Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44311   clinical trials with a EudraCT protocol, of which   7356   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Etrasimod in Adult Subjects With Eosinophilic Esophagitis

    Summary
    EudraCT number
    		 2020-003226-23
    Trial protocol
    		 BE   NL   DE  
    Global end of trial date
    30 Jun 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    18 May 2024
    First version publication date
    18 May 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    C5041009
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04682639
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    05 Dec 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Jun 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the effects of Etrasimod on esophageal eosinophilia in adult subjects with active eosinophilic esophagitis (EoE). To evaluate the dose-response relationship of 2 doses of Etrasimod versus placebo in adult subjects with active EoE. To select an Etrasimod dose based on efficacy and safety for continued development.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Dec 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 80
    Country: Number of subjects enrolled
    Belgium: 6
    Country: Number of subjects enrolled
    Spain: 4
    Country: Number of subjects enrolled
    Switzerland: 4
    Country: Number of subjects enrolled
    Australia: 14
    Worldwide total number of subjects
    108
    EEA total number of subjects
    10
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    108
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study consisted of a Double-Blind treatment period (24 weeks) and an Open Label Extension (OLE) period (28 weeks). Subjects who were in the placebo group during the Double-Blind treatment period were re-randomized to Etrasimod 1 milligram (mg) or Etrasimod 2 mg at entry into the Open Label Extension period.

    Pre-assignment
    Screening details
    		 A total of 262 subjects were screened in the study. Out of 262, 154 subjects were screen failures and 108 subjects were randomised and treated.

    Period 1
    Period 1 title
    Double-Blind Treatment Period (24 weeks)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Monitor, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Experimental: Etrasimod 2 mg
    Arm description
    		 Subjects received Etrasimod 2 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etrasimod
    Investigational medicinal product code
    Other name
    APD334
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Etrasimod 2 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period.

    Arm title
    		 Experimental: Etrasimod 1 mg
    Arm description
    		 Subjects received Etrasimod 1 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etrasimod
    Investigational medicinal product code
    Other name
    APD334
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Etrasimod 1 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period.

    Arm title
    		 Placebo Then Etrasimod Any Dose
    Arm description
    		 Subjects received Etrasimod matching placebo orally, once daily for 24 weeks in Double-blind treatment and re-randomized to receive Etrasimod tablet 1 or 2 mg orally, once daily for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Etrasimod
    Investigational medicinal product code
    Other name
    APD334
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Etrasimod orally, once daily for 24 weeks in Double-blind treatment and re-randomized to receive Etrasimod tablet 1 or 2 mg orally, once daily for 28 weeks in OLE period.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Etrasimod matching placebo orally, once daily for 24 weeks in Double-blind treatment and re-randomized to receive Etrasimod tablet 1 or 2 mg orally, once daily for 28 weeks in OLE period.

    Number of subjects in period 1
    		Experimental: Etrasimod 2 mg Experimental: Etrasimod 1 mg Placebo Then Etrasimod Any Dose
    Started
    41
    39
    28
    Completed
    30
    31
    24
    Not completed
    11
    8
    4
         Consent withdrawn by subject
    5
    5
    2
         Adverse event, non-fatal
    1
    -
    1
         Pregnancy
    -
    1
    -
         Non-compliance
    2
    -
    -
         Lost to follow-up
    2
    1
    -
         Lack of efficacy
    1
    1
    1
    Period 2
    Period 2 title
    OLE Period (28 weeks)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Experimental: Etrasimod 2 mg
    Arm description
    		 Subjects received Etrasimod 2 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etrasimod
    Investigational medicinal product code
    Other name
    APD334
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Etrasimod 2 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period.

    Arm title
    		 Experimental: Etrasimod 1 mg
    Arm description
    		 Subjects received Etrasimod 1 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etrasimod
    Investigational medicinal product code
    Other name
    APD334
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oromucosal use, Oral use
    Dosage and administration details
    Subjects received Etrasimod 1 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period.

