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    Clinical Trial Results:
    A Phase 3, Randomised, Multicenter, Open-Label, Crossover Study Assessing Subject Perception of Treatment Burden With Use of Weekly Growth Hormone (Somatrogon) Versus Daily Growth Hormone (Genotropin) Injections in Children With Growth Hormone Deficiency

    Summary
    EudraCT number
    2018-000918-38
    Trial protocol
    GB   SK   CZ   BG  
    Global end of trial date
    28 Aug 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    04 Mar 2021
    First version publication date
    04 Mar 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    C0311002
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03831880
    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., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, 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
    17 Dec 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Aug 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the treatment burden of a weekly Somatrogon injection schedule and a daily Genotropin injection schedule.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    07 Feb 2019
    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
    United States: 52
    Country: Number of subjects enrolled
    Bulgaria: 10
    Country: Number of subjects enrolled
    Slovakia: 5
    Country: Number of subjects enrolled
    Czechia: 16
    Country: Number of subjects enrolled
    United Kingdom: 4
    Worldwide total number of subjects
    87
    EEA total number of subjects
    31
    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)
    46
    Adolescents (12-17 years)
    41
    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
    A total of 107 subjects were enrolled and 87 subjects aged 3 to less than (<) 18 years, with growth hormone deficiency (GHD) who were stable on treatment with daily Genotropin were randomised in this study.

    Period 1
    Period 1 title
    Baseline Period
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Daily Genotropin Then Weekly Somatrogon
    Arm description
    Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug.
    Arm type
    Experimental

    Investigational medicinal product name
    Genotropin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received Genotropin, daily subcutaneous at the same dose as their daily hGH which they were receiving at the time of enrollment.

    Arm title
    Weekly Somatrogon Then Daily Genotropin
    Arm description
    Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug.
    Arm type
    Experimental

    Investigational medicinal product name
    Somatrogon
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week.

    Number of subjects in period 1
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Started
    43
    44
    Completed
    43
    44
    Period 2
    Period 2 title
    Period 1 (12 Weeks)
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Daily Genotropin Then Weekly Somatrogon
    Arm description
    Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug.
    Arm type
    Experimental

    Investigational medicinal product name
    Genotropin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received Genotropin, daily subcutaneous at the same dose as their daily hGH which they were receiving at the time of enrollment.

    Arm title
    Weekly Somatrogon Then Daily Genotropin
    Arm description
    Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug.
    Arm type
    Experimental

    Investigational medicinal product name
    Somatrogon
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week.

    Number of subjects in period 2
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Started
    43
    44
    Completed
    43
    43
    Not completed
    0
    1
         Adverse event, not serious
    -
    1
    Period 3
    Period 3 title
    Period 2 (12 Weeks)
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Daily Genotropin Then Weekly Somatrogon
    Arm description
    Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug.
    Arm type
    Experimental

    Investigational medicinal product name
    Genotropin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received Genotropin, daily subcutaneous at the same dose as their daily hGH which they were receiving at the time of enrollment.

    Arm title
    Weekly Somatrogon Then Daily Genotropin
    Arm description
    Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug.
    Arm type
    Experimental

    Investigational medicinal product name
    Somatrogon
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week.

    Number of subjects in period 3
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Started
    43
    43
    Completed
    43
    42
    Not completed
    0
    1
         Protocol Deviation
    -
    1
    Period 4
    Period 4 title
    Follow-up
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Daily Genotropin Then Weekly Somatrogon
    Arm description
    Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    Weekly Somatrogon Then Daily Genotropin
    Arm description
    Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 4
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Started
    43
    42
    Completed
    43
    43
    Joined
    0
    1
         Continued Follow-up
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Daily Genotropin Then Weekly Somatrogon
    Reporting group description
    Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug.

    Reporting group title
    Weekly Somatrogon Then Daily Genotropin
    Reporting group description
    Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug.

    Reporting group values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin Total
    Number of subjects
    43 44 87
    Age categorical
    Units: Subjects
        In Utero
    0 0 0
        Pre-term newborn - gestational age < 37 wk
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    21 25 46
        Adolescents (12-17 years)
    22 19 41
        Adults (18-64 years)
    0 0 0
        From 65-84 years
    0 0 0
        85 years and over
    0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    10.8 ± 3.4 10.7 ± 3.7 -
    Sex: Female, Male
    Units: Subjects
        Female
    9 6 15
        Male
    34 38 72
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0
        Asian
    0 1 1
        Native Hawaiian or Other Pacific Islander
    0 0 0
        Black or African American
    3 1 4
        White
    39 42 81
        More than one race
    0 0 0
        Unknown or Not Reported
    1 0 1
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    3 2 5
        Not Hispanic or Latino
    39 42 81
        Unknown or Not Reported
    1 0 1

    End points

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    End points reporting groups
    Reporting group title
    Daily Genotropin Then Weekly Somatrogon
    Reporting group description
    Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug.

    Reporting group title
    Weekly Somatrogon Then Daily Genotropin
    Reporting group description
    Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug.
    Reporting group title
    Daily Genotropin Then Weekly Somatrogon
    Reporting group description
    Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug.

    Reporting group title
    Weekly Somatrogon Then Daily Genotropin
    Reporting group description
    Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug.
    Reporting group title
    Daily Genotropin Then Weekly Somatrogon
    Reporting group description
    Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug.

    Reporting group title
    Weekly Somatrogon Then Daily Genotropin
    Reporting group description
    Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug.
    Reporting group title
    Daily Genotropin Then Weekly Somatrogon
    Reporting group description
    Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug.

    Reporting group title
    Weekly Somatrogon Then Daily Genotropin
    Reporting group description
    Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug.

    Subject analysis set title
    Genotropin
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received Genotropin, daily subcutaneously, in overall study (either in Period 1 or in Period 2).

    Subject analysis set title
    Somatrogon
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received Somatrogon, weekly subcutaneously, at a dose of 0.66 mg/kg/week, in overall study (either in Period 1 or in Period 2).

