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    Clinical Trial Results:
    A 24-week Safety, Efficacy, Pharmacodynamic, and Pharmacokinetic Study of Teduglutide in Japanese Pediatric Subjects, Aged 4 Months through 15 Years, with Short Bowel Syndrome who are Dependent on Parenteral Support

    Summary
    EudraCT number
    2020-005791-35
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    21 Jan 2020

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

    Trial information

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    Trial identification
    Sponsor protocol code
    SHP633-302
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02980666
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Shire
    Sponsor organisation address
    300 Shire Way, Lexington, United States, MA 02421
    Public contact
    Study Director, Shire, +1 866 842 5335, ClinicalTransparency@shire.com
    Scientific contact
    Study Director, Shire, +1 866 842 5335, ClinicalTransparency@shire.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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    21 Jan 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Jan 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate the safety, tolerability, efficacy, pharmacodynamics (PD), and pharmacokinetics (PK) of teduglutide in Japanese pediatric subjects (4 months through 15 years of age) with short bowel syndrome (SBS) who were dependent on parenteral support (PS).
    Protection of trial subjects
    The study was conducted in accordance with current applicable industry regulations, International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 (1996) and any updates, European Union (EU) Directive 2001/20/EC and its updates, the ethical principles in the Declaration of Helsinki, and local ethical and legal requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    13 Jan 2017
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Efficacy, Safety
    Long term follow-up duration
    9 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Japan: 10
    Worldwide total number of subjects
    10
    EEA total number of subjects
    0
    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)
    2
    Children (2-11 years)
    8
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study was conducted at 6 centers in Japan between 13 January 2017 (first subject first visit) and 21 January 2020 (last subject last visit).

    Pre-assignment
    Screening details
    A total of 10 Japanese subjects were enrolled into the study, including 8 children age 1 through 15 years of age and 2 infants aged 4 months through < 12 months of corrected gestational age. All the subjects received treatment and completed the study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Total Children (Aged: 1 to 15 Years)
    Arm description
    Subjects aged from 1 through 15 years received teduglutide 0.05 milligram per kilogram per day (mg/kg/day) subcutaneous (SC) injection once daily for 24 weeks and completed the study at Week 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Teduglutide
    Investigational medicinal product code
    SHP633
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received teduglutide 0.05 mg/kg/day SC injection into either thigh or arm or 1 of 4 quadrants of the abdomen.

    Arm title
    Infants (Corrected Gestational Age: 4 to < 12 months)
    Arm description
    Subjects (Infants) from 4 through < 12 months of corrected gestational age received teduglutide 0.05 mg/kg/day SC injection once daily for 24 weeks and completed the study at Week 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Teduglutide
    Investigational medicinal product code
    SHP633
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received teduglutide 0.05 mg/kg/day SC injection into either thigh or arm or 1 of 4 quadrants of the abdomen.

    Number of subjects in period 1
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Started
    8
    2
    Completed
    8
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Total Children (Aged: 1 to 15 Years)
    Reporting group description
    Subjects aged from 1 through 15 years received teduglutide 0.05 milligram per kilogram per day (mg/kg/day) subcutaneous (SC) injection once daily for 24 weeks and completed the study at Week 28.

    Reporting group title
    Infants (Corrected Gestational Age: 4 to < 12 months)
    Reporting group description
    Subjects (Infants) from 4 through < 12 months of corrected gestational age received teduglutide 0.05 mg/kg/day SC injection once daily for 24 weeks and completed the study at Week 28.

    Reporting group values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months) Total
    Number of subjects
    8 2 10
    Age Categorical
    Units: Subjects
        1 to 15 Years
    8 0 8
        4 to < 12 months
    0 2 2
    Sex: Female, Male
    Units: Subjects
        Female
    1 1 2
        Male
    7 1 8
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    0 0 0
        Not Hispanic or Latino
    8 2 10
        Unknown or Not Reported
    0 0 0
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0
        Asian
    8 2 10
        Native Hawaiian or Other Pacific Islander
    0 0 0
        Black or African American
    0 0 0
        White
    0 0 0
        More than one race
    0 0 0
        Unknown or Not Reported
    0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Total Children (Aged: 1 to 15 Years)
    Reporting group description
    Subjects aged from 1 through 15 years received teduglutide 0.05 milligram per kilogram per day (mg/kg/day) subcutaneous (SC) injection once daily for 24 weeks and completed the study at Week 28.

    Reporting group title
    Infants (Corrected Gestational Age: 4 to < 12 months)
    Reporting group description
    Subjects (Infants) from 4 through < 12 months of corrected gestational age received teduglutide 0.05 mg/kg/day SC injection once daily for 24 weeks and completed the study at Week 28.

