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    Clinical Trial Results:
    An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of A4250 in Children with Progressive Familial Intrahepatic Cholestasis Types 1 and 2 (PEDFIC 2)

    Summary
    EudraCT number
    		 2017-002325-38
    Trial protocol
    		 DE   FR   SE   GB   NL   BE   ES   IT   PL  
    Global end of trial date

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Oct 2025
    First version publication date
    23 Oct 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    A4250-008
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03659916
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Ipsen Pharma
    Sponsor organisation address
    Arvid Wallgrens backe 20, Gӧteborg, Sweden, 41346
    Public contact
    Medical Director, Ipsen Pharma, clinical.trials@ipsen.com
    Scientific contact
    Medical Director, Ipsen Pharma, clinical.trials@ipsen.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-002054-PIP01-16
    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
    Interim
    Date of interim/final analysis
    15 Feb 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Feb 2024
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to demonstrate a sustained effect of odevixibat on serum bile acid (s-BAs) and pruritus in children with progressive familial intrahepatic cholestasis (PFIC) Types 1 and 2 and to evaluate the effect of odevixibat on serum bile acids and pruritus in participants with PFIC who either did not meet eligibility criteria for Study A4250-005 (2017-002338-21) or who did meet the eligibility criteria for Study A4250-005 (2017-002338-21) after recruitment of Study A4250-005 (2017-002338-21) had been completed.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles that have their origins in the Declaration of Helsinki and with Good Clinical Practice guidelines as denoted in the International Council for Harmonization E6 requirements. These practices include Independent Ethics Committee/Institutional Review Board procedures, informed consent, protocol adherence, administrative documents, drug-supply accountability, data collection, participant records (source documents), adverse event (AE) recording and reporting, inspection and audit preparation, and record retention. All participant identities were kept confidential.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Sep 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    France: 14
    Country: Number of subjects enrolled
    Germany: 11
    Country: Number of subjects enrolled
    Israel: 6
    Country: Number of subjects enrolled
    Italy: 4
    Country: Number of subjects enrolled
    Netherlands: 11
    Country: Number of subjects enrolled
    Poland: 5
    Country: Number of subjects enrolled
    Saudi Arabia: 5
    Country: Number of subjects enrolled
    Türkiye: 21
    Country: Number of subjects enrolled
    United Kingdom: 15
    Country: Number of subjects enrolled
    United States: 17
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Belgium: 2
    Worldwide total number of subjects
    116
    EEA total number of subjects
    47
    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)
    39
    Children (2-11 years)
    56
    Adolescents (12-17 years)
    14
    Adults (18-64 years)
    7
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This Phase III, open-label extension was conducted in participants with PFIC at 43 centers in 13 countries. The first participant was enrolled on 28 September 2018 and data cut-off (DCO) date was 15 February 2024.

    Pre-assignment
    Screening details
    		 This study consisted of a 72-week treatment period and a 4-week follow-up period. An optional extension period for continued treatment until commercial availability of odevixibat followed the 72-week treatment period. A total of 116 participants were enrolled in the study. Results are presented up to DCO of 15 February 2024.

    Period 1
    Period 1 title
    Treatment Period (72 Weeks)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1: Placebo/Odevixibat
    Arm description
    		 Participants who previously received placebo in study A4250-005 for 24 weeks received odevixibat capsule orally at a dose of 120 microgram/kilogram/day (mcg/kg/day) for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Odevixibat
    Investigational medicinal product code
    A4250
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    120 mcg/kg/day odevixibat was administered once daily for 72 weeks, if participant was unable to swallow the capsules, capsules were opened and the content sprinkled on soft foods.

    Arm title
    		 Cohort 1: Odevixibat/Odevixibat
    Arm description
    		 Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Odevixibat
    Investigational medicinal product code
    A4250
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    120 mcg/kg/day odevixibat was administered once daily for 72 weeks, if participant was unable to swallow the capsules, capsules were opened and the content sprinkled on soft foods.

    Arm title
    		 Cohort 2: Odevixibat
    Arm description
    		 Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 or were eligible for enrolment in A4250-005 after recruitment was complete received odevixibat at a dose of 120 mcg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Odevixibat
    Investigational medicinal product code
    A4250
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Starting with 40 mcg/kg/day and escalate to 120 mcg/kg/day odevixibat was administered once daily for 72 weeks, if participant was unable to swallow the capsules, capsules were opened and the content sprinkled on soft foods.

    Number of subjects in period 1
    		Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Started
    19
    37
    60
    Completed
    15
    28
    40
    Not completed
    4
    9
    20
         Consent withdrawn by subject
    1
    4
    4
         Physician decision
    -
    1
    -
         Adverse event, non-fatal
    2
    1
    6
         Unspecified
    1
    3
    9
         Lost to follow-up
    -
    -
    1
    Period 2
    Period 2 title
    Optional Extension Treatment (176 Weeks)
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1: Placebo/Odevixibat
    Arm description
    		 Participants who previously received placebo in study A4250-005 for 24 weeks received odevixibat capsule orally at a dose of 120 microgram/kilogram/day (mcg/kg/day) for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues. Participants continued receiving study treatment until commercial availability of odevixibat.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Odevixibat
    Investigational medicinal product code
    A4250
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    120 mcg/kg/day odevixibat was administered once daily for 72 weeks, if participant was unable to swallow the capsules, capsules were opened and the content sprinkled on soft foods.

    Arm title
    		 Cohort 1: Odevixibat/Odevixibat
    Arm description
    		 Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues. Participants continued receiving study treatment until commercial availability of odevixibat.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Odevixibat
    Investigational medicinal product code
    A4250
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    120 mcg/kg/day odevixibat was administered once daily for 72 weeks, if participant was unable to swallow the capsules, capsules were opened and the content sprinkled on soft foods.

    Arm title
    		 Cohort 2: Odevixibat
    Arm description
    		 Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 or were eligible for enrolment in A4250-005 after recruitment was complete received odevixibat at a dose of 120 mcg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks. Participants continued receiving study treatment until commercial availability of odevixibat.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Odevixibat
    Investigational medicinal product code
    A4250
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Starting with 40 mcg/kg/day and escalate to 120 mcg/kg/day odevixibat was administered once daily for 72 weeks, if participant was unable to swallow the capsules, capsules were opened and the content sprinkled on soft foods.

    Number of subjects in period 2 [1]
    		Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Started
    14
    27
    33
    Completed
    0
    0
    0
    Not completed
    14
    27
    33
         Consent withdrawn by subject
    -
    1
    -
         Physician decision
    -
    -
    1
         Adverse event, non-fatal
    -
    -
    1
         Transition to Commercial Drug
    5
    17
    11
         Unspecified
    4
    -
    3
         Ongoing Optional Extension Period
    5
    9
    17
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: One participant each from Cohort 1: Placebo/Odevixibat and Cohort 1: Odevixibat/Odevixibat, and 7 participants from Cohort 2: Odevixibat did not enter optional extension treatment period.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: Placebo/Odevixibat
    Reporting group description
    		 Participants who previously received placebo in study A4250-005 for 24 weeks received odevixibat capsule orally at a dose of 120 microgram/kilogram/day (mcg/kg/day) for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.

    Reporting group title
    Cohort 1: Odevixibat/Odevixibat
    Reporting group description
    		 Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.

    Reporting group title
    Cohort 2: Odevixibat
    Reporting group description
    		 Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 or were eligible for enrolment in A4250-005 after recruitment was complete received odevixibat at a dose of 120 mcg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.