    Primary: Total Score Related to Overall Life Interference Assessed at Baseline, Using Dyad Clinical Outcomes Assessment 1 (DCOA 1) Questionnaire

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    End point title
    Total Score Related to Overall Life Interference Assessed at Baseline, Using Dyad Clinical Outcomes Assessment 1 (DCOA 1) Questionnaire [1]
    End point description
    Subjects were assessed for their treatment burden using DCOA 1 questionnaire completed by subject/caregiver dyads. The subject life interference questionnaire component of the DCOA 1 had 7 questions (life interference [5 questions]: a measure of life interference [daily activities/social activities/leisure/night away from home/travel]; life interference-changes to life routine [1 question]: a measure of how often changes are made to life routine; and life interference-bother of growth hormone [GH] injections [1 question]: a measure of how often the growth hormone injections cause bother) and all questions used a 5-point scale: 1= never, 2= rarely, 3= sometimes, 4= often, 5= always. The overall life interference total score was sum of all 7 questions, scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant less life interference (better outcome). FAS was analysed. ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Baseline
    Notes
    [1] - 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 analysis was planned for this endpoint
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    42
    40
    Units: units on a scale
        arithmetic mean (standard deviation)
    29.5 ± 18.0
    27.1 ± 19.8
    No statistical analyses for this end point

    Primary: Total Score Related to Overall Life Interference Assessed at Week 12, Using DCOA 1 Questionnaire

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    End point title
    Total Score Related to Overall Life Interference Assessed at Week 12, Using DCOA 1 Questionnaire [2]
    End point description
    Subjects were assessed for their treatment burden using DCOA 1 questionnaire completed by subject/caregiver dyads. The subject life interference questionnaire component of the DCOA 1 had 7 questions (life interference [5 questions]: a measure of life interference [daily activities/social activities/leisure/night away from home/travel]; life interference-changes to life routine [1 question]: a measure of how often changes are made to life routine; and life interference-bother of growth hormone [GH] injections [1 question]: a measure of how often the growth hormone injections cause bother) and all questions used a 5-point scale: 1= never, 2= rarely, 3= sometimes, 4= often, 5= always. The overall life interference total score was sum of all 7 questions, scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant less life interference (better outcome). FAS was analysed. ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Week 12
    Notes
    [2] - 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 analysis was planned for this endpoint
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    43
    40
    Units: units on a scale
        arithmetic mean (standard deviation)
    25.2 ± 17.3
    7.1 ± 7.8
    No statistical analyses for this end point

    Primary: Total Score Related to Overall Life Interference Assessed at Week 24, Using DCOA 1 Questionnaire

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    End point title
    Total Score Related to Overall Life Interference Assessed at Week 24, Using DCOA 1 Questionnaire [3]
    End point description
    Subjects were assessed for their treatment burden using DCOA 1 questionnaire completed by subject/caregiver dyads. The subject life interference questionnaire component of the DCOA 1 had 7 questions (life interference [5 questions]: a measure of life interference [daily activities/social activities/leisure/night away from home/travel]; life interference-changes to life routine [1 question]: a measure of how often changes are made to life routine; and life interference-bother of growth hormone [GH] injections [1 question]: a measure of how often the growth hormone injections cause bother) and all questions used a 5-point scale: 1= never, 2= rarely, 3= sometimes, 4= often, 5= always. The overall life interference total score was sum of all 7 questions, scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant less life interference (better outcome). FAS was analysed. ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Week 24
    Notes
    [3] - 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 analysis was planned for this endpoint
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    42
    42
    Units: units on a scale
        arithmetic mean (standard deviation)
    9.5 ± 13.3
    23.0 ± 22.6
    No statistical analyses for this end point

    Primary: Total Score Related to Overall Life Interference by Treatment in Overall Study, Using DCOA 1 Questionnaire

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    End point title
    Total Score Related to Overall Life Interference by Treatment in Overall Study, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment burden using DCOA 1 questionnaire completed by subject/caregiver dyads. The subject life interference questionnaire component of the DCOA 1 had 7 questions (life interference [5 questions]: a measure of life interference [daily activities/social activities/leisure/night away from home/travel]; life interference-changes to life routine [1 question]: a measure of how often changes are made to life routine; and life interference-bother of growth hormone [GH] injections [1 question]: a measure of how often the growth hormone injections cause bother) and all questions used a 5-point scale: 1= never, 2= rarely, 3= sometimes, 4= often, 5= always. The overall life interference total score was sum of all 7 questions, scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant less life interference (better outcome). FAS was analysed. ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Baseline up to Week 24
    End point values
    Genotropin Somatrogon
    Number of subjects analysed
    85
    82
    Units: units on a scale
        arithmetic mean (confidence interval 95%)
    24.13 (20.61 to 27.65)
    8.63 (5.05 to 12.22)
    Statistical analysis title
    Genotropin versus Somatrogon
    Comparison groups
    Genotropin v Somatrogon
    Number of subjects included in analysis
    167
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [4]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -15.49
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -19.71
         upper limit
    -11.27
    Notes
    [4] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

    Secondary: Total Score Related to Pen Ease of Use Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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    End point title
    Total Score Related to Pen Ease of Use Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked 5 questions from Section I of the Injection Pen Assessment Questionnaire (IPAQ) patient-reported outcome (PRO) tool related to pen ease of use and used a 5-point scale: 1= very easy, 2= somewhat easy, 3= neither easy nor difficult, 4= somewhat difficult, 5= very difficult. The total score related to pen ease of use was sum of all 5 questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    43
    44
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 42, 40)
    10.6 ± 11.3
    11.6 ± 12.8
        Week 12 (n= 43, 40)
    12.0 ± 13.8
    5.1 ± 7.6
        Week 24 (n= 42, 42)
    5.5 ± 9.3
    9.4 ± 13.0
    No statistical analyses for this end point

    Secondary: Total Score Related to Pen Ease of Use by Treatment in Overall Study, Using DCOA 1 Questionnaire

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    End point title
    Total Score Related to Pen Ease of Use by Treatment in Overall Study, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked 5 questions from Section I of the IPAQ PRO tool related to pen ease of use and used a 5-point scale: 1= very easy, 2= somewhat easy, 3= neither easy nor difficult, 4= somewhat difficult, 5= very difficult. The total score related to pen ease of use was sum of all 5 questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    End point values
    Genotropin Somatrogon
    Number of subjects analysed
    85
    82
    Units: units on a scale
        arithmetic mean (confidence interval 95%)
    10.71 (8.27 to 13.14)
    5.32 (2.84 to 7.80)
    Statistical analysis title
    Genotropin versus Somatrogon
    Comparison groups
    Genotropin v Somatrogon
    Number of subjects included in analysis
    167
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0017 [5]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -5.39
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.69
         upper limit
    -2.09
    Notes
    [5] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

