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    Clinical Trial Results:
    A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Study of Baricitinib in Patients with Systemic Lupus Erythematosus

    Summary
    EudraCT number
    		 2017-005026-37
    Trial protocol
    		 GB   AT   BE   HU   CZ   GR   NL   HR  
    Global end of trial date
    09 Mar 2022

    Results information
    Results version number
    		 v1
    This version publication date
    27 Oct 2022
    First version publication date
    27 Oct 2022
    Other versions
    		 v2

    Trial information

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    Trial identification
    Sponsor protocol code
    I4V-MC-JAHZ
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03616912
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 16676
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,
    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
    09 Mar 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Mar 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The reason for this study is to see how effective and safe the study drug known as baricitinib is in participants with systemic lupus erythematosus (SLE).
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Aug 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
    Austria: 3
    Country: Number of subjects enrolled
    Australia: 31
    Country: Number of subjects enrolled
    Brazil: 83
    Country: Number of subjects enrolled
    China: 116
    Country: Number of subjects enrolled
    Israel: 8
    Country: Number of subjects enrolled
    Mexico: 136
    Country: Number of subjects enrolled
    Taiwan: 39
    Country: Number of subjects enrolled
    United States: 146
    Country: Number of subjects enrolled
    Czechia: 38
    Country: Number of subjects enrolled
    Germany: 45
    Country: Number of subjects enrolled
    Greece: 18
    Country: Number of subjects enrolled
    Netherlands: 2
    Country: Number of subjects enrolled
    Switzerland: 8
    Country: Number of subjects enrolled
    Belgium: 4
    Country: Number of subjects enrolled
    Croatia: 10
    Country: Number of subjects enrolled
    Hungary: 50
    Country: Number of subjects enrolled
    Russian Federation: 71
    Country: Number of subjects enrolled
    United Kingdom: 13
    Worldwide total number of subjects
    821
    EEA total number of subjects
    170
    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)
    1
    Adults (18-64 years)
    789
    From 65 to 84 years
    31
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 As only year of birth was collected on case report form, for one participant, age at enrollment was calculated as 17 years old, using the imputed day and month of “01Jul ”. Therefore, not necessarily indicating the participant's actual age.

    Pre-assignment
    Screening details
    		 One investigational site with seven participants was excluded from analysis due to confirmed misconduct.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received two placebo tablets: one matching 4 mg Baricitinib and one matching 2 mg Baricitinib administered orally every day (QD) for 52 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received two placebo tablets: one matching 4 mg Baricitinib and one matching 2 mg Baricitinib administered orally QD for 52 weeks.

    Arm title
    		 2 mg Baricitinib
    Arm description
    		 Participants received one 2 mg Baricitinib tablet and one placebo tablet matching 4 mg Baricitinib administered orally QD for 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    Other name
    LY3009104
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received one 2 mg Baricitinib tablet and one placebo tablet matching 4 mg Baricitinib administered orally QD for 52 weeks.

    Arm title
    		 4 mg Baricitinib
    Arm description
    		 Participants received one 4 mg Baricitinib tablet and one placebo tablet matching 2 mg Baricitinib administered orally every day (QD) for 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    Other name
    LY3009104
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received one 4 mg Baricitinib tablet and one placebo tablet matching 2 mg Baricitinib administered orally every day (QD) for 52 weeks.

    Arm title
    		 Placebo Maximum Extended Enrollment (MEE)
    Arm description
    		 Participants received two placebo tablets: one matching 4 mg Baricitinib and one matching 2 mg Baricitinib administered orally QD for 52 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received two placebo tablets: one matching 4 mg Baricitinib and one matching 2 mg Baricitinib administered orally QD for 52 weeks.

    Arm title
    		 2 mg Baricitinib (MEE)
    Arm description
    		 Participants received one 2 mg Baricitinib tablet and 1 placebo tablet matching 4 mg Baricitinib administered QD for 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    Other name
    LY3009104
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received one 2 mg Baricitinib tablet and 1 placebo tablet matching 4 mg Baricitinib administered QD for 52 weeks.

