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   43929   clinical trials with a EudraCT protocol, of which   7307   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 Multicenter, Randomized, Double-Blind, Placebo Controlled Induction Study to Evaluate the Efficacy and Safety of Risankizumab in Subjects With Moderately to Severely Active Ulcerative Colitis

    Summary
    EudraCT number
    2016-004677-40
    Trial protocol
    BE   SK   AT   SE   ES   NL   PT   GR   DK   LT   PL   DE   GB   LV   SI   BG   HR   FR   IT  
    Global end of trial date
    11 May 2023

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

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    M16-067
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03398148
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AbbVie Deutschland GmbH & Co. KG
    Sponsor organisation address
    AbbVie House, Vanwall Business Park, Vanwall Road,, Maidenhead, Berkshire, United Kingdom, SL6 4UB
    Public contact
    Global Medical Services, AbbVie, AbbVie Deutschland GmbH & Co. KG, 001 8006339110, abbvieclinicaltrials@abbvie.com
    Scientific contact
    Global Medical Services, AbbVie, AbbVie Deutschland GmbH & Co. KG, 001 8006339110, abbvieclinicaltrials@abbvie.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
    11 May 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    11 May 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study comprises two sub-studies: The purpose of Substudy 1 (SS1) is to characterize the efficacy, safety, and pharmacokinetics of Risankizumab as induction treatment in subjects with moderately to severely active Ulcerative Colitis (UC) and to identify the appropriate induction dose of Risankizumab for further evaluation in Substudy 2 (SS2). The purpose of SS2 is to evaluate the efficacy and safety of Risankizumab compared to placebo in inducing clinical remission in subjects with moderately to severely active UC.
    Protection of trial subjects
    Subject and/or legal guardian read and understood the information provided about the study and gave written permission.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    01 Apr 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Israel: 55
    Country: Number of subjects enrolled
    Argentina: 12
    Country: Number of subjects enrolled
    Netherlands: 20
    Country: Number of subjects enrolled
    Poland: 118
    Country: Number of subjects enrolled
    Portugal: 15
    Country: Number of subjects enrolled
    Slovakia: 37
    Country: Number of subjects enrolled
    Slovenia: 4
    Country: Number of subjects enrolled
    Spain: 38
    Country: Number of subjects enrolled
    United Kingdom: 28
    Country: Number of subjects enrolled
    Croatia: 20
    Country: Number of subjects enrolled
    Austria: 40
    Country: Number of subjects enrolled
    Belgium: 75
    Country: Number of subjects enrolled
    Bulgaria: 5
    Country: Number of subjects enrolled
    Czechia: 10
    Country: Number of subjects enrolled
    Denmark: 4
    Country: Number of subjects enrolled
    France: 17
    Country: Number of subjects enrolled
    Germany: 102
    Country: Number of subjects enrolled
    Greece: 26
    Country: Number of subjects enrolled
    Italy: 109
    Country: Number of subjects enrolled
    Latvia: 7
    Country: Number of subjects enrolled
    Lithuania: 15
    Country: Number of subjects enrolled
    Brazil: 29
    Country: Number of subjects enrolled
    Canada: 52
    Country: Number of subjects enrolled
    Chile: 19
    Country: Number of subjects enrolled
    Colombia: 2
    Country: Number of subjects enrolled
    China: 88
    Country: Number of subjects enrolled
    Egypt: 22
    Country: Number of subjects enrolled
    Japan: 207
    Country: Number of subjects enrolled
    Korea, Republic of: 39
    Country: Number of subjects enrolled
    Mexico: 1
    Country: Number of subjects enrolled
    New Zealand: 31
    Country: Number of subjects enrolled
    Romania: 15
    Country: Number of subjects enrolled
    Russian Federation: 20
    Country: Number of subjects enrolled
    Serbia: 37
    Country: Number of subjects enrolled
    Singapore: 2
    Country: Number of subjects enrolled
    South Africa: 22
    Country: Number of subjects enrolled
    Sweden: 3
    Country: Number of subjects enrolled
    Switzerland: 19
    Country: Number of subjects enrolled
    Taiwan: 15
    Country: Number of subjects enrolled
    Ukraine: 8
    Country: Number of subjects enrolled
    United States: 167
    Country: Number of subjects enrolled
    Türkiye: 3
    Worldwide total number of subjects
    1558
    EEA total number of subjects
    680
    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)
    1451
    From 65 to 84 years
    107
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Induction study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). Both sub studies included Periods 1 and 2: S1P1 12 weeks-Double-Blind and Open-Label; S1P2 12 weeks for clinical non-responders in S1P1; S2P1: 12 weeks; S2P2 12 weeks for clinical non-responders from S2P1.

    Pre-assignment
    Screening details
    In SS1 Double-blind (DB) Dose Finding Induction Period 1 (S1P1) (ITT1A), 240 subjects enrolled 180 received at least 1 dose of study drug ; Open-Label (ITT1B), 341 subjects enrolled 340 received drug. S1P2 (ITT1P2): 215 subjects enrolled 214 received drug. In S2P1 (ITT2), 977 randomized 650 received drug. S2P2 (ITT2P2), 384 enrolled and 382 treated

    Period 1
    Period 1 title
    S1P1 and S2P1
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator
    Blinding implementation details
    During Substudy 1, Induction Period 1 (S1P1), Participants received Risankizumab 1800mg administered by intravenous (IV) infusion in an Open-Label manner. All other Substudies were Double-Blinded.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    S1P1: DB - Placebo IV
    Arm description
    Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Placebo for Risankizumab administered by intravenous (IV) infusion.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo for Risankizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo for Risankizumab administered by intravenous (IV) infusion.

    Arm title
    S1P1: DB - Risankizumab 600mg IV
    Arm description
    Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 600mg administered by intravenous (IV) infusion.
    Arm type
    Experimental

    Investigational medicinal product name
    Risankizumab
    Investigational medicinal product code
    Other name
    ABBV-066, BI 655066
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Risankizumab 600mg administered by intravenous (IV) infusion

    Arm title
    S1P1: DB - Risankizumab 1200mg IV
    Arm description
    Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 1200mg administered by intravenous (IV) infusion.
    Arm type
    Experimental

    Investigational medicinal product name
    Risankizumab
    Investigational medicinal product code
    Other name
    ABBV-066, BI 655066
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Risankizumab 1200mg administered by intravenous (IV) infusion

    Arm title
    S1P1: DB - Risankizumab 1800mg IV
    Arm description
    Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 1800mg administered by intravenous (IV) infusion.
    Arm type
    Experimental

    Investigational medicinal product name
    Risankizumab
    Investigational medicinal product code
    Other name
    ABBV-066, BI 655066
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Risankizumab 1800mg administered by intravenous (IV) infusion

    Arm title
    S1P1: OL - Risankizumab 1800mg IV
    Arm description
    Substudy 1, Induction Period 1 (S1P1): Open-label (OL) Participants received Risankizumab 1800mg administered by intravenous (IV) infusion.
    Arm type
    Experimental

    Investigational medicinal product name
    Risankizumab
    Investigational medicinal product code
    Other name
    ABBV-066, BI 655066
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Risankizumab 1800mg administered by intravenous (IV) infusion

    Arm title
    S2P1: DB – Placebo IV
    Arm description
    Substudy 2, Induction Period 1 (S2P1): Double-blind (DB) received placebo for risankizumab administered by intravenous (IV) infusion.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo for risankizumab administered by intravenous (IV) infusion.

    Arm title
    S2P1: DB Risankizumab 1200mg IV
    Arm description
    Substudy 2, Induction Period 1 (S2P1): Double-blind (DB) received risankizumab 1200mg administered by intravenous (IV) infusion.
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    ABBV-066, BI 655066
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    risankizumab 1200mg administered by intravenous (IV) infusion.