    Primary: Absolute Change From Baseline in Parenteral Support (PS) Volume at End of Treatment (EOT) Based on Dairy Data

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    End point title
    Absolute Change From Baseline in Parenteral Support (PS) Volume at End of Treatment (EOT) Based on Dairy Data [1]
    End point description
    Absolute change from baseline in PS volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. Here, milliliter per kilogram per day is abbreviated as mL/kg/day. Intention-to-treat (ITT) population consisted of all subjects who were enrolled into the study and met all eligible criteria for the study.
    End point type
    Primary
    End point timeframe
    Baseline, EOT (up to Week 24)
    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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: mL/kg/day
        arithmetic mean (standard deviation)
    -11.8 ± 8.47
    -26.2 ± 13.61
    No statistical analyses for this end point

    Primary: Percent Change From Baseline in Parenteral Support (PS) Volume at End of Treatment (EOT) Based on Dairy Data

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    End point title
    Percent Change From Baseline in Parenteral Support (PS) Volume at End of Treatment (EOT) Based on Dairy Data [2]
    End point description
    Percent change from baseline in PS volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for the study.
    End point type
    Primary
    End point timeframe
    Baseline, EOT (up to Week 24)
    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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: Percent Change
        arithmetic mean (standard deviation)
    -27.7 ± 31.79
    -26.7 ± 15.14
    No statistical analyses for this end point

    Primary: Absolute Change From Baseline in Parenteral Support (PS) Caloric Intake at End of Treatment (EOT) Based on Dairy Data

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    End point title
    Absolute Change From Baseline in Parenteral Support (PS) Caloric Intake at End of Treatment (EOT) Based on Dairy Data [3]
    End point description
    Absolute change from baseline in PS caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. Here, kilo-calories per kilogram per day was abbreviated as (kcal/kg/day). ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for the study.
    End point type
    Primary
    End point timeframe
    Baseline, EOT (up to 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: kcal/kg/day
        arithmetic mean (standard deviation)
    -7.2 ± 8.70
    -13.8 ± 3.17
    No statistical analyses for this end point

    Primary: Percent Change From Baseline in Parenteral Support (PS) Caloric Intake at End of Treatment (EOT) Based on Dairy Data

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    End point title
    Percent Change From Baseline in Parenteral Support (PS) Caloric Intake at End of Treatment (EOT) Based on Dairy Data [4]
    End point description
    Percent change from baseline in PS caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for the study.
    End point type
    Primary
    End point timeframe
    Baseline, EOT (up to Week 24)
    Notes
    [4] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: Percent change
        arithmetic mean (standard deviation)
    -26.2 ± 33.00
    -25.7 ± 2.73
    No statistical analyses for this end point

    Primary: Absolute Change From Baseline in Plasma Citrulline at End of Treatment (EOT)

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    End point title
    Absolute Change From Baseline in Plasma Citrulline at End of Treatment (EOT) [5]
    End point description
    Absolute change from baseline in plasma citrulline at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for the study.
    End point type
    Primary
    End point timeframe
    Baseline, EOT (up to Week 24)
    Notes
    [5] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    0 [6]
    Units: Micromoles per liter (mcmol/L)
        arithmetic mean (standard deviation)
    3.2 ± 4.28
    ±
    Notes
    [6] - Data for this end point was not planned to be collected and analysed for infants.
    No statistical analyses for this end point

    Primary: Percent Change From Baseline in Plasma Citrulline at End of Treatment (EOT)

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    End point title
    Percent Change From Baseline in Plasma Citrulline at End of Treatment (EOT) [7]
    End point description
    Percent change from baseline in plasma citrulline at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for the study.
    End point type
    Primary
    End point timeframe
    Baseline, EOT (up to Week 24)
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    0 [8]
    Units: Percent change
        arithmetic mean (standard deviation)
    39.2 ± 39.46
    ±
    Notes
    [8] - Data for this endpoint was not planned to be collected and analysed for infants.
    No statistical analyses for this end point

    Primary: Absolute Change From Baseline in Enteral Nutritional (EN) Volume at End of Treatment (EOT) Based on Dairy Data

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    End point title
    Absolute Change From Baseline in Enteral Nutritional (EN) Volume at End of Treatment (EOT) Based on Dairy Data [9]
    End point description
    Absolute change from baseline in EN volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study.
    End point type
    Primary
    End point timeframe
    Baseline, EOT (up to Week 24)
    Notes
    [9] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: mL/kg/day
        arithmetic mean (standard deviation)
    1.0 ± 7.14
    0.6 ± 2.15
    No statistical analyses for this end point

    Primary: Percent Change From Baseline in Enteral Nutritional (EN) Volume at End of Treatment (EOT) Based on Dairy Data