    Arm title
    		 OLE: Placebo then Etrasimod 2 mg
    Arm description
    		 Subjects received Etrasimod matching placebo orally, once daily for 24 weeks in Double-blind treatment and re-randomized to receive Etrasimod tablet 2 mg orally, once daily for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etrasimod
    Investigational medicinal product code
    Other name
    APD334
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Etrasimod matching placebo orally, once daily for 24 weeks in Double-blind treatment and re-randomized to receive Etrasimod tablet 2 mg orally, once daily for 28 weeks in OLE period.

    Arm title
    		 OLE: Placebo then Etrasimod 1 mg
    Arm description
    		 Subjects received Etrasimod matching placebo orally, once daily for 24 weeks in Double-blind treatment and re-randomized to receive Etrasimod tablet 1 mg orally, once daily for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etrasimod
    Investigational medicinal product code
    Other name
    APD334
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Etrasimod matching placebo orally, once daily for 24 weeks in Double-blind treatment and re-randomized to receive Etrasimod tablet 1 mg orally, once daily for 28 weeks in OLE period.

    Number of subjects in period 2
    		Experimental: Etrasimod 2 mg Experimental: Etrasimod 1 mg OLE: Placebo then Etrasimod 2 mg OLE: Placebo then Etrasimod 1 mg
    Started
    30
    31
    12
    12
    Completed
    22
    28
    11
    10
    Not completed
    8
    3
    1
    2
         Consent withdrawn by subject
    1
    1
    -
    -
         Adverse event, non-fatal
    3
    -
    1
    -
         Non-compliance
    1
    -
    -
    1
         Unspecified
    -
    -
    -
    1
         Lost to follow-up
    1
    -
    -
    -
         Lack of efficacy
    2
    2
    -
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Experimental: Etrasimod 2 mg
    Reporting group description
    		 Subjects received Etrasimod 2 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Reporting group title
    Experimental: Etrasimod 1 mg
    Reporting group description
    		 Subjects received Etrasimod 1 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Reporting group title
    Placebo Then Etrasimod Any Dose
    Reporting group description
    		 Subjects received Etrasimod matching placebo orally, once daily for 24 weeks in Double-blind treatment and re-randomized to receive Etrasimod tablet 1 or 2 mg orally, once daily for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Reporting group values
    		 Experimental: Etrasimod 2 mg Experimental: Etrasimod 1 mg Placebo Then Etrasimod Any Dose Total
    Number of subjects
    		 41 39 28 108
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 41 39 28 108
        From 65-84 years
    		 0 0 0 0
        85 years and over
    		 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 35.6 ( 9.80 ) 39.9 ( 12.87 ) 39.1 ( 11.65 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 20 17 14 51
        Male
    		 21 22 14 57
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0
        Asian
    		 1 0 0 1
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        Black or African American
    		 1 1 0 2
        White
    		 39 38 28 105
        More than one race
    		 0 0 0 0
        Unknown or Not Reported
    		 0 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 4 5 0 9
        Not Hispanic or Latino
    		 36 34 28 98
        Unknown or Not Reported
    		 1 0 0 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Experimental: Etrasimod 2 mg
    Reporting group description
    		 Subjects received Etrasimod 2 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Reporting group title
    Experimental: Etrasimod 1 mg
    Reporting group description
    		 Subjects received Etrasimod 1 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Reporting group title
    Placebo Then Etrasimod Any Dose
    Reporting group description
    		 Subjects received Etrasimod matching placebo orally, once daily for 24 weeks in Double-blind treatment and re-randomized to receive Etrasimod tablet 1 or 2 mg orally, once daily for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.
    Reporting group title
    Experimental: Etrasimod 2 mg
    Reporting group description
    		 Subjects received Etrasimod 2 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Reporting group title
    Experimental: Etrasimod 1 mg
    Reporting group description
    		 Subjects received Etrasimod 1 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Reporting group title
    OLE: Placebo then Etrasimod 2 mg
    Reporting group description
    		 Subjects received Etrasimod matching placebo orally, once daily for 24 weeks in Double-blind treatment and re-randomized to receive Etrasimod tablet 2 mg orally, once daily for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Reporting group title
    OLE: Placebo then Etrasimod 1 mg
    Reporting group description
    		 Subjects received Etrasimod matching placebo orally, once daily for 24 weeks in Double-blind treatment and re-randomized to receive Etrasimod tablet 1 mg orally, once daily for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Primary: Percent Change From Baseline in Esophageal Peak Eosinophil Count (PEC) at Week 16