    Number of subjects in period 1 [1]
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Started
    60
    61
    61
    58
    340
    325
    650
    Completed
    53
    55
    58
    57
    306
    297
    637
    Not completed
    7
    6
    3
    1
    34
    28
    13
         COVID-19 INFECTION
    -
    -
    -
    -
    -
    -
    1
         Consent withdrawn by subject
    1
    2
    -
    1
    3
    6
    4
         Adverse event, non-fatal
    5
    2
    2
    -
    8
    12
    2
         COVID-19 LOGISTICAL RESTRICTIONS
    -
    -
    -
    -
    -
    -
    1
         Not Specified
    -
    1
    -
    -
    3
    4
    4
         Lack of efficacy
    1
    1
    1
    -
    20
    6
    1
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: In S1P1: Open-label Risankizumab 1800mg IV arm, a total of 341 subjects were enrolled, but only 340 subjects were treated. In the S2P1: Double-blind Risankizumab 1200mg IV arm, a total of 652 subjects were randomized, but only 650 subjects were treated.
    Period 2
    Period 2 title
    S1P2 and S2P2
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    S1P2: DB - Risankizumab 180mg SC
    Arm description
    Substudy 1, Induction Period 2 (S1P2): Double-blind (DB) Participants who received risankizumab with inadequate response in Induction 1 randomized to receive risankizumab 180mg administered by subcutaneous (SC) injection.
    Arm type
    Experimental

    Investigational medicinal product name
    Risankizumab
    Investigational medicinal product code
    Other name
    ABBV-066, BI 655066
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Risankizumab 180mg administered by subcutaneous (SC) injection.

    Arm title
    S1P2: DB – Risankizumab 360mg SC
    Arm description
    Substudy 1, Induction Period 2 (S1P2): Double-blind (DB) Participants who received risankizumab with inadequate response in Induction 1 randomized to receive Risankizumab 360mg administered by subcutaneous (SC) injection.
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    ABBV-066, BI 655066
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Risankizumab 360mg administered by subcutaneous (SC) injection

    Arm title
    S1P2: DB – Risankizumab 1800mg IV
    Arm description
    Substudy 1, Induction Period 2 (S1P2): Double-blind (DB) Participants who received risankizumab with inadequate response in Induction 1 randomized to receive 1800mg administered by intravenous (IV) infusion
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    ABBV-066, BI 655066
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Risankizumab 1800mg administered by intravenous (IV) infusion

    Arm title
    S1P2: DB – Risankizumab 1800mg IV Pbo
    Arm description
    Substudy 1, Induction Period 2 (S1P2): Double-blind (DB) participants who received placebo with inadequate response in Induction 1 receive risankizumab 1800mg administered by intravenous (IV) infusion
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    ABBV-066, BI 655066
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    risankizumab 1800mg administered by intravenous (IV) infusion

    Arm title
    S2P2 DB – Risankizumab 180mg SC
    Arm description
    Substudy 2, Induction Period 2 (S2P2): Double-blind (DB) participants who received risankizumab with inadequate response in Induction 1 randomized to receive risankizumab 180mg administered by subcutaneous (SC) injection
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    ABBV-066, BI 655066
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    risankizumab 180mg administered by subcutaneous (SC) injection

    Arm title
    S2P2 DB – Risankizumab 360mg SC
    Arm description
    Substudy 2, Induction Period 2 (S2P2): Double-blind (DB) participants who received risankizumab with inadequate response in Induction 1 randomized to receive risankizumab 360mg administered by subcutaneous (SC) injection.
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    ABBV-066, BI 655066
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Risankizumab 360mg administered by subcutaneous (SC) injection.

    Arm title
    S2P2 DB – Risankizumab 1200mg IV
    Arm description
    Substudy 2, Induction Period 2 (S2P2): Double-blind (DB) participants who received risankizumab with inadequate response in Induction 1 randomized to receive Risankizumab 1200mg administered by intravenous (IV) infusion.
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    ABBV-066, BI 655066
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Risankizumab 1200mg administered by intravenous (IV) infusion.

    Arm title
    S2P2 DB – Risankizumab 1200mg IV Pbo
    Arm description
    Substudy 2, Induction Period 2 (S2P2): Double-blind (DB) participants received placebo with inadequate response in Induction 1 randomized to receive risankizumab 1200mg administered by intravenous (IV) infusion.
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    ABBV-066, BI 655066
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Risankizumab 1200mg administered by intravenous (IV) infusion.

    Number of subjects in period 2 [2]
    S1P2: DB - Risankizumab 180mg SC S1P2: DB – Risankizumab 360mg SC S1P2: DB – Risankizumab 1800mg IV S1P2: DB – Risankizumab 1800mg IV Pbo S2P2 DB – Risankizumab 180mg SC S2P2 DB – Risankizumab 360mg SC S2P2 DB – Risankizumab 1200mg IV S2P2 DB – Risankizumab 1200mg IV Pbo
    Started
    72
    69
    36
    37
    71
    70
    68
    173
    Completed
    65
    57
    34
    35
    65
    65
    61
    164
    Not completed
    7
    12
    2
    2
    6
    5
    7
    9
         Consent withdrawn by subject
    -
    1
    2
    -
    4
    -
    2
    1
         Adverse event, non-fatal
    2
    4
    -
    -
    -
    -
    1
    3
         COVID-19 LOGISTICAL RESTRICTIONS
    -
    1
    -
    -
    -
    -
    -
    -
         Not Specified
    -
    1
    -
    -
    -
    -
    1
    1
         Lost to follow-up
    -
    -
    -
    -
    1
    1
    -
    -
         Lack of efficacy
    5
    5
    -
    2
    1
    4
    3
    4
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). Both sub studies included a Period 1 followed by a Period 2. Within Substudy 1 and 2, subjects who did not achieve clinical response at Week 12 in the respective substudy were eligible to receive blinded risankizumab treatment in the study period 2.

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    S1P1: DB - Placebo IV
    Reporting group description
    Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Placebo for Risankizumab administered by intravenous (IV) infusion.

    Reporting group title
    S1P1: DB - Risankizumab 600mg IV
    Reporting group description
    Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 600mg administered by intravenous (IV) infusion.

    Reporting group title
    S1P1: DB - Risankizumab 1200mg IV
    Reporting group description
    Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 1200mg administered by intravenous (IV) infusion.

    Reporting group title
    S1P1: DB - Risankizumab 1800mg IV
    Reporting group description
    Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 1800mg administered by intravenous (IV) infusion.

    Reporting group title
    S1P1: OL - Risankizumab 1800mg IV
    Reporting group description
    Substudy 1, Induction Period 1 (S1P1): Open-label (OL) Participants received Risankizumab 1800mg administered by intravenous (IV) infusion.

    Reporting group title
    S2P1: DB – Placebo IV
    Reporting group description
    Substudy 2, Induction Period 1 (S2P1): Double-blind (DB) received placebo for risankizumab administered by intravenous (IV) infusion.

    Reporting group title
    S2P1: DB Risankizumab 1200mg IV
    Reporting group description
    Substudy 2, Induction Period 1 (S2P1): Double-blind (DB) received risankizumab 1200mg administered by intravenous (IV) infusion.

    Reporting group values
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV Total
    Number of subjects
    60 61 61 58 340 325 650 1555
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    44.4 ( 14.09 ) 43.0 ( 14.90 ) 41.8 ( 13.80 ) 40.9 ( 13.73 ) 40.4 ( 14.17 ) 42.8 ( 14.30 ) 41.8 ( 13.47 ) -
    Gender categorical
    Units: Subjects
        Female
    24 21 26 27 145 124 265 632
        Male
    36 40 35 31 195 201 385 923
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    3 2 6 1 21 20 44 97
        Not Hispanic or Latino
    57 59 55 57 319 305 606 1458
        Unknown or Not Reported
    0 0 0 0 0 0 0 0
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0 0 0 0 1 1
        Asian
    14 11 15 11 47 96 171 365
        Native Hawaiian or Other Pacific Islander
    0 0 0 0 0 0 0 0
        Black or African American
    2 1 1 2 3 7 12 28
        White
    44 49 45 45 290 218 461 1152
        More than one race
    0 0 0 0 0 4 5 9
        Unknown or Not Reported
    0 0 0 0 0 0 0 0
    Adapted Mayo Score
    Measure Description: The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) 3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration) The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease.
    Units: Adapted Mayo Score 0 - 9
        arithmetic mean (standard deviation)
    7.012 ( 1.1645 ) 6.929 ( 1.2240 ) 7.011 ( 1.1288 ) 7.15 ( 1.3908 ) 7.179 ( 1.2279 ) 7.052 ( 1.2800 ) 7.068 ( 1.2173 ) -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    S1P1: DB - Placebo IV
    Reporting group description
    Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Placebo for Risankizumab administered by intravenous (IV) infusion.