    Arm title
    		 4 mg Baricitinib (MEE)
    Arm description
    		 Participants received one 4 mg Baricitinib tablet and one placebo tablet matching 2 mg Baricitinib administered orally QD for 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    Other name
    LY3009104
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received one 4 mg Baricitinib tablet and one placebo tablet matching 2 mg Baricitinib administered orally QD for 52 weeks.

    Number of subjects in period 1
    		Placebo 2 mg Baricitinib 4 mg Baricitinib Placebo Maximum Extended Enrollment (MEE) 2 mg Baricitinib (MEE) 4 mg Baricitinib (MEE)
    Started
    253
    255
    252
    21
    20
    20
    Received at Least One Dose of Study Drug
    253
    255
    252
    21
    20
    20
    Completed
    200
    210
    206
    5
    5
    6
    Not completed
    53
    45
    46
    16
    15
    14
         Adverse event, serious fatal
    1
    1
    -
    -
    -
    -
         Consent withdrawn by subject
    12
    12
    15
    2
    -
    2
         Physician decision
    2
    -
    -
    -
    1
    -
         Adverse event, non-fatal
    17
    21
    9
    -
    -
    -
         Due to Epidemic/Pandemic
    4
    2
    5
    -
    -
    -
         Protocol Deviation
    1
    1
    -
    -
    -
    -
         Pregnancy
    1
    -
    4
    -
    -
    -
         Protocol Violation
    1
    -
    2
    -
    -
    -
         Study Terminated by Sponsor
    -
    -
    -
    10
    9
    11
         Lost to follow-up
    1
    2
    3
    -
    -
    -
         Lack of efficacy
    13
    6
    8
    4
    5
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received two placebo tablets: one matching 4 mg Baricitinib and one matching 2 mg Baricitinib administered orally every day (QD) for 52 weeks.

    Reporting group title
    2 mg Baricitinib
    Reporting group description
    		 Participants received one 2 mg Baricitinib tablet and one placebo tablet matching 4 mg Baricitinib administered orally QD for 52 weeks.

    Reporting group title
    4 mg Baricitinib
    Reporting group description
    		 Participants received one 4 mg Baricitinib tablet and one placebo tablet matching 2 mg Baricitinib administered orally every day (QD) for 52 weeks.

    Reporting group title
    Placebo Maximum Extended Enrollment (MEE)
    Reporting group description
    		 Participants received two placebo tablets: one matching 4 mg Baricitinib and one matching 2 mg Baricitinib administered orally QD for 52 weeks.

    Reporting group title
    2 mg Baricitinib (MEE)
    Reporting group description
    		 Participants received one 2 mg Baricitinib tablet and 1 placebo tablet matching 4 mg Baricitinib administered QD for 52 weeks.

    Reporting group title
    4 mg Baricitinib (MEE)
    Reporting group description
    		 Participants received one 4 mg Baricitinib tablet and one placebo tablet matching 2 mg Baricitinib administered orally QD for 52 weeks.

