positive effects of growth hormone on bone density, bone structure and enhancement of bone stability were eliminated from the secondary objectives; performance of bone densitometry using pqCT was eliminated from all the visits; measurement of insulin, glucose and glycosylated haemoglobin were changed from optional to obligatory.
    04 Dec 2009
    The primary endpoint was changed from ''changes in PJP, PJF and maximal jump velocity after six months'' to ''efficiency of muscular function after six months''; efficiency of muscular function (Emf) after 12 months, changes in PJP, PJF and maximal jump velocity were added to the secondary endpoints; changes in evaluating attention performance were made due to practicability issues (vigilanz was changed to an optional subtest); measurement of Emf was added to Neuropsychological evaluation.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The study was prematurely discontinued, therefore not all data was powered.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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