    Reporting group title
    S1P1: DB - Risankizumab 600mg IV
    Reporting group description
    Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 600mg administered by intravenous (IV) infusion.

    Reporting group title
    S1P1: DB - Risankizumab 1200mg IV
    Reporting group description
    Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 1200mg administered by intravenous (IV) infusion.

    Reporting group title
    S1P1: DB - Risankizumab 1800mg IV
    Reporting group description
    Substudy 1, Induction Period 1 (S1P1): Double-blind (DB) Participants randomized to receive Risankizumab 1800mg administered by intravenous (IV) infusion.

    Reporting group title
    S1P1: OL - Risankizumab 1800mg IV
    Reporting group description
    Substudy 1, Induction Period 1 (S1P1): Open-label (OL) Participants received Risankizumab 1800mg administered by intravenous (IV) infusion.

    Reporting group title
    S2P1: DB – Placebo IV
    Reporting group description
    Substudy 2, Induction Period 1 (S2P1): Double-blind (DB) received placebo for risankizumab administered by intravenous (IV) infusion.

    Reporting group title
    S2P1: DB Risankizumab 1200mg IV
    Reporting group description
    Substudy 2, Induction Period 1 (S2P1): Double-blind (DB) received risankizumab 1200mg administered by intravenous (IV) infusion.
    Reporting group title
    S1P2: DB - Risankizumab 180mg SC
    Reporting group description
    Substudy 1, Induction Period 2 (S1P2): Double-blind (DB) Participants who received risankizumab with inadequate response in Induction 1 randomized to receive risankizumab 180mg administered by subcutaneous (SC) injection.

    Reporting group title
    S1P2: DB – Risankizumab 360mg SC
    Reporting group description
    Substudy 1, Induction Period 2 (S1P2): Double-blind (DB) Participants who received risankizumab with inadequate response in Induction 1 randomized to receive Risankizumab 360mg administered by subcutaneous (SC) injection.

    Reporting group title
    S1P2: DB – Risankizumab 1800mg IV
    Reporting group description
    Substudy 1, Induction Period 2 (S1P2): Double-blind (DB) Participants who received risankizumab with inadequate response in Induction 1 randomized to receive 1800mg administered by intravenous (IV) infusion

    Reporting group title
    S1P2: DB – Risankizumab 1800mg IV Pbo
    Reporting group description
    Substudy 1, Induction Period 2 (S1P2): Double-blind (DB) participants who received placebo with inadequate response in Induction 1 receive risankizumab 1800mg administered by intravenous (IV) infusion

    Reporting group title
    S2P2 DB – Risankizumab 180mg SC
    Reporting group description
    Substudy 2, Induction Period 2 (S2P2): Double-blind (DB) participants who received risankizumab with inadequate response in Induction 1 randomized to receive risankizumab 180mg administered by subcutaneous (SC) injection

    Reporting group title
    S2P2 DB – Risankizumab 360mg SC
    Reporting group description
    Substudy 2, Induction Period 2 (S2P2): Double-blind (DB) participants who received risankizumab with inadequate response in Induction 1 randomized to receive risankizumab 360mg administered by subcutaneous (SC) injection.

    Reporting group title
    S2P2 DB – Risankizumab 1200mg IV
    Reporting group description
    Substudy 2, Induction Period 2 (S2P2): Double-blind (DB) participants who received risankizumab with inadequate response in Induction 1 randomized to receive Risankizumab 1200mg administered by intravenous (IV) infusion.

    Reporting group title
    S2P2 DB – Risankizumab 1200mg IV Pbo
    Reporting group description
    Substudy 2, Induction Period 2 (S2P2): Double-blind (DB) participants received placebo with inadequate response in Induction 1 randomized to receive risankizumab 1200mg administered by intravenous (IV) infusion.

    Primary: Sub-Study 1: Percentage of Participants Achieving Clinical Remission Per Adapted Mayo Score

    Close Top of page
    End point title
    Sub-Study 1: Percentage of Participants Achieving Clinical Remission Per Adapted Mayo Score [1]
    End point description
    The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) 3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration) The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. For Sub-Study 1, clinical remission was defined as SFS ≤ 1, and not greater than baseline, RBS of 0, and endoscopic subscore ≤ 1.
    End point type
    Primary
    End point timeframe
    Week 12
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV
    Number of subjects analysed
    60 [2]
    61 [3]
    61 [4]
    58 [5]
    340 [6]
    Units: Participants
    1
    7
    6
    6
    42
    Notes
    [2] - ITT1A randomized subjects who received at least 1 dose of drug during Induction Period 1 Substudy 1.
    [3] - ITT1A randomized subjects who received at least 1 dose of drug during Induction Period 1 Substudy 1
    [4] - ITT1A randomized subjects who received at least 1 dose of drug during Induction Period 1 Substudy 1
    [5] - ITT1A randomized subjects who received at least 1 dose of drug during Induction Period 1 Substudy 1
    [6] - ITT1B includes all the additional subjects who received at least one dose of risankizumab 1800 mg IV
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0324 [7]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    9.6
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    2.2
         upper limit
    17
    Notes
    [7] - P-value ≤ 0.05. Based on Cochran-Mantel-Haenszel (CMH) test stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (≤ 7, > 7). Risk difference = (risankizumab – Placebo).
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.046 [8]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    8.4
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    1.5
         upper limit
    15.3
    Notes
    [8] - P-value ≤ 0.05. Based on Cochran-Mantel-Haenszel (CMH) test stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (≤ 7, > 7). Risk difference = (risankizumab – Placebo).
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0397 [9]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    8.7
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    1.7
         upper limit
    15.6
    Notes
    [9] - P-value ≤ 0.05. Based on Cochran-Mantel-Haenszel (CMH) test stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (≤ 7, > 7). Risk difference = (risankizumab – Placebo)

    Primary: Sub-Study 2: Percentage of Participants Achieving Clinical Remission Per Adapted Mayo Score

    Close Top of page
    End point title
    Sub-Study 2: Percentage of Participants Achieving Clinical Remission Per Adapted Mayo Score [10]
    End point description
    The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) 3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration) The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. For Sub-Study 2, clinical remission was defined as SFS ≤ 1, and not greater than baseline, RBS of 0, and endoscopic subscore ≤ 1. Evidence of friability during endoscopy in subjects with otherwise "mild" endoscopic activity will confer an endoscopic subscore of 2.
    End point type
    Primary
    End point timeframe
    Week 12
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    325 [11]
    650 [12]
    Units: Percentage of Participants
        arithmetic mean (confidence interval 95%)
    6.2 (3.6 to 8.9)
    20.3 (17.2 to 23.4)
    Notes
    [11] - ITT2 population.
    [12] - ITT2 population.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV
    Number of subjects included in analysis
    975
    Analysis specification
    Pre-specified
    Analysis type
    superiority [13]
    P-value
    < 0.0001 [14]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    14
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    10
         upper limit
    18
    Notes
    [13] - Stratified by Advanced Therapy-IR status (yes vs no), Baseline steroid use (yes vs. no) and Baseline Adapted Mayo Score (≤ 7, > 7).
    [14] - Achieved statistical significance at the 2-sided α level of 0.05 under overall Type I error rate control.