    		 Close Top of page
    End point title
    		 Percent Change From Baseline in Esophageal Peak Eosinophil Count (PEC) at Week 16
    End point description
    Eosinophils was counted in the areas of greatest eosinophil density. Counts were reported as the number of eosinophils/high power field (eos/hpf) and multiple hpfs analysed until the PEC was clearly identified after taking into account all biopsies from all esophageal levels. The Full Analysis Set (FAS) included all randomised subjects in the double-blind treatment period who received at least 1 dose of study treatment. Here, "Number of Subjects Analysed" signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Baseline, Week 16
    End point values
    		 Experimental: Etrasimod 2 mg Experimental: Etrasimod 1 mg Placebo Then Etrasimod Any Dose
    Number of subjects analysed
    33
    35
    20
    Units: Percent change
        median (inter-quartile range (Q1-Q3))
    -58.4 (-86.21 to -26.25)
    -39.4 (-71.08 to 78.95)
    -21.5 (-57.20 to 55.42)
    Statistical analysis title
    		 Etrasimod 2 mg versus placebo
    Comparison groups
    Experimental: Etrasimod 2 mg v Placebo Then Etrasimod Any Dose
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 = 0.0103
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -18.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -32.6
         upper limit
    		 -4.49
    Notes
    [1] - Estimates were from ANCOVA model for rank score of percent change from baseline in esophageal PEC.
    Statistical analysis title
    		 Etrasimod 1 mg versus placebo
    Comparison groups
    Experimental: Etrasimod 1 mg v Placebo Then Etrasimod Any Dose
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 other [2]
    P-value
    		 = 0.2861
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -7.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.48
         upper limit
    		 6.42
    Notes
    [2] - Estimates were from ANCOVA model for rank score of percent change from baseline in esophageal PEC.

    Secondary: Absolute Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Score at Week 16

    		 Close Top of page
    End point title
    		 Absolute Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Score at Week 16
    End point description
    The DSQ was used to measure the frequency and intensity of dysphagia to solid food. DSQ consisted of 4 questions, all subjects used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the subject's answer to Question 2 was 'No', the diary ended for that day. If a subject answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the subject experienced pain while swallowing). DSQ score = (Sum of points from questions 2+3 in the daily DSQ)×14 days/(Number of diaries reported with non-missing data). DSQ scores can range from 0 to 84, with a higher score indicating worse dysphagia. The FAS included all randomised subjects in the double-blind treatment period who received at least 1 dose of study treatment. Here, "Number of Subjects Analysed" signifies number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    End point values
    		 Experimental: Etrasimod 2 mg Experimental: Etrasimod 1 mg Placebo Then Etrasimod Any Dose
    Number of subjects analysed
    32
    36
    24
    Units: Units on a scale
        least squares mean (standard error)
    -17.11 ( 2.247 )
    -14.78 ( 2.166 )
    -19.49 ( 2.602 )
    Statistical analysis title
    		 Etrasimod 1 mg versus placebo
    Comparison groups
    Experimental: Etrasimod 1 mg v Placebo Then Etrasimod Any Dose
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1671
    Method
    		 Linear mixed effects model
    Parameter type
    		 LS mean difference
    Point estimate
    4.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 11.41
    Statistical analysis title
    		 Etrasimod 2 mg versus placebo
    Comparison groups
    Experimental: Etrasimod 2 mg v Placebo Then Etrasimod Any Dose
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4894
    Method
    		 Linear mixed effects model
    Parameter type
    		 LS mean difference
    Point estimate
    2.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.43
         upper limit
    		 9.19

    Secondary: Absolute Change From Baseline in Esophageal Peak Eosinophil Count (PEC) at Week 16