    Reporting group values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat Total
    Number of subjects
    		 19 37 60 116
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 4.34 ( 3.962 ) 4.75 ( 3.711 ) 7.62 ( 7.208 ) -
    Gender categorical
    Units: Subjects
        Female
    		 7 20 25 52
        Male
    		 12 17 35 64
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 1 0 2 3
        Not Hispanic or Latino
    		 18 37 50 105
        Unknown or Not Reported
    		 0 0 8 8
    Race
    Units: Subjects
        White
    		 16 31 53 100
        Black/African American
    		 0 1 2 3
        Asian
    		 2 3 2 7
        Other
    		 1 2 3 6

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1: Placebo/Odevixibat
    Reporting group description
    		 Participants who previously received placebo in study A4250-005 for 24 weeks received odevixibat capsule orally at a dose of 120 microgram/kilogram/day (mcg/kg/day) for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.

    Reporting group title
    Cohort 1: Odevixibat/Odevixibat
    Reporting group description
    		 Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.

    Reporting group title
    Cohort 2: Odevixibat
    Reporting group description
    		 Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 or were eligible for enrolment in A4250-005 after recruitment was complete received odevixibat at a dose of 120 mcg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
    Reporting group title
    Cohort 1: Placebo/Odevixibat
    Reporting group description
    		 Participants who previously received placebo in study A4250-005 for 24 weeks received odevixibat capsule orally at a dose of 120 microgram/kilogram/day (mcg/kg/day) for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues. Participants continued receiving study treatment until commercial availability of odevixibat.

    Reporting group title
    Cohort 1: Odevixibat/Odevixibat
    Reporting group description
    		 Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues. Participants continued receiving study treatment until commercial availability of odevixibat.

    Reporting group title
    Cohort 2: Odevixibat
    Reporting group description
    		 Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 or were eligible for enrolment in A4250-005 after recruitment was complete received odevixibat at a dose of 120 mcg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks. Participants continued receiving study treatment until commercial availability of odevixibat.

    Primary: Change From Baseline in Serum Bile Acids

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    End point title
    		 Change From Baseline in Serum Bile Acids [1]
    End point description
    Blood samples for analysis of fasting total s-BAs were drawn at specified timepoints. Participants were to fast (water intake only) for at least 4 hours prior to the collection of samples for s-BAs. Exceptions were made for infants <12 months of age if unable to fast for the full 4 hours. Baseline for Cohort 1 placebo/odevixibat and Cohort 2 groups was defined as the average of last 2 values before the first dose of study treatment in the study. Baseline for Cohort 1 odevixibat/odevixibat group was defined as average of last 2 values before the first dose of study treatment in study A4250-005 (2017-002338-21). The Full Analysis Set (FAS) consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at specified timepoints are reported.
    End point type
    Primary
    End point timeframe
    Baseline and Week 72
    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 additional statistical analysis was prespecified for this endpoint.
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    15
    28
    43
    Units: micromole per liter (mcmol/L)
        arithmetic mean (standard deviation)
    -104.00 ( 167.318 )
    -139.84 ( 172.070 )
    -57.97 ( 137.990 )
    No statistical analyses for this end point

    Primary: Proportion of Positive Pruritus Assessments at the Participant Level Over 72-Week Using the Albireo Observer-Reported Outcome (ObsRo) Instrument

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    End point title
    		 Proportion of Positive Pruritus Assessments at the Participant Level Over 72-Week Using the Albireo Observer-Reported Outcome (ObsRo) Instrument [2]
    End point description
    A positive pruritus assessment was defined as a scratching score of <=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The proportion of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant. The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at Baseline and Week 72 are reported.
    End point type
    Primary
    End point timeframe
    Baseline and Week 72
    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 additional statistical analysis was prespecified for this endpoint.
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    12
    26
    31
    Units: proportion of pruritus-participant-level
        arithmetic mean (standard deviation)
    55.20 ( 38.733 )
    38.58 ( 34.877 )
    77.28 ( 28.084 )
    No statistical analyses for this end point

    Secondary: Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument From Weeks 0-4, 0-12, 0-22, 0-24, 0-36, 0-46, 0-48, 0-60, and 0-70

    		 Close Top of page
    End point title
    		 Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument From Weeks 0-4, 0-12, 0-22, 0-24, 0-36, 0-46, 0-48, 0-60, and 0-70
    End point description
    A positive pruritus assessment was defined as a scratching score of <=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The proportion of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant. The FAS consisted of all participants who had received at least 1 dose of the study treatment. Here, ‘n’ = number of participants analyzed at specific time point.
    End point type
    Secondary
    End point timeframe
    Weeks 0-4, Weeks 0-12, Weeks 0-22, Weeks 0-24, Weeks 0-36, Weeks 0-46, Weeks 0-48, Weeks 0-60, and Weeks 0-70
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    19
    37
    53
    Units: proportion of pruritus-participant-level
    arithmetic mean (standard deviation)
        Weeks 0-4 (n = 19,37,53)
    45.72 ( 34.300 )
    23.64 ( 27.005 )
    60.14 ( 33.985 )
        Weeks 0-12 (n = 19,37,50)
    51.05 ( 37.670 )
    27.34 ( 28.687 )
    67.63 ( 33.645 )
        Weeks 0-22 (n = 17,36,48)
    56.01 ( 38.537 )
    31.09 ( 31.859 )
    70.05 ( 33.858 )
        Weeks 0-24 (n = 17,36,45)
    56.00 ( 38.331 )
    31.45 ( 32.324 )
    68.55 ( 34.116 )
        Weeks 0-36 (n = 16,31,43)
    54.63 ( 38.243 )
    33.66 ( 33.704 )
    69.97 ( 33.872 )
        Weeks 0-46 (n = 14,28,37)
    60.41 ( 39.491 )
    34.70 ( 35.593 )
    75.46 ( 29.801 )
        Weeks 0-48 (n = 14,29,41)
    61.61 ( 39.936 )
    33.56 ( 35.668 )
    74.79 ( 30.843 )
        Weeks 0-60 (n = 13,31,35)
    57.80 ( 38.873 )
    33.18 ( 34.935 )
    74.89 ( 30.434 )
        Weeks 0-70 (n = 13,22,29)
    58.18 ( 38.766 )
    40.59 ( 34.928 )
    75.60 ( 29.514 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Serum Bile Acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72