    Secondary: Sub-Study 1: Percentage of Participants Achieving Endoscopic Improvement

    Close Top of page
    End point title
    Sub-Study 1: Percentage of Participants Achieving Endoscopic Improvement [15]
    End point description
    Endoscopic improvement is defined as endoscopy subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV
    Number of subjects analysed
    60 [16]
    61 [17]
    61 [18]
    58 [19]
    340 [20]
    Units: Participants
    3
    15
    8
    9
    61
    Notes
    [16] - Includes ITT1A population.
    [17] - Includes ITT1A population.
    [18] - Includes ITT1A population.
    [19] - Includes ITT1A population.
    [20] - Includes ITT1B population.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0028 [21]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    18.7
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    8.4
         upper limit
    29
    Notes
    [21] - P-value ≤ 0.01. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab – Placebo).
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0968 [22]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    8.4
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.1
         upper limit
    16.7
    Notes
    [22] - P-value ≤ 0.1. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab – Placebo).
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0512 [23]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    10.5
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    1.6
         upper limit
    19.3
    Notes
    [23] - P-value ≤ 0.1. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab – Placebo).

    Secondary: Sub-Study 1: Percentage of Participants Achieving Clinical Remission Per Full Mayo Score in Participants With a FullMayo Score of 6 to 12 at Baseline

    Close Top of page
    End point title
    Sub-Study 1: Percentage of Participants Achieving Clinical Remission Per Full Mayo Score in Participants With a FullMayo Score of 6 to 12 at Baseline [24]
    End point description
    The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Full Mayo score (FMS) ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV
    Number of subjects analysed
    0 [25]
    0 [26]
    0 [27]
    0 [28]
    0 [29]
    Units: Participants
    Notes
    [25] - Data could not be analyzed due to data gathering/validation issues.
    [26] - Data could not be analyzed due to data gathering/validation issues.
    [27] - Data could not be analyzed due to data gathering/validation issues.
    [28] - Data could not be analyzed due to data gathering/validation issues.
    [29] - Data could not be analyzed due to data gathering/validation issues.
    No statistical analyses for this end point

    Secondary: Sub-Study 1: Percentage of Participants Achieving Clinical Response Per Adapted Mayo Score

    Close Top of page
    End point title
    Sub-Study 1: Percentage of Participants Achieving Clinical Response Per Adapted Mayo Score [30]
    End point description
    The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) 3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration) The overall Adapted Mayo Score ranges from 0 to 9 where higher scores represent more severe disease. Clinical response per Adapted Mayo Score was defined as decrease from baseline in Adapted Mayo Score ≥ 2 points and ≥ 30%, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV
    Number of subjects analysed
    60 [31]
    61 [32]
    61 [33]
    58 [34]
    340 [35]
    Units: Participants
    12
    26
    28
    31
    157
    Notes
    [31] - Includes ITT1A population.
    [32] - Includes ITT1A population.
    [33] - Includes ITT1A population.
    [34] - Includes ITT1A population.
    [35] - Includes ITT1B population.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0022 [36]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    23.9
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    11
         upper limit
    36.7
    Notes
    [36] - P-value ≤ 0.01. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0002 [37]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    28.4
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    15.7
         upper limit
    41.1
    Notes
    [37] - P-value ≤ 0.001. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [38]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    33.8
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    20.7
         upper limit
    46.9
    Notes
    [38] - P-value ≤ 0.001. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

    Secondary: Sub-Study 1: Percentage of Participants Achieving Clinical Response Per Partial Adapted Mayo Score

    Close Top of page
    End point title
    Sub-Study 1: Percentage of Participants Achieving Clinical Response Per Partial Adapted Mayo Score [39]
    End point description
    Clinical response per Partial Adapted Mayo Score (without endoscopy). The Partial Mayo Score is a composite score of UC disease activity based on the following 2 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) The overall Partial Mayo Score ranges from 0 to 6 with higher scores representing more severe disease. Clinical response per Partial Mayo Score is defined as a decrease in Partial Adapted Mayo score >= 1 point and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.
    End point type
    Secondary
    End point timeframe
    Week 4
    Notes
    [39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV
    Number of subjects analysed
    60 [40]
    61 [41]
    61 [42]
    58 [43]
    340 [44]
    Units: Participants
    15
    20
    28
    22
    148
    Notes
    [40] - Includes ITT1A population.
    [41] - Includes ITT1A population.
    [42] - Includes ITT1A population.
    [43] - Includes ITT1A population.
    [44] - Includes ITT1B population.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1842 [45]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    10.2
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -2.4
         upper limit
    22.9
    Notes
    [45] - Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0041 [46]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    23.2
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    9.9
         upper limit
    36.4
    Notes
    [46] - P-value ≤ 0.01. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1117 [47]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    13.1
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    26.6
    Notes
    [47] - Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

    Secondary: Sub-Study 1: Percentage of Participants Achieving Endoscopic Remission

    Close Top of page
    End point title
    Sub-Study 1: Percentage of Participants Achieving Endoscopic Remission [48]
    End point description
    Endoscopic remission was defined as endoscopy subscore of 0.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [48] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV
    Number of subjects analysed
    60 [49]
    61 [50]
    61 [51]
    58 [52]
    340 [53]
    Units: Participants
    0
    5
    3
    5
    22
    Notes
    [49] - Includes ITT1A population.
    [50] - Includes ITT1A population.
    [51] - Includes ITT1A population.
    [52] - Includes ITT1A population.
    [53] - Includes ITT1B population.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0192 [54]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    8.3
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    2.5
         upper limit
    14.1
    Notes
    [54] - P-value ≤ 0.05. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0706 [55]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    4.8
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.4
         upper limit
    9.1
    Notes
    [55] - P-value ≤ 0.1. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.017 [56]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    8.7
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    2.7
         upper limit
    14.6
    Notes
    [56] - P-value ≤ 0.05. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

    Secondary: Sub-Study 1: Percentage of Participants With Hospitalization

    Close Top of page
    End point title
    Sub-Study 1: Percentage of Participants With Hospitalization [57]
    End point description
    Participants with an event that results in admission to the hospital.
    End point type
    Secondary
    End point timeframe
    Through Week 12
    Notes
    [57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV
    Number of subjects analysed
    60 [58]
    61 [59]
    61 [60]
    58 [61]
    340 [62]
    Units: Participants
    5
    6
    4
    3
    19
    Notes
    [58] - Includes ITT1A population.
    [59] - Includes ITT1A population.
    [60] - Includes ITT1A population.
    [61] - Includes ITT1A population.
    [62] - Includes ITT1B population.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7737 [63]
    Method
    Chi-squared
    Confidence interval
    Notes
    [63] - P value for comparisons between treatment groups and placebo group using chi-square test or Fisher's exact test.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7432 [64]
    Method
    Fisher exact
    Confidence interval
    Notes
    [64] - P value for comparisons between treatment groups and placebo group using chi-square test or Fisher's exact test.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7172 [65]
    Method
    Fisher exact
    Confidence interval
    Notes
    [65] - P value for comparisons between treatment groups and placebo group using chi-square test or Fisher's exact test.

    Secondary: Sub-Study 1: Percentage of Participants Achieving Histologic Endoscopic Mucosal Remission (HEMR)

    Close Top of page
    End point title
    Sub-Study 1: Percentage of Participants Achieving Histologic Endoscopic Mucosal Remission (HEMR) [66]
    End point description
    Mucosal healing defined as endoscopic and histologic remission. Mucosal healing is defined as an endoscopic score of 0 and Geboes score < 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation;Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; andGrade 5, erosions or ulceration.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV
    Number of subjects analysed
    60 [67]
    61 [68]
    61 [69]
    58 [70]
    340 [71]
    Units: Participants
    0
    3
    2
    1
    10
    Notes
    [67] - Includes ITT1A population.
    [68] - Includes ITT1A population.
    [69] - Includes ITT1A population.
    [70] - Includes ITT1A population.
    [71] - Includes ITT1B population.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0722 [72]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    4.7
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.4
         upper limit
    9
    Notes
    [72] - P-value ≤ 0.1. Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.148 [73]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    3.1
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    6.6
    Notes
    [73] - Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3042 [74]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    1.7
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -1
         upper limit
    4.5
    Notes
    [74] - Stratified by baseline corticosteroid use (yes, no) and baseline adapted mayo score (<= 7, > 7). Risk difference = (risankizumab - Placebo).