    Reporting group values
    		 Placebo 2 mg Baricitinib 4 mg Baricitinib Placebo Maximum Extended Enrollment (MEE) 2 mg Baricitinib (MEE) 4 mg Baricitinib (MEE) Total
    Number of subjects
    		 253 255 252 21 20 20 821
    Age categorical
    Units: Subjects
    Age continuous
    Analysis Population Description (APD): All randomized participants who receive at least one dose of study drug.
    Units: years
        arithmetic mean (standard deviation)
    		 42.00 ( 11.98 ) 42.90 ( 12.44 ) 41.50 ( 12.88 ) 32.90 ( 10.83 ) 37.70 ( 11.38 ) 34.60 ( 8.31 ) -
    Gender categorical
    APD: All randomized participants who receive at least one dose of study drug.
    Units: Subjects
        Female
    		 237 238 237 20 19 20 771
        Male
    		 16 17 15 1 1 0 50
    Ethnicity (NIH/OMB)
    APD: All randomized participants who receive at least one dose of study drug.
    Units: Subjects
        Hispanic or Latino
    		 4 13 11 0 0 0 28
        Not Hispanic or Latino
    		 42 35 38 0 0 0 115
        Unknown or Not Reported
    		 207 207 203 21 20 20 678
    Race (NIH/OMB)
    APD: All randomized participants who receive at least one dose of study drug.
    Units: Subjects
        American Indian or Alaska Native
    		 12 15 7 0 0 0 34
        Asian
    		 33 39 34 21 20 20 167
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0 0
        Black or African American
    		 36 23 30 0 0 0 89
        White
    		 168 172 177 0 0 0 517
        More than one race
    		 1 2 0 0 0 0 3
        Unknown or Not Reported
    		 3 4 4 0 0 0 11
    Region of Enrollment
    APD: All randomized participants who receive at least one dose of study drug.
    Units: Subjects
        Australia
    		 10 9 12 0 0 0 31
        Austria
    		 0 1 2 0 0 0 3
        Belgium
    		 2 1 1 0 0 0 4
        Brazil
    		 38 22 23 0 0 0 83
        China
    		 16 21 18 21 20 20 116
        Croatia
    		 5 3 2 0 0 0 10
        Czechia
    		 18 11 9 0 0 0 38
        Germany
    		 14 14 17 0 0 0 45
        Greece
    		 4 9 5 0 0 0 18
        Hungary
    		 13 18 19 0 0 0 50
        Israel
    		 1 3 4 0 0 0 8
        Mexico
    		 36 51 49 0 0 0 136
        Netherlands
    		 0 1 1 0 0 0 2
        Russia
    		 26 25 20 0 0 0 71
        Switzerland
    		 3 2 3 0 0 0 8
        Taiwan
    		 15 11 13 0 0 0 39
        United Kingdom
    		 5 4 4 0 0 0 13
        United States
    		 47 49 50 0 0 0 146

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received two placebo tablets: one matching 4 mg Baricitinib and one matching 2 mg Baricitinib administered orally every day (QD) for 52 weeks.

    Reporting group title
    2 mg Baricitinib
    Reporting group description
    		 Participants received one 2 mg Baricitinib tablet and one placebo tablet matching 4 mg Baricitinib administered orally QD for 52 weeks.

    Reporting group title
    4 mg Baricitinib
    Reporting group description
    		 Participants received one 4 mg Baricitinib tablet and one placebo tablet matching 2 mg Baricitinib administered orally every day (QD) for 52 weeks.

    Reporting group title
    Placebo Maximum Extended Enrollment (MEE)
    Reporting group description
    		 Participants received two placebo tablets: one matching 4 mg Baricitinib and one matching 2 mg Baricitinib administered orally QD for 52 weeks.

    Reporting group title
    2 mg Baricitinib (MEE)
    Reporting group description
    		 Participants received one 2 mg Baricitinib tablet and 1 placebo tablet matching 4 mg Baricitinib administered QD for 52 weeks.

    Reporting group title
    4 mg Baricitinib (MEE)
    Reporting group description
    		 Participants received one 4 mg Baricitinib tablet and one placebo tablet matching 2 mg Baricitinib administered orally QD for 52 weeks.

    Subject analysis set title
    2 mg Baricitinib
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Participants received one Baricitinib 2 mg tablet and one placebo tablet matching Baricitinib 4 mg administered orally QD for 52 weeks.

    Subject analysis set title
    4 mg Baricitinib
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Participants received one Baricitinib 4 mg tablet and one placebo tablet matching baricitinib 2 mg administered orally QD for 52 weeks.