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    End point title
    		 Change From Baseline in Serum Bile Acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72
    End point description
    Blood samples for analysis of fasting total s-BAs were drawn at specified timepoints. Participants were to fast (water intake only) for at least 4 hours prior to the collection of samples for s-BAs. Exceptions were made for infants <12 months of age if unable to fast for the full 4 hours. Baseline for Cohort 1 placebo/odevixibat, and Cohort 2 groups was defined as the average of last 2 values before the first dose of study treatment in the study. Baseline for Cohort 1 odevixibat/odevixibat group was defined as average of last 2 values before the first dose of study treatment in study A4250-005 (2017-002338-21). The FAS consisted of all participants who had received at least 1 dose of the study treatment. Here, ‘n’ = number of participants analyzed at specific time point.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    18
    35
    54
    Units: mcmol/L
    arithmetic mean (standard deviation)
        Week 4 (n = 17,34,53)
    -115.76 ( 151.014 )
    -118.78 ( 172.353 )
    -76.92 ( 94.662 )
        Week 12 (n = 18,35,54)
    -98.39 ( 149.118 )
    -109.90 ( 176.472 )
    -65.01 ( 136.303 )
        Week 22 (n = 15,25,38)
    -138.67 ( 147.069 )
    -125.18 ( 165.395 )
    -73.24 ( 126.319 )
        Week 24 (n = 14,30,50)
    -112.96 ( 175.107 )
    -133.52 ( 191.550 )
    -65.37 ( 128.580 )
        Week 36 (n = 17,29,49)
    -129.41 ( 179.357 )
    -114.19 ( 200.789 )
    -60.90 ( 128.520 )
        Week 46 (n = 11,25,38)
    -166.05 ( 195.963 )
    -156.88 ( 157.687 )
    -63.80 ( 128.199 )
        Week 48 (n = 13,26,45)
    -145.65 ( 177.520 )
    -121.73 ( 114.214 )
    -57.90 ( 143.238 )
        Week 60 (n = 13,27,47)
    -86.46 ( 159.360 )
    -133.17 ( 162.933 )
    -43.31 ( 125.923 )
        Week 70 (n = 10,23,33)
    -149.02 ( 186.918 )
    -146.43 ( 196.501 )
    -50.08 ( 140.232 )
        Week 72 (n = 13,26,40)
    -101.31 ( 169.631 )
    -123.44 ( 143.220 )
    -52.39 ( 156.473 )
    No statistical analyses for this end point

    Secondary: Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument From Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 44-46, 47-48, 58-60, 68-70, 71-72, 73-76

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    End point title
    		 Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument From Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 44-46, 47-48, 58-60, 68-70, 71-72, 73-76
    End point description
    A positive pruritus assessment was defined as a scratching score of <=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The proportion of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant. The FAS consisted of all participants who had received at least 1 dose of the study treatment. Here, ‘n’ = number of participants analyzed at specific time point.
    End point type
    Secondary
    End point timeframe
    Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 44-46, 47-48, 58-60, 68-70, 71-72, 73-76
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    19
    37
    53
    Units: proportion of pruritus-participant-level
    arithmetic mean (standard deviation)
        Weeks 1-4 (n = 19,37,53)
    45.72 ( 34.300 )
    23.64 ( 27.005 )
    60.14 ( 33.985 )
        Weeks 5-8 (n = 19,37,51)
    53.75 ( 39.894 )
    28.76 ( 32.349 )
    71.14 ( 34.866 )
        Weeks 9-12 (n = 19,37,50)
    54.01 ( 41.345 )
    29.64 ( 35.594 )
    71.03 ( 36.961 )
        Weeks 13-16 (n = 18,37,50)
    57.47 ( 42.420 )
    31.78 ( 36.364 )
    72.19 ( 39.221 )
        Weeks 17-20 (n = 18,36,48)
    55.28 ( 41.441 )
    36.15 ( 38.564 )
    73.95 ( 38.051 )
        Weeks 21-24 (n = 17,36,45)
    55.62 ( 42.927 )
    35.83 ( 40.132 )
    73.11 ( 37.875 )
        Weeks 34-36 (n = 16,31,43)
    58.24 ( 41.117 )
    32.79 ( 39.066 )
    72.39 ( 35.581 )
        Weeks 44-46 (n = 14,28,37)
    67.33 ( 39.242 )
    38.40 ( 43.144 )
    77.11 ( 31.712 )
        Weeks 47-48 (n = 14,29,41)
    67.31 ( 43.702 )
    34.71 ( 42.594 )
    71.86 ( 39.020 )
        Weeks 58-60 (n = 13,31,35)
    65.82 ( 40.745 )
    44.22 ( 43.534 )
    72.31 ( 38.008 )
        Weeks 68-70 (n = 13,22,29)
    62.43 ( 40.321 )
    56.79 ( 42.935 )
    69.40 ( 39.034 )
        Weeks 71-72 (n = 12,26,31)
    57.65 ( 39.797 )
    55.75 ( 45.076 )
    72.26 ( 38.680 )
        Weeks 73-76 (n = 3,8,9)
    41.59 ( 39.923 )
    63.48 ( 29.003 )
    69.23 ( 33.797 )
    No statistical analyses for this end point

    Secondary: Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score)

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    End point title
    		 Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score)
    End point description
    A positive pruritus assessment was defined as a scratching score of <=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The proportion of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant. AM score represents night-time itching/scratching and sleep disturbance. The FAS consisted of all participants who had received at least 1 dose of the study treatment. Here, ‘n’ = number of participants analyzed at specific time point.
    End point type
    Secondary
    End point timeframe
    Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 44-46, 47-48, 58-60, 68-70, 71-72, and 73-76
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    19
    36
    53
    Units: proportion of pruritus-participant-level
    arithmetic mean (standard deviation)
        Weeks 1-4 (n = 19,36,53)
    42.38 ( 36.177 )
    23.72 ( 29.373 )
    58.19 ( 36.799 )
        Weeks 5-8 (n = 19,36,51)
    48.16 ( 42.655 )
    27.70 ( 34.144 )
    69.00 ( 38.199 )
        Weeks 9-12 (n = 19,36,49)
    50.57 ( 42.880 )
    28.41 ( 37.802 )
    68.96 ( 38.876 )
        Weeks 13-16 (n = 18,36,48)
    53.47 ( 43.689 )
    31.70 ( 38.438 )
    69.03 ( 41.902 )
        Weeks 17-20 (n = 18,36,47)
    53.94 ( 42.837 )
    35.37 ( 40.673 )
    71.30 ( 40.934 )
        Weeks 21-24 (n = 17,36,45)
    55.52 ( 44.798 )
    35.15 ( 41.940 )
    69.63 ( 40.353 )
        Weeks 34-36 (n = 16,29,43)
    57.49 ( 43.512 )
    34.80 ( 39.644 )
    69.92 ( 37.610 )
        Weeks 44-46 (n = 14,27,36)
    67.07 ( 42.321 )
    40.11 ( 43.580 )
    73.62 ( 37.122 )
        Weeks 47-48 (n = 14,28,41)
    63.67 ( 46.870 )
    35.60 ( 42.748 )
    69.18 ( 42.923 )
        Weeks 58-60 (n = 13,30,33)
    59.54 ( 45.249 )
    46.44 ( 44.871 )
    70.83 ( 40.675 )
        Weeks 68-70 (n = 13,21,28)
    62.42 ( 42.359 )
    63.21 ( 43.450 )
    64.35 ( 44.147 )
        Weeks 71-72 (n = 12,27,30)
    60.18 ( 41.743 )
    60.74 ( 43.254 )
    71.45 ( 41.406 )
        Weeks 73-76 (n = 3,8,10)
    33.22 ( 52.059 )
    62.66 ( 29.530 )
    69.93 ( 36.023 )
    No statistical analyses for this end point

    Secondary: Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score)