    Secondary: Sub-Study 1: Change in Ulcerative Colitis Symptom Questionnaire (UC-SQ)

    Close Top of page
    End point title
    Sub-Study 1: Change in Ulcerative Colitis Symptom Questionnaire (UC-SQ) [75]
    End point description
    The UC-SQ is a patient questionnaire to assess severity of Ulcerative Colitis Symptom
    End point type
    Secondary
    End point timeframe
    Baseline Through Week 12
    Notes
    [75] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV
    Number of subjects analysed
    50 [76]
    52 [77]
    56 [78]
    53 [79]
    286 [80]
    Units: Units on a scale
        least squares mean (standard error)
    -7.4 ( 1.53 )
    -13.8 ( 1.50 )
    -15.6 ( 1.46 )
    -15.1 ( 1.51 )
    -17.1 ( 0.58 )
    Notes
    [76] - Includes ITT1A population.
    [77] - Includes ITT1A population.
    [78] - Includes ITT1A population.
    [79] - Includes ITT1A population.
    [80] - Includes ITT1B population.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003 [81]
    Method
    Mixed-effect model repeated measurement
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    -6.4
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.94
         upper limit
    -2.89
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.13
    Notes
    [81] - P-value ≤ 0.01.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0001 [82]
    Method
    Mixed-effect model repeated measurement
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    -8.2
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.67
         upper limit
    -4.71
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.11
    Notes
    [82] - P-value ≤ 0.001
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0004 [83]
    Method
    Mixed-effect model repeated measurement
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    -7.7
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.27
         upper limit
    -4.19
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.14
    Notes
    [83] - P-value ≤ 0.001

    Secondary: Sub-Study 1: Change in Inflammatory Bowel Disease Questionnaire (IBDQ)

    Close Top of page
    End point title
    Sub-Study 1: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) [84]
    End point description
    The IBDQ is used to assess the quality of life of patients with inflammatory bowel disease. The IBDQ is a 32-item (ranges 1 - 7) self-report questionnaire for patients with IBD to evaluate the patient reported outcomes across 4 dimensions: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). The IBDQ total Score ranges from 32 to 224 with a higher score indicating better outcome.
    End point type
    Secondary
    End point timeframe
    Baseline Through Week 12
    Notes
    [84] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV
    Number of subjects analysed
    51 [85]
    55 [86]
    59 [87]
    54 [88]
    305 [89]
    Units: Units on a scale
        least squares mean (standard error)
    20.1 ( 4.67 )
    37.4 ( 4.56 )
    40.3 ( 4.38 )
    40.0 ( 4.55 )
    49.5 ( 1.86 )
    Notes
    [85] - Includes ITT1A population.
    [86] - Includes ITT1A population.
    [87] - Includes ITT1A population.
    [88] - Includes ITT1A population.
    [89] - Includes ITT1B population.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0081 [90]
    Method
    Mixed-effect model repeated measurement
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    17.3
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    6.61
         upper limit
    28
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.47
    Notes
    [90] - P-value ≤ 0.01.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0017 [91]
    Method
    Mixed-effect model repeated measurement
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    20.3
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    9.74
         upper limit
    30.79
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.37
    Notes
    [91] - P-value ≤ 0.01
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0024 [92]
    Method
    Mixed-effect model repeated measurement
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    19.9
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    9.22
         upper limit
    30.67
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.49
    Notes
    [92] - P-value ≤ 0.01

    Secondary: Sub-Study 1: Change in Short Form-36 (SF-36) - Physical Component

    Close Top of page
    End point title
    Sub-Study 1: Change in Short Form-36 (SF-36) - Physical Component [93]
    End point description
    The SF-36 is an indicator of overall health status. The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).
    End point type
    Secondary
    End point timeframe
    Baseline Through Week 12
    Notes
    [93] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV
    Number of subjects analysed
    51 [94]
    54 [95]
    59 [96]
    54 [97]
    298 [98]
    Units: Units on a scale
        least squares mean (standard error)
    3.904 ( 0.8907 )
    5.112 ( 0.8751 )
    6.350 ( 0.8341 )
    6.296 ( 0.8675 )
    7.719 ( 0.3929 )
    Notes
    [94] - Includes ITT1A population.
    [95] - Includes ITT1A population.
    [96] - Includes ITT1A population.
    [97] - Includes ITT1A population.
    [98] - Includes ITT1B population.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3315
    Method
    Mixed-effect model repeated measurement
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    1.208
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -0.8429
         upper limit
    3.2596
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.2416
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0451 [99]
    Method
    Mixed-effect model repeated measurement
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    2.447
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.4415
         upper limit
    4.4519
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.2137
    Notes
    [99] - P-value ≤ 0.05
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0543 [100]
    Method
    Mixed-effect model repeated measurement
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    2.392
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.3498
         upper limit
    4.4352
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.2364
    Notes
    [100] - P-value ≤ 0.1

    Secondary: Sub-Study 1: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)

    Close Top of page
    End point title
    Sub-Study 1: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) [101]
    End point description
    The FACIT-Fatigue Scale is a validated self-administered 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four-point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from baseline indicates improvement.
    End point type
    Secondary
    End point timeframe
    Baseline Through Week 12
    Notes
    [101] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV
    Number of subjects analysed
    51 [102]
    54 [103]
    59 [104]
    54 [105]
    298 [106]
    Units: units on a scale
        least squares mean (standard error)
    3.7 ( 1.37 )
    7.6 ( 1.35 )
    9.0 ( 1.29 )
    8.3 ( 1.33 )
    10.7 ( 0.54 )
    Notes
    [102] - Includes ITT1A population.
    [103] - Includes ITT1A population..
    [104] - Includes ITT1A population.
    [105] - Includes ITT1A population.
    [106] - Includes ITT1B population.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0422 [107]
    Method
    Mixed-effect model repeated measurement
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    3.9
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.75
         upper limit
    7.06
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.91
    Notes
    [107] - P-value ≤ 0.05
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0049 [108]
    Method
    Mixed-effect model repeated measurement
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    5.3
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    2.23
         upper limit
    8.42
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.87
    Notes
    [108] - P-value ≤ 0.01
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0156 [109]
    Method
    Mixed-effect model repeated measurement
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    4.6
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    1.5
         upper limit
    7.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.91
    Notes
    [109] - P-value ≤ 0.05

    Secondary: Sub-Study 1: Percentage of Participants Undergoing Ulcerative Colitis (UC)-Related Surgeries

    Close Top of page
    End point title
    Sub-Study 1: Percentage of Participants Undergoing Ulcerative Colitis (UC)-Related Surgeries [110]
    End point description
    Participants who underwent surgery related to UC.
    End point type
    Secondary
    End point timeframe
    Through Week 12
    Notes
    [110] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV
    Number of subjects analysed
    60 [111]
    61 [112]
    61 [113]
    58 [114]
    340 [115]
    Units: Participants
    0
    1
    0
    0
    7
    Notes
    [111] - Includes ITT1A population.
    [112] - Includes ITT1A population.
    [113] - Includes ITT1A population.
    [114] - Includes ITT1A population.
    [115] - Includes ITT1B population.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 1 [116]
    Method
    Fisher exact
    Confidence interval
    Notes
    [116] - P-Value for comparisons between treatment groups and placebo group using Fisher's exact test.