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    End point title
    Percent Change From Baseline in Enteral Nutritional (EN) Volume at End of Treatment (EOT) Based on Dairy Data [10]
    End point description
    Percent change from baseline in EN volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Baseline, EOT (up to Week 24)
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    4
    2
    Units: Percent change
        arithmetic mean (standard deviation)
    53.1 ± 111.01
    -23.2 ± 36.89
    No statistical analyses for this end point

    Primary: Absolute Change From Baseline in Enteral Nutritional (EN) Caloric Intake at End of Treatment (EOT) Based on Dairy Data

    Close Top of page
    End point title
    Absolute Change From Baseline in Enteral Nutritional (EN) Caloric Intake at End of Treatment (EOT) Based on Dairy Data [11]
    End point description
    Absolute change from baseline in EN caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study.
    End point type
    Primary
    End point timeframe
    Baseline, EOT (up to Week 24)
    Notes
    [11] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: kcal/kg/day
        arithmetic mean (standard deviation)
    0.8 ± 5.60
    0.3 ± 1.03
    No statistical analyses for this end point

    Primary: Percent Change From Baseline in Enteral Nutritional (EN) Caloric Intake at End of Treatment (EOT) Based on Dairy Data

    Close Top of page
    End point title
    Percent Change From Baseline in Enteral Nutritional (EN) Caloric Intake at End of Treatment (EOT) Based on Dairy Data [12]
    End point description
    Percent change from baseline in EN caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Baseline, EOT (up to Week 24)
    Notes
    [12] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    4
    2
    Units: Percent change
        arithmetic mean (standard deviation)
    56.8 ± 117.88
    -24.2 ± 38.06
    No statistical analyses for this end point

    Primary: Number of Subjects Who Achieved At least 20 Percent (%) Reduction in Parenteral Support (PS) Volume at Week 24

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    End point title
    Number of Subjects Who Achieved At least 20 Percent (%) Reduction in Parenteral Support (PS) Volume at Week 24 [13]
    End point description
    Number of subjects who achieved at least 20% reduction in PS volume at Week 24 was reported. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Week 24
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    7
    2
    Units: Subjects
    4
    1
    No statistical analyses for this end point

    Primary: Number of Subjects Who Achieved At least 20 Percent (%) Reduction in Parenteral Support (PS) Volume at End of Treatment (EOT)

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    End point title
    Number of Subjects Who Achieved At least 20 Percent (%) Reduction in Parenteral Support (PS) Volume at End of Treatment (EOT) [14]
    End point description
    Number of subjects who achieved at least 20% reduction in PS volume at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study.
    End point type
    Primary
    End point timeframe
    EOT (up to Week 24)
    Notes
    [14] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: Subjects
    4
    1
    No statistical analyses for this end point

    Primary: Number of Subjects Who Achieved 100 Percent (%) Reduction in Complete Weaning of Parenteral Support (PS) Volume at End of Treatment (EOT)

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    End point title
    Number of Subjects Who Achieved 100 Percent (%) Reduction in Complete Weaning of Parenteral Support (PS) Volume at End of Treatment (EOT) [15]
    End point description
    Number of subjects who achieved at least 100% reduction in complete weaning of PS volume at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study.
    End point type
    Primary
    End point timeframe
    EOT (up to Week 24)
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: Subjects
    1
    0
    No statistical analyses for this end point

    Primary: Number of Subjects Who Achieved Greater Than or Equal to (>=) 20 Percent (%) Reduction in Parenteral Support (PS) Volume at Week 28

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    End point title
    Number of Subjects Who Achieved Greater Than or Equal to (>=) 20 Percent (%) Reduction in Parenteral Support (PS) Volume at Week 28 [16]
    End point description
    Number of subjects who achieved >= 20% reduction in PS volume at Week 28 was reported. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study.
    End point type
    Primary
    End point timeframe
    Week 28
    Notes
    [16] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: Subjects
    3
    1
    No statistical analyses for this end point

    Primary: Absolute Change From End of Treatment (EOT) in Parenteral Support (PS) Volume at End of Study (EOS) Based on Dairy Data

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    End point title
    Absolute Change From End of Treatment (EOT) in Parenteral Support (PS) Volume at End of Study (EOS) Based on Dairy Data [17]
    End point description
    Absolute change from EOT (up to Week 24) in PS volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study.
    End point type
    Primary
    End point timeframe
    EOT (up to Week 24), EOS (up to Week 28)
    Notes
    [17] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: mL/kg/day
        arithmetic mean (standard deviation)
    3.9 ± 7.06
    -3.8 ± 0.67
    No statistical analyses for this end point

    Primary: Percent Change From End of Treatment (EOT) in Parenteral Support (PS) Volume at End of Study (EOS) Based on Dairy Data