    Secondary: Total Score Related to Ease of the Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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    End point title
    Total Score Related to Ease of the Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to ease of injection schedule and used a 5-point scale: 1= very easy, 2= somewhat easy, 3= neither easy nor difficult, 4= somewhat difficult, 5= very difficult. The total score related to ease of the injection schedule ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    43
    44
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 42, 40)
    18.5 ± 20.0
    16.3 ± 17.5
        Week 12 (n= 43, 40)
    23.3 ± 25.2
    4.4 ± 11.2
        Week 24 (n= 42, 42)
    9.5 ± 18.3
    17.9 ± 22.3
    No statistical analyses for this end point

    Secondary: Total Score Related to Ease of the Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire

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    End point title
    Total Score Related to Ease of the Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to ease of injection schedule and used a 5-point scale: 1= very easy, 2= somewhat easy, 3= neither easy nor difficult, 4= somewhat difficult, 5= very difficult. The total score related to ease of the injection schedule ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    End point values
    Genotropin Somatrogon
    Number of subjects analysed
    85
    82
    Units: units on a scale
        arithmetic mean (confidence interval 95%)
    20.56 (16.22 to 24.89)
    6.96 (2.54 to 11.37)
    Statistical analysis title
    Genotropin versus Somatrogon
    Comparison groups
    Genotropin v Somatrogon
    Number of subjects included in analysis
    167
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [6]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -13.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -19.74
         upper limit
    -7.45
    Notes
    [6] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

    Secondary: Total Score Related to Convenience of the Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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    End point title
    Total Score Related to Convenience of the Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to ease of injection schedule and used a 7-point scale: 1=extremely convenient to 7=extremely inconvenient. The total score related to convenience of injection schedule ranged from 1 to 7; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    43
    44
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 42, 40)
    34.5 ± 21.0
    32.5 ± 21.3
        Week 12 (n= 43, 40)
    35.3 ± 23.9
    7.9 ± 10.7
        Week 24 (n= 42, 42)
    11.9 ± 14.4
    33.3 ± 24.1
    No statistical analyses for this end point

    Secondary: Total Score Related to Convenience of the Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire

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    End point title
    Total Score Related to Convenience of the Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to ease of injection schedule and used a 7-point scale: 1=extremely convenient to 7=extremely inconvenient. The total score related to convenience of injection schedule ranged from 1 to 7; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    End point values
    Genotropin Somatrogon
    Number of subjects analysed
    85
    82
    Units: units on a scale
        arithmetic mean (confidence interval 95%)
    34.30 (30.13 to 38.47)
    9.96 (5.71 to 14.21)
    Statistical analysis title
    Genotropin versus Somatrogon
    Comparison groups
    Genotropin v Somatrogon
    Number of subjects included in analysis
    167
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [7]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -24.34
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -30.1
         upper limit
    -18.57
    Notes
    [7] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

    Secondary: Total Score Related to Satisfaction With Overall Treatment Experience Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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    End point title
    Total Score Related to Satisfaction With Overall Treatment Experience Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to subject satisfaction with treatment and used a 5-point scale: 1=very satisfied to 5=very dissatisfied. The total score related to satisfaction with overall treatment ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    43
    44
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 42, 40)
    28.0 ± 21.5
    29.4 ± 23.3
        Week 12 (n= 43, 40)
    27.3 ± 27.2
    20.0 ± 31.1
        Week 24 (n= 42, 42)
    22.0 ± 32.3
    30.4 ± 27.9
    No statistical analyses for this end point

    Secondary: Total Score Related to Satisfaction With Overall Treatment Experience by Treatment in Overall Study, Using DCOA 1 Questionnaire

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    End point title
    Total Score Related to Satisfaction With Overall Treatment Experience by Treatment in Overall Study, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to subject satisfaction with treatment and used a 5-point scale: 1=very satisfied to 5=very dissatisfied. The total score related to satisfaction with overall treatment ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    End point values
    Genotropin Somatrogon
    Number of subjects analysed
    85
    82
    Units: units on a scale
        arithmetic mean (confidence interval 95%)
    28.95 (22.55 to 35.36)
    21.13 (14.61 to 27.65)
    Statistical analysis title
    Genotropin versus Somatrogon
    Comparison groups
    Genotropin v Somatrogon
    Number of subjects included in analysis
    167
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0739 [8]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -7.83
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -16.42
         upper limit
    0.77
    Notes
    [8] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

    Secondary: Total Scores Related to Willingness to Continue Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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    End point title
    Total Scores Related to Willingness to Continue Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to subject willingness to continue treatment and used a 5-point scale: 1=extremely willing to 5=not at all willing. The total score related to willingness to continue injection schedule ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    43
    44
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 42, 40)
    18.5 ± 20.0
    22.5 ± 23.9
        Week 12 (n= 43, 40)
    28.5 ± 27.6
    10.6 ± 21.1
        Week 24 (n= 42, 42)
    13.1 ± 24.8
    30.4 ± 29.0
    No statistical analyses for this end point

    Secondary: Total Scores Related to Willingness to Continue Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire

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    End point title
    Total Scores Related to Willingness to Continue Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to subject willingness to continue treatment and used a 5-point scale: 1=extremely willing to 5=not at all willing. The total score related to willingness to continue injection schedule ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    End point values
    Genotropin Somatrogon
    Number of subjects analysed
    85
    82
    Units: units on a scale
        arithmetic mean (confidence interval 95%)
    29.54 (23.95 to 35.12)
    11.93 (6.24 to 17.62)
    Statistical analysis title
    Genotropin versus Somatrogon
    Comparison groups
    Genotropin v Somatrogon
    Number of subjects included in analysis
    167
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [9]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -17.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -25.15
         upper limit
    -10.06
    Notes
    [9] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

    Secondary: Total Scores Related to Injection Signs and Symptoms for Subjects Aged 8 Years and Above Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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    End point title
    Total Scores Related to Injection Signs and Symptoms for Subjects Aged 8 Years and Above Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subjects (8-17 years old). Subjects were asked 4 questions from Section I of the IPAQ PRO tool related to subject's injection signs and symptoms and used a 11-point scale: 0=no pain to 10=worst possible pain; 0=no stinging to 10=worst possible stinging; 0=no bruising to 10=worst possible bruising; and 0=no bleeding to 10=worst possible bleeding, respectively. The total score was sum of all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for injection signs and symptoms meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    43
    44
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 35, 29)
    15.0 ± 10.4
    13.8 ± 11.9
        Week 12 (n= 34, 25)
    16.2 ± 12.2
    13.7 ± 10.3
        Week 24 (n= 32, 32)
    13.6 ± 12.2
    10.9 ± 9.6
    No statistical analyses for this end point