    Secondary: Sub-Study 2: Percentage of Participants Achieving Clinical Response Per Adapted Mayo Score

    Close Top of page
    End point title
    Sub-Study 2: Percentage of Participants Achieving Clinical Response Per Adapted Mayo Score [117]
    End point description
    The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration) The overall Adapted Mayo Score ranges from 0 to 9 where higher scores represent more severe disease. Clinical Response is defined as a decrease from baseline in the Adapted Mayo Score ≥ 2 points and ≥ 30% from baseline, and a decrease in RBS ≥ 1 or an absolute RBS ≤ 1).
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [117] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    325 [118]
    650 [119]
    Units: Participants
    116
    418
    Notes
    [118] - ITT2
    [119] - ITT2
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB Risankizumab 1200mg IV v S2P1: DB – Placebo IV
    Number of subjects included in analysis
    975
    Analysis specification
    Pre-specified
    Analysis type
    superiority [120]
    P-value
    < 0.0001 [121]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    28.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    22.3
         upper limit
    34.8
    Notes
    [120] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
    [121] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

    Secondary: Sub-Study 2: Percentage of Participants Achieving Endoscopic Improvement

    Close Top of page
    End point title
    Sub-Study 2: Percentage of Participants Achieving Endoscopic Improvement [122]
    End point description
    Endoscopic Improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [122] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    325 [123]
    650 [124]
    Units: Participants
    39
    237
    Notes
    [123] - ITT2
    [124] - ITT2
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV
    Number of subjects included in analysis
    975
    Analysis specification
    Pre-specified
    Analysis type
    superiority [125]
    P-value
    < 0.0001 [126]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    24.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    19.3
         upper limit
    29.4
    Notes
    [125] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
    [126] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

    Secondary: Sub-Study 2: Percentage of Participants Achieving Histologic Endoscopic Mucosal Improvement (HEMI)

    Close Top of page
    End point title
    Sub-Study 2: Percentage of Participants Achieving Histologic Endoscopic Mucosal Improvement (HEMI) [127]
    End point description
    Histologic-Endoscopic Mucosal Improvement is defined as an endoscopic subscore of 0 or 1 without evidence of friability and a Geboes score ≤ 3.1. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [127] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    325 [128]
    650 [129]
    Units: Participants
    25
    159
    Notes
    [128] - ITT2
    [129] - ITT2
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV
    Number of subjects included in analysis
    975
    Analysis specification
    Pre-specified
    Analysis type
    superiority [130]
    P-value
    < 0.0001 [131]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    16.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    12.3
         upper limit
    21
    Notes
    [130] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
    [131] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level. Adjusted Risk Difference.

    Secondary: Sub-Study 2: Percentage of Participants Achieving Endoscopic Remission

    Close Top of page
    End point title
    Sub-Study 2: Percentage of Participants Achieving Endoscopic Remission [132]
    End point description
    Endoscopic remission per endoscopy subscore. Endoscopic Remission: SES-CD ≤ 4 and at least a 2-point reduction versus baseline and no subscore greater than 1 in any individual variable.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [132] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    325 [133]
    650 [134]
    Units: Participants
    11
    69
    Notes
    [133] - ITT2
    [134] - ITT2
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV
    Number of subjects included in analysis
    975
    Analysis specification
    Pre-specified
    Analysis type
    superiority [135]
    P-value
    < 0.0001 [136]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    7.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.2
         upper limit
    10.2
    Notes
    [135] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
    [136] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

    Secondary: Sub-Study 2: Percentage of Participants Achieving Clinical Response Per Partial Adapted Mayo Score at Week 4

    Close Top of page
    End point title
    Sub-Study 2: Percentage of Participants Achieving Clinical Response Per Partial Adapted Mayo Score at Week 4 [137]
    End point description
    Clinical response per Partial Adapted Mayo Score (without endoscopy). The Partial Mayo Score is a composite score of UC disease activity based on the following 2 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) The overall Partial Mayo Score ranges from 0 to 6 with higher scores representing more severe disease. Clinical Response per Partial Mayo Score is defined as a decrease in Partial Adapted Mayo Score ≥ 1 points and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.
    End point type
    Secondary
    End point timeframe
    Week 4
    Notes
    [137] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    325 [138]
    650 [139]
    Units: Participants
    99
    339
    Notes
    [138] - ITT2
    [139] - ITT2
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV
    Number of subjects included in analysis
    975
    Analysis specification
    Pre-specified
    Analysis type
    superiority [140]
    P-value
    < 0.0001 [141]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    21.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    15.6
         upper limit
    28.1
    Notes
    [140] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
    [141] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

    Secondary: Sub-Study 2: Percentage of Participants Achieving No Bowel Urgency

    Close Top of page
    End point title
    Sub-Study 2: Percentage of Participants Achieving No Bowel Urgency [142]
    End point description
    Percentage of participants who reported no bowel urgency. Bowel urgency was assessed by participants in a subject diary completed once a day.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [142] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    325 [143]
    650 [144]
    Units: Participants
    90
    287
    Notes
    [143] - ITT2
    [144] - ITT2
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV
    Number of subjects included in analysis
    975
    Analysis specification
    Pre-specified
    Analysis type
    superiority [145]
    P-value
    < 0.0001 [146]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    16.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    10.3
         upper limit
    22.4
    Notes
    [145] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
    [146] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

    Secondary: Sub-Study 2: Percentage of Participants Achieving No Abdominal Pain

    Close Top of page
    End point title
    Sub-Study 2: Percentage of Participants Achieving No Abdominal Pain [147]
    End point description
    Percentage of participants who reported no abdominal pain. Abdominal pain was assessed by participants in a subject diary completed once a day.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [147] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    325 [148]
    650 [149]
    Units: Participants
    86
    232
    Notes
    [148] - ITT2
    [149] - ITT2
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV
    Number of subjects included in analysis
    975
    Analysis specification
    Pre-specified
    Analysis type
    superiority [150]
    P-value
    = 0.0021 [151]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    9.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.4
         upper limit
    15.3
    Notes
    [150] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
    [151] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

    Secondary: Sub-Study 2: Percentage of Participants Achieving Histologic Endoscopic Mucosal Remission (HEMR): Endoscopy Subscore of 0 and Geboes Score < 2.0) at Week 12

    Close Top of page
    End point title
    Sub-Study 2: Percentage of Participants Achieving Histologic Endoscopic Mucosal Remission (HEMR): Endoscopy Subscore of 0 and Geboes Score < 2.0) at Week 12 [152]
    End point description
    Mucosal healing defined as endoscopic and histologic remission. Mucosal healing is defined as an endoscopic score of 0 and Geboes score < 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [152] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    325 [153]
    650 [154]
    Units: Participants
    2
    41
    Notes
    [153] - ITT2
    [154] - ITT2
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV
    Number of subjects included in analysis
    975
    Analysis specification
    Pre-specified
    Analysis type
    superiority [155]
    P-value
    < 0.0001 [156]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    5.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.5
         upper limit
    7.7
    Notes
    [155] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
    [156] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

    Secondary: Sub-Study 2: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)

    Close Top of page
    End point title
    Sub-Study 2: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) [157]
    End point description
    The FACIT-Fatigue Scale is a validated self-administered 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four-point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from baseline indicates improvement.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [157] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    308 [158]
    614 [159]
    Units: Units on scale
        least squares mean (confidence interval 95%)
    3.3 (2.12 to 4.50)
    7.9 (7.03 to 8.69)
    Notes
    [158] - ITT2
    [159] - ITT2
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV
    Number of subjects included in analysis
    922
    Analysis specification
    Pre-specified
    Analysis type
    superiority [160]
    P-value
    < 0.0001 [161]
    Method
    ANCOVA
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    4.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.13
         upper limit
    5.97
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.72
    Notes
    [160] - Between-group diff. and 95% CI calculated using ANCOVA/MMRM with RTB-MI for continuous endpoints.
    [161] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

    Secondary: Sub-Study 2: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score

    Close Top of page
    End point title
    Sub-Study 2: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score [162]
    End point description
    The IBDQ is used to assess the quality of life of patients with inflammatory bowel disease. The IBDQ is a 32-item (ranges 1 - 7) self-report questionnaire for patients with IBD to evaluate the patient reported outcomes across 4 dimensions: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). The IBDQ total Score ranges from 32 to 224 with a higher score indicating better outcome.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12
    Notes
    [162] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    310 [163]
    619 [164]
    Units: Units on scale
        least squares mean (confidence interval 95%)
    24.3 (20.19 to 28.46)
    42.6 (39.72 to 45.57)
    Notes
    [163] - ITT2
    [164] - ITT2
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV
    Number of subjects included in analysis
    929
    Analysis specification
    Pre-specified
    Analysis type
    superiority [165]
    P-value
    < 0.0001 [166]
    Method
    ANCOVA
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    18.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    13.38
         upper limit
    23.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.52
    Notes
    [165] - Between-group diff. and 95% CI calculated using ANCOVA/MMRM with RTB-MI for continuous endpoints.
    [166] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