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    End point title
    Percent Change From End of Treatment (EOT) in Parenteral Support (PS) Volume at End of Study (EOS) Based on Dairy Data [18]
    End point description
    Percent change from EOT (up to Week 24) in PS volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    EOT (up to Week 24), EOS (up to Week 28)
    Notes
    [18] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    7
    2
    Units: Percent change
        arithmetic mean (standard deviation)
    9.8 ± 19.59
    -5.5 ± 2.35
    No statistical analyses for this end point

    Primary: Absolute Change From End of Treatment (EOT) in Parenteral Support (PS) Caloric Intake at End of Study (EOS) Based on Dairy Data

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    End point title
    Absolute Change From End of Treatment (EOT) in Parenteral Support (PS) Caloric Intake at End of Study (EOS) Based on Dairy Data [19]
    End point description
    Absolute change from EOT (up to Week 24) in PS caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study.
    End point type
    Primary
    End point timeframe
    EOT (up to Week 24), EOS (up to Week 28)
    Notes
    [19] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: kcal/kg/day
        arithmetic mean (standard deviation)
    0.5 ± 6.16
    -4.0 ± 1.38
    No statistical analyses for this end point

    Primary: Percent Change From End of Treatment (EOT) in Parenteral Support (PS) Caloric Intake at End of Study (EOS) Based on Dairy Data

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    End point title
    Percent Change From End of Treatment (EOT) in Parenteral Support (PS) Caloric Intake at End of Study (EOS) Based on Dairy Data [20]
    End point description
    Percent change from EOT (up to Week 24) in PS caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    EOT (up to Week 24), EOS (up to Week 28)
    Notes
    [20] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    7
    2
    Units: Percent change
        arithmetic mean (standard deviation)
    3.5 ± 19.17
    -10.3 ± 4.40
    No statistical analyses for this end point

    Primary: Absolute Change From End of Treatment (EOT) in Plasma Citrulline at End of Study (EOS)

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    End point title
    Absolute Change From End of Treatment (EOT) in Plasma Citrulline at End of Study (EOS) [21]
    End point description
    Absolute change from EOT (up to Week 24) in plasma citrulline at EOS (up to Week 28) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study.
    End point type
    Primary
    End point timeframe
    EOT (up to Week 24), EOS (up to Week 28)
    Notes
    [21] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    0 [22]
    Units: Micromoles (mcM)
        arithmetic mean (standard deviation)
    -2.9 ± 2.87
    ±
    Notes
    [22] - Data for this endpoint was not planned to be collected and analysed for infants.
    No statistical analyses for this end point

    Primary: Percent Change From End of Treatment (EOT) in Plasma Citrulline at End of Study (EOS)

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    End point title
    Percent Change From End of Treatment (EOT) in Plasma Citrulline at End of Study (EOS) [23]
    End point description
    Percent change from EOT (up to Week 24) in plasma citrulline at EOS (up to Week 28) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study.
    End point type
    Primary
    End point timeframe
    EOT (up to Week 24), EOS (up to Week 28)
    Notes
    [23] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    0 [24]
    Units: Percent change
        arithmetic mean (standard deviation)
    -20.0 ± 24.16
    ±
    Notes
    [24] - Data for this endpoint was not planned to be collected and analysed for infants.
    No statistical analyses for this end point

    Primary: Absolute Change From End of Treatment (EOT) in Enteral Nutritional (EN) Volume at End of Study (EOS) Based on Dairy Data

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    End point title
    Absolute Change From End of Treatment (EOT) in Enteral Nutritional (EN) Volume at End of Study (EOS) Based on Dairy Data [25]
    End point description
    Absolute change from EOT (up to Week 24) in EN volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study.
    End point type
    Primary
    End point timeframe
    EOT (up to Week 24), EOS (up to Week 28)
    Notes
    [25] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: mL/kg/day
        arithmetic mean (standard deviation)
    -1.5 ± 3.24
    -2.8 ± 3.98
    No statistical analyses for this end point

    Primary: Percent Change From End of Treatment (EOT) in Enteral Nutritional (EN) Volume at End of Study (EOS) Based on Dairy Data

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    End point title
    Percent Change From End of Treatment (EOT) in Enteral Nutritional (EN) Volume at End of Study (EOS) Based on Dairy Data [26]
    End point description
    Percent change from EOT (up to Week 24) in EN volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    EOT (up to Week 24), EOS (up to Week 28)
    Notes
    [26] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    4
    2
    Units: Percent change
        arithmetic mean (standard deviation)
    -22.1 ± 28.06
    -1.4 ± 8.25
    No statistical analyses for this end point

    Primary: Absolute Change From End of Treatment (EOT) in Enteral Nutritional (EN) Caloric Intake at End of Study (EOS) Based on Dairy Data