    Primary: Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response (4 mg Baricitinib)

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    End point title
    		 Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response (4 mg Baricitinib) [1]
    End point description
    SRI-4 response defined as 1)greater than or equal to (>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score 2)no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and 3)no worsening in Physician Global Assessment (PGA) of Disease Activity (worsening defined as an increase of >=0.3 from baseline on a 0-3 visual analogue scale). SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms,or laboratory parameters related to Systemic Lupus Erythematosus (SLE),divided into 9 organ systems. For each organ system A=severe disease,B=moderate disease,C=mild stable disease,D=inactive,but previously active,E=inactive and never affected. PGA assess disease activity on a visual analogue scale from 0 to 3 (1=mild, 2=moderate, 3=severe).
    End point type
    Primary
    End point timeframe
    Week 52 APD: All randomized participants who received at least one dose of study drug (modified intent-to-treat (mITT) population). Missing data was imputed using the hybrid imputation method [nonresponder imputation (NRI) + multiple imputation (MI)].
    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 analysis is planned only for these reporting arms. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
    End point values
    		 Placebo 4 mg Baricitinib
    Number of subjects analysed
    253
    252
    Units: percentage of participants
        number (not applicable)
    45.9
    56.7
    Statistical analysis title
    		 SRI-4 Response (4 mg )
    Comparison groups
    Placebo v 4 mg Baricitinib
    Number of subjects included in analysis
    505
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.016
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.09
         upper limit
    		 2.27

    Secondary: Percentage of Participants Achieving SRI-4 Response - 2 mg Baricitinib

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    End point title
    		 Percentage of Participants Achieving SRI-4 Response - 2 mg Baricitinib [2]
    End point description
    SRI-4 response defined as 1)greater than or equal to (>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score 2)no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and 3)no worsening in Physician Global Assessment (PGA) of Disease Activity (worsening defined as an increase of >=0.3 from baseline on a 0-3 visual analogue scale). SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms,or laboratory parameters related to Systemic Lupus Erythematosus (SLE),divided into 9 organ systems. For each organ system A=severe disease,B=moderate disease,C=mild stable disease,D=inactive,but previously active,E=inactive and never affected. PGA assess disease activity on a visual analogue scale from 0 to 3 (1=mild, 2=moderate, 3=severe).
    End point type
    Secondary
    End point timeframe
    Week 52 APD: All randomized participants who receive at least one dose of study drug (mITT population). Missing data was imputed using the hybrid imputation method [nonresponder imputation (NRI) + multiple imputation (MI)].
    Notes
    [2] - 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 analysis is planned only for these reporting arms. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
    End point values
    		 Placebo 2 mg Baricitinib
    Number of subjects analysed
    253
    255
    Units: percentage of participants
        number (not applicable)
    45.9
    49.8
    Statistical analysis title
    		 SRI-4 Response (2 mg)
    Comparison groups
    Placebo v 2 mg Baricitinib
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.47
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.65

    Secondary: Percentage of Participants Achieving a Lupus Low Disease Activity State (LLDAS)

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    End point title
    		 Percentage of Participants Achieving a Lupus Low Disease Activity State (LLDAS) [3]
    End point description
    The LLDAS is a composite measure designed to identify patients achieving a state of low disease activity. The LLDAS response criteria were: (1) SLEDAI-2K <=4, with no activity in major organ systems (CNS, vascular, renal, cardiorespiratory and constitutional); where "no activity" is defined as all items of SLEDAI-2K within these major organ systems equal to 0. (2)no new features of lupus disease activity compared to previous occurred visit, where the "new feature" is defined as any of the SLEDAI-2K 24 items changed from 0 to greater than 0; (3) PGA (scale 0-3), <=1; (4) current prednisolone (or equivalent) dose <=7.5 mg daily. APD: All randomized participants who receive at least one dose of study drug (mITT population). Missing data was imputed using the hybrid imputation method [nonresponder imputation (NRI) + multiple imputation (MI)].
    End point type
    Secondary
    End point timeframe
    Week 52
    Notes
    [3] - 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: As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
    End point values
    		 Placebo 2 mg Baricitinib 4 mg Baricitinib
    Number of subjects analysed
    253
    255
    252
    Units: percentage of participants
        number (not applicable)
    26.2
    25.7
    29.7
    Statistical analysis title
    		 Lupus Low Disease Activity State (2 mg)
    Comparison groups
    Placebo v 2 mg Baricitinib
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.839
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.45
    Statistical analysis title
    		 Lupus Low Disease Activity State (4 mg)
    Comparison groups
    Placebo v 4 mg Baricitinib
    Number of subjects included in analysis
    505
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.391
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 1.79