    Secondary: Sub-Study 2: Occurrence of UC-related Hospitalizations

    Close Top of page
    End point title
    Sub-Study 2: Occurrence of UC-related Hospitalizations [167]
    End point description
    Participants with an UC-related event that results in admission to the hospital.
    End point type
    Secondary
    End point timeframe
    Baseline Through Week 12
    Notes
    [167] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    325 [168]
    650 [169]
    Units: Count of participants
        least squares mean (confidence interval 95%)
    5.5 (3.1 to 8.0)
    0.8 (0.1 to 1.4)
    Notes
    [168] - ITT2
    [169] - ITT2
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV
    Number of subjects included in analysis
    975
    Analysis specification
    Pre-specified
    Analysis type
    superiority [170]
    P-value
    < 0.0001 [171]
    Method
    Chi-squared
    Parameter type
    Risk difference=(Risankizumab - Placebo)
    Point estimate
    -4.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.3
         upper limit
    -2.2
    Notes
    [170] - 95% CI for treatment differences is based on normal approximation of the binomial proportions
    [171] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

    Secondary: Sub-Study 2: Percentage of Participants Achieving No Nocturnal Bowel Movements

    Close Top of page
    End point title
    Sub-Study 2: Percentage of Participants Achieving No Nocturnal Bowel Movements [172]
    End point description
    Percentage of participants who reported no nocturnal bowel movements.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [172] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    325 [173]
    650 [174]
    Units: Participants
    140
    437
    Notes
    [173] - ITT2
    [174] - ITT2
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV
    Number of subjects included in analysis
    975
    Analysis specification
    Pre-specified
    Analysis type
    superiority [175]
    P-value
    < 0.0001 [176]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    24.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    17.9
         upper limit
    30.5
    Notes
    [175] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate difference. (Greenland and Robins (1985)).
    [176] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

    Secondary: Sub-Study 2: Percentage of Participants Achieving No Tenesmus

    Close Top of page
    End point title
    Sub-Study 2: Percentage of Participants Achieving No Tenesmus [177]
    End point description
    Percentage of participants who reported no tenesmus.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [177] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    325 [178]
    650 [179]
    Units: Participants
    98
    317
    Notes
    [178] - ITT2
    [179] - ITT2
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV
    Number of subjects included in analysis
    975
    Analysis specification
    Pre-specified
    Analysis type
    superiority [180]
    P-value
    < 0.0001 [181]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Adjusted Risk Difference
    Point estimate
    18.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    12.4
         upper limit
    24.8
    Notes
    [180] - Between-group diff. and 95% CI calculated using Mantel-Haenszel common rate diff. (Greenland and Robins (1985)).
    [181] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

    Secondary: Sub-Study 2: Change in Number of Fecal Incontinence Episodes Per Week

    Close Top of page
    End point title
    Sub-Study 2: Change in Number of Fecal Incontinence Episodes Per Week [182]
    End point description
    Change in number of fecal incontinence episodes per week.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12
    Notes
    [182] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    288
    602
    Units: Count of participants
        least squares mean (confidence interval 95%)
    -2.213 (-2.8526 to -1.5726)
    -3.839 (-4.2687 to -3.4099)
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV
    Number of subjects included in analysis
    890
    Analysis specification
    Pre-specified
    Analysis type
    superiority [183]
    P-value
    < 0.0001 [184]
    Method
    Mixed-Effect Model Repeated Measures
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    -1.627
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.3846
         upper limit
    -0.8689
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3865
    Notes
    [183] - Between-group diff. and 95% CI calculated using ANCOVA/MMRM with RTB-MI for continuous endpoints.
    [184] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

    Secondary: Sub-Study 2: Change in Number of Days Per Week With Sleep Interrupted Due to UC Symptoms

    Close Top of page
    End point title
    Sub-Study 2: Change in Number of Days Per Week With Sleep Interrupted Due to UC Symptoms [185]
    End point description
    Change from baseline in number of days per week with sleep interrupted due to UC symptoms.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12
    Notes
    [185] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S2P1: DB – Placebo IV S2P1: DB Risankizumab 1200mg IV
    Number of subjects analysed
    288 [186]
    602 [187]
    Units: Count of Participants
        least squares mean (confidence interval 95%)
    -1.505 (-1.7969 to -1.2122)
    -2.485 (-2.6872 to -2.2831)
    Notes
    [186] - ITT2
    [187] - ITT2
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S2P1: DB – Placebo IV v S2P1: DB Risankizumab 1200mg IV
    Number of subjects included in analysis
    890
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001 [188]
    Method
    Mixed-effect model repeated measurement
    Parameter type
    Least Squares (LS) Mean Difference
    Point estimate
    -0.981
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.3285
         upper limit
    -0.6326
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1775
    Notes
    [188] - Statistical significance is determined via the graphical multiple testing procedure controlling the overall type I error rate of primary and key secondary endpoints at the 0.05 level.

    Secondary: Sub-Study 1: Change From Baseline in Short Form-36 (SF-36) - Mental Component

    Close Top of page
    End point title
    Sub-Study 1: Change From Baseline in Short Form-36 (SF-36) - Mental Component [189]
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline through Week 12
    Notes
    [189] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study included Sub Studies 1 and 2 (Phase 2b dose-finding induction and Phase 3 efficacy/safety induction studies, respectively). The arms as shown are aligned with the sub study and planned analysis population for this end point per protocol and statistical analysis plan.
    End point values
    S1P1: DB - Placebo IV S1P1: DB - Risankizumab 600mg IV S1P1: DB - Risankizumab 1200mg IV S1P1: DB - Risankizumab 1800mg IV S1P1: OL - Risankizumab 1800mg IV
    Number of subjects analysed
    51 [190]
    54 [191]
    59 [192]
    54 [193]
    298 [194]
    Units: Units on a scale
        least squares mean (standard error)
    3.094 ( 1.2533 )
    6.756 ( 1.2319 )
    7.284 ( 1.1739 )
    5.442 ( 1.2185 )
    7.777 ( 0.4777 )
    Notes
    [190] - Includes ITT1A population.
    [191] - Includes ITT1A population.
    [192] - Includes ITT1A population.
    [193] - Includes ITT1A population.
    [194] - Includes ITT1B population.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 600mg IV
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0367 [195]
    Method
    Mixed-effect model repeated measurement
    Parameter type
    LS Mean of Difference
    Point estimate
    3.662
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.7841
         upper limit
    6.5402
    Notes
    [195] - P-value for test of difference between each Risankizumab dose group and placebo for mean change from baseline using the mixed-effect repeated measure model The unstructured covariance structure was used to estimate within subject errors.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1200mg IV
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0151 [196]
    Method
    Mixed-effect model repeated measurement
    Parameter type
    LS Mean of Difference
    Point estimate
    4.19
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    1.3656
         upper limit
    7.0144
    Notes
    [196] - P-value for test of difference between each Risankizumab dose group and placebo for mean change from baseline using the mixed-effect repeated measure model The unstructured covariance structure was used to estimate within subject errors.
    Statistical analysis title
    Primary Analysis
    Comparison groups
    S1P1: DB - Placebo IV v S1P1: DB - Risankizumab 1800mg IV
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1795 [197]
    Method
    Mixed-effect model repeated measurement
    Parameter type
    LS Mean of Difference
    Point estimate
    2.348
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -0.5322
         upper limit
    5.2281
    Notes
    [197] - P-value for test of difference between each Risankizumab dose group and placebo for mean change from baseline using the mixed-effect repeated measure model The unstructured covariance structure was used to estimate within subject errors.