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    End point title
    Absolute Change From End of Treatment (EOT) in Enteral Nutritional (EN) Caloric Intake at End of Study (EOS) Based on Dairy Data [27]
    End point description
    Absolute change from EOT (up to Week 24) in EN caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study.
    End point type
    Primary
    End point timeframe
    EOT (up to Week 24), EOS (up to Week 28)
    Notes
    [27] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: kcal/kg/day
        arithmetic mean (standard deviation)
    -1.1 ± 2.64
    -1.4 ± 1.97
    No statistical analyses for this end point

    Primary: Percent Change From End of Treatment (EOT) in Enteral Nutritional (EN) Caloric Intake at End of Study (EOS) Based on Dairy Data

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    End point title
    Percent Change From End of Treatment (EOT) in Enteral Nutritional (EN) Caloric Intake at End of Study (EOS) Based on Dairy Data [28]
    End point description
    Percent change from EOT (up to Week 24) in EN caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    EOT (up to Week 24), EOS (up to Week 28)
    Notes
    [28] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    4
    2
    Units: Percent change
        arithmetic mean (standard deviation)
    -22.1 ± 28.16
    -3.0 ± 6.03
    No statistical analyses for this end point

    Primary: Absolute Change From Baseline in Number of Hours per Day of Parenteral Support (PS) Usage at End of Treatment (EOT) Based on Dairy Data

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    End point title
    Absolute Change From Baseline in Number of Hours per Day of Parenteral Support (PS) Usage at End of Treatment (EOT) Based on Dairy Data [29]
    End point description
    Absolute change from baseline in number of hours per day of PS Usage at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study.
    End point type
    Primary
    End point timeframe
    Baseline, EOT (up to Week 24)
    Notes
    [29] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: Hours per day (hours/day)
        arithmetic mean (standard deviation)
    -2.1 ± 4.16
    0.0 ± 0.00
    No statistical analyses for this end point

    Primary: Absolute Change From Baseline in Number of Days per Week of Parenteral Support (PS) Usage at End of Treatment (EOT) Based on Dairy Data

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    End point title
    Absolute Change From Baseline in Number of Days per Week of Parenteral Support (PS) Usage at End of Treatment (EOT) Based on Dairy Data [30]
    End point description
    Absolute change from baseline in number of days per Week of PS usage at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. ITT population consisted of all subjects who were enrolled into the study and met all eligible criteria for this study.
    End point type
    Primary
    End point timeframe
    Baseline, EOT (up to Week 24)
    Notes
    [30] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: Days per week
        arithmetic mean (standard deviation)
    -0.9 ± 2.47
    0.0 ± 0.00
    No statistical analyses for this end point

    Primary: Number of Subjects With Treatment-emergent Adverse Events (TEAEs)

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    End point title
    Number of Subjects With Treatment-emergent Adverse Events (TEAEs) [31]
    End point description
    An Adverse Event (AE) was any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs were defined as any AEs whose onset occurred, severity worsened, or intensity increased after receiving the investigational product. Safety population consisted of all subjects in the ITT population who received at least 1 administration of investigational product with any safety follow-up.
    End point type
    Primary
    End point timeframe
    From start of study drug administration up to EOS (up to Week 28)
    Notes
    [31] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: Subjects
    8
    2
    No statistical analyses for this end point

    Primary: Change From Baseline in Body Weight for age Z-score at Week 28

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    End point title
    Change From Baseline in Body Weight for age Z-score at Week 28 [32]
    End point description
    Body weight was measured using age Z-score. A Z-score was defined as the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in body weight for age Z-score at Week 28 was reported. Safety population consisted of all subjects in the ITT population who received at least 1 administration of investigational product with any safety follow-up.
    End point type
    Primary
    End point timeframe
    Baseline, Week 28
    Notes
    [32] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: Z-score
        arithmetic mean (standard deviation)
    0.177 ± 0.3625
    2.332 ± 1.1503
    No statistical analyses for this end point

    Primary: Change From Baseline in Height for Age Z-score at Week 28

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    End point title
    Change From Baseline in Height for Age Z-score at Week 28 [33]
    End point description
    Height was measured using age Z-score. A Z-score was defined as the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in height for age Z-score at Week 28 was reported. Safety population consisted of all subjects in the ITT population who received at least 1 administration of investigational product with any safety follow-up.
    End point type
    Primary
    End point timeframe
    Baseline, Week 28
    Notes
    [33] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: Z-score
        arithmetic mean (standard deviation)
    0.024 ± 0.4841
    1.056 ± 0.6968
    No statistical analyses for this end point

