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    Clinical Trial Results:
    A phase 2 trial testing ZP1848 in patients with SBS A proof-of-concept, dose-finding, controlled, single-center, randomized, cross-over, double-blind, fixed dose trial

    Summary
    EudraCT number
    		 2015-002826-38
    Trial protocol
    		 DK  
    Global end of trial date
    04 May 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Jun 2018
    First version publication date
    01 Jun 2018
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ZP1848-15073
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02690025
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Zealand Pharma A/S
    Sponsor organisation address
    Smedeland 36, Glostrup, Denmark, 2600
    Public contact
    Gertrud Koefoed Rasmussen, Zealand Pharma A/S, 0045 50603773, gkr@zealandpharma.com
    Scientific contact
    Gertrud Koefoed Rasmussen, Zealand Pharma A/S, 0045 50603773, gkr@zealandpharma.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
    04 May 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    04 May 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    04 May 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective is to evaluate the effect of three different doses of ZP1848 on intestinal absorption in SBS patients after three week treatment periods.
    Protection of trial subjects
    The trial was conducted in accordance of the World Medical Association Declaration of Helsinki, current guidelines for GCP and local regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Feb 2016
    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
    Denmark: 18
    Worldwide total number of subjects
    18
    EEA total number of subjects
    18
    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)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    12
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 22 patients were screened at one Danish site. The first patient was screened on 5 Feb 2016 and the last patient was enrolled on 25 Jan 2017. 18 Patients were randomized in the trial and 16 patients completed the trial.

    Pre-assignment
    Screening details
    		 4 patients failed screening. 18 patients were randomized and received treatment. 2 patients dropped out during their first treatment period (did not start the second treatment period). Hence, totally 34 treatment periods were started/32 were completed. The screening assessments occurred up to 27 days prior to baseline assessments.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Monitor, Data analyst, Subject

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 0.1 mg/day
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    ZP1848
    Investigational medicinal product code
    Other name
    glepaglutide
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    0.1 mg injected daily subcutaneously in abdomen or thighs for 3 weeks

    Arm title
    		 1 mg/day
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    ZP1848
    Investigational medicinal product code
    Other name
    glepaglutide
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1 mg injected daily subcutaneously in abdomen or thighs for 3 weeks

    Arm title
    		 10 mg/day
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    ZP1848
    Investigational medicinal product code
    Other name
    glepaglutide
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    10 mg injected daily subcutaneously in abdomen or thighs for 3 weeks

    Number of subjects in period 1
    		0.1 mg/day 1 mg/day 10 mg/day
    Started
    11
    11
    12
    Completed
    10
    11
    11
    Not completed
    1
    0
    1
         Consent withdrawn by subject
    1
    -
    -
         Adverse event, non-fatal
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall trial Total
    Number of subjects
    		 18 18
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 12 12
        From 65-84 years
    		 6 6
        85 years and over
    		 0 0
    Gender categorical
    Units: Subjects
        Female
    		 9 9
        Male
    		 9 9
    Subject analysis sets

    Subject analysis set title
    FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The full analysis set comprises all randomized patients delivering post-baseline efficacy data

    Subject analysis sets values
    		 FAS
    Number of subjects
    16
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
        Newborns (0-27 days)
    0
        Infants and toddlers (28 days-23 months)
    0
        Children (2-11 years)
    0
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    11
        From 65-84 years
    5
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    ( )
    Gender categorical
    Units: Subjects
        Female
    8
        Male
    8

    End points

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    End points reporting groups
    Reporting group title
    0.1 mg/day
    Reporting group description
    		 -

    Reporting group title
    1 mg/day
    Reporting group description
    		 -

    Reporting group title
    10 mg/day
    Reporting group description
    		 -

    Subject analysis set title
    FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The full analysis set comprises all randomized patients delivering post-baseline efficacy data

    Primary: Absolute change from baseline to the end of the 3-week treatment periods of wet weight output or diarrhea