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All-cause mortality and Serious AE were reported from time of informed consent until 140 days following last dose of study drug, or the first dose of next period/study, whichever occurs first.
    Adverse event reporting additional description
    All other AE were reported from time of first dose until 140 days following last dose of study drug, or the first dose of next period/study, whichever occurs earlier.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    SS1_P1_PlbIV
    Reporting group description
    -

    Reporting group title
    SS1_P1_Risa_1200mgIV
    Reporting group description
    -

    Reporting group title
    SS1_P1_Risa_600mgIV
    Reporting group description
    -

    Reporting group title
    SS1_P2_Risa_1800mgIV
    Reporting group description
    -

    Reporting group title
    SS1_P2_PlbIV_Risa_1800mgIV
    Reporting group description
    -

    Reporting group title
    SS1_P1_OL_Risa_1800mgIV
    Reporting group description
    -

    Reporting group title
    SS1_P1_DB_Risa_1800mgIV
    Reporting group description
    -

    Reporting group title
    SS1_P2_Risa_180mgSC
    Reporting group description
    -

    Reporting group title
    SS2_P2_PlbIV_Risa_1200mgIV
    Reporting group description
    -

    Reporting group title
    SS2_P1_Risa_1200mgIV
    Reporting group description
    -

    Reporting group title
    SS1_P2_Risa_360mgSC
    Reporting group description
    -

    Reporting group title
    SS2_P1_PlbIV
    Reporting group description
    -

    Reporting group title
    SS2_P2_Risa_180mgSC
    Reporting group description
    -

    Reporting group title
    SS2_P2_Risa_1200mgIV
    Reporting group description
    -

    Reporting group title
    SS2_P2_Risa_360mgSC
    Reporting group description
    -

    Serious adverse events
    SS1_P1_PlbIV SS1_P1_Risa_1200mgIV SS1_P1_Risa_600mgIV SS1_P2_Risa_1800mgIV SS1_P2_PlbIV_Risa_1800mgIV SS1_P1_OL_Risa_1800mgIV SS1_P1_DB_Risa_1800mgIV SS1_P2_Risa_180mgSC SS2_P2_PlbIV_Risa_1200mgIV SS2_P1_Risa_1200mgIV SS1_P2_Risa_360mgSC SS2_P1_PlbIV SS2_P2_Risa_180mgSC SS2_P2_Risa_1200mgIV SS2_P2_Risa_360mgSC
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 59 (10.17%)
    4 / 61 (6.56%)
    6 / 62 (9.68%)
    1 / 37 (2.70%)
    3 / 36 (8.33%)
    20 / 340 (5.88%)
    3 / 58 (5.17%)
    6 / 71 (8.45%)
    4 / 173 (2.31%)
    15 / 651 (2.30%)
    7 / 70 (10.00%)
    33 / 324 (10.19%)
    4 / 71 (5.63%)
    1 / 68 (1.47%)
    1 / 70 (1.43%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BREAST CANCER
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PITUITARY TUMOUR BENIGN
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PROSTATE CANCER
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RENAL CANCER
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    ARTERIAL OCCLUSIVE DISEASE
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    1 / 71 (1.41%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    1 / 62 (1.61%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    1 / 651 (0.15%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPERTENSION
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    1 / 70 (1.43%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL ARTERY OCCLUSION
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    1 / 71 (1.41%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    PYREXIA
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    1 / 62 (1.61%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    1 / 71 (1.41%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    ANAPHYLACTIC REACTION
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    1 / 70 (1.43%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    UTERINE PROLAPSE
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    1 / 71 (1.41%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    PLEURAL EFFUSION
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    1 / 340 (0.29%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    2 / 651 (0.31%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY DISTRESS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    1 / 70 (1.43%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    ADJUSTMENT DISORDER
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GENERALISED ANXIETY DISORDER
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MAJOR DEPRESSION
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    1 / 651 (0.15%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SUICIDAL IDEATION
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    1 / 340 (0.29%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    HAEMOGLOBIN DECREASED
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    ROAD TRAFFIC ACCIDENT
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    1 / 173 (0.58%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    1 / 71 (1.41%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SKELETAL INJURY
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    1 / 651 (0.15%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SKIN LACERATION
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    1 / 651 (0.15%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SUBDURAL HAEMATOMA
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    1 / 651 (0.15%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    ARTERIOSCLEROSIS CORONARY ARTERY
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TACHYCARDIA
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    1 / 70 (1.43%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    CEREBRAL MASS EFFECT
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    1 / 651 (0.15%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CEREBROVASCULAR ACCIDENT
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    1 / 70 (1.43%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIZZINESS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    0 / 59 (0.00%)
    2 / 61 (3.28%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    2 / 651 (0.31%)
    1 / 70 (1.43%)
    2 / 324 (0.62%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    CATARACT
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    1 / 340 (0.29%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ANAL FISTULA
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    2 / 324 (0.62%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ANAL PROLAPSE
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    1 / 340 (0.29%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COLITIS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    1 / 62 (1.61%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    1 / 58 (1.72%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COLITIS ULCERATIVE
         subjects affected / exposed
    3 / 59 (5.08%)
    0 / 61 (0.00%)
    1 / 62 (1.61%)
    0 / 37 (0.00%)
    1 / 36 (2.78%)
    12 / 340 (3.53%)
    0 / 58 (0.00%)
    3 / 71 (4.23%)
    1 / 173 (0.58%)
    2 / 651 (0.31%)
    2 / 70 (2.86%)
    16 / 324 (4.94%)
    1 / 71 (1.41%)
    0 / 68 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    1 / 12
    0 / 0
    0 / 3
    0 / 1
    1 / 2
    1 / 2
    2 / 17
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ENTERITIS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    1 / 71 (1.41%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTRITIS EROSIVE
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    1 / 651 (0.15%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HAEMATEMESIS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    1 / 173 (0.58%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    HEPATIC CIRRHOSIS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    ERYTHEMA NODOSUM
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PEMPHIGOID
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    1 / 36 (2.78%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    CALCULUS URINARY
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    1 / 71 (1.41%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NEPHROLITHIASIS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    1 / 71 (1.41%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RENAL COLIC
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 61 (1.64%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RENAL FAILURE
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    1 / 340 (0.29%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    FLANK PAIN
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    1 / 340 (0.29%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OSTEONECROSIS
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    1 / 36 (2.78%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    1 / 651 (0.15%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    ABSCESS LIMB
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    1 / 651 (0.15%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ANAL ABSCESS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    2 / 340 (0.59%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    APPENDICITIS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    1 / 58 (1.72%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CLOSTRIDIUM DIFFICILE INFECTION
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    1 / 173 (0.58%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    1 / 651 (0.15%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    1 / 68 (1.47%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 PNEUMONIA
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    1 / 651 (0.15%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CYSTITIS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    1 / 173 (0.58%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CYTOMEGALOVIRUS INFECTION
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    1 / 62 (1.61%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    1 / 340 (0.29%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DEVICE RELATED SEPSIS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    1 / 58 (1.72%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ENDOCARDITIS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ENTERITIS INFECTIOUS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ERYSIPELAS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    1 / 36 (2.78%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINE INFECTION
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 61 (1.64%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LUNG ABSCESS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    1 / 36 (2.78%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PAROTID ABSCESS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PHARYNGEAL ABSCESS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    1 / 324 (0.31%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    1 / 651 (0.15%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA HAEMOPHILUS
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    1 / 62 (1.61%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA MYCOPLASMAL
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    0 / 340 (0.00%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    1 / 70 (1.43%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    POST PROCEDURAL INFECTION
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 61 (0.00%)
    0 / 62 (0.00%)
    0 / 37 (0.00%)
    0 / 36 (0.00%)
    1 / 340 (0.29%)
    0 / 58 (0.00%)
    0 / 71 (0.00%)
    0 / 173 (0.00%)
    0 / 651 (0.00%)
    0 / 70 (0.00%)
    0 / 324 (0.00%)
    0 / 71 (0.00%)
    0 / 68 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    POSTOPERATIVE WOUND INFECTION