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    End point title
    		 Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score)
    End point description
    A positive pruritus assessment was defined as a scratching score of <=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The proportion of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant. PM score represents daytime itching/scratching and tiredness. The FAS consisted of all participants who had received at least 1 dose of the study treatment. Here, ‘n’ = number of participants analyzed at specific time point.
    End point type
    Secondary
    End point timeframe
    Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 44-46, 47-48, 58-60, 68-70, 71-72, and 73-76
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    19
    37
    53
    Units: proportion of pruritus-participant-level
    arithmetic mean (standard deviation)
        Weeks 1-4 (n = 19,37,53)
    49.01 ( 35.687 )
    24.13 ( 30.344 )
    62.08 ( 34.404 )
        Weeks 5-8 (n = 19,37,51)
    60.03 ( 39.300 )
    30.45 ( 35.987 )
    73.11 ( 36.284 )
        Weeks 9-12 (n = 19,37,50)
    57.77 ( 42.435 )
    31.73 ( 38.223 )
    72.42 ( 37.687 )
        Weeks 13-16 (n = 18,37,50)
    61.36 ( 41.530 )
    33.08 ( 39.999 )
    74.13 ( 38.607 )
        Weeks 17-20 (n = 18,37,48)
    56.49 ( 41.590 )
    36.22 ( 41.689 )
    76.12 ( 36.907 )
        Weeks 21-24 (n = 17,36,46)
    55.78 ( 43.495 )
    36.28 ( 41.318 )
    77.23 ( 37.626 )
        Weeks 34-36 (n = 16,31,43)
    58.75 ( 39.774 )
    30.28 ( 39.297 )
    75.11 ( 36.650 )
        Weeks 44-46 (n = 14,28,37)
    67.01 ( 39.601 )
    38.02 ( 43.252 )
    81.00 ( 30.974 )
        Weeks 47-48 (n = 14,29,41)
    71.08 ( 41.878 )
    34.98 ( 43.148 )
    74.62 ( 38.856 )
        Weeks 58-60 (n = 13,31,33)
    72.28 ( 38.149 )
    43.53 ( 43.694 )
    73.17 ( 38.473 )
        Weeks 68-70 (n = 13,21,28)
    62.63 ( 40.626 )
    55.65 ( 42.883 )
    74.85 ( 38.702 )
        Weeks 71-72 (n = 12,26,32)
    55.12 ( 42.336 )
    53.97 ( 45.611 )
    75.38 ( 39.038 )
        Weeks 73-76 (n = 3,8,10)
    49.36 ( 36.671 )
    63.35 ( 31.538 )
    68.11 ( 32.377 )
    No statistical analyses for this end point

    Secondary: Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM)

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    End point title
    		 Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM)
    End point description
    A responder is defined as a participant who reports a decrease in pruritus score from unrounded baseline equivalent to or greater than the threshold of meaningful change estimated from the blinded psychometric analysis. The averaged pruritus score was used to calculate the percentage of participants achieving meaningful reduction at specified Week against the thresholds value of 1.00 based on bi-weekly scores at specified Week obtained from blinded psychometric analysis across all anchors support a threshold of 1.0 point for AM, PM and AM and PM scratching scores. ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with score from 0 to 4 where 0 is no scratching and 4 is worst possible scratching. The FAS consisted of all participants who had received at least 1 dose of the study treatment. Here, ‘n’ = number of participants analyzed at specific time point.
    End point type
    Secondary
    End point timeframe
    Weeks 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, 13-14, 15-16, 17-18, 19-20, 21-22, 23-24, 35-36, 47-48, 59-60, and 71-72
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    19
    36
    53
    Units: percentage of participants
    number (confidence interval 95%)
        Weeks 1-2 (n = 19,36,53)
    15.8 (3.38 to 39.58)
    2.8 (0.07 to 14.53)
    28.3 (16.79 to 42.35)
        Weeks 3-4 (n = 19,36,53)
    36.8 (16.29 to 61.64)
    2.8 (0.07 to 14.53)
    52.8 (38.64 to 66.70)
        Weeks 5-6 (n = 19,36,52)
    36.8 (16.29 to 61.64)
    5.6 (0.68 to 18.66)
    55.8 (41.33 to 69.53)
        Weeks 7-8 (n = 19,36,51)
    36.8 (16.29 to 61.64)
    13.9 (4.67 to 29.50)
    54.9 (40.34 to 68.87)
        Weeks 9-10 (n = 19,36,50)
    31.6 (12.58 to 56.55)
    8.3 (1.75 to 22.47)
    58.0 (43.21 to 71.81)
        Weeks 11-12 (n = 18,36,50)
    33.3 (13.34 to 59.01)
    13.9 (4.67 to 29.50)
    56.0 (41.25 to 70.01)
        Weeks 13-14 (n = 18,36,50)
    50.0 (26.02 to 73.98)
    11.1 (3.11 to 26.06)
    58.0 (43.21 to 71.81)
        Weeks 15-16 (n = 18,36,49)
    50.0 (26.02 to 73.98)
    13.9 (4.67 to 29.50)
    57.1 (42.21 to 71.18)
        Weeks 17-18 (n = 18,36,47)
    44.4 (21.53 to 69.24)
    16.7 (6.37 to 32.81)
    55.3 (40.12 to 69.83)
        Weeks 19-20 (n = 16,36,48)
    50.0 (24.65 to 75.35)
    22.2 (10.12 to 39.15)
    56.3 (41.18 to 70.52)
        Weeks 21-22 (n = 17,36,45)
    41.2 (18.44 to 67.08)
    16.7 (6.37 to 32.81)
    57.8 (42.15 to 72.34)
        Weeks 23-24 (n = 17,36,46)
    41.2 (18.44 to 67.08)
    19.4 (8.19 to 36.02)
    56.5 (41.11 to 71.07)
        Weeks 35-36 (n = 15,27,39)
    33.3 (11.82 to 61.62)
    18.5 (6.30 to 38.08)
    56.4 (39.62 to 72.19)
        Weeks 47-48 (n = 14,28,39)
    57.1 (28.86 to 82.34)
    25.0 (10.69 to 44.87)
    64.1 (47.18 to 78.80)
        Weeks 59-60 (n = 11,30,30)
    36.4 (10.93 to 69.21)
    30.0 (14.73 to 49.40)
    60.0 (40.60 to 77.34)
        Weeks 71-72 (n = 12,26,31)
    41.7 (15.17 to 72.33)
    34.6 (17.21 to 55.67)
    61.3 (42.19 to 78.15)
    No statistical analyses for this end point

    Secondary: Percentage of Responders for Pruritus Assessments Monthly (AM and PM)

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    End point title
    		 Percentage of Responders for Pruritus Assessments Monthly (AM and PM)
    End point description
    A responder is defined as a participant who reports a decrease in pruritus score from unrounded baseline equivalent to or greater than the threshold of meaningful change estimated from the blinded psychometric analysis. The averaged pruritus score was used to calculate the percentage of participants achieving meaningful reduction at specified Week against the thresholds value of 1.00 based on monthly scores at specified Week obtained from blinded psychometric analysis across all anchors support a threshold of 1.0 point for AM, PM and AM and PM scratching scores. ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with score from 0 to 4 where 0 is no scratching and 4 is worst possible scratching. The FAS consisted of all participants who had received at least 1 dose of the study treatment. Here, ‘n’ = number of participants analyzed at specific time point.
    End point type
    Secondary
    End point timeframe
    Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 45-48, 58-60, and 68-72
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    19
    36
    53
    Units: percentage of participants
    number (confidence interval 95%)
        Weeks 1-4 (n = 19,36,53)
    21.1 (6.05 to 45.57)
    2.8 (0.07 to 14.53)
    43.4 (29.84 to 57.72)
        Weeks 5-8 (n = 19,36,51)
    36.8 (16.29 to 61.64)
    8.3 (1.75 to 22.47)
    54.9 (40.34 to 68.87)
        Weeks 9-12 (n = 19,36,50)
    36.8 (16.29 to 61.64)
    11.1 (3.11 to 26.06)
    56.0 (41.25 to 70.01)
        Weeks 13-16 (n = 18,36,50)
    50.0 (26.02 to 73.98)
    13.9 (4.67 to 29.50)
    60.0 (45.18 to 73.59)
        Weeks 17-20 (n = 18,36,48)
    38.9 (17.30 to 64.25)
    16.7 (6.37 to 32.81)
    56.3 (41.18 to 70.52)
        Weeks 21-24 (n = 17,36,45)
    35.3 (14.21 to 61.67)
    16.7 (6.37 to 32.81)
    53.3 (37.87 to 68.34)
        Weeks 34-36 (n = 16,30,43)
    43.8 (19.75 to 70.12)
    23.3 (9.93 to 42.28)
    58.1 (42.13 to 72.99)
        Weeks 45-48 (n = 15,29,39)
    53.3 (26.59 to 78.73)
    24.1 (10.30 to 43.54)
    64.1 (47.18 to 78.80)
        Weeks 58-60 (n = 13,31,35)
    46.2 (19.22 to 74.87)
    29.0 (14.22 to 48.04)
    57.1 (39.35 to 73.68)
        Weeks 68-72 (n = 13,24,31)
    53.8 (25.13 to 80.78)
    37.5 (18.80 to 59.41)
    64.5 (45.37 to 80.77)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving a Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO (AM and PM)