    		 Close Top of page
    End point title
    		 Absolute Change From Baseline in Esophageal Peak Eosinophil Count (PEC) at Week 16
    End point description
    Eosinophils was counted in the areas of greatest eosinophil density. Counts were reported as the number of eos/hpf and multiple hpfs analysed until the PEC was clearly identified after taking into account all biopsies from all esophageal levels.The FAS included all randomised subjects in the double-blind treatment period who received at least 1 dose of study treatment. Here, "Number of Subjects Analysed" signifies number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    End point values
    		 Experimental: Etrasimod 2 mg Experimental: Etrasimod 1 mg Placebo Then Etrasimod Any Dose
    Number of subjects analysed
    33
    35
    20
    Units: eos/hpf
        least squares mean (standard error)
    -46.3 ( 17.46 )
    -5.7 ( 16.99 )
    8.3 ( 22.37 )
    Statistical analysis title
    		 Etrasimod 1 mg versus placebo
    Comparison groups
    Experimental: Etrasimod 1 mg v Placebo Then Etrasimod Any Dose
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6193
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -13.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -69.61
         upper limit
    		 41.71
    Statistical analysis title
    		 Etrasimod 2 mg versus placebo
    Comparison groups
    Experimental: Etrasimod 2 mg v Placebo Then Etrasimod Any Dose
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0565
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -54.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -110.59
         upper limit
    		 1.54

    Secondary: Percentage Of Subjects With Esophageal PEC Less Than (<) 15 eos/hpf at Week 16

    		 Close Top of page
    End point title
    		 Percentage Of Subjects With Esophageal PEC Less Than (<) 15 eos/hpf at Week 16
    End point description
    The FAS included all randomised subjects in the double-blind treatment period who received at least 1 dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Experimental: Etrasimod 2 mg Experimental: Etrasimod 1 mg Placebo Then Etrasimod Any Dose
    Number of subjects analysed
    41
    39
    28
    Units: Percentage of subjects
        number (not applicable)
    22.0
    12.8
    0
    Statistical analysis title
    		 Etrasimod 1 mg versus placebo
    Comparison groups
    Experimental: Etrasimod 1 mg v Placebo Then Etrasimod Any Dose
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0121
    Method
    		 Mantel-Haenszel
    Parameter type
    		 Adjusted difference from placebo
    Point estimate
    13.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.03
         upper limit
    		 24.66
    Statistical analysis title
    		 Etrasimod 2 mg versus placebo
    Comparison groups
    Experimental: Etrasimod 2 mg v Placebo Then Etrasimod Any Dose
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0007
    Method
    		 Mantel-Haenszel
    Parameter type
    		 Adjusted difference from placebo
    Point estimate
    21.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9.23
         upper limit
    		 34.57

    Secondary: Percentage of Subjects with Esophageal PEC Less Than or Equal to (<=) 6 eos/hpf at Week 16

    		 Close Top of page
    End point title
    		 Percentage of Subjects with Esophageal PEC Less Than or Equal to (<=) 6 eos/hpf at Week 16
    End point description
    The FAS included all randomised subjects in the double-blind treatment period who received at least 1 dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Experimental: Etrasimod 2 mg Experimental: Etrasimod 1 mg Placebo Then Etrasimod Any Dose
    Number of subjects analysed
    41
    39
    28
    Units: Percentage of subjects
        number (not applicable)
    12.2
    7.7
    0
    Statistical analysis title
    		 Etrasimod 1 mg versus placebo
    Comparison groups
    Experimental: Etrasimod 1 mg v Placebo Then Etrasimod Any Dose
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.059
    Method
    		 Mantel-Haenszel
    Parameter type
    		 Adjusted difference from placebo
    Point estimate
    8.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.32
         upper limit
    		 17.07
    Statistical analysis title
    		 Etrasimod 2 mg versus placebo
    Comparison groups
    Experimental: Etrasimod 2 mg v Placebo Then Etrasimod Any Dose
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0173
    Method
    		 Mantel-Haenszel
    Parameter type
    		 Adjusted difference from placebo
    Point estimate
    12.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.15
         upper limit
    		 22.16

    Other pre-specified: Number of Subjects With Treatment Emergent Adverse Events (TEAEs) by Maximum Severity During 24 Week Double Blind Treatment Period