    Secondary: Time to First Severe Flare

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    End point title
    		 Time to First Severe Flare [4]
    End point description
    Time to first severe flare was analyzed using a Cox proportional hazards model with treatment group, baseline disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K ] <10; SLEDAI-2K ≥10), baseline corticosteroid dose (<10 mg/day; ≥10 mg/day prednisone or equivalent), and region fitted as explanatory variables. Participants who did not have severe flare during the flare exposure time period were censored at the end of the flare exposure time. APD: All randomized participants who receive at least one dose of study drug (mITT population). 9999=Data Not Available (N/A) as < 50% of participants experienced first flare, median was not reached, and 95% confidence interval could not be calculated.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 52
    Notes
    [4] - 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: As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
    End point values
    		 Placebo 2 mg Baricitinib 4 mg Baricitinib
    Number of subjects analysed
    253
    255
    252
    Units: weeks
        median (confidence interval 95%)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Whose Average Prednisone Dose Had Been Reduced by >=25% From Baseline to <=7.5 mg/Day During Weeks 40 Through 52 in Participants Receiving Greater Than 7.5 mg/Day at Baseline

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    End point title
    		 Percentage of Participants Whose Average Prednisone Dose Had Been Reduced by >=25% From Baseline to <=7.5 mg/Day During Weeks 40 Through 52 in Participants Receiving Greater Than 7.5 mg/Day at Baseline [5]
    End point description
    For the analysis of steroid use, steroid dosages were converted to a prednisone equivalent in mg. A responder was defined as having a prednisone reduction by >=25% from Baseline to <=7.5 mg/day during Weeks 40 through 52. APD: All randomized participants who received at least one dose of study drug (mITT population) and received >7.5 mg prednisone at baseline. Missing data was imputed using the hybrid imputation method [NRI + mLOCF (modified last observation carried forward)].
    End point type
    Secondary
    End point timeframe
    Baseline, Week 40 through Week 52
    Notes
    [5] - 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: As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
    End point values
    		 Placebo 2 mg Baricitinib 4 mg Baricitinib
    Number of subjects analysed
    117
    106
    106
    Units: percentage of participants
        number (not applicable)
    30.8
    29.2
    34.0
    Statistical analysis title
    		 Prednisone Dose Reduction (2 mg)
    Comparison groups
    Placebo v 2 mg Baricitinib
    Number of subjects included in analysis
    223
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.82
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.53
         upper limit
    		 1.66
    Statistical analysis title
    		 Prednisone Reduction (4 mg)
    Comparison groups
    Placebo v 4 mg Baricitinib
    Number of subjects included in analysis
    223
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.565
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 2.08

    Secondary: Change from Baseline in Worst Pain Numeric Rating Scale (NRS)

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    End point title
    		 Change from Baseline in Worst Pain Numeric Rating Scale (NRS) [6]
    End point description
    Participants assessed their worst pain in the last 24 hours on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (pain as bad as you can imagine). The average worst daily pain score was calculated as the mean of the scores over the last 7 days prior to each assessment time point. Higher score indicated severe pain. Least Squares (LS) mean was calculated using Mixed Model Repeated Measures (MMRM) analysis with treatment, baseline disease activity (total SLEDAI-2K <10; >=10), baseline corticosteroid dose (<10 mg/day; >= 10 mg/day prednisone or equivalent), region (North America, Central/South, America/Mexico, Europe, Asia Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52 APD: All randomized participants who received at least 1 dose of study drug (mITT population) and had baseline and post-baseline values at the specified time point. Missing data was imputed using the hybrid imputation method NRI + MMRM.
    Notes
    [6] - 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: As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
    End point values
    		 Placebo 2 mg Baricitinib 4 mg Baricitinib
    Number of subjects analysed
    173
    173
    182
    Units: score on a scale
        least squares mean (standard error)
    -1.62 ( 0.15 )
    -1.73 ( 0.15 )
    -1.71 ( 0.15 )
    Statistical analysis title
    		 Change from Baseline in Worst Pain NRS (2 mg)
    Comparison groups
    Placebo v 2 mg Baricitinib
    Number of subjects included in analysis
    346
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.598
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference Final Values
    Point estimate
    -0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.52
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.21
    Statistical analysis title
    		 Change from Baseline in Worst Pain NRS (4 mg)
    Comparison groups
    Placebo v 4 mg Baricitinib
    Number of subjects included in analysis
    355
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.674
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference Final Values
    Point estimate
    -0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 0.32
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.21