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    End point title
    		 Percentage of Participants Achieving a Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO (AM and PM)
    End point description
    The percentage of participants who achieved positive pruritus assessment for more than 50% of the time for Weeks 0-72 is reported. A positive pruritus assessment is defined as a scratching score of <=1 or at least a 1-point decrease from baseline on the Albireo ObsRO instrument based on rounded baseline and was calculated based on reported eDiary data. At each assessment, the AM score was compared to the baseline AM average, and the PM score was compared to the baseline PM average. All assessments after intercurrent events (premature treatment discontinuation, death, or initiation of rescue treatments such as biliary diversion surgery or liver transplantation) or follow-up assessments (>= last dose day + 15 days) were excluded from analysis. The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with non-missing value when >50% were included.
    End point type
    Secondary
    End point timeframe
    Week 72
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    12
    26
    31
    Units: percentage of participants
        number (confidence interval 95%)
    58.3 (27.67 to 84.83)
    34.6 (17.21 to 55.67)
    83.9 (66.27 to 94.55)
    No statistical analyses for this end point

    Secondary: Number of Participants Who Underwent Biliary Diversion Surgery and Liver Transplantation

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    End point title
    		 Number of Participants Who Underwent Biliary Diversion Surgery and Liver Transplantation
    End point description
    Participants who underwent biliary diversion surgery and or liver transplantation data has been reported. The FAS consisted of all participants who had received at least 1 dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 24, 48, and 72
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    19
    37
    60
    Units: participants
    number (not applicable)
        Weeks 0-24: Biliary Diversion Surgery
    0
    0
    0
        Weeks 0-24: Liver Transplantation
    1
    0
    0
        Weeks 0-48: Biliary Diversion Surgery
    1
    0
    1
        Weeks 0-48: Liver Transplantation
    2
    0
    2
        Weeks 0-72: Biliary Diversion Surgery
    1
    0
    1
        Weeks 0-72: Liver Transplantation
    2
    0
    5
    No statistical analyses for this end point

    Secondary: Change From Baseline in Height Z-Scores

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    End point title
    		 Change From Baseline in Height Z-Scores
    End point description
    Growth factors like height was measured by standardized assessments outlined in US food and drug administration (FDA) guidance document. Height was measured using certified stadiometer. Change in growth parameters was assessed using linear growth compared to standard growth curve (Z-score) calculated by using software/methods from centers for disease control(CDC) website for participants with age >=2 years old and from world health organization (WHO) website for participants with age <2 years old. Participants whose accurate age was not available, Z-score was not calculated. Baseline is last available assessment prior to first dose of study treatment. A Z-score indicates how many standard deviation's (SD) a participant's measurement, was from average for their age and sex.A Z-score of 0 represents median or 50th percentile, while positive or negative values show how far above or below average a measurement was. FAS. n=participants with data collected specified timepoints are reported.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 24, 48, 70 and 72
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    15
    28
    46
    Units: Z-score
    median (full range (min-max))
        Week 24 (n = 14,28,46)
    0.181 (-0.28 to 1.53)
    0.341 (-1.04 to 2.26)
    0.089 (-1.34 to 1.97)
        Week 48 (n = 14,27,41)
    0.485 (0.02 to 1.42)
    0.662 (-0.75 to 2.08)
    0.095 (-1.46 to 2.03)
        Average of Weeks 70-72 (n = 15,28,39)
    0.556 (-0.01 to 1.57)
    0.543 (-0.83 to 2.12)
    0.224 (-1.42 to 2.62)
    No statistical analyses for this end point

    Secondary: Change From Baseline in Weight Z-Scores

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    End point title
    		 Change From Baseline in Weight Z-Scores
    End point description
    Growth factors like weight was measured by the standardized assessments outlined in the US FDA guidance document. Weight was measured using certified weight scale. Change in growth parameters was assessed using linear growth (weight) compared to standard growth curve (Z-score), calculated by using the software or methods from the CDC website for participants with age >=2 years old and from the WHO website for participants with age <2 years old. Participants whose accurate age was not available, Z-score was not calculated. Baseline is the last available assessment prior to the first dose of study treatment. The Z-score indicates how many SDs a participant's measurement (like weight), was from the average for their age and sex. A Z-score of 0 represents the median or 50th percentile, while positive or negative values show how far above or below the average a measurement was. FAS. Here, 'n'= participants with data collected at specified timepoints are reported.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 24, 48, 70 and 72
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    15
    29
    48
    Units: Z-score
    median (full range (min-max))
        Week 24 (n = 14,29,48)
    0.155 (-0.49 to 1.40)
    0.383 (-0.75 to 1.57)
    0.169 (-0.68 to 1.74)
        Week 48 (n = 14,27,42)
    0.544 (-1.15 to 1.43)
    0.494 (-1.04 to 2.14)
    0.246 (-0.54 to 1.29)
        Average of Weeks 70-72 (n = 15,28,40)
    0.098 (-1.13 to 2.17)
    0.389 (-1.21 to 2.11)
    0.400 (-0.86 to 2.27)
    No statistical analyses for this end point

    Secondary: Change From Baseline in Body Mass Index (BMI) Z-Scores

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    End point title
    		 Change From Baseline in Body Mass Index (BMI) Z-Scores
    End point description
    Growth factors like BMI was measured by the standardized assessments outlined in the US FDA guidance document. BMI was calculated by weight (kg) / height (m^2). Change in growth parameters was assessed using linear growth (BMI) compared to standard growth curve (Z-score), calculated by using the software or methods from the CDC website for participants with age >=2 years old and from the WHO website for participants with age <2 years old. Participants whose accurate age was not available, Z-score was not calculated. Baseline is the last available assessment prior to the first dose of study treatment. The Z-score indicates how many SDs a participant's measurement (like BMI), was from the average for their age and sex. A Z-score of 0 represents the median or 50th percentile, while positive or negative values show how far above or below the average a measurement was. FAS. Here, 'n'= participants with data collected at specified timepoints are reported.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 24, 48, 70 and 72
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    15
    28
    46
    Units: Z-score
    median (full range (min-max))
        Week 24 (n = 14,28,46)
    -0.106 (-0.66 to 1.86)
    0.150 (-2.00 to 2.21)
    0.202 (-1.60 to 2.08)
        Week 48 (n = 14,27,41)
    0.028 (-0.88 to 1.23)
    -0.135 (-2.44 to 2.59)
    0.129 (-1.34 to 2.45)
        Average of Weeks 70-72 (n = 15,28,39)
    -0.059 (-1.24 to 3.12)
    -0.007 (-1.64 to 2.25)
    0.182 (-0.99 to 2.68)
    No statistical analyses for this end point

    Secondary: Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72

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    End point title
    		 Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72
    End point description
    Data for the number of participants with use of UDCA and rifampicin are reported. The FAS consisted of all participants who had received at least 1 dose of the study treatment. Here, ‘n’ = number of participants collected at specific time point.
    End point type
    Secondary
    End point timeframe
    Weeks 24, 48, and 72
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    19
    37
    60
    Units: participants
    number (not applicable)
        Week 24: Use of UDCA (n=19,37,60)
    17
    29
    43
        Week 24: Use of Rifampicin (n=19,37,60)
    17
    19
    37
        Week 24: Use of UDCA or Rifampicin (n=19,37,60)
    19
    33
    50
        Week 24: Use of UDCA and Rifampicin(n=19,37,60)
    15
    15
    30
        Week 48: Use of UDCA (n=18,35,56)
    16
    27
    39
        Week 48: Use of Rifampicin (n=18,35,56)
    16
    20
    31
        Week 48: Use of UDCA or Rifampicin (n=18,35,56)
    18
    33
    46
        Week 48: Use of UDCA and Rifampicin (n=18,35,56)
    14
    14
    24
        Week 72: Use of UDCA (n=16,31,50)
    14
    24
    34
        Week 72: Use of Rifampicin (n=16,31,50)
    14
    15
    26
        Week 72: Use of UDCA or Rifampicin (n=16,31,50)
    16
    29
    41
        Week 72: Use of UDCA and Rifampicin (n=16,31,50)
    12
    10
    19
    No statistical analyses for this end point

    Secondary: Change From Baseline to Week 72 in Pediatric End-Stage Liver Disease (PELD) Score

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    End point title
    		 Change From Baseline to Week 72 in Pediatric End-Stage Liver Disease (PELD) Score
    End point description
    PELD score was calculated for children under 12 years of age, ranged across negative to positive values. Calculation of PELD score was done by converting laboratory parameters: total bilirubin in milligram/deciliter (mg/dL), albumin in gram (g)/dL, and creatinine in mg/dL laboratory parameters were converted to units. PELD score was calculated as 4.80*ln(total bilirubin)+18.57*ln [international normalized ratio (INR)]-6.87*ln(albumin) + 4.36 (if participant <1 year: scores for participants listed for liver transplantation before participant's first birthday continued to include value assigned for age (<1 year) until participant reached the age of 24 months) + 6.67 (if participant has growth failure [<-2 SD]). Laboratory values <1.0 were set to 1.0 for calculation of PELD score. Lower scores represent less severe hepatic disease. Baseline is last available assessment prior to first dose of study treatment. FAS. Only participants with data collected at specified timepoint reported.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 72
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    11
    20
    23
    Units: score on a scale
        arithmetic mean (standard deviation)
    -0.397 ( 3.6168 )
    1.361 ( 2.5083 )
    -0.303 ( 9.4631 )
    No statistical analyses for this end point

    Secondary: Change From Baseline to Week 72 in Model for End-stage Liver Disease (MELD) Score for Children 12 Years of Age or Older

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    End point title
    		 Change From Baseline to Week 72 in Model for End-stage Liver Disease (MELD) Score for Children 12 Years of Age or Older
    End point description
    The calculation of MELD score was done by converting laboratory parameters in following units: total bilirubin in mg/dL, albumin in g/dL, and creatinine in mg/dL laboratory parameters were converted to units. MELD score for children 12 years of age or older ranges from 6 to 40 was calculated as 9.57*ln (creatinine)+3.78*ln (total bilirubin)+11.2 *ln (INR)+6.43. Laboratory values <1.0 were set to 1.0 and serum creatinine values >4.0 mg/dL were set to 4.0 for calculation of MELD score. Lower scores represent less severe hepatic disease. Baseline is last available assessment prior to first dose of study treatment. FAS. Only participants 12 years of age or older are included in this analysis and reported. For Cohort 1: Placebo/Odevixibat change from baseline data was not collected as participant was under 12 years old, that aligns with MELD score calculation.n=number of participants with data collected. 9999=standard deviation not calculated for 1 participant.99999=0 participant analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 72
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    1
    3
    17
    Units: score on a scale
    arithmetic mean (standard deviation)
        Baseline (n = 1,3,17)
    6.869 ( 9999 )
    9.795 ( 2.4694 )
    11.574 ( 4.0801 )
        Change from Baseline (n = 0,1,9)
    99999 ( 99999 )
    1.286 ( 9999 )
    -2.221 ( 5.7744 )
    No statistical analyses for this end point

    Secondary: Change From Baseline to Week 72 in Aspartate Aminotransferase (AST) to Platelet Ratio Index (APRI) Score

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    End point title
    		 Change From Baseline to Week 72 in Aspartate Aminotransferase (AST) to Platelet Ratio Index (APRI) Score
    End point description
    AST to APRI score was calculated as [(AST in units per liter {U/L})/ (AST upper limit of normal {ULN} in U/L)] * 100/ (platelets in 10^9/L). The APRI score is a way to assess fibrosis of the liver. The lower the APRI score (< 0.5), the greater the negative predictive value and ability to rule out cirrhosis; the higher the value (> 1.5) the greater the positive predictive value and ability to rule in cirrhosis. Lower values indicate less severe hepatic fibrosis. Baseline is the last available assessment prior to the first dose of study treatment. The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at Baseline and Week 72 are reported.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 72
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    13
    21
    22
    Units: score on a scale
        arithmetic mean (standard deviation)
    0.044 ( 0.3435 )
    0.071 ( 0.3951 )
    0.411 ( 0.9690 )
    No statistical analyses for this end point

    Secondary: Change From Baseline to Week 72 in Fibrosis-4 (Fib-4) Score

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    End point title
    		 Change From Baseline to Week 72 in Fibrosis-4 (Fib-4) Score
    End point description
    Fib-4 score was calculated as (age * AST in U/L)/ (platelets in 10^9/L * square root of ( alanine aminotransferase [ALT] in U/L). The FIB-4 score estimates the amount of scarring in the liver. A FIB-4 score <1.45 has a negative predictive value of 90% for advanced fibrosis (Ishak fibrosis score 4-6 which includes early bridging fibrosis to cirrhosis). In contrast, a FIB-4 > 3.25 would have a 97% specificity and a positive predictive value of 65% for advanced fibrosis. Lower values indicate less severe hepatic fibrosis. Baseline is the last available assessment prior to the first dose of study treatment. The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at Baseline and Week 72 are reported.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 72
    End point values
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Number of subjects analysed
    13
    21
    21
    Units: score on a scale
        arithmetic mean (standard deviation)
    0.050 ( 0.1187 )
    0.106 ( 0.2696 )
    0.113 ( 0.2820 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All treatment emergent AEs were collected from the start of study treatment administration (Day 1) up to 28 days after last dose of study treatment (248 weeks) and death was assessed from signing of informed consent form till DCO (281 weeks).
    Adverse event reporting additional description
    The FAS consisted of all participants who had received at least 1 dose of the study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Cohort 1: Placebo/Odevixibat
    Reporting group description
    		 Participants who previously received placebo in study A4250-005 for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues. Participants continued receiving study treatment until commercial availability of odevixibat.

    Reporting group title
    Cohort 1: Odevixibat/Odevixibat
    Reporting group description
    		 Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues. Participants continued receiving study treatment until commercial availability of odevixibat.