    Secondary: Total Scores Related to Injection Signs and Symptoms for Subjects Aged 8 Years and Above by Treatment in Overall Study, Using DCOA 1 Questionnaire

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    End point title
    Total Scores Related to Injection Signs and Symptoms for Subjects Aged 8 Years and Above by Treatment in Overall Study, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subjects (8-17 years old). Subjects were asked 4 questions from Section I of the IPAQ PRO tool related to subject's injection signs and symptoms and used a 11-point scale: 0=no pain to 10=worst possible pain; 0=no stinging to 10=worst possible stinging; 0=no bruising to 10=worst possible bruising; and 0=no bleeding to 10=worst possible bleeding, respectively. The total score was sum of all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for injection signs and symptoms meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    End point values
    Genotropin Somatrogon
    Number of subjects analysed
    66
    57
    Units: units on a scale
        arithmetic mean (confidence interval 95%)
    13.56 (10.78 to 16.34)
    14.27 (11.32 to 17.21)
    Statistical analysis title
    Genotropin versus Somatrogon
    Comparison groups
    Genotropin v Somatrogon
    Number of subjects included in analysis
    123
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.6137 [10]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.71
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.09
         upper limit
    3.51
    Notes
    [10] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

    Secondary: Total Scores Related to Assessment of Signs, Completed by Caregiver for Children Aged <8 Years Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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    End point title
    Total Scores Related to Assessment of Signs, Completed by Caregiver for Children Aged <8 Years Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by caregiver for children under 8 years. Subjects were asked 2 questions from Section I of the IPAQ PRO tool related to subject's assessment of signs and used a 11-point scale: 0=no bruising to 10=worst possible bruising and 0=no bleeding to 10=worst possible bleeding, respectively. The total score was sum of all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for assessment of signs meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    43
    44
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 6, 10)
    14.2 ± 14.6
    13.5 ± 11.3
        Week 12 (n= 7, 10)
    9.3 ± 10.6
    13.0 ± 15.8
        Week 24 (n= 8, 9)
    5.6 ± 7.8
    9.4 ± 8.8
    No statistical analyses for this end point

    Secondary: Total Scores Related to Assessment of Signs, Completed by Caregiver for Children Aged <8 Years by Treatment in Overall Study, Using DCOA 1 Questionnaire

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    End point title
    Total Scores Related to Assessment of Signs, Completed by Caregiver for Children Aged <8 Years by Treatment in Overall Study, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by caregiver for children under 8 years. Subjects were asked 2 questions from Section I of the IPAQ PRO tool related to subject's assessment of signs and used a 11-point scale: 0=no bruising to 10=worst possible bruising and 0=no bleeding to 10=worst possible bleeding, respectively. The total score was sum of all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for assessment of signs meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    End point values
    Genotropin Somatrogon
    Number of subjects analysed
    16
    18
    Units: units on a scale
        arithmetic mean (confidence interval 95%)
    8.75 (2.65 to 14.86)
    9.31 (3.47 to 15.16)
    Statistical analysis title
    Genotropin versus Somatrogon
    Comparison groups
    Genotropin v Somatrogon
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.8404 [11]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.56
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.29
         upper limit
    6.41
    Notes
    [11] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

    Secondary: Total Scores Related to Caregiver Life Interference, Including Family Life Interference Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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    End point title
    Total Scores Related to Caregiver Life Interference, Including Family Life Interference Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by caregiver. Subjects were asked 13 questions from Section I of the IPAQ PRO tool related to caregiver life interference and used a 5-point scale: 1= never to 5= always. The total score ranged was sum of scores from all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for caregiver and family life interference meant less life interference (a better outcome). FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    43
    44
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 41, 40)
    17.8 ± 17.5
    20.0 ± 20.1
        Week 12 (n= 43, 40)
    15.9 ± 16.7
    3.1 ± 5.5
        Week 24 (n= 42, 42)
    3.8 ± 6.0
    18.1 ± 23.4
    No statistical analyses for this end point

    Secondary: Total Scores Related to Caregiver Life Interference, Including Family Life Interference by Treatment in Overall Study, Using DCOA 1 Questionnaire

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    End point title
    Total Scores Related to Caregiver Life Interference, Including Family Life Interference by Treatment in Overall Study, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by caregiver. Subjects were asked 13 questions from Section I of the IPAQ PRO tool related to caregiver life interference and used a 5-point scale: 1= never to 5= always. The total score ranged was sum of scores from all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for caregiver and family life interference meant less life interference (a better outcome). FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    End point values
    Genotropin Somatrogon
    Number of subjects analysed
    85
    82
    Units: units on a scale
        arithmetic mean (confidence interval 95%)
    17.01 (13.77 to 20.25)
    3.54 (0.24 to 6.84)
    Statistical analysis title
    Genotropin versus Somatrogon
    Comparison groups
    Genotropin v Somatrogon
    Number of subjects included in analysis
    167
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [12]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -13.47
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -17.59
         upper limit
    -9.35
    Notes
    [12] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

    Secondary: Total Scores Related to Missed Injections Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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    End point title
    Total Scores Related to Missed Injections Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to number of missed injections (daily or weekly administration) during past 4 weeks. The total scores ranged from 0 to 31 for daily administration (Genotropin) and from 0 to 5 for weekly administration (Somatrogon). All scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for missed injections meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    43
    44
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 41, 40)
    7.8 ± 15.1
    7.3 ± 16.1
        Week 12 (n= 43, 40)
    4.3 ± 8.2
    0.0 ± 0.0
        Week 24 (n= 42, 42)
    1.9 ± 7.4
    3.1 ± 10.8
    No statistical analyses for this end point

    Secondary: Total Scores Related to Missed Injections by Treatment in Overall Study, Using DCOA 1 Questionnaire