    Primary: Change From Baseline in Head Circumference for Age Z-score at Week 28

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    End point title
    Change From Baseline in Head Circumference for Age Z-score at Week 28 [34]
    End point description
    Head circumference was measured using age Z-score. A Z-score was defined as the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in head circumference for age Z-score at Week 28 was reported. Safety population consisted of all subjects in the ITT population who received at least 1 administration of investigational product with any safety follow-up.
    End point type
    Primary
    End point timeframe
    Baseline, Week 28
    Notes
    [34] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    0 [35]
    2
    Units: Z-score
        arithmetic mean (standard deviation)
    ±
    1.559 ± 0.6116
    Notes
    [35] - Data for this endpoint was not planned to be collected and analysed for Total Children.
    No statistical analyses for this end point

    Primary: Number of Subjects With Clinically Significant Changes in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs)

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    End point title
    Number of Subjects With Clinically Significant Changes in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs) [36]
    End point description
    Vital sign assessments included pulse rate, blood pressure, or body temperature. Number of subjects with clinically significant changes in vital signs by the investigator were recorded as TEAEs. Safety population consisted of all subjects in the ITT population who received at least 1 administration of investigational product with any safety follow-up.
    End point type
    Primary
    End point timeframe
    From start of study drug administration up to EOS (up to Week 28)
    Notes
    [36] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: Subjects
    0
    0
    No statistical analyses for this end point

    Primary: Number of Subjects With Clinically Significant Changes in Electrocardiogram (ECG) Reported as Treatment Emergent Adverse Events (TEAEs)

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    End point title
    Number of Subjects With Clinically Significant Changes in Electrocardiogram (ECG) Reported as Treatment Emergent Adverse Events (TEAEs) [37]
    End point description
    12-lead ECG was performed. Any change in ECG assessments which were deemed to be clinically significant changes were recorded as TEAEs. Safety population consisted of all subjects in the ITT population who received at least 1 administration of investigational product with any safety follow-up.
    End point type
    Primary
    End point timeframe
    From start of study drug administration up to EOS (up to Week 28)
    Notes
    [37] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: Subjects
    0
    0
    No statistical analyses for this end point

    Primary: Number of Subjects With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)

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    End point title
    Number of Subjects With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) [38]
    End point description
    Clinical laboratory assessments included biochemistry, hematology, coagulation, urinalysis. The number of subjects with clinically significant laboratory abnormalities were reported as TEAEs. Safety population consisted of all subjects in the ITT population who received at least 1 administration of investigational product with any safety follow-up.
    End point type
    Primary
    End point timeframe
    From start of study drug administration up to EOS (up to Week 28)
    Notes
    [38] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: Subjects
    0
    0
    No statistical analyses for this end point

    Primary: Change From Baseline in the Average Urine Output at Week 28

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    End point title
    Change From Baseline in the Average Urine Output at Week 28 [39]
    End point description
    Average urine output was recorded in measured volume at Week 28 was reported. Safety population consisted of all subjects in the ITT population who received at least 1 administration of investigational product with any safety follow-up. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint. Here, '99999' indicates that standard deviation was not estimated as only single subject was analysed for the specified arm.
    End point type
    Primary
    End point timeframe
    Baseline, Week 28
    Notes
    [39] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    7
    1
    Units: mL/kg/day
        arithmetic mean (standard deviation)
    -22.317 ± 34.8252
    -48.879 ± 99999
    No statistical analyses for this end point

    Primary: Change From Baseline in the Fecal Output at Week 28

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    End point title
    Change From Baseline in the Fecal Output at Week 28 [40]
    End point description
    Change from baseline in the fecal output (Average number of stools per day) at Week 28 was recorded. Safety population consisted of all subjects in the ITT population who received at least 1 administration of investigational product with any safety follow-up. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint. Here, '99999' indicates that standard deviation was not estimated as only single subject was analysed for the specified arm.
    End point type
    Primary
    End point timeframe
    Baseline, Week 28
    Notes
    [40] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    7
    1
    Units: Average number of stools per day
        arithmetic mean (standard deviation)
    -0.64 ± 1.547
    2.50 ± 99999
    No statistical analyses for this end point

    Primary: Number of Subjects With Positive Specific Antibodies to Teduglutide

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    End point title
    Number of Subjects With Positive Specific Antibodies to Teduglutide [41]
    End point description
    Number of subjects with positive specific antibodies to teduglutide were used to summarize the presence of antibodies. Safety population consisted of all subjects in the ITT population who received at least 1 administration of investigational product with any safety follow-up.
    End point type
    Primary
    End point timeframe
    From start of study drug administration up to EOS (up to Week 28)
    Notes
    [41] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    2
    Units: Subjects
    1
    2
    No statistical analyses for this end point

    Primary: Number of Subjects With Clinically Significant Abnormal Findings in Gastrointestinal (GI) Specific Testing