    Reporting group title
    Cohort 2: Odevixibat
    Reporting group description
    		 Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 or were eligible for enrolment in A4250-005 after recruitment was complete received odevixibat at a dose of 120 mcg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks. Participants continued receiving study treatment until commercial availability of odevixibat.

    Serious adverse events
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 19 (26.32%)
    7 / 37 (18.92%)
    23 / 60 (38.33%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    2 / 60 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alpha 1 foetoprotein increased
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood sodium decreased
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fracture displacement
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 37 (2.70%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 37 (2.70%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Progressive familial intrahepatic cholestasis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 37 (2.70%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Epilepsy
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coagulopathy
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    2 / 60 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemolysis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis ulcerative
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 37 (2.70%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 37 (2.70%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocutaneous fistula
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 37 (2.70%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 37 (2.70%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mouth haemorrhage
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 37 (2.70%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Varices oesophageal
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    2 / 60 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic hepatic failure
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 37 (2.70%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 37 (2.70%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 37 (2.70%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic arthritis streptococcal
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 37 (2.70%)
    2 / 60 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    2 / 60 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort 1: Placebo/Odevixibat Cohort 1: Odevixibat/Odevixibat Cohort 2: Odevixibat
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    18 / 19 (94.74%)
    35 / 37 (94.59%)
    57 / 60 (95.00%)
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    7 / 19 (36.84%)
    12 / 37 (32.43%)
    16 / 60 (26.67%)
         occurrences all number
    17
    25
    29
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    2
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    4 / 19 (21.05%)
    13 / 37 (35.14%)
    10 / 60 (16.67%)
         occurrences all number
    6
    23
    14
    Epistaxis
         subjects affected / exposed
    1 / 19 (5.26%)
    3 / 37 (8.11%)
    6 / 60 (10.00%)
         occurrences all number
    2
    5
    12
    Nasal congestion
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    2 / 60 (3.33%)
         occurrences all number
    1
    0
    2
    Oropharyngeal pain
         subjects affected / exposed
    2 / 19 (10.53%)
    2 / 37 (5.41%)
    1 / 60 (1.67%)
         occurrences all number
    6
    3
    1
    Respiratory disorder
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 37 (2.70%)
    0 / 60 (0.00%)
         occurrences all number
    1
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    1 / 19 (5.26%)
    3 / 37 (8.11%)
    2 / 60 (3.33%)
         occurrences all number
    1
    3
    2
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Autism spectrum disorder
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Insomnia
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 37 (5.41%)
    0 / 60 (0.00%)
         occurrences all number
    0
    2
    0
    Irritability
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 37 (5.41%)
    0 / 60 (0.00%)
         occurrences all number
    1
    2
    0
    Sleep disorder
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    1
    0
    1
    Tic
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 19 (10.53%)
    3 / 37 (8.11%)
    6 / 60 (10.00%)
         occurrences all number
    3
    3
    10
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 37 (5.41%)
    5 / 60 (8.33%)
         occurrences all number
    1
    2
    10
    Bile acids increased
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 37 (5.41%)
    2 / 60 (3.33%)
         occurrences all number
    0
    2
    2
    Bilirubin conjugated increased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    3 / 60 (5.00%)
         occurrences all number
    1
    0
    6
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 19 (0.00%)
    3 / 37 (8.11%)
    0 / 60 (0.00%)
         occurrences all number
    0
    4
    0
    Blood bilirubin increased
         subjects affected / exposed
    4 / 19 (21.05%)
    10 / 37 (27.03%)
    13 / 60 (21.67%)
         occurrences all number
    6
    17
    20
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 37 (2.70%)
    1 / 60 (1.67%)
         occurrences all number
    2
    1
    1
    Blood sodium increased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 37 (5.41%)
    0 / 60 (0.00%)
         occurrences all number
    0
    2
    0
    International normalised ratio increased
         subjects affected / exposed
    3 / 19 (15.79%)
    5 / 37 (13.51%)
    11 / 60 (18.33%)
         occurrences all number
    3
    7
    13
    Lymph node palpable
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Platelet count increased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Prothrombin time prolonged
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    1
    0
    1
    Transaminases increased
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 37 (5.41%)
    3 / 60 (5.00%)
         occurrences all number
    0
    2
    4
    Vitamin A increased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Vitamin D decreased
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 37 (5.41%)
    2 / 60 (3.33%)
         occurrences all number
    1
    4
    2
    Vitamin E decreased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    3 / 60 (5.00%)
         occurrences all number
    2
    0
    3
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Contusion
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    2
    0
    0
    Fall
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Foot fracture
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Immunisation reaction
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Limb injury
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Post vaccination fever
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Scar
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Scratch
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 37 (2.70%)
    0 / 60 (0.00%)
         occurrences all number
    1
    1
    0
    Nervous system disorders
    Dyslexia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Headache
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    2 / 60 (3.33%)
         occurrences all number
    2
    0
    3
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 37 (2.70%)
    4 / 60 (6.67%)
         occurrences all number
    0
    1
    4
    Coagulopathy
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    3 / 60 (5.00%)
         occurrences all number
    0
    0
    3
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 37 (5.41%)
    0 / 60 (0.00%)
         occurrences all number
    1
    2
    0
    Splenomegaly
         subjects affected / exposed
    2 / 19 (10.53%)
    3 / 37 (8.11%)
    4 / 60 (6.67%)
         occurrences all number
    2
    3
    4
    Ear and labyrinth disorders
    Ear discomfort
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    2
    0
    0
    Ear haemorrhage
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 37 (2.70%)
    0 / 60 (0.00%)
         occurrences all number
    1
    1
    0
    Ear pain
         subjects affected / exposed
    1 / 19 (5.26%)
    3 / 37 (8.11%)
    1 / 60 (1.67%)
         occurrences all number
    3
    3
    1
    Otorrhoea
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 37 (5.41%)
    0 / 60 (0.00%)
         occurrences all number
    0
    4
    0
    Eye disorders
    Keratoconus
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 37 (2.70%)
    0 / 60 (0.00%)
         occurrences all number
    1
    1
    0
    Abdominal pain
         subjects affected / exposed
    1 / 19 (5.26%)
    3 / 37 (8.11%)
    2 / 60 (3.33%)
         occurrences all number
    1
    4
    4
    Abdominal pain upper
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    1
    0
    1
    Constipation
         subjects affected / exposed
    2 / 19 (10.53%)
    3 / 37 (8.11%)
    4 / 60 (6.67%)
         occurrences all number
    2
    6
    4
    Dental caries
         subjects affected / exposed
    1 / 19 (5.26%)
    3 / 37 (8.11%)
    1 / 60 (1.67%)
         occurrences all number
    1
    3
    1
    Diarrhoea
         subjects affected / exposed
    2 / 19 (10.53%)
    8 / 37 (21.62%)
    16 / 60 (26.67%)
         occurrences all number
    3
    16
    20
    Diarrhoea haemorrhagic
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 37 (2.70%)
    0 / 60 (0.00%)
         occurrences all number
    1
    1
    0
    Faeces soft
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 37 (2.70%)
    0 / 60 (0.00%)
         occurrences all number
    1
    1
    0
    Nausea
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 37 (0.00%)
    3 / 60 (5.00%)
         occurrences all number
    0
    0
    4
    Tooth impacted
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Toothache
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    2 / 60 (3.33%)
         occurrences all number
    1
    0
    3
    Umbilical hernia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Vomiting
         subjects affected / exposed
    2 / 19 (10.53%)
    2 / 37 (5.41%)
    10 / 60 (16.67%)
         occurrences all number
    2
    2
    15
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 37 (2.70%)
    0 / 60 (0.00%)
         occurrences all number
    1
    1
    0
    Hepatomegaly
         subjects affected / exposed
    1 / 19 (5.26%)
    4 / 37 (10.81%)
    1 / 60 (1.67%)
         occurrences all number
    1
    4
    1
    Hepatosplenomegaly
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    1
    0
    1
    Jaundice
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 37 (5.41%)
    3 / 60 (5.00%)
         occurrences all number
    0
    2
    3
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    1
    0
    1
    Dermatitis allergic
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    2
    0
    0
    Dermatitis atopic
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 37 (5.41%)
    0 / 60 (0.00%)
         occurrences all number
    0
    2
    0
    Eczema
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 37 (5.41%)
    2 / 60 (3.33%)
         occurrences all number
    1
    3
    2
    Pruritus
         subjects affected / exposed
    3 / 19 (15.79%)
    7 / 37 (18.92%)
    7 / 60 (11.67%)
         occurrences all number
    4
    10
    8
    Psoriasis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Urticaria
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 37 (5.41%)
    0 / 60 (0.00%)
         occurrences all number
    0
    2
    0
    Renal and urinary disorders
    Bladder dysfunction
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Pain in extremity
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    1
    0
    1
    Trigger finger
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Infections and infestations
    Boston exanthema
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Bronchitis
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 37 (2.70%)
    2 / 60 (3.33%)
         occurrences all number
    1
    4
    4
    COVID-19
         subjects affected / exposed
    3 / 19 (15.79%)
    3 / 37 (8.11%)
    15 / 60 (25.00%)
         occurrences all number
    3
    3
    17
    Conjunctivitis
         subjects affected / exposed
    1 / 19 (5.26%)
    3 / 37 (8.11%)
    0 / 60 (0.00%)
         occurrences all number
    1
    3
    0
    Ear infection
         subjects affected / exposed
    2 / 19 (10.53%)
    2 / 37 (5.41%)
    3 / 60 (5.00%)
         occurrences all number
    4
    2
    3
    Gastroenteritis
         subjects affected / exposed
    1 / 19 (5.26%)
    5 / 37 (13.51%)
    6 / 60 (10.00%)
         occurrences all number
    2
    5
    6
    Gastroenteritis viral
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    2 / 60 (3.33%)
         occurrences all number
    1
    0
    2
    Gastrointestinal candidiasis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Hand-foot-and-mouth disease
         subjects affected / exposed
    0 / 19 (0.00%)
    3 / 37 (8.11%)
    1 / 60 (1.67%)
         occurrences all number
    0
    3
    1
    Influenza
         subjects affected / exposed
    0 / 19 (0.00%)
    7 / 37 (18.92%)
    8 / 60 (13.33%)
         occurrences all number
    0
    10
    11
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    2 / 60 (3.33%)
         occurrences all number
    2
    0
    2
    Nasopharyngitis
         subjects affected / exposed
    3 / 19 (15.79%)
    9 / 37 (24.32%)
    9 / 60 (15.00%)
         occurrences all number
    4
    16
    10
    Oral candidiasis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Otitis externa
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 37 (0.00%)
    2 / 60 (3.33%)
         occurrences all number
    2
    0
    2
    Otitis media
         subjects affected / exposed
    2 / 19 (10.53%)
    3 / 37 (8.11%)
    2 / 60 (3.33%)
         occurrences all number
    3
    9
    2
    Paronychia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Pharyngitis
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 37 (2.70%)
    1 / 60 (1.67%)
         occurrences all number
    1
    1
    1
    Pneumonia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    2 / 60 (3.33%)
         occurrences all number
    1
    0
    4
    Postoperative wound infection
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 37 (2.70%)
    0 / 60 (0.00%)
         occurrences all number
    1
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 37 (5.41%)
    1 / 60 (1.67%)
         occurrences all number
    1
    2
    1
    Rhinitis
         subjects affected / exposed
    2 / 19 (10.53%)
    3 / 37 (8.11%)
    0 / 60 (0.00%)
         occurrences all number
    2
    4
    0
    Tonsillitis
         subjects affected / exposed
    3 / 19 (15.79%)
    3 / 37 (8.11%)
    1 / 60 (1.67%)
         occurrences all number
    4
    4
    1
    Upper respiratory tract infection
         subjects affected / exposed
    7 / 19 (36.84%)
    10 / 37 (27.03%)
    12 / 60 (20.00%)
         occurrences all number
    21
    19
    17
    Varicella
         subjects affected / exposed
    3 / 19 (15.79%)
    2 / 37 (5.41%)
    3 / 60 (5.00%)
         occurrences all number
    3
    2
    3
    Viral infection
         subjects affected / exposed
    1 / 19 (5.26%)
    4 / 37 (10.81%)
    5 / 60 (8.33%)
         occurrences all number
    2
    5
    5
    Viral upper respiratory tract infection
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 37 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    2
    0
    1
    Vulvovaginal mycotic infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 37 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 37 (5.41%)
    1 / 60 (1.67%)
         occurrences all number
    0
    2
    1
    Vitamin D deficiency
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 37 (5.41%)
    8 / 60 (13.33%)
         occurrences all number
    1
    2
    9
    Vitamin E deficiency
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 37 (5.41%)
    3 / 60 (5.00%)
         occurrences all number
    0
    2
    3