    		 Close Top of page
    End point title
    		 Number of Subjects With Treatment Emergent Adverse Events (TEAEs) by Maximum Severity During 24 Week Double Blind Treatment Period
    End point description
    An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Treatment-emergent AE was defined as an AE that started or worsened in severity on or after the first dose of study treatment. Severity of AE was graded according to Common Terminology Criteria for Adverse Events (CTCAE) as Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe or medically significant but not immediately life-threatening hospitalization or prolongation of hospitalization indicated; disabling, limiting self-care activities of daily living (ADL), Grade 4: Life-Threatening consequences, urgent intervention indicated, Grade 5: Death Related to AE. The safety set included all randomised subjects who received at least 1 dose of study treatment during the specified treatment period. Here, "Number of Subjects Analysed" signifies number of subjects evaluable for this endpoint.
    End point type
    Other pre-specified
    End point timeframe
    Baseline, up to Week 24
    End point values
    		 Experimental: Etrasimod 2 mg Experimental: Etrasimod 1 mg Placebo Then Etrasimod Any Dose
    Number of subjects analysed
    29
    27
    21
    Units: Subjects
        TEAE: Grade 1
    19
    15
    8
        TEAE: Grade 2
    9
    12
    11
        TEAE: Grade 3
    1
    0
    2
        TEAE: Grade 4
    0
    0
    0
        TEAE: Grade 5
    0
    0
    0
    No statistical analyses for this end point

    Other pre-specified: Number of Subjects With Serious TEAEs, TEAEs Leading to Study Treatment Discontinuation, TEAEs Leading to Death and TEAEs of Special Interest During 24 Week Double Blind Treatment Period

    		 Close Top of page
    End point title
    		 Number of Subjects With Serious TEAEs, TEAEs Leading to Study Treatment Discontinuation, TEAEs Leading to Death and TEAEs of Special Interest During 24 Week Double Blind Treatment Period
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of death); new or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 24 weeks after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to Etrasimod was assessed by the investigator (Yes/No). Subjects with multiple occurrences of an AE within a category were counted once within the category. The safety set included all randomised subjects who received at least 1 dose of study treatment during the specified treatment period.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to Week 24
    End point values
    		 Experimental: Etrasimod 2 mg Experimental: Etrasimod 1 mg Placebo Then Etrasimod Any Dose
    Number of subjects analysed
    41
    39
    28
    Units: Subjects
        Serious TEAEs
    0
    0
    0
        TEAEs leading to study treatment discontinuation
    1
    0
    1
        TEAEs leading to death
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to a maximum of 61 weeks (35 days screening period, 24 weeks of double-blind treatment period, 28 weeks of active extended treatment, and 4 weeks of follow-up period)
    Adverse event reporting additional description
    Same event may appear as both non-SAE and a serious AE. However, what is presented are distinct events. An event may be categorised as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study. Safety set was evaluated.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    Experimental: Etrasimod 1 mg
    Reporting group description
    		 Subjects received Etrasimod 1 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Reporting group title
    Placebo Then Etrasimod Any Dose
    Reporting group description
    		 Subjects received Etrasimod matching placebo orally, once daily for 24 weeks in Double-blind treatment and re-randomized to receive Etrasimod tablet 1 or 2 mg orally, once daily for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Reporting group title
    OLE: Placebo then Etrasimod 2 mg
    Reporting group description
    		 Subjects received Etrasimod matching placebo orally, once daily for 24 weeks in Double-blind treatment and re-randomized to receive Etrasimod tablet 2 mg orally, once daily for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Reporting group title
    OLE: Etrasimod 1 mg
    Reporting group description
    		 Subjects received Etrasimod 1 mg tablet orally, once daily for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Reporting group title
    Experimental: Etrasimod 2 mg
    Reporting group description
    		 Subjects received Etrasimod 2 mg tablet orally, once daily for 24 weeks in Double-blind treatment and for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Reporting group title
    OLE: Etrasimod 2 mg
    Reporting group description
    		 Subjects received Etrasimod 2 mg tablet orally, once daily for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Reporting group title
    OLE: Placebo then Etrasimod 1 mg
    Reporting group description
    		 Subjects received Etrasimod matching placebo orally, once daily for 24 weeks in Double-blind treatment and re-randomized to receive Etrasimod tablet 1 mg orally, once daily for 28 weeks in OLE period. Subjects were then followed up for safety for up to 4 weeks.