    Secondary: Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Total Score

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    End point title
    		 Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Total Score [7]
    End point description
    FACIT-Fatigue score calculated according to a 13-item questionnaire that assess self reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status. Least Squares (LS) mean was calculated using MMRM analysis with treatment, baseline disease activity (total SLEDAI-2K <10; >=10), baseline corticosteroid dose (<10 mg/day; >= 10 mg/day prednisone or equivalent), region (North America, Central/South, America/Mexico, Europe, Asia Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52 APD: All randomized participants who received at least one dose of study drug (mITT population) and had baseline and post-baseline values at the specified time point. Missing data was imputed using hybrid the imputation method NRI+MMRM.
    Notes
    [7] - 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: As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
    End point values
    		 Placebo 2 mg Baricitinib 4 mg Baricitinib
    Number of subjects analysed
    188
    201
    204
    Units: score on a scale
        least squares mean (standard error)
    7.44 ( 0.62 )
    7.46 ( 0.60 )
    7.08 ( 0.61 )
    Statistical analysis title
    		 Change from Baseline in FACIT-Fatigue (2 mg)
    Comparison groups
    Placebo v 2 mg Baricitinib
    Number of subjects included in analysis
    389
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.979
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference Final Values
    Point estimate
    0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.65
         upper limit
    		 1.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.85
    Statistical analysis title
    		 Change from Baseline in FACIT-Fatigue (4 mg)
    Comparison groups
    Placebo v 4 mg Baricitinib
    Number of subjects included in analysis
    392
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.678
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference Final Values
    Point estimate
    -0.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.03
         upper limit
    		 1.32
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.86

    Secondary: Percentage of Participants with Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Total Activity Score ≥10 at Baseline with ≥50% Reduction in CLASI Total Activity Score

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    End point title
    		 Percentage of Participants with Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Total Activity Score ≥10 at Baseline with ≥50% Reduction in CLASI Total Activity Score [8]
    End point description
    The CLASI is a single-page tool that separately quantifies disease activity and damage. For the activity score, points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. The total score represents the sum of the individual scores and ranges from 0 to 70. Higher scores are awarded for more severe manifestations. APD: All randomized participants who received at least one dose of study drug (mITT population) and had baseline CLASI score of >= 10. Missing data was imputed using NRI method.
    End point type
    Secondary
    End point timeframe
    Week 52
    Notes
    [8] - 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: As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
    End point values
    		 Placebo 2 mg Baricitinib 4 mg Baricitinib
    Number of subjects analysed
    49
    46
    43
    Units: percentage of participants
        number (not applicable)
    49.0
    54.3
    55.8
    Statistical analysis title
    		 50% Reduction in CLASI Score (2 mg)
    Comparison groups
    Placebo v 2 mg Baricitinib
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.965
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 2.42
    Statistical analysis title
    		 50% Reduction in CLASI Score (4 mg)
    Comparison groups
    Placebo v 4 mg Baricitinib
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.661
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 2.92