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    End point title
    Number of Subjects With Clinically Significant Abnormal Findings in Gastrointestinal (GI) Specific Testing [42]
    End point description
    GI specific testing included colonoscopy or sigmoidoscopy, abdominal ultrasound, fecal occult blood testing, upper GI series with small bowel follow-through (UGI/SBFT). EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. Number of subjects with clinically significant abnormal findings in gastrointestinal specific testing were reported. Safety population consisted of all subjects in the ITT population who received at least 1 administration of investigational product with any safety follow-up.
    End point type
    Primary
    End point timeframe
    Baseline, EOT (up to Week 24)
    Notes
    [42] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    8
    0 [43]
    Units: Subjects
    0
    Notes
    [43] - Data for this endpoint was not planned to be collected and analysed for infants.
    No statistical analyses for this end point

    Primary: Area Under the Concentration-time Curve at Steady State (AUCtau,ss) of Teduglutide in Plasma

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    End point title
    Area Under the Concentration-time Curve at Steady State (AUCtau,ss) of Teduglutide in Plasma [44]
    End point description
    Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analysed using this study samples. Therefore, no PK parameters were reported in this study.
    End point type
    Primary
    End point timeframe
    Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose
    Notes
    [44] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    0 [45]
    0 [46]
    Units: hour*nanogram per milliliter (hr*ng/mL)
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [45] - PK was planned to be reported with other clinical studies. Hence,no individual PK data was reported.
    [46] - PK was planned to be reported with other clinical studies. Hence,no individual PK data was reported.
    No statistical analyses for this end point

    Primary: Maximum Plasma Concentration at Steady-state (Cmax,ss) of Teduglutide in Plasma

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    End point title
    Maximum Plasma Concentration at Steady-state (Cmax,ss) of Teduglutide in Plasma [47]
    End point description
    Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analysed using this study samples. Therefore, no PK parameters were reported in this study.
    End point type
    Primary
    End point timeframe
    Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose
    Notes
    [47] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    0 [48]
    0 [49]
    Units: nanogram per milliliter (ng/mL)
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [48] - PK was planned to be reported with other clinical studies. Hence,no individual PK data was reported.
    [49] - PK was planned to be reported with other clinical studies. Hence,no individual PK data was reported.
    No statistical analyses for this end point

    Primary: Minimum Plasma Concentration at Steady-state (Cmin.ss) of Teduglutide in Plasma

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    End point title
    Minimum Plasma Concentration at Steady-state (Cmin.ss) of Teduglutide in Plasma [50]
    End point description
    Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analysed using this study samples. Therefore, no PK parameters were reported in this study.
    End point type
    Primary
    End point timeframe
    Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose
    Notes
    [50] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    0 [51]
    0 [52]
    Units: ng/mL
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [51] - PK was planned to be reported with other clinical studies. Hence,no individual PK data was reported.
    [52] - PK was planned to be reported with other clinical studies. Hence,no individual PK data was reported.
    No statistical analyses for this end point

    Primary: Time to Reach Maximum Observed Drug Concentration (Tmax) of Teduglutide in Plasma

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    End point title
    Time to Reach Maximum Observed Drug Concentration (Tmax) of Teduglutide in Plasma [53]
    End point description
    Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analysed using this study samples. Therefore, no PK parameters were reported in this study.
    End point type
    Primary
    End point timeframe
    Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose
    Notes
    [53] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    0 [54]
    0 [55]
    Units: hour
        median (full range (min-max))
    ( to )
    ( to )
    Notes
    [54] - PK was planned to be reported with other clinical studies. Hence,no individual PK data was reported.
    [55] - PK was planned to be reported with other clinical studies. Hence,no individual PK data was reported.
    No statistical analyses for this end point

    Primary: Terminal-Phase Half-life (t1/2) of Teduglutide in Plasma

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    End point title
    Terminal-Phase Half-life (t1/2) of Teduglutide in Plasma [56]
    End point description
    Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analysed using this study samples. Therefore, no PK parameters were reported in this study.
    End point type
    Primary
    End point timeframe
    Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose
    Notes
    [56] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    0 [57]
    0 [58]
    Units: hour
        median (full range (min-max))
    ( to )
    ( to )
    Notes
    [57] - PK was planned to be reported with other clinical studies. Hence,no individual PK data was reported.
    [58] - PK was planned to be reported with other clinical studies. Hence,no individual PK data was reported.
    No statistical analyses for this end point

    Primary: Apparent Clearance (CL/F) of Teduglutide

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    End point title
    Apparent Clearance (CL/F) of Teduglutide [59]
    End point description
    Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analysed using this study samples. Therefore, no PK parameters were reported in this study.
    End point type
    Primary
    End point timeframe
    Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose
    Notes
    [59] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    0 [60]
    0 [61]
    Units: Liter per hour (L/hr)
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [60] - PK was planned to be reported with other clinical studies. Hence,no individual PK data was reported.
    [61] - PK was planned to be reported with other clinical studies. Hence,no individual PK data was reported.
    No statistical analyses for this end point