    Serious adverse events
    		 Experimental: Etrasimod 1 mg Placebo Then Etrasimod Any Dose OLE: Placebo then Etrasimod 2 mg OLE: Etrasimod 1 mg Experimental: Etrasimod 2 mg OLE: Etrasimod 2 mg OLE: Placebo then Etrasimod 1 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    1 / 12 (8.33%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Craniocerebral injury
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Experimental: Etrasimod 1 mg Placebo Then Etrasimod Any Dose OLE: Placebo then Etrasimod 2 mg OLE: Etrasimod 1 mg Experimental: Etrasimod 2 mg OLE: Etrasimod 2 mg OLE: Placebo then Etrasimod 1 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    27 / 39 (69.23%)
    23 / 28 (82.14%)
    11 / 12 (91.67%)
    19 / 31 (61.29%)
    30 / 41 (73.17%)
    16 / 30 (53.33%)
    7 / 12 (58.33%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lipoma
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 28 (7.14%)
    1 / 12 (8.33%)
    0 / 31 (0.00%)
    2 / 41 (4.88%)
    1 / 30 (3.33%)
    1 / 12 (8.33%)
         occurrences all number
    0
    2
    1
    0
    3
    1
    1
    Influenza like illness
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    Fatigue
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    0
    Pain
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    1 / 12 (8.33%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    Chills
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Chest pain
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Chest discomfort
         subjects affected / exposed
    1 / 39 (2.56%)
    2 / 28 (7.14%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    2
    0
    0
    0
    0
    0
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    Hypersensitivity
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Reproductive system and breast disorders
    Vulvovaginal discomfort
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Breast discomfort
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 39 (2.56%)
    2 / 28 (7.14%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    2 / 41 (4.88%)
    2 / 30 (6.67%)
    0 / 12 (0.00%)
         occurrences all number
    1
    2
    0
    0
    2
    2
    0
    Oropharyngeal pain
         subjects affected / exposed
    2 / 39 (5.13%)
    2 / 28 (7.14%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    2
    2
    0
    0
    1
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    2 / 41 (4.88%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    2
    1
    0
    Dyspnoea
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 28 (3.57%)
    1 / 12 (8.33%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    2
    1
    2
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Obstructive airways disorder
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Oropharyngeal spasm
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Throat tightness
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    1 / 12 (8.33%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    1
    0
    0
    Anxiety
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    1
    Attention deficit hyperactivity disorder
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    1 / 12 (8.33%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    0
    0
    Panic attack
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Stress
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Investigations
    Heart rate decreased
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Blood pressure increased
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Liver function test increased
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    3 / 41 (7.32%)
    4 / 30 (13.33%)
    2 / 12 (16.67%)
         occurrences all number
    2
    0
    0
    0
    3
    6
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    Helicobacter test positive
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    White blood cell count decreased
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Transaminases increased
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    SARS-CoV-2 test positive
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Pulmonary function test decreased
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Pulmonary function test abnormal
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Injury, poisoning and procedural complications
    Procedural pain
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    Contusion
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Skin laceration
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Procedural nausea
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Ligament sprain
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Hand fracture
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Stress fracture
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Procedural complication
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Limb fracture
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Joint injury
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    1 / 12 (8.33%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Clavicle fracture
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Wound dehiscence
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    1 / 12 (8.33%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Cardiac disorders
    Sinus bradycardia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Bradycardia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    2 / 41 (4.88%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Nervous system disorders
    Hypoaesthesia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    1 / 12 (8.33%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    Balance disorder
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Headache
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 28 (3.57%)
    2 / 12 (16.67%)
    1 / 31 (3.23%)
    3 / 41 (7.32%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    4
    1
    2
    1
    4
    2
    0
    Dizziness
         subjects affected / exposed
    4 / 39 (10.26%)
    1 / 28 (3.57%)
    1 / 12 (8.33%)
    1 / 31 (3.23%)
    4 / 41 (9.76%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    5
    1
    1
    1
    4
    0
    0
    Hypoglossal nerve paralysis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Somnolence
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    Sciatica
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Paraesthesia
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Migraine
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    1 / 12 (8.33%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    2
    1
    0
    1
    0
    1
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    1 / 12 (8.33%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    Tinnitus
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Ear pain
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Eye disorders
    Eye irritation
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Dry eye
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    0
    0
    Cataract
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Blepharospasm
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Blepharitis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Conjunctivitis allergic
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    Meibomian gland dysfunction
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Vitreous floaters