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    End point title
    		 Absolute change from baseline to the end of the 3-week treatment periods of wet weight output or diarrhea
    End point description
    End point type
    Primary
    End point timeframe
    Change measured between baseline and end of the 3-week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: g per day
        least squares mean (confidence interval 95%)
    173 (-160 to 506)
    -592 (-913 to -272)
    -833 (-1152 to -515)
    Statistical analysis title
    		 Test 1 Effect in the pooled 10 and 1 mg dose group
    Statistical analysis description
    Effect in the pooled medium and high dose groups
    Comparison groups
    10 mg/day v 1 mg/day
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [1] - The primary endpoint was analyzed using a linear model having period (1,2) and treatment doses (0.1, 1 and 10.0 mg) as fixed effects and patient as random effect, adjusting for the baseline value within each dosing period, the total oral intake (solid and liquid combined in grams) and the PS volume. The model was analyzed using a mixed-effects analysis of covariance (ANCOVA).
    Statistical analysis title
    		 Test 2 Effect in the 10 mg dose
    Statistical analysis description
    Effect in the high dose group
    Comparison groups
    10 mg/day v 1 mg/day
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 other [2]
    P-value
    		 = 0.0002 [3]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [2] - The primary endpoint was analyzed using a linear model having period (1,2) and treatment doses (0.1, 1 and 10.0 mg) as fixed effects and patient as random effect, adjusting for the baseline value within each dosing period, the total oral intake (solid and liquid combined in grams) and the PS volume.The model was analyzed using a mixed-effects analysis of covariance (ANCOVA).
    [3] - The primary hypotheses were tested sequentially in a hierarchical testing procedure.
    Statistical analysis title
    		 Test 3 Effect in the 1 mg dose group
    Statistical analysis description
    Effect of the medium dose
    Comparison groups
    1 mg/day v 0.1 mg/day
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    		 other [4]
    P-value
    		 = 0.0021 [5]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [4] - The primary endpoint was analyzed using a linear model having period (1,2) and treatment doses (0.1, 1 and 10.0 mg) as fixed effects and patient as random effect, adjusting for the baseline value within each dosing period, the total oral intake (solid and liquid combined in grams) and the PS volume. The model was analyzed using a mixed-effects analysis of covariance (ANCOVA).
    [5] - The primary hypotheses were tested sequentially in a hierarchical testing procedure.
    Statistical analysis title
    		 Test 4 Effect in the 0.1 mg dose group
    Comparison groups
    0.1 mg/day v 1 mg/day
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    		 other [6]
    P-value
    		 = 0.2743 [7]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [6] - The primary endpoint was analyzed using a linear model having period (1,2) and treatment doses (0.1, 1 and 10.0 mg) as fixed effects and patient as random effect, adjusting for the baseline value within each dosing period, the total oral intake (solid and liquid combined in grams) and the PS volume. The model was analyzed using a mixed-effects analysis of covariance (ANCOVA).
    [7] - The primary hypotheses were tested sequentially in a hierarchical testing procedure. The test procedure stopped at test 4

    Secondary: Relative change from baseline to the end of treatment of wet weight of ostomy output or diarrhea

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    End point title
    		 Relative change from baseline to the end of treatment of wet weight of ostomy output or diarrhea
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: percent
        least squares mean (confidence interval 95%)
    10 (-3 to 22)
    -23 (-35 to -11)
    -30 (-42 to -19)
    No statistical analyses for this end point

    Secondary: Absolute change from baseline to the end of treatment of urine weight

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    End point title
    		 Absolute change from baseline to the end of treatment of urine weight
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: g per day
        least squares mean (confidence interval 95%)
    90 (-208 to 389)
    530 (245 to 816)
    368 (82 to 654)
    No statistical analyses for this end point

    Secondary: Relative change from baseline to the end of treatment of urine weight

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    End point title
    		 Relative change from baseline to the end of treatment of urine weight
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: percent
        least squares mean (confidence interval 95%)
    11 (-11 to 34)
    40 (18 to 61)
    32 (11 to 54)
    No statistical analyses for this end point

    Secondary: Absolute change from baseline to the end of treatment of wet weight absorption (measured by oral intake minus fecal excretion)

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    End point title
    		 Absolute change from baseline to the end of treatment of wet weight absorption (measured by oral intake minus fecal excretion)
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: g per day
        least squares mean (confidence interval 95%)
    -211 (-487 to 64)
    650 (385 to 914)
    786 (523 to 1049)
    No statistical analyses for this end point