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Apr 2018
    Protocol Amendment 1 was the initial protocol submitted to regulatory and competent authorities.
    18 Jan 2019
    Cohort 2 added for participant enrollment. Revision of inclusion and exclusion criteria. Secondary and exploratory endpoints added. Removal of exploratory endpoint “proportion of patients achieving meaningful reduction in caregiver reported observed scratching”. Baseline definitions revised. Sample size determination added. Clarification added for data review and dose titration guidelines. Liver biopsy text revised and criteria for withdrawal from study revised. List of food items that can be mixed with study treatment expanded. Amendment of derived variable calculation for primary endpoint. Definition of FAS updated, and safety analysis set removed. Revision of concomitant medication guidelines. Pediatric quality of life inventory for participants ages 18 to 25 added.
    11 Mar 2019
    Cohort 2 participant population revised. The secondary objective revised for additional clarification. Exclusion criteria revised. The list of genes analyzed to confirm PFIC diagnosis added.
    25 Oct 2019
    Clarification added for primary analysis performed after the last participant from either Cohort 1 or 2. Addition of optional extension period. Revision of inclusion and exclusion criteria. Revision of concomitant medication guidelines. Voluntary photography assessment removed. Estimated blood volumes required for optional extension period added.
    18 Mar 2020
    Addition of collection of a blood sample for pharmacokinetic analysis as close to onset as possible for hepatic AEs including liver decompensation
    21 Dec 2021
    Clarification added for participant population. Starting dose for participant in Cohort 2 revised. Clarification added for follow-up requirements for participants. Use of certified stadiometer for height and length measurements added. Clarification added for autotaxin, plasma 7-alpha-hydroxy-4-cholesten-3-one concentration (p-C4), pharmacokinetic samples added. Home nursing and local lab collection added. Extended screening period due to Coronavirus Disease 2019 (COVID-19) added. Baseline data requirements for participants added. Inclusion and exclusion criteria modified. Clarification added for end of treatment visit for optional extension period. Addition of allowance for participants vaccinated against COVID-19 while in the study added. Follow-up requirements added.

    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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