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    2 / 31 (6.45%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    Hypermetropia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Visual field defect
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Retinal degeneration
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Photopsia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    Ocular discomfort
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Visual impairment
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    3 / 39 (7.69%)
    3 / 28 (10.71%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    6 / 41 (14.63%)
    2 / 30 (6.67%)
    0 / 12 (0.00%)
         occurrences all number
    3
    3
    0
    1
    6
    2
    0
    Gastritis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    1
    0
    0
    Eosinophilic oesophagitis
         subjects affected / exposed
    1 / 39 (2.56%)
    3 / 28 (10.71%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    6
    0
    0
    0
    1
    0
    Dysphagia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Abdominal pain
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 28 (3.57%)
    1 / 12 (8.33%)
    0 / 31 (0.00%)
    2 / 41 (4.88%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    2
    1
    0
    2
    1
    0
    Abdominal distension
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    Oesophageal food impaction
         subjects affected / exposed
    1 / 39 (2.56%)
    5 / 28 (17.86%)
    4 / 12 (33.33%)
    1 / 31 (3.23%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    6
    5
    1
    1
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    2
    1
    0
    0
    1
    1
    0
    Diarrhoea
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 28 (3.57%)
    1 / 12 (8.33%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    1
    0
    Odynophagia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Inguinal hernia
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Frequent bowel movements
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Food poisoning
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Dyspepsia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    Duodenal ulcer
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Dry mouth
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Dental caries
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    Constipation
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Colitis microscopic
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Oesophageal pain
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    Abdominal discomfort
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Swollen tongue
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Regurgitation
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Oesophageal rupture
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    Hiatus hernia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    2
    Haemorrhoids
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    1 / 12 (8.33%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    Bile acid malabsorption
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    1 / 12 (8.33%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    1 / 12 (8.33%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    Erosive oesophagitis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Acquired oesophageal web
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Oesophageal obstruction
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Gastric ulcer
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Hepatobiliary disorders
    Hepatic steatosis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Excessive granulation tissue
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Skin lesion
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Petechiae
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Acne
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Skin odour abnormal
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Rash
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Urinary hesitation
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    1 / 12 (8.33%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    1
    0
    Femoroacetabular impingement
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Joint effusion
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Muscle contracture
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Myalgia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Pain in extremity
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Arthralgia
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    1
    0
    Tendonitis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Bursitis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Osteochondrosis
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    2 / 30 (6.67%)
    1 / 12 (8.33%)
         occurrences all number
    2
    0
    0
    0
    0
    2
    1
    Nasopharyngitis
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    3 / 41 (7.32%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    1
    3
    1
    0
    COVID-19
         subjects affected / exposed
    4 / 39 (10.26%)
    6 / 28 (21.43%)
    1 / 12 (8.33%)
    5 / 31 (16.13%)
    4 / 41 (9.76%)
    2 / 30 (6.67%)
    1 / 12 (8.33%)
         occurrences all number
    4
    6
    1
    5
    4
    2
    1
    Gastroenteritis viral
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Pharyngitis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Fungal skin infection
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Folliculitis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Sinusitis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Ear infection
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Diarrhoea infectious
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Cellulitis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Bronchitis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Influenza
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    Epstein-Barr virus infection
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Viral infection
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 28 (3.57%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Vulvovaginal candidiasis
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Tonsillitis
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Tooth abscess
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Tooth infection
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Hordeolum
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    1 / 30 (3.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Metabolism and nutrition disorders
    Vitamin D deficiency
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Hypophosphataemia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    1 / 41 (2.44%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Decreased appetite
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    0 / 31 (0.00%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 28 (0.00%)
    0 / 12 (0.00%)
    1 / 31 (3.23%)
    0 / 41 (0.00%)
    0 / 30 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0

    More information

    		 Close Top of page

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

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    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.

    European Medicines Agency © 1995-2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA