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    Clinical Trial Results:
    A Phase 3, Randomized, Double Blind, Placebo Controlled, 12 Week Study to Assess the Efficacy and Safety of Etrasimod in Subjects with Moderately to Severely Active Ulcerative Colitis

    Summary
    EudraCT number
    		 2018-003986-33
    Trial protocol
    		 SK   BE   NL   GB   EE   DE   AT   CZ   FR   DK   LT   BG   PT   LV   HU   PL   HR   ES   IT   RO  
    Global end of trial date
    07 Dec 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    22 Jun 2022
    First version publication date
    22 Jun 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    APD334-302
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03996369
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Arena Pharmaceuticals, Inc.
    Sponsor organisation address
    6154 Nancy Ridge Drive, San Diego, United States,
    Public contact
    Fabio Cataldi, Arena Pharmaceuticals, Inc., 001 8584537200, ct.gov@arenapharm.com
    Scientific contact
    Fabio Cataldi, Arena Pharmaceuticals, Inc., 001 8584537200, ct.gov@arenapharm.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    17 Feb 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Dec 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective is to assess the efficacy of etrasimod when administered for 12 weeks on clinical remission in subjects with moderately to severely active ulcerative colitis (UC).
    Protection of trial subjects
    The study was conducted in compliance with the ICH Guidelines for Good Clinical Practice (GCP) and applicable regulatory requirements, the study protocol, and where applicable, Sponsor and/or CRO Standard Operating Procedures.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Aug 2020
    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
    United States: 29
    Country: Number of subjects enrolled
    Belarus: 6
    Country: Number of subjects enrolled
    Georgia: 11
    Country: Number of subjects enrolled
    Moldova, Republic of: 6
    Country: Number of subjects enrolled
    Russian Federation: 35
    Country: Number of subjects enrolled
    Serbia: 6
    Country: Number of subjects enrolled
    Ukraine: 25
    Country: Number of subjects enrolled
    Argentina: 2
    Country: Number of subjects enrolled
    Australia: 10
    Country: Number of subjects enrolled
    Chile: 2
    Country: Number of subjects enrolled
    India: 17
    Country: Number of subjects enrolled
    Israel: 3
    Country: Number of subjects enrolled
    Japan: 48
    Country: Number of subjects enrolled
    Korea, Republic of: 4
    Country: Number of subjects enrolled
    Lebanon: 1
    Country: Number of subjects enrolled
    Mexico: 10
    Country: Number of subjects enrolled
    South Africa: 3
    Country: Number of subjects enrolled
    Thailand: 1
    Country: Number of subjects enrolled
    Turkey: 7
    Country: Number of subjects enrolled
    Poland: 44
    Country: Number of subjects enrolled
    Portugal: 2
    Country: Number of subjects enrolled
    Romania: 6
    Country: Number of subjects enrolled
    Slovakia: 7
    Country: Number of subjects enrolled
    Spain: 1
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    Croatia: 1
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Bulgaria: 4
    Country: Number of subjects enrolled
    Czechia: 15
    Country: Number of subjects enrolled
    Denmark: 1
    Country: Number of subjects enrolled
    Estonia: 5
    Country: Number of subjects enrolled
    France: 8
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Hungary: 15
    Country: Number of subjects enrolled
    Italy: 9
    Country: Number of subjects enrolled
    Lithuania: 4
    Worldwide total number of subjects
    354
    EEA total number of subjects
    125
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    2
    Adults (18-64 years)
    334
    From 65 to 84 years
    18
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study included a screening period (up to 28 days), a double-blind induction treatment period (12 weeks), and a 2-week and a 4-week follow-up period. The target population consisted of male or female subjects aged between 16 and 80 years (inclusive), with moderately to severely active ulcerative colitis.

    Pre-assignment
    Screening details
    		 During the screening period, subjects were evaluated for study entry based on the inclusion and exclusion criteria. Screening procedures to evaluate subject eligibility for the study were to be conducted within 28 days prior to study drug administration on Day 1.

    Period 1
    Period 1 title
    Induction Treatment Period - Safety Set (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Assessor
    Blinding implementation details
    All study personnel directly related to this study (investigators, study site personnel, monitors, and CRO and Sponsor personnel), with the exception of the clinical supply staff, some safety staff, and the unblinded statistician supporting the DSMB, were blinded to the identity of study drug. Randomization codes were generated by a CRO statistician not directly involved with the study.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Etrasimod 2 mg
    Arm description
    		 Etrasimod 2 mg was administered orally once daily (QD) for 12 weeks. One tablet is to be taken each day (with water, either with or without food).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etrasimod 2 mg
    Investigational medicinal product code
    Other name
    APD334, 2 mg
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 × 2 mg etrasimod tablet orally QD for 12 weeks

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 × matching etrasimod tablet orally QD for 12 weeks

    Arm title
    		 Placebo
    Arm description
    		 Placebo was administered orally once daily (QD) for 12 weeks. One tablet is to be taken each day (with water, either with or without food).
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 × matching etrasimod tablet orally QD for 12 weeks

    Number of subjects in period 1
    		Etrasimod 2 mg Placebo
    Started
    238
    116
    Completed
    213
    103
    Not completed
    25
    13
         Consent withdrawn by subject
    6
    8
         Physician decision
    4
    2
         Participant decision
    -
    1
         Adverse event, non-fatal
    9
    -
         Lost to follow-up
    -
    1
         Didn't meet I/E criteria
    1
    -
         Lack of efficacy
    4
    -
         Protocol deviation
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Etrasimod 2 mg
    Reporting group description
    		 Etrasimod 2 mg was administered orally once daily (QD) for 12 weeks. One tablet is to be taken each day (with water, either with or without food).

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo was administered orally once daily (QD) for 12 weeks. One tablet is to be taken each day (with water, either with or without food).

    Reporting group values
    		 Etrasimod 2 mg Placebo Total
    Number of subjects
    		 238 116 354
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 1 1 2
        Adults (18-64 years)
    		 225 109 334
        From 65-84 years
    		 12 6 18
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 37.5 (16 to 73) 38.0 (17 to 72) -
    Gender categorical
    Units: Subjects
        Female
    		 103 43 146
        Male
    		 135 73 208
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 6 1 7
        Asian
    		 47 25 72
        Black or African American
    		 2 2 4
        White
    		 176 88 264
        Multiple
    		 1 0 1
        Not Reported
    		 6 0 6

    End points

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    End points reporting groups
    Reporting group title
    Etrasimod 2 mg
    Reporting group description
    		 Etrasimod 2 mg was administered orally once daily (QD) for 12 weeks. One tablet is to be taken each day (with water, either with or without food).

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo was administered orally once daily (QD) for 12 weeks. One tablet is to be taken each day (with water, either with or without food).

    Primary: Percentage of participants achieving clinical remission at Week 12

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    End point title
    		 Percentage of participants achieving clinical remission at Week 12
    End point description
    Remission is a composite score of participant reported symptoms using daily e-diary and centrally read endoscopy as follows: stool frequency sub-score 0 or 1 with at least a 1-point change from induction study baseline; and rectal bleeding sub-score of 0; and endoscopic sub-score 0 or 1 (modified, excludes friability). The primary efficacy analysis was conducted using the FAS with Baseline MMS 5 to 9.
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    222
    112
    Units: Percentage of participants
        number (not applicable)
    24.8
    15.2
    Statistical analysis title
    		 Statistical Analysis
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0264
    Method
    		 Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    9.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.14
         upper limit
    		 18.23

    Secondary: Percentage of participants achieving endoscopic improvement at Week 12

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    End point title
    		 Percentage of participants achieving endoscopic improvement at Week 12
    End point description
    Participant reported symptoms using daily e-diary and centrally read endoscopy as follows: stool frequency sub-score 0 or 1 with at least a 1-point change from induction study baseline; and rectal bleeding sub-score of 0; and endoscopic sub-score 0 or 1 (excluding friability).
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    222
    112
    Units: Percentage of participants
        number (not applicable)
    30.6
    18.8
    Statistical analysis title
    		 Statistical Analysis
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0092
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    12.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3
         upper limit
    		 21.23

    Secondary: Percentage of participants achieving symptomatic remission at Week 12

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    End point title
    		 Percentage of participants achieving symptomatic remission at Week 12
    End point description
    Symptomatic remission is a composite score of participant reported symptoms using daily e-diary and centrally read endoscopy as: stool frequency sub-score 0 or 1 with at least a 1-point change from induction study baseline; and rectal bleeding sub-score of 0.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    222
    112
    Units: Percentage of participants
        number (not applicable)
    46.8
    29.5
    Statistical analysis title
    		 Statistical Analysis
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0013
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    17.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.81
         upper limit
    		 28.15

    Secondary: Percentage of participants with mucosal healing at Week 12

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    End point title
    		 Percentage of participants with mucosal healing at Week 12
    End point description
    Mucosal healing was defined as an endoscopic sub score of less than or equal to 1 (Excluding friability) with histologic remission measured by a Geboes Index score < 2.0). The centrally read endoscopic sub-score of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. Geboes score grading system, was a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicates more severe disease.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    222
    112
    Units: Percentage of participants
        number (not applicable)
    16.2
    8.9
    Statistical analysis title
    		 Statistical Analysis
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0358
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    7.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 14.39

    Secondary: Percentage of participants achieving clinical response at Week 12

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    End point title
    		 Percentage of participants achieving clinical response at Week 12
    End point description
    Clinical response was defined as a greater than equal to (>=) 2-point and >= 30 percent decrease from baseline in modified Mayo score (MMS), and a >= 1-point decrease from Baseline in rectal bleeding (RB) sub-score or an absolute RB sub-score <= 1.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    222
    112
    Units: Percentage of participants
        number (not applicable)
    62.2
    41.1
    Statistical analysis title
    		 Statistical Analysis
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0002
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    21.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.18
         upper limit
    		 32.29

    Secondary: Percentage of participants achieving endoscopic normalization at Week 12

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    End point title
    		 Percentage of participants achieving endoscopic normalization at Week 12
    End point description
    Endoscopic normalization was defined as an endoscopic score (ES) = 0.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    222
    112
    Units: Percentage of participants
        number (not applicable)
    17.1
    8.0
    Statistical analysis title
    		 Statistical Analysis
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0093
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    9.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.27
         upper limit
    		 16.2

    Secondary: Percentage of participants achieving symptomatic remission at Weeks 2, 4 and 8

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    End point title
    		 Percentage of participants achieving symptomatic remission at Weeks 2, 4 and 8
    End point description
    Symptomatic remission is a composite score of participant reported symptoms using daily e-diary and centrally read endoscopy as: stool frequency sub-score 0 or 1 with at least a 1-point change from induction study baseline; and rectal bleeding sub-score of 0.
    End point type
    Secondary
    End point timeframe
    Weeks 2, 4 and 8
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    222
    112
    Units: Percentage of participants
    number (not applicable)
        Week 2
    16.2
    10.7
        Week 4
    27.5
    16.1
        Week 8
    38.7
    24.1
    Statistical analysis title
    		 Statistical Analysis
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.1149
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    5.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.42
         upper limit
    		 13.13
    Notes
    [1] - Weeks 2
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Week 4
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.0073
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    11.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.19
         upper limit
    		 20.47
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Week 8
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0032
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    14.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.98
         upper limit
    		 24.69

    Secondary: Percentage of participants achieving complete symptomatic remission at each study visit at Weeks 2, 4, 8 and 12

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    End point title
    		 Percentage of participants achieving complete symptomatic remission at each study visit at Weeks 2, 4, 8 and 12
    End point description
    Complete symptomatic remission was defined as stool frequency sub-score = 0 and rectal bleeding sub-score = 0.
    End point type
    Secondary
    End point timeframe
    Weeks 2, 4, 8 and 12
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    222
    112
    Units: Percentage of participants
    number (not applicable)
        Week 2
    4.5
    1.8
        Week 4
    11.7
    3.6
        Week 8
    14.0
    7.1
        Week 12
    18.0
    8.9
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Week 2
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1277
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    2.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.81
         upper limit
    		 6.48
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Week 4
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0022
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    8.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.01
         upper limit
    		 13.64
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Week 8
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0316
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    7.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 13.49
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Week 12
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0145
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    9.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.82
         upper limit
    		 16.54

    Secondary: Percentage of participants achieving noninvasive clinical response at Weeks 2, 4, 8 and 12

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    End point title
    		 Percentage of participants achieving noninvasive clinical response at Weeks 2, 4, 8 and 12
    End point description
    A noninvasive clinical response was defined as >= 30% decrease from Baseline in composite rectal bleeding and stool frequency sub-scores, and a >= 1-point decrease from Baseline in rectal bleeding sub score or an absolute rectal bleeding sub score =< 1.
    End point type
    Secondary
    End point timeframe
    Weeks 2, 4, 8 and 12
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    222
    112
    Units: Percentage of participants
    number (not applicable)
        Week 2
    39.2
    24.1
        Week 4
    55.9
    41.1
        Week 8
    68.0
    45.5
        Week 12
    67.6
    50.0
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Week 2
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0021
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    15.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.65
         upper limit
    		 25.46
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Week 4
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0072
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    14.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.05
         upper limit
    		 25.91
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Week 8
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 1
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    22.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.95
         upper limit
    		 33.25
    Statistical analysis title
    		 Copy of Statistical Analysis
    Statistical analysis description
    Week 12
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0015
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    17.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.7
         upper limit
    		 28.47

    Secondary: Percentage of participants achieving symptomatic response at Weeks 2, 4, 8 and 12

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    End point title
    		 Percentage of participants achieving symptomatic response at Weeks 2, 4, 8 and 12
    End point description
    Symptomatic response was defined as decrease from baseline >= 30% in composite rectal bleeding and Stool frequency sub scores.
    End point type
    Secondary
    End point timeframe
    Weeks 2, 4, 8 and 12
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    222
    112
    Units: Percentage of participants
    number (not applicable)
        Week 2
    39.6
    24.1
        Week 4
    56.3
    41.1
        Week 8
    68.5
    46.4
        Week 12
    68.5
    50.0
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Week 2
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0016
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    15.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.07
         upper limit
    		 25.91
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Week 4
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0055
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    15.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.54
         upper limit
    		 26.36
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Week 8
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 1
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    22.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.43
         upper limit
    		 32.85
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Week 12
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    334
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0008
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    18.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.65
         upper limit
    		 29.33

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All-cause mortality, non-serious TEAEs and SAEs were collected from the beginning of participant's participation to 30 days following discontinuation of the study drug.
    Adverse event reporting additional description
    Safety set population was used to collect the adverse events. The Safety Set includes all randomized participants who received at least 1 dose of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo was administered orally once daily (QD) for 12 weeks. One tablet is to be taken each day (with water, either with or without food).

    Reporting group title
    Etrasimod 2 mg
    Reporting group description
    		 Etrasimod 2 mg was administered orally once daily (QD) for 12 weeks. One tablet is to be taken each day (with water, either with or without food).

    Serious adverse events
    		 Placebo Etrasimod 2 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 116 (1.72%)
    6 / 238 (2.52%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Hepatobiliary procedural complication
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Coronary artery disease
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Migraine
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis ulcerative
         subjects affected / exposed
    0 / 116 (0.00%)
    3 / 238 (1.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo Etrasimod 2 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    54 / 116 (46.55%)
    112 / 238 (47.06%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Papilloma
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 116 (0.86%)
    3 / 238 (1.26%)
         occurrences all number
    1
    3
    Venous thrombosis
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Essential hypertension
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 116 (0.00%)
    3 / 238 (1.26%)
         occurrences all number
    0
    3
    Pyrexia
         subjects affected / exposed
    3 / 116 (2.59%)
    8 / 238 (3.36%)
         occurrences all number
    3
    8
    Chest discomfort
         subjects affected / exposed
    1 / 116 (0.86%)
    1 / 238 (0.42%)
         occurrences all number
    1
    1
    Feeling abnormal
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Injection site reaction
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Malaise
         subjects affected / exposed
    1 / 116 (0.86%)
    1 / 238 (0.42%)
         occurrences all number
    1
    1
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 116 (0.86%)
    1 / 238 (0.42%)
         occurrences all number
    1
    1
    Thirst
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Asthenia
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Vaccination site pain
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Oedema
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Immune system disorders
    Food allergy
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Testicular torsion
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 116 (0.00%)
    2 / 238 (0.84%)
         occurrences all number
    0
    2
    Cough
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Asthma
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Nasal congestion
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Dry throat
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Initial insomnia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Investigations
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 116 (0.00%)
    5 / 238 (2.10%)
         occurrences all number
    0
    5
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 116 (0.00%)
    3 / 238 (1.26%)
         occurrences all number
    0
    3
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 116 (0.86%)
    3 / 238 (1.26%)
         occurrences all number
    1
    3
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 116 (0.00%)
    2 / 238 (0.84%)
         occurrences all number
    0
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 116 (0.00%)
    2 / 238 (0.84%)
         occurrences all number
    0
    2
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 116 (0.00%)
    2 / 238 (0.84%)
         occurrences all number
    0
    2
    Blood cholesterol increased
         subjects affected / exposed
    1 / 116 (0.86%)
    2 / 238 (0.84%)
         occurrences all number
    1
    2
    Blood triglycerides increased
         subjects affected / exposed
    0 / 116 (0.00%)
    2 / 238 (0.84%)
         occurrences all number
    0
    2
    Weight decreased
         subjects affected / exposed
    0 / 116 (0.00%)
    2 / 238 (0.84%)
         occurrences all number
    0
    2
    Blood glucose increased
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Blood pressure increased
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Blood thyroid stimulating hormone decreased
         subjects affected / exposed
    1 / 116 (0.86%)
    1 / 238 (0.42%)
         occurrences all number
    1
    1
    Heart rate increased
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Heart rate decreased
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Prothrombin time prolonged
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Liver function test abnormal
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    International normalised ratio increased
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Pulmonary function test decreased
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Transaminases increased
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    FEV1/FVC ratio decreased
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Lipase increased
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Lung diffusion test decreased
         subjects affected / exposed
    2 / 116 (1.72%)
    0 / 238 (0.00%)
         occurrences all number
    2
    0
    Platelet count increased
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Microcytic anaemia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Vaccination complication
         subjects affected / exposed
    1 / 116 (0.86%)
    1 / 238 (0.42%)
         occurrences all number
    1
    1
    Wound complication
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Contusion
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Sinus bradycardia
         subjects affected / exposed
    0 / 116 (0.00%)
    4 / 238 (1.68%)
         occurrences all number
    0
    4
    Tachycardia
         subjects affected / exposed
    2 / 116 (1.72%)
    2 / 238 (0.84%)
         occurrences all number
    2
    2
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Bradycardia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Sinus tachycardia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Sinus arrhythmia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Palpitations
         subjects affected / exposed
    1 / 116 (0.86%)
    1 / 238 (0.42%)
         occurrences all number
    1
    1
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 116 (1.72%)
    11 / 238 (4.62%)
         occurrences all number
    2
    11
    Somnolence
         subjects affected / exposed
    1 / 116 (0.86%)
    3 / 238 (1.26%)
         occurrences all number
    1
    3
    Dizziness
         subjects affected / exposed
    0 / 116 (0.00%)
    3 / 238 (1.26%)
         occurrences all number
    0
    3
    Dizziness postural
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Drug withdrawal headache
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Migraine
         subjects affected / exposed
    4 / 116 (3.45%)
    1 / 238 (0.42%)
         occurrences all number
    4
    1
    Sinus headache
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Presyncope
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    8 / 116 (6.90%)
    14 / 238 (5.88%)
         occurrences all number
    8
    14
    Iron deficiency anaemia
         subjects affected / exposed
    3 / 116 (2.59%)
    3 / 238 (1.26%)
         occurrences all number
    3
    3
    Blood loss anaemia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Thrombocytosis
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Tinnitus
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Eye disorders
    Uveitis
         subjects affected / exposed
    0 / 116 (0.00%)
    2 / 238 (0.84%)
         occurrences all number
    0
    2
    Vision blurred
         subjects affected / exposed
    0 / 116 (0.00%)
    2 / 238 (0.84%)
         occurrences all number
    0
    2
    Blepharitis
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Eye pain
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Conjunctivitis allergic
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Eyelid margin crusting
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Glaucoma
         subjects affected / exposed
    1 / 116 (0.86%)
    1 / 238 (0.42%)
         occurrences all number
    1
    1
    Meibomian gland dysfunction
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Macular oedema
         subjects affected / exposed
    1 / 116 (0.86%)
    1 / 238 (0.42%)
         occurrences all number
    1
    1
    Macular hole
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Visual impairment
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Pigment dispersion syndrome
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Metamorphopsia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Visual snow syndrome
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Chorioretinopathy
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Exudative retinopathy
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Ocular hypertension
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    2 / 116 (1.72%)
    10 / 238 (4.20%)
         occurrences all number
    2
    10
    Colitis ulcerative
         subjects affected / exposed
    1 / 116 (0.86%)
    8 / 238 (3.36%)
         occurrences all number
    1
    8
    Vomiting
         subjects affected / exposed
    0 / 116 (0.00%)
    5 / 238 (2.10%)
         occurrences all number
    0
    5
    Abdominal pain
         subjects affected / exposed
    3 / 116 (2.59%)
    3 / 238 (1.26%)
         occurrences all number
    3
    3
    Diarrhoea
         subjects affected / exposed
    0 / 116 (0.00%)
    3 / 238 (1.26%)
         occurrences all number
    0
    3
    Flatulence
         subjects affected / exposed
    1 / 116 (0.86%)
    2 / 238 (0.84%)
         occurrences all number
    1
    2
    Abdominal tenderness
         subjects affected / exposed
    0 / 116 (0.00%)
    2 / 238 (0.84%)
         occurrences all number
    0
    2
    Abdominal pain lower
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    1 / 116 (0.86%)
    1 / 238 (0.42%)
         occurrences all number
    1
    1
    Anal eczema
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Frequent bowel movements
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Gingival bleeding
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Toothache
         subjects affected / exposed
    2 / 116 (1.72%)
    1 / 238 (0.42%)
         occurrences all number
    2
    1
    Chronic gastritis
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Gastritis
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal hypermotility
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal pain
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Hyperaesthesia teeth
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Lip blister
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Stomatitis
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Abdominal distension
         subjects affected / exposed
    0 / 116 (0.00%)
    5 / 238 (2.10%)
         occurrences all number
    0
    5
    Dyspepsia
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Hepatobiliary disorders
    Liver disorder
         subjects affected / exposed
    0 / 116 (0.00%)
    3 / 238 (1.26%)
         occurrences all number
    0
    3
    Hepatic function abnormal
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Hepatic cytolysis
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Cholestasis
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 116 (0.86%)
    2 / 238 (0.84%)
         occurrences all number
    1
    2
    Alopecia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Cutaneous vasculitis
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Dermatitis contact
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Dry skin
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Night sweats
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Nail bed bleeding
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Miliaria
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Photosensitivity reaction
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Blister
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Nephrolithiasis
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    1 / 116 (0.86%)
    2 / 238 (0.84%)
         occurrences all number
    1
    2
    Back pain
         subjects affected / exposed
    0 / 116 (0.00%)
    4 / 238 (1.68%)
         occurrences all number
    0
    4
    Muscular weakness
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Arthralgia
         subjects affected / exposed
    3 / 116 (2.59%)
    4 / 238 (1.68%)
         occurrences all number
    3
    4
    Musculoskeletal pain
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Myalgia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Osteochondrosis
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Pain in extremity
         subjects affected / exposed
    1 / 116 (0.86%)
    1 / 238 (0.42%)
         occurrences all number
    1
    1
    Spinal pain
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    0 / 116 (0.00%)
    4 / 238 (1.68%)
         occurrences all number
    0
    4
    COVID-19
         subjects affected / exposed
    3 / 116 (2.59%)
    3 / 238 (1.26%)
         occurrences all number
    3
    3
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 116 (0.86%)
    2 / 238 (0.84%)
         occurrences all number
    1
    2
    Sinusitis
         subjects affected / exposed
    0 / 116 (0.00%)
    2 / 238 (0.84%)
         occurrences all number
    0
    2
    Nasopharyngitis
         subjects affected / exposed
    2 / 116 (1.72%)
    3 / 238 (1.26%)
         occurrences all number
    2
    3
    Anal abscess
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Campylobacter infection
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Clostridium difficile infection
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Cystitis
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Conjunctivitis
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Gastroenteritis
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Genitourinary tract infection
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Hordeolum
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Infected dermal cyst
         subjects affected / exposed
    1 / 116 (0.86%)
    1 / 238 (0.42%)
         occurrences all number
    1
    1
    Influenza
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Localised infection
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Oral herpes
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Herpes zoster
         subjects affected / exposed
    2 / 116 (1.72%)
    0 / 238 (0.00%)
         occurrences all number
    2
    0
    Enterocolitis bacterial
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Laryngitis
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Rash pustular
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Tooth infection
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Viral infection
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 116 (0.00%)
    2 / 238 (0.84%)
         occurrences all number
    0
    2
    Metabolism and nutrition disorders
    Hypophosphataemia
         subjects affected / exposed
    0 / 116 (0.00%)
    4 / 238 (1.68%)
         occurrences all number
    0
    4
    Iron deficiency
         subjects affected / exposed
    0 / 116 (0.00%)
    3 / 238 (1.26%)
         occurrences all number
    0
    3
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 116 (0.00%)
    2 / 238 (0.84%)
         occurrences all number
    0
    2
    Folate deficiency
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Gout
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Hyperkalaemia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Hypomagnesaemia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Hypokalaemia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Hypoproteinaemia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Hypovolaemia
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Underweight
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Increased appetite
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Vitamin D deficiency
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 238 (0.42%)
         occurrences all number
    0
    1
    Hyperglycaemia
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0
    Hypoglycaemia
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 238 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Mar 2019
    Amendment 1 - provides additional guidance for the cardiac monitoring procedures required on Day 1 after the first dose of study treatment. These additional monitoring procedures are based feedback from the Food and Drug Administration. In particular, post-dose safety vital signs, 12-lead ECGs, monitoring of subjects who do not meet the discharge criteria, and discontinuation rules have been revised.
    07 Feb 2020
    Amendment 2 - update eligibility criteria (eg, contraception use). Additional instructions for safety monitoring related to ophthalmoscopy and optical coherence tomography testing were included. The prohibition of concomitant use of QT prolonging drugs was removed based on the results of the QT study (Study APD334-008). In addition, a 4-Week Safety Follow-Up visit was added. Clarification and further instructions for tuberculosis testing were added and the tuberculosis screening questionnaire was updated.
    22 Feb 2021
    Amendment 3 - includes guidance for conducting virtual and offsite visits. Also, information on anti-arrhythmic drugs was added to prohibited concomitant therapies. Language was updated regarding timing of screening optical coherence tomography (OCTs) and pulmonary function tests (PFTs). Additionally, an exclusion criterion was added regarding treatment with topical rectal Chinese medicine, enemas or suppositories prior to randomization. Minor corrections were made for consistency within the protocol.

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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