    Secondary: Change from Baseline in Tender Joint Count

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    End point title
    		 Change from Baseline in Tender Joint Count [9]
    End point description
    The number of tender and painful joints is determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. The joints are assessed and classified as tender or not tender. LS mean was calculated using Mixed Model Repeated Measures (MMRM) analysis with treatment, baseline disease activity (total SLEDAI-2K <10; >=10), baseline corticosteroid dose (<10 mg/day; >=10 mg/day prednisone or equivalent), region (North America, Central/South America/Mexico, Europe, Asia and Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction. APD: All randomized participants who receive at least one dose of study drug (mITT population) and had baseline and post-baseline values at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    Notes
    [9] - 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: As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
    End point values
    		 Placebo 2 mg Baricitinib 4 mg Baricitinib
    Number of subjects analysed
    183
    198
    195
    Units: tender joint count
        least squares mean (standard error)
    -7.50 ( 0.312 )
    -7.26 ( 0.305 )
    -7.94 ( 0.307 )
    Statistical analysis title
    		 Change from Baseline Tender Joint Count (2 mg)
    Comparison groups
    Placebo v 2 mg Baricitinib
    Number of subjects included in analysis
    381
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.578
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference Final Values
    Point estimate
    0.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.61
         upper limit
    		 1.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.43
    Statistical analysis title
    		 Change from Baseline Tender Joint Count (4 mg)
    Comparison groups
    Placebo v 4 mg Baricitinib
    Number of subjects included in analysis
    378
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.309
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference Final Values
    Point estimate
    -0.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.29
         upper limit
    		 0.41
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.433

    Secondary: Change from Baseline in Swollen Joint Count

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    End point title
    		 Change from Baseline in Swollen Joint Count [10]
    End point description
    The number of swollen joints is determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. The joints are assessed and classified as swollen or not swollen. LS mean was calculated using MMRM analysis with treatment, baseline disease activity (total SLEDAI-2K <10; >=10), baseline corticosteroid dose (<10 mg/day; >=10 mg/day prednisone or equivalent), region (North America, Central/South America/Mexico, Europe, Asia and Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction. APD: All randomized participants who receive at least one dose of study drug (mITT population) and had baseline and post-baseline values at the specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    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: As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
    End point values
    		 Placebo 2 mg Baricitinib 4 mg Baricitinib
    Number of subjects analysed
    183
    198
    195
    Units: swollen joint count
        least squares mean (standard error)
    -5.37 ( 0.201 )
    -5.67 ( 0.196 )
    -5.81 ( 0.198 )
    Statistical analysis title
    		 Change from Baseline in Swollen Joint Count (2 mg)
    Comparison groups
    Placebo v 2 mg Baricitinib
    Number of subjects included in analysis
    381
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.287
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference Final Values
    Point estimate
    -0.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.84
         upper limit
    		 0.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.277
    Statistical analysis title
    		 Change from Baseline in Swollen Joint Count (4 mg)
    Comparison groups
    Placebo v 4 mg Baricitinib
    Number of subjects included in analysis
    378
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.113
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference Final Values
    Point estimate
    -0.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.99
         upper limit
    		 0.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.278

    Secondary: Population Pharmacokinetics (PK): Area Under the Concentration-Time Curve of Baricitinib at Steady State (AUCτ, ss)

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    End point title
    		 Population Pharmacokinetics (PK): Area Under the Concentration-Time Curve of Baricitinib at Steady State (AUCτ, ss)
    End point description
    PK: Area Under the Concentration-Time Curve of Baricitinib at Steady State (AUCτ, ss) was evaluated using population PK approach. APD: All randomized participants who received at least one dose of study drug and had evaluable PK data. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
    End point type
    Secondary
    End point timeframe
    Week 0 (Baseline): 15 minutes (min) and 60 min postdose; Week 4: 2 to 4 hours (hr) postdose; Week 8: 4 to 6 hr postdose; Week 12 and Week 16 predose
    End point values
    		 2 mg Baricitinib 4 mg Baricitinib
    Number of subjects analysed
    248
    220
    Units: hour*nanograms per milliliter (h*ng/mL)
        geometric mean (geometric coefficient of variation)
    256 ( 52 )
    502 ( 52 )
    No statistical analyses for this end point