    Primary: Apparent Volume of Distribution (V[lambda z]/F) of Teduglutide

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    End point title
    Apparent Volume of Distribution (V[lambda z]/F) of Teduglutide [62]
    End point description
    Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analysed using this study samples. Therefore, no PK parameters were reported in this study.
    End point type
    Primary
    End point timeframe
    Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose
    Notes
    [62] - 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 and comparison analyses were performed for this endpoint.
    End point values
    Total Children (Aged: 1 to 15 Years) Infants (Corrected Gestational Age: 4 to < 12 months)
    Number of subjects analysed
    0 [63]
    0 [64]
    Units: per hour
        arithmetic mean (standard deviation)
    ±
    ±
    Notes
    [63] - PK was planned to be reported with other clinical studies. Hence,no individual PK data was reported.
    [64] - PK was planned to be reported with other clinical studies. Hence,no individual PK data was reported.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From start of study drug administration up to end of the study (up to Week 28)
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Total Children (1 - 15 years)
    Reporting group description
    Subjects with aged from 1 through 15 years received teduglutide 0.05 mg/kg/day SC injection once daily for 24 weeks and completed the study at Week 28.

    Reporting group title
    Infants (4 - 12 months)
    Reporting group description
    Subjects with Infants aged from 4 through less than 12 months received teduglutide 0.05 mg/kg/day SC injection once daily for 24 weeks and completed the study at Week 28.

    Serious adverse events
    Total Children (1 - 15 years) Infants (4 - 12 months)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 8 (75.00%)
    2 / 2 (100.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Upper respiratory tract inflammation
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 2 (50.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 2 (100.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    2 / 8 (25.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device damage
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Adenovirus infection
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    3 / 8 (37.50%)
    1 / 2 (50.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand-foot-and-mouth disease
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical device site infection
         subjects affected / exposed
    2 / 8 (25.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 2 (50.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Total Children (1 - 15 years) Infants (4 - 12 months)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    8 / 8 (100.00%)
    1 / 2 (50.00%)
    Injury, poisoning and procedural complications
    Frostbite
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Gastrostomy tube site complication
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Vaccination complication
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    1
    Investigations
    Amylase increased
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Upper respiratory tract inflammation
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    2
    Immune system disorders
    Food allergy
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Catheter site granuloma
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Injection site bruising
         subjects affected / exposed
    2 / 8 (25.00%)
    0 / 2 (0.00%)
         occurrences all number
    9
    0
    Injection site erythema
         subjects affected / exposed
    3 / 8 (37.50%)
    0 / 2 (0.00%)
         occurrences all number
    12
    0
    Injection site haematoma
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Injection site induration
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Injection site pain
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Injection site reaction
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Injection site rash
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    4
    0
    Pyrexia
         subjects affected / exposed
    2 / 8 (25.00%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Abdominal pain
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    2 / 8 (25.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Dental caries
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Enteritis
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Enterocolitis
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    1
    Gastritis
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Proctalgia
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Balanoposthitis
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Dermatitis contact
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    1
    Dermatitis diaper
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 2 (50.00%)
         occurrences all number
    1
    2
    Dry skin
         subjects affected / exposed
    2 / 8 (25.00%)
    1 / 2 (50.00%)
         occurrences all number
    2
    1
    Eczema
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Rash
         subjects affected / exposed
    4 / 8 (50.00%)
    0 / 2 (0.00%)
         occurrences all number
    5
    0
    Product issues
    Device damage
         subjects affected / exposed
    2 / 8 (25.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Hyperlipasaemia
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Hyperzincaemia
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Device related infection
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Gingivitis
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Influenza
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Hand-foot-and-mouth disease
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Medical device site infection
         subjects affected / exposed
    2 / 8 (25.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Otitis media
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    1
    Pharyngitis streptococcal
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Rhinitis
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    6 / 8 (75.00%)
    1 / 2 (50.00%)
         occurrences all number
    6
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Apr 2016
    Amendment 1: - Identification of age range (1 through 15 years old). - Update of severity of AEs (Utility of severity criteria of AE from National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) to evaluate dose interruption). - Addition of continuation of output diary data collection over a 48-hour period of PS and enteral nutrition (EN) stability before every site visit.
    06 Jun 2017
    Amendment 2: - Change of examination (removal of urine osmolality and urine sodium from the urinalysis).
    24 Jan 2018
    Amendment 3: - Addition of direct bilirubin in laboratory tests.
    12 Jun 2018
    Amendment 4: - Addition of infants with 4 months through <12 months corrected gestational age.

    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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