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    End point title
    Total Scores Related to Missed Injections by Treatment in Overall Study, Using DCOA 1 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to number of missed injections (daily or weekly administration) during past 4 weeks. The total scores ranged from 0 to 31 for daily administration (Genotropin) and from 0 to 5 for weekly administration (Somatrogon). All scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for missed injections meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    End point values
    Genotropin Somatrogon
    Number of subjects analysed
    85
    82
    Units: units on a scale
        arithmetic mean (confidence interval 95%)
    3.71 (2.03 to 5.39)
    0.95 (-0.76 to 2.66)
    Statistical analysis title
    Genotropin versus Somatrogon
    Comparison groups
    Genotropin v Somatrogon
    Number of subjects included in analysis
    167
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0245 [13]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.76
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.16
         upper limit
    -0.36
    Notes
    [13] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

    Secondary: Number of Subjects as per Responses to Choice of Injection Pen Assessed at Week 24, Using DCOA 2 Questionnaire

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    End point title
    Number of Subjects as per Responses to Choice of Injection Pen Assessed at Week 24, Using DCOA 2 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregivers responded to question from Section II of the IPAQ PRO tool “If you were given the choice between the daily growth hormone injection pen and the weekly growth hormone injection pen, which pen would you choose?” Response was: 1) the daily injection pen (Genotropin) or 2) the weekly injection pen (Somatrogon). FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    42
    42
    Units: subjects
        Somatrogon
    38
    36
        Genotropin
    4
    6
    No statistical analyses for this end point

    Secondary: Number of Subjects as per Responses to Preferred Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

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    End point title
    Number of Subjects as per Responses to Preferred Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregivers responded to question from Section II of the IPAQ PRO tool “Which growth hormone injection schedule do you prefer overall?” by choosing from any 1 option from: 1) prefer the daily injection schedule; 2) prefer the weekly injection schedule; 3) no preference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    42
    42
    Units: subjects
        Somatrogon
    40
    37
        Genotropin
    2
    4
        No Preference
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects as per Responses to Convenience of the Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

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    End point title
    Number of Subjects as per Responses to Convenience of the Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregivers responded to question from Section II of the IPAQ PRO tool “Which growth hormone injection schedule was more convenient overall?” by choosing from any 1 option from: 1) daily injection schedule was more convenient; 2) weekly injection schedule was more convenient; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    42
    42
    Units: subjects
        Somatrogon
    40
    40
        Genotropin
    2
    2
        No Difference
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects as per Responses to Ease of Following Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

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    End point title
    Number of Subjects as per Responses to Ease of Following Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregivers responded to question from Section II of the IPAQ PRO tool “Which growth hormone injection schedule was easier to follow overall?” by choosing from any 1 option from: 1) easier to follow daily injection schedule; 2) easier to follow weekly injection schedule; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    42
    42
    Units: subjects
        Somatrogon
    38
    34
        Genotropin
    4
    4
        No Difference
    0
    4
    No statistical analyses for this end point

    Secondary: Number of Subjects as per Responses to Pen Ease of Use Assessed at Week 24, Using DCOA 2 Questionnaire

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    End point title
    Number of Subjects as per Responses to Pen Ease of Use Assessed at Week 24, Using DCOA 2 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregiver were asked a question “Which pen was easier to use?” from Section II of the IPAQ PRO tool. Question had 4 parts: preparing the injection pen (Part I), setting the dose (Part II), injecting the medicine (Part III) and storing the pen (Part IV). Subjects/caregiver expressed their preference by choosing from any 1 option for each activity from: 1) daily pen easier to use; 2) weekly pen easier to use; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    42
    42
    Units: subjects
        Part I: Somatrogon
    29
    25
        Part I: Genotropin
    3
    4
        Part I: No difference
    10
    13
        Part II: Somatrogon
    21
    17
        Part II: Genotropin
    6
    8
        Part II: No Difference
    15
    17
        Part III: Somatrogon
    13
    18
        Part III: Genotropin
    16
    12
        Part III: No Difference
    13
    12
        Part IV: Somatrogon
    12
    14
        Part IV: Genotropin
    2
    2
        Part IV: No Difference
    28
    26
    No statistical analyses for this end point

    Secondary: Number of Subjects as per Responses to Subject Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire

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    End point title
    Number of Subjects as per Responses to Subject Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregiver were asked a question “Which injection schedule interfered less?” from Section II of the IPAQ PRO tool related to subject life interference. Subjects were assessed for 5 activities: daily activities (Activity 1), social activities (Activity 2), recreation/leisure activities (Activity 3), spending night away from home (Activity 4) and travel (Activity 5). The subjects expressed their preference by choosing from any 1 option for each activity from: 1) daily injection schedule interfered less; 2) weekly injection schedule interfered less; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    42
    42
    Units: subjects
        Activity 1: Somatrogon
    35
    31
        Activity 1: Genotropin
    2
    1
        Activity 1: No Difference
    5
    10
        Activity 2: Somatrogon
    34
    34
        Activity 2: Genotropin
    2
    0
        Activity 2: No Difference
    6
    8
        Activity 3: Somatrogon
    34
    33
        Activity 3: Genotropin
    2
    1
        Activity 3: No Difference
    6
    8
        Activity 4: Somatrogon
    36
    37
        Activity 4: Genotropin
    2
    1
        Activity 4: No Difference
    4
    4
        Activity 5: Somatrogon
    33
    37
        Activity 5: Genotropin
    3
    0
        Activity 5: No Difference
    6
    5
    No statistical analyses for this end point

    Secondary: Number of Subjects as per Responses to Caregiver Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire

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    End point title
    Number of Subjects as per Responses to Caregiver Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire
    End point description
    Caregivers of subjects were asked a question “Which injection schedule interfered less?” from Section II of the IPAQ PRO tool related to caregiver life interference and were assessed for 5 activities: daily activities (Activity 1), social activities (Activity 2), recreation/leisure activities (Activity 3), spending night away from home (Activity 4) and travel (Activity 5). Preference was expressed by choosing from any 1 option for each activity from: 1) daily injection schedule interfered less; 2) weekly injection schedule interfered less; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    42
    42
    Units: subjects
        Activity 1: Somatrogon
    36
    31
        Activity 1: Genotropin
    2
    0
        Activity 1: No Difference
    4
    11
        Activity 2: Somatrogon
    36
    32
        Activity 2: Genotropin
    2
    0
        Activity 2: No Difference
    4
    10
        Activity 3: Somatrogon
    35
    34
        Activity 3: Genotropin
    2
    0
        Activity 3: No Difference
    5
    8
        Activity 4: Somatrogon
    35
    37
        Activity 4: Genotropin
    1
    0
        Activity 4: No Difference
    6
    5
        Activity 5: Somatrogon
    35
    37
        Activity 5: Genotropin
    2
    0
        Activity 5: No Difference
    5
    5
    No statistical analyses for this end point