    Secondary: Population PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss)

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    End point title
    		 Population PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss)
    End point description
    Population PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss) was evaluated using population PK approach. APD: All randomized participants who received at least one dose of study drug and had evaluable PK data. As pre-specified in the analysis plan, outcome measures will not be reported for the MEE arms/groups but only for the main global study arms/groups.
    End point type
    Secondary
    End point timeframe
    Week 0 (Baseline): 15 minutes (min) and 60 min postdose; Week 4: 2 to 4 hours (hr) postdose; Week 8: 4 to 6 hr postdose; Week 12 and Week 16 predose
    End point values
    		 2 mg Baricitinib 4 mg Baricitinib
    Number of subjects analysed
    248
    220
    Units: nanograms per milliliter (ng/mL)
        geometric mean (geometric coefficient of variation)
    26.7 ( 24 )
    53.0 ( 23 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline through Follow-up (Up to 56 Weeks)
    Adverse event reporting additional description
    All randomized participants who received at least one dose of investigational product and who did not discontinue from the study for the reason "Lost to Follow-up" at the first postbaseline visit. Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received two placebo tablets: one matching baricitinib 4 mg and one matching baricitinib 2 mg administered orally QD for 52 weeks.

    Reporting group title
    2 mg Baricitinib
    Reporting group description
    		 Participants received one Baricitinib 2 mg tablet and one placebo tablet matching Baricitinib 4 mg administered QD for 52 weeks.

    Reporting group title
    4 mg Baricitinib
    Reporting group description
    		 Participants received one Baricitinib 4 mg tablet and one placebo tablet matching baricitinib 2 mg administered orally QD for 52 weeks.

    Reporting group title
    Placebo Maximum Extended Enrollment (MEE)
    Reporting group description
    		 Participants received two placebo tablets: one matching baricitinib 4 mg and one matching baricitinib 2 mg administered orally QD for 52 weeks

    Reporting group title
    2 mg Baricitinib (MEE)
    Reporting group description
    		 Participants received one Baricitinib 2 mg tablet and 1 placebo tablet matching Baricitinib 4 mg administered QD for 52 weeks.

    Reporting group title
    4 mg Baricitinib (MEE)
    Reporting group description
    		 Participants received one Baricitinib 4 mg tablet and one placebo tablet matching baricitinib 2 mg administered orally QD for 52 weeks.

    Serious adverse events
    		 Placebo 2 mg Baricitinib 4 mg Baricitinib Placebo Maximum Extended Enrollment (MEE) 2 mg Baricitinib (MEE) 4 mg Baricitinib (MEE)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    19 / 253 (7.51%)
    27 / 255 (10.59%)
    31 / 252 (12.30%)
    1 / 21 (4.76%)
    4 / 20 (20.00%)
    3 / 20 (15.00%)
         number of deaths (all causes)
    1
    1
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    1
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    adenocarcinoma of the cervix
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed [1]
    1 / 237 (0.42%)
    0 / 238 (0.00%)
    0 / 237 (0.00%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    burkitt's lymphoma
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    haemangioma of liver
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    lung carcinoma cell type unspecified stage 0
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    melanocytic naevus
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    papillary thyroid cancer
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    uterine leiomyoma
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed [2]
    1 / 237 (0.42%)
    0 / 238 (0.00%)
    1 / 237 (0.42%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    deep vein thrombosis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    vasculitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    Pregnancy, puerperium and perinatal conditions
    abortion spontaneous
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed [3]
    0 / 237 (0.00%)
    0 / 238 (0.00%)
    1 / 237 (0.42%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    General disorders and administration site conditions
    death
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    non-cardiac chest pain
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    pyrexia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    Immune system disorders
    drug hypersensitivity
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    Reproductive system and breast disorders
    adnexal torsion
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed [4]
    0 / 237 (0.00%)
    0 / 238 (0.00%)
    1 / 237 (0.42%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    cervical dysplasia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed [5]