    Secondary: Relative change from baseline to the end of treatment of wet weight absorption (measured by oral intake minus fecal excretion)

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    End point title
    		 Relative change from baseline to the end of treatment of wet weight absorption (measured by oral intake minus fecal excretion)
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: percent
        least squares mean (confidence interval 95%)
    -34 (-228 to 159)
    21 (-165 to 207)
    87 (-98 to 272)
    No statistical analyses for this end point

    Secondary: Absolute change from baseline to the end of treatment of urine weight minus oral intake

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    End point title
    		 Absolute change from baseline to the end of treatment of urine weight minus oral intake
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: g per day
        least squares mean (confidence interval 95%)
    118 (-244 to 479)
    487 (140 to 833)
    411 (65 to 758)
    No statistical analyses for this end point

    Secondary: Relative change from baseline to the end of treatment of urine weight minus oral intake

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    End point title
    		 Relative change from baseline to the end of treatment of urine weight minus oral intake
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: percent
        least squares mean (confidence interval 95%)
    -4 (-39 to 31)
    -45 (-79 to -11)
    -50 (-84 to -16)
    No statistical analyses for this end point

    Secondary: Absolute change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of sodium

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    End point title
    		 Absolute change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of sodium
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: mmol per day
        least squares mean (confidence interval 95%)
    -17 (-58 to 24)
    47 (7 to 86)
    40 (1 to 80)
    No statistical analyses for this end point

    Secondary: Absolute change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of magnesium

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    End point title
    		 Absolute change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of magnesium
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: mmol per day
        least squares mean (confidence interval 95%)
    -3 (-6 to -1)
    1 (-2 to 3)
    -1 (-4 to 1)
    No statistical analyses for this end point

    Secondary: Absolute change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of calcium

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    End point title
    		 Absolute change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of calcium
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: mmol per day
        least squares mean (confidence interval 95%)
    -5 (-9 to -1)
    0 (-4 to 4)
    0 (-4 to 4)
    No statistical analyses for this end point

    Secondary: Absolute change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of potassium

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    End point title
    		 Absolute change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of potassium
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: mmol per day
        least squares mean (confidence interval 95%)
    0 (-16 to 17)
    16 (0 to 31)
    10 (-5 to 25)
    No statistical analyses for this end point

    Secondary: Relative change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of sodium

    		 Close Top of page
    End point title
    		 Relative change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of sodium
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: percent
        least squares mean (confidence interval 95%)
    13 (-235 to 260)
    60 (-176 to 295)
    131 (-102 to 364)
    No statistical analyses for this end point

    Secondary: Relative change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of magnesium

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    End point title
    		 Relative change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of magnesium
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: percent
        least squares mean (confidence interval 95%)
    128 (-200 to 457)
    -90 (-403 to 223)
    -109 (-418 to 200)
    No statistical analyses for this end point

    Secondary: Relative change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of calcium

    		 Close Top of page
    End point title
    		 Relative change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of calcium
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: percent
        least squares mean (confidence interval 95%)
    -242 (-453 to -30)
    -17 (-220 to 186)
    74 (-127 to 276)
    No statistical analyses for this end point

    Secondary: Relative change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of potassium

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    End point title
    		 Relative change from baseline to the end of treatment of the intestinal absorption (oral intake minus fecal excretion) of potassium
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: percent
        least squares mean (confidence interval 95%)
    -90 (-326 to 146)
    -80 (-306 to 146)
    57 (-164 to 279)
    No statistical analyses for this end point

    Secondary: Absolute change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of energy assessed by bomb calorimetry

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    End point title
    		 Absolute change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of energy assessed by bomb calorimetry
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: kJ per day
        least squares mean (confidence interval 95%)
    -377 (-1234 to 481)
    435 (-393 to 1263)
    588 (-227 to 1403)
    No statistical analyses for this end point

    Secondary: Relative change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of energy assessed by bomb calorimetry

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    End point title
    		 Relative change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of energy assessed by bomb calorimetry
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: percent
        least squares mean (confidence interval 95%)
    6 (-66 to 78)
    24 (-46 to 94)
    21 (-48 to 90)
    No statistical analyses for this end point