    Secondary: Number of Subjects as per Responses to Family Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire

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    End point title
    Number of Subjects as per Responses to Family Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/ caregiver were asked a question “Which injection schedule interfered less?” from Section II of the IPAQ PRO tool related to family life interference and assessed for 5 activities: daily activities (Activity 1), social activities (Activity 2), recreation/leisure activities (Activity 3), spending night away from home (Activity 4) and travel (Activity 5). Preference was expressed by choosing from any 1 option for each activity from: 1) daily injection schedule interfered less; 2) weekly injection schedule interfered less; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    42
    42
    Units: subjects
        Activity 1: Somatrogon
    32
    29
        Activity 1: Genotropin
    1
    0
        Activity 1: No Difference
    9
    13
        Activity 2: Somatrogon
    32
    30
        Activity 2: Genotropin
    1
    0
        Activity 2: No Difference
    9
    12
        Activity 3: Somatrogon
    32
    32
        Activity 3: Genotropin
    1
    0
        Activity 3: No Difference
    9
    10
        Activity 4: Somatrogon
    31
    34
        Activity 4: Genotropin
    1
    0
        Activity 4: No Difference
    10
    8
        Activity 5: Somatrogon
    31
    36
        Activity 5: Genotropin
    1
    0
        Activity 5: No Difference
    10
    6
    No statistical analyses for this end point

    Secondary: Number of Subjects as per Response to Benefit Relating to the Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

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    End point title
    Number of Subjects as per Response to Benefit Relating to the Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire
    End point description
    Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/ caregiver were asked a question “How beneficial was to take injections less often?” from Section II of the IPAQ PRO tool pertaining to benefit relating to the Injection schedule and used a 5-point scale: 1= extremely beneficial, 2= very beneficial, 3= moderately beneficial, 4= slightly beneficial and 5= not at all beneficial. Lower score of benefit relating to injection schedule meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    42
    42
    Units: subjects
        Extremely Beneficial
    28
    20
        Very Beneficial
    11
    14
        Moderately Beneficial
    1
    3
        Slightly Beneficial
    0
    3
        Not At All Beneficial
    2
    2
    No statistical analyses for this end point

    Secondary: Number of Subjects as per Responses to Intention to Comply Assessed at Week 24, Using DCOA 2 Questionnaire

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    End point title
    Number of Subjects as per Responses to Intention to Comply Assessed at Week 24, Using DCOA 2 Questionnaire
    End point description
    Subjects/caregiver dyads were asked 4 questions “Which schedule would be better able to follow?” (Question 1), “Which schedule would be more likely to follow for a longer time?” (Question 2), “Which schedule would be better able to follow for a longer time?” (Question 3) and “Which schedule would be more likely to follow?” (Question 4) from Section II of the IPAQ PRO tool related to subject intention to comply with treatment. Options for each question were: 1) daily injection (Genotropin), 2) weekly injection (Somatrogon) or 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    42
    42
    Units: subjects
        Question 1: Somatrogon
    33
    31
        Question 1: Genotropin
    2
    2
        Question 1: No Difference
    7
    9
        Question 2: Somatrogon
    29
    32
        Question 2: Genotropin
    1
    2
        Question 2: No Difference
    12
    8
        Question 3: Somatrogon
    34
    35
        Question 3: Genotropin
    1
    1
        Question 3: No Difference
    7
    6
        Question 4: Somatrogon
    26
    31
        Question 4: Genotropin
    3
    2
        Question 4: No Difference
    13
    9
    No statistical analyses for this end point

    Secondary: Patient Global Impression Severity-Impact on Daily Activities (PGIS-IDA) Score Assessed at Baseline, Week 12 and Week 24

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    End point title
    Patient Global Impression Severity-Impact on Daily Activities (PGIS-IDA) Score Assessed at Baseline, Week 12 and Week 24
    End point description
    The PGIS-IDA rated the severity of the impact on daily activities due to the treatment administration during the past 4 weeks on a 7-point scale (1= not present to 7= extremely severe). Scores were transformed from raw scores to a 0 to 100 scale. Lower scores meant less impact on daily activities (better outcome). FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    43
    44
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 41, 40)
    15.0 ± 14.8
    16.3 ± 16.2
        Week 12 (n= 43, 40)
    19.0 ± 19.4
    4.6 ± 7.5
        Week 24 (n= 42, 42)
    7.1 ± 9.8
    22.2 ± 20.4
    No statistical analyses for this end point

    Secondary: Patient Global Impression Severity-Impact on Daily Activities (PGIS-IDA) Score by Treatment in Overall Study

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    End point title
    Patient Global Impression Severity-Impact on Daily Activities (PGIS-IDA) Score by Treatment in Overall Study
    End point description
    The PGIS-IDA rated the severity of the impact on daily activities due to the treatment administration during the past 4 weeks on a 7-point scale (1= not present to 7= extremely severe). Scores were transformed from raw scores to a 0 to 100 scale. Lower scores meant less impact on daily activities (better outcome). FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    End point values
    Genotropin Somatrogon
    Number of subjects analysed
    85
    82
    Units: units on a scale
        arithmetic mean (confidence interval 95%)
    20.64 (17.30 to 23.99)
    6.06 (2.66 to 9.46)
    Statistical analysis title
    Genotropin versus Somatrogon
    Comparison groups
    Genotropin v Somatrogon
    Number of subjects included in analysis
    167
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [14]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -14.58
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -18.72
         upper limit
    -10.44
    Notes
    [14] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

    Other pre-specified: Number of Subjects With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Emergent Treatment Related AEs and SAEs

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    End point title
    Number of Subjects With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Emergent Treatment Related AEs and SAEs
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that: resulted in death, was life threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), resulted in congenital anomaly/birth defect. Treatment-emergent AEs (TEAEs) were defined as events that occurred between first dose of study drug up to 35 days after last dose of study drug. Related TEAEs were those AEs who had relation to the study treatment and was judged by investigator. The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to 29 Weeks
    End point values
    Genotropin Somatrogon
    Number of subjects analysed
    86
    87
    Units: subjects
        Treatment-Emergent AEs
    38
    47
        Treatment-Emergent SAEs
    0
    0
        Treatment-Emergent Treatment Related AEs
    14
    21
        Treatment-Emergent Treatment Related SAEs
    0
    0
    No statistical analyses for this end point