    Secondary: Absolute change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of lipids

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    End point title
    		 Absolute change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of lipids
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: kJ per day
        least squares mean (confidence interval 95%)
    -330 (-864 to 205)
    516 (3 to 1029)
    103 (-407 to 612)
    No statistical analyses for this end point

    Secondary: Relative change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of lipids

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    End point title
    		 Relative change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of lipids
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: percent
        least squares mean (confidence interval 95%)
    -31 (-72 to 10)
    48 (9 to 87)
    0 (-38 to 39)
    No statistical analyses for this end point

    Secondary: Absolute change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of nitrogen (a marker of proteins)

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    End point title
    		 Absolute change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of nitrogen (a marker of proteins)
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: g per day
        least squares mean (confidence interval 95%)
    -1 (-3 to 1)
    2 (0 to 3)
    1 (-1 to 2)
    No statistical analyses for this end point

    Secondary: Relative change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of nitrogen (a marker of proteins)

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    End point title
    		 Relative change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of nitrogen (a marker of proteins)
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: percent
        least squares mean (confidence interval 95%)
    -83 (-220 to 55)
    -63 (-196 to 70)
    -42 (-173 to 89)
    No statistical analyses for this end point

    Secondary: Absolute change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of carbohydrates

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    End point title
    		 Absolute change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of carbohydrates
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: kJ per day
        least squares mean (confidence interval 95%)
    -11 (-399 to 377)
    368 (-6 to 743)
    336 (-31 to 703)
    No statistical analyses for this end point

    Secondary: Mean score change in mental component score (MCS)

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    End point title
    		 Mean score change in mental component score (MCS)
    End point description
    SF-36v2 1 week-recall version
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: Score
        arithmetic mean (standard deviation)
    2.7 ( 9.5 )
    1.8 ( 7.0 )
    -4.8 ( 13.7 )
    No statistical analyses for this end point

    Secondary: Relative change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of carbohydrates

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    End point title
    		 Relative change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of carbohydrates
    End point description
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: percent
        least squares mean (confidence interval 95%)
    -2 (-20 to 17)
    18 (-1 to 36)
    21 (3 to 39)
    No statistical analyses for this end point

    Secondary: Mean score change in physical component score (PCS)

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    End point title
    		 Mean score change in physical component score (PCS)
    End point description
    SF-36v2 1-week recall version used
    End point type
    Secondary
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: Score
        arithmetic mean (standard deviation)
    1.3 ( 6.1 )
    2.5 ( 5.6 )
    -2.5 ( 6.8 )
    No statistical analyses for this end point

    Other pre-specified: Absolute change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of energy calculated as the sum of the energy content

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    End point title
    		 Absolute change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of energy calculated as the sum of the energy content
    End point description
    Energy was calculated as the sum of the energy content from lipids, nitrogen (as a marker for proteins) and carbohydrates and used as an approximation
    End point type
    Other pre-specified
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    10
    10
    Units: kJ per day
        least squares mean (confidence interval 95%)
    -491 (-1402 to 419)
    1099 (223 to 1976)
    544 (-317 to 1406)
    No statistical analyses for this end point

    Other pre-specified: Relative change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of energy calculated as the sum of the energy content

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    End point title
    		 Relative change from baseline to the end of treatment of intestinal absorption (oral intake minus fecal excretion) of energy calculated as the sum of the energy content
    End point description
    Energy was calculated as the sum of the energy content from lipids, nitrogen (as a marker for proteins) and carbohydrates and used as an approximation
    End point type
    Other pre-specified
    End point timeframe
    Change measured between baseline and end of the 3 week treatment period
    End point values
    		 0.1 mg/day 1 mg/day 10 mg/day
    Number of subjects analysed
    10
    11
    11
    Units: percent
        least squares mean (confidence interval 95%)
    -10 (-33 to 13)
    25 (3 to 47)
    11 (-11 to 34)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse event reporting was done from informed consent was signed and until the follow up visit
    Adverse event reporting additional description
    Due to the size of the trial population any event reported would result in >5% frequency
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    0.1 mg/day
    Reporting group description
    		 -