    Other pre-specified: Number of Subjects With Adverse Events per Severity

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    End point title
    Number of Subjects With Adverse Events per Severity
    End point description
    AE was assessed according to severity; mild (did not interfered with subject's usual function), moderate (interfered to some extent with subject's usual function) and severe (interfered significantly with subject's usual function). The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to 29 Weeks
    End point values
    Genotropin Somatrogon
    Number of subjects analysed
    86
    87
    Units: subjects
        Mild
    34
    41
        Moderate
    4
    6
        Severe
    0
    0
    No statistical analyses for this end point

    Other pre-specified: Number of Subjects With Discontinuations due to Adverse Events (AEs)

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    End point title
    Number of Subjects With Discontinuations due to Adverse Events (AEs)
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. The discontinuations due to adverse events was defined for subjects. The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to 29 Weeks
    End point values
    Genotropin Somatrogon
    Number of subjects analysed
    86
    87
    Units: subjects
    0
    1
    No statistical analyses for this end point

    Other pre-specified: Number of Subjects With Laboratory Abnormalities

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    End point title
    Number of Subjects With Laboratory Abnormalities
    End point description
    The laboratory abnormality parameters included Hematology: erythrocyte (ery.) mean corpuscular volume, ery. mean corpuscular hemoglobin:<0.9*lower limit normal (LLN), leukocytes:<0.6*LLN, lymphocytes:<0.8*LLN, neutrophils:<0.8*LLN greater than (>) 1.2*upper limit normal (ULN), eosinophils, monocytes:>1.2*ULN. Clinical chemistry: bilirubin, direct bilirubin, indirect bilirubin:>1.5*ULN, gamma glutamyl transferase:>3.0*ULN, albumin:>1.2*ULN, blood urea nitrogen:>1.3*ULN, urate:>1.2*ULN, high-density lipoprotein (HDL) cholesterol:<0.8*LLN, potassium, magnesium:>1.1*ULN, phosphate:>1.2*ULN, bicarbonate:<0.9*LLN, creatine kinase:>2.0*ULN. Urinalysis: specific gravity:>1.030, ketones, urine protein, urine hemoglobin, nitrite, leukocyte esterase:>=1. The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug. Here 'n' signifies number of subjects evaluable for specified time points.
    End point type
    Other pre-specified
    End point timeframe
    Week 1 to Week 12, Week 13 to Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    43
    44
    Units: subjects
        Week 1 to Week 12 (n= 41, 36)
    19
    19
        Week 13 to Week 24 (n= 42, 43)
    24
    21
    No statistical analyses for this end point

    Other pre-specified: Number of Subjects With Positive Anti-Recombinant Human Growth Hormone (rhGH) Antibodies and Neutralising Antibodies (NAb)

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    End point title
    Number of Subjects With Positive Anti-Recombinant Human Growth Hormone (rhGH) Antibodies and Neutralising Antibodies (NAb)
    End point description
    Blood samples were collected for determination of rhGH and NAb. The subjects who tested positive for antibodies were reported. The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug.
    End point type
    Other pre-specified
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    43
    44
    Units: subjects
        Baseline: Non-neutralising
    5
    0
        Baseline: Neutralising
    0
    0
        Week 12: Non-neutralising
    3
    3
        Week 12: Neutralising
    0
    0
        Week 24: Non-neutralising
    4
    6
        Week 24: Neutralising
    0
    0
    No statistical analyses for this end point

    Other pre-specified: Number of Subjects With Positive Anti-Somatrogon Antibodies and Neutralising Antibodies (NAb)

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    End point title
    Number of Subjects With Positive Anti-Somatrogon Antibodies and Neutralising Antibodies (NAb)
    End point description
    Blood samples were collected for determination of anti-somatrogon antibodies and NAb. The subjects who tested positive for antibodies were reported. The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug. Here, “99999” signifies subjects were not tested for anti-somatrogon antibodies.
    End point type
    Other pre-specified
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Daily Genotropin Then Weekly Somatrogon Weekly Somatrogon Then Daily Genotropin
    Number of subjects analysed
    43
    44
    Units: subjects
        Baseline: Non-neutralising
    0
    0
        Baseline: Neutralising
    0
    0
        Week 12: Non-neutralising
    99999
    4
        Week 12: Neutralising
    99999
    0
        Week 24: Non-neutralising
    0
    99999
        Week 24: Neutralising
    0
    99999
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to 35 days after last dose (up to 29 weeks)
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Genotropin
    Reporting group description
    Subjects received Genotropin, daily subcutaneously, in overall study (either in Period 1 or in Period 2).

    Reporting group title
    Somatrogon
    Reporting group description
    Subjects received Somatrogon, weekly subcutaneously, at a dose of 0.66 mg/kg/week, in overall study (either in Period 1 or in Period 2).