    Reporting group title
    Safety analysis set
    Reporting group description
    		 -

    Reporting group title
    10 mg/day
    Reporting group description
    		 -

    Reporting group title
    1 mg/day
    Reporting group description
    		 -

    Serious adverse events
    		 0.1 mg/day Safety analysis set 10 mg/day 1 mg/day
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 12 (16.67%)
    7 / 18 (38.89%)
    6 / 12 (50.00%)
    0 / 12 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Injury, poisoning and procedural complications
    Stoma obstruction
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Catheter removal
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mechanical ileus
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Device related sepsis
    Additional description: Cross-over design.One patient in group 0.1 mg is the same patient as in the 10 mg group, hence this patient experienced 2 events both of them assessed not related.
         subjects affected / exposed
    2 / 12 (16.67%)
    2 / 18 (11.11%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 12 (8.33%)
    2 / 18 (11.11%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 0.1 mg/day Safety analysis set 10 mg/day 1 mg/day
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 12 (91.67%)
    18 / 18 (100.00%)
    12 / 12 (100.00%)
    11 / 12 (91.67%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    0 / 12 (0.00%)
    3 / 18 (16.67%)
    3 / 12 (25.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    4
    4
    0
    Peripheral coldness
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Hypertension
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    1
    1
    Surgical and medical procedures
    Enterostomy
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    General disorders and administration site conditions
    Injection site reaction
    Additional description: This was a cross-over design, hence subjects may appear in 2 groups. Injection site reactions (ISRs) were captured separately from AEs. ISRs were recorded on a symptom level: itching, redness, induration/infiltration, pain, edema and other
         subjects affected / exposed
    2 / 12 (16.67%)
    11 / 18 (61.11%)
    8 / 12 (66.67%)
    7 / 12 (58.33%)
         occurrences all number
    11
    498
    327
    160
    Oedema peripheral
         subjects affected / exposed
    2 / 12 (16.67%)
    10 / 18 (55.56%)
    5 / 12 (41.67%)
    6 / 12 (50.00%)
         occurrences all number
    3
    21
    9
    9
    Fatigue
         subjects affected / exposed
    1 / 12 (8.33%)
    6 / 18 (33.33%)
    4 / 12 (33.33%)
    2 / 12 (16.67%)
         occurrences all number
    1
    7
    4
    2
    Malaise
         subjects affected / exposed
    2 / 12 (16.67%)
    3 / 18 (16.67%)
    2 / 12 (16.67%)
    0 / 12 (0.00%)
         occurrences all number
    3
    5
    2
    0
    Thirst
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    2
    0
    Impaired healing
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Device occlusion
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Chills
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Reproductive system and breast disorders
    Oedema genital
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 18 (11.11%)
    2 / 12 (16.67%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    2
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 12 (8.33%)
    4 / 18 (22.22%)
    2 / 12 (16.67%)
    1 / 12 (8.33%)
         occurrences all number
    1
    4
    2
    1
    Oropharyngeal pain
         subjects affected / exposed
    2 / 12 (16.67%)
    2 / 18 (11.11%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    2
    3
    1
    0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Psychiatric disorders
    Restlessness
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 18 (11.11%)
    0 / 12 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    2
    0
    2
    Irritability
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Insomnia
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Depressed mood
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Investigations
    Gastrointestinal stoma output increased
         subjects affected / exposed
    0 / 12 (0.00%)
    3 / 18 (16.67%)
    3 / 12 (25.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    4
    4
    0
    Weight increased
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Weight decreased
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Urine output increased
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Serum ferritin decreased
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0
    International normalised ratio abnormal
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Haemoglobin decreased
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Gastrointestinal stoma output decreased
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Injury, poisoning and procedural complications
    Stoma complication
         subjects affected / exposed
    2 / 12 (16.67%)
    13 / 18 (72.22%)
    10 / 12 (83.33%)
    6 / 12 (50.00%)
         occurrences all number
    2
    20
    12
    6
    Gastrointestinal stoma complication
         subjects affected / exposed
    3 / 12 (25.00%)