    Serious adverse events
    Genotropin Somatrogon
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 86 (0.00%)
    0 / 87 (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
    Genotropin Somatrogon
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    38 / 86 (44.19%)
    47 / 87 (54.02%)
    General disorders and administration site conditions
    Administration site pain
         subjects affected / exposed
    0 / 86 (0.00%)
    2 / 87 (2.30%)
         occurrences all number
    0
    2
    Administration site oedema
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Application site pruritus
         subjects affected / exposed
    1 / 86 (1.16%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    Fat tissue increased
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Injection site bruising
         subjects affected / exposed
    2 / 86 (2.33%)
    1 / 87 (1.15%)
         occurrences all number
    3
    3
    Influenza like illness
         subjects affected / exposed
    1 / 86 (1.16%)
    1 / 87 (1.15%)
         occurrences all number
    1
    1
    Injection site erythema
         subjects affected / exposed
    1 / 86 (1.16%)
    1 / 87 (1.15%)
         occurrences all number
    1
    1
    Injection site haematoma
         subjects affected / exposed
    8 / 86 (9.30%)
    4 / 87 (4.60%)
         occurrences all number
    10
    5
    Injection site haemorrhage
         subjects affected / exposed
    2 / 86 (2.33%)
    0 / 87 (0.00%)
         occurrences all number
    3
    0
    Injection site reaction
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Injection site pain
         subjects affected / exposed
    11 / 86 (12.79%)
    13 / 87 (14.94%)
         occurrences all number
    23
    19
    Injection site swelling
         subjects affected / exposed
    2 / 86 (2.33%)
    2 / 87 (2.30%)
         occurrences all number
    2
    2
    Pyrexia
         subjects affected / exposed
    4 / 86 (4.65%)
    2 / 87 (2.30%)
         occurrences all number
    4
    2
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 86 (1.16%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    Social circumstances
    Excessive exercise
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Nasal congestion
         subjects affected / exposed
    1 / 86 (1.16%)
    2 / 87 (2.30%)
         occurrences all number
    1
    2
    Cough
         subjects affected / exposed
    2 / 86 (2.33%)
    4 / 87 (4.60%)
         occurrences all number
    3
    4
    Oropharyngeal pain
         subjects affected / exposed
    1 / 86 (1.16%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    Respiratory tract congestion
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Rhinitis allergic
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    1 / 86 (1.16%)
    1 / 87 (1.15%)
         occurrences all number
    1
    1
    Psychiatric disorders
    Emotional distress
         subjects affected / exposed
    1 / 86 (1.16%)
    1 / 87 (1.15%)
         occurrences all number
    1
    4
    Insomnia
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Irritability
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Investigations
    Body temperature increased
         subjects affected / exposed
    1 / 86 (1.16%)
    3 / 87 (3.45%)
         occurrences all number
    2
    3
    Insulin-like growth factor increased
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Ligament sprain
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Limb injury
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Procedural pain
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 86 (5.81%)
    6 / 87 (6.90%)
         occurrences all number
    6
    6
    Lethargy
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Migraine
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Paraesthesia
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Hyperacusis
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Eye disorders
    Eye pruritus
         subjects affected / exposed
    1 / 86 (1.16%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    Vision blurred
         subjects affected / exposed
    1 / 86 (1.16%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Nausea
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Tongue ulceration
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 86 (0.00%)
    2 / 87 (2.30%)
         occurrences all number
    0
    2
    Skin and subcutaneous tissue disorders
    Blister
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Endocrine disorders
    Adrenocortical insufficiency acute
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 86 (0.00%)
    3 / 87 (3.45%)
         occurrences all number
    0
    3
    Muscle twitching
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Neck pain
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Pain in extremity
         subjects affected / exposed
    1 / 86 (1.16%)
    2 / 87 (2.30%)
         occurrences all number
    1
    3
    Infections and infestations
    Conjunctivitis
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Conjunctivitis viral
         subjects affected / exposed
    1 / 86 (1.16%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    Ear infection
         subjects affected / exposed
    2 / 86 (2.33%)
    3 / 87 (3.45%)
         occurrences all number
    2
    3
    Gastroenteritis
         subjects affected / exposed
    1 / 86 (1.16%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    Impetigo
         subjects affected / exposed
    1 / 86 (1.16%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    Influenza
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Laryngitis
         subjects affected / exposed
    1 / 86 (1.16%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    5 / 86 (5.81%)
    6 / 87 (6.90%)
         occurrences all number
    5
    6
    Otitis media
         subjects affected / exposed
    1 / 86 (1.16%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    Pharyngitis
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Pharyngitis streptococcal
         subjects affected / exposed
    1 / 86 (1.16%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    Pneumonia
         subjects affected / exposed
    1 / 86 (1.16%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 86 (1.16%)
    1 / 87 (1.15%)
         occurrences all number
    2
    1
    Rhinitis
         subjects affected / exposed
    0 / 86 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    Tonsillitis
         subjects affected / exposed
    1 / 86 (1.16%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 86 (2.33%)
    4 / 87 (4.60%)
         occurrences all number
    2
    4
    Urinary tract infection
         subjects affected / exposed
    1 / 86 (1.16%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    Viral infection
         subjects affected / exposed
    3 / 86 (3.49%)
    1 / 87 (1.15%)
         occurrences all number
    3
    1
    Viral rash
         subjects affected / exposed
    1 / 86 (1.16%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    2 / 86 (2.33%)
    0 / 87 (0.00%)
         occurrences all number
    2
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Jul 2018
    (A) Schedule of Activities. Medication dispensation added for Genotropin at Visits 3 and 6. (B) Schedule of Activities. DYAD Questionnaire (completed by Clinical Site Staff) added at Visits 1, 4 and 7. (C) Section 4.1. Inclusion criterion #2 (Currently on treatment with either Genotropin Pen®, Genotropin GoQuick Pen®, HumatroPen® [United States of America {USA} only], or Omnitrope® Pen [USA only]) >=3 months and had been compliant on a stable dose (+/-10%) for at least 3 months prior to screening), was modified to allow for GHD subjects on a wider range of doses to enroll in the study. (D) Section 4.2. Exclusion criterion #5 (Other causes of short stature such as uncontrolled primary hypothyroidism and rickets), was modified to remove celiac disease as exclusionary. As this is not an efficacy study assessing linear growth, children with celiac disease (which can impact growth) need not be excluded. (E) Section 5. Clarification added regarding which body weight measurement is to be used for dosing of somatrogon at Visits 1 and 4. (F) Sections 6.2.3 and 6.2.6. Genotropin drug dispensation added.
    28 Aug 2018
    (A) Schedule of Activities. Anti-rhGH antibodies (and neutralising antibodies) added at Screening, and Visits 4 and 7 at the request of the FDA. (B) Section 2 and Protocol Summary. Detection of anti-rhGH antibodies (and neutralising antibodies) added to align with FDA request. (C) Section 5.4. Arm included as an allowable injection site for Genotropin; its prior omission was in error.
    08 Nov 2018
    (A) Added free thyroxine (FT4) testing at Screening and at Visits 4 and 7 at the request of the MHRA. (B) Modified Section 13, definition of end of trial to be last subject last visit (LSLV) at the request of the MHRA.
    03 May 2019
    (A) Section 4.2. Addition of children with closed epiphyses to the Exclusion Criteria to address the request of EU Health Authorities. (B) Section 4.2. Exclusion criteria regarding allowable injectable medications clarified. (C) Sections 5.5, 6.1.1, 6.2.3, & 6.2.4. Dosing windows expanded for Genotropin (36 hours +/- 24 hours) and somatrogon (7 days +/- 72 hours) prior to Visits 1 and 4 providing increased flexibility in dosing for subjects/caregivers prior to visits. (D) Section 5.8.1. Allowable injectable concomitant medications clarified.

    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.
    None reported
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