    13 / 18 (72.22%)
    10 / 12 (83.33%)
    6 / 12 (50.00%)
         occurrences all number
    3
    19
    10
    6
    Stoma obstruction
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Procedural pain
         subjects affected / exposed
    2 / 12 (16.67%)
    3 / 18 (16.67%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    2
    3
    1
    0
    Stoma site haemorrhage
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Stoma site oedema
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Stoma site erythema
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Ligament sprain
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Scar
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Excoriation
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Accidental overdose
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    1 / 12 (8.33%)
    3 / 18 (16.67%)
    2 / 12 (16.67%)
    1 / 12 (8.33%)
         occurrences all number
    1
    5
    3
    1
    Palpitations
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    2
    3
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 12 (8.33%)
    3 / 18 (16.67%)
    2 / 12 (16.67%)
    1 / 12 (8.33%)
         occurrences all number
    2
    13
    5
    6
    Dizziness
         subjects affected / exposed
    2 / 12 (16.67%)
    5 / 18 (27.78%)
    3 / 12 (25.00%)
    0 / 12 (0.00%)
         occurrences all number
    4
    8
    4
    0
    Migraine
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 18 (11.11%)
    1 / 12 (8.33%)
    2 / 12 (16.67%)
         occurrences all number
    0
    3
    1
    2
    Paraesthesia
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    2
    0
    2
    Restless legs syndrome
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Hypoaesthesia
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Eye disorders
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    4 / 12 (33.33%)
    8 / 18 (44.44%)
    6 / 12 (50.00%)
    1 / 12 (8.33%)
         occurrences all number
    6
    21
    14
    1
    Abdominal pain
         subjects affected / exposed
    5 / 12 (41.67%)
    7 / 18 (38.89%)
    2 / 12 (16.67%)
    2 / 12 (16.67%)
         occurrences all number
    12
    17
    3
    2
    Gastrointestinal sounds abnormal
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    10
    11
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    2 / 12 (16.67%)
    4 / 18 (22.22%)
    3 / 12 (25.00%)
    1 / 12 (8.33%)
         occurrences all number
    2
    8
    5
    1
    Vomiting
         subjects affected / exposed
    3 / 12 (25.00%)
    5 / 18 (27.78%)
    3 / 12 (25.00%)
    1 / 12 (8.33%)
         occurrences all number
    3
    8
    4
    1
    Abdominal distension
         subjects affected / exposed
    3 / 12 (25.00%)
    5 / 18 (27.78%)
    2 / 12 (16.67%)
    2 / 12 (16.67%)
         occurrences all number
    3
    7
    2
    2
    Dry mouth
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 18 (11.11%)
    2 / 12 (16.67%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    2
    0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Abdominal pain lower
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Abdominal tenderness
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Abdominal discomfort
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Renal and urinary disorders
    Polyuria
         subjects affected / exposed
    1 / 12 (8.33%)
    6 / 18 (33.33%)
    3 / 12 (25.00%)
    3 / 12 (25.00%)
         occurrences all number
    1
    7
    3
    3
    Pollakiuria
         subjects affected / exposed
    0 / 12 (0.00%)
    2 / 18 (11.11%)
    2 / 12 (16.67%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    2
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 12 (8.33%)
    3 / 18 (16.67%)
    1 / 12 (8.33%)
    2 / 12 (16.67%)
         occurrences all number
    1
    4
    1
    2
    Myalgia
         subjects affected / exposed
    1 / 12 (8.33%)
    2 / 18 (11.11%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    2
    1
    0
    Muscular weakness
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Fistula discharge
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    1 / 12 (8.33%)
    3 / 18 (16.67%)
    2 / 12 (16.67%)
    1 / 12 (8.33%)
         occurrences all number
    1
    5
    2
    2
    Influenza
         subjects affected / exposed
    1 / 12 (8.33%)
    3 / 18 (16.67%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    1
    3
    1
    1
    Infection
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 12 (16.67%)
    2 / 18 (11.11%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Tooth infection
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 12 (8.33%)
    4 / 18 (22.22%)
    2 / 12 (16.67%)
    1 / 12 (8.33%)
         occurrences all number
    1
    4
    2
    1
    Iron deficiency
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    Hypokalaemia
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 18 (5.56%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Abnormal weight gain
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Vitamin D deficiency
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 18 (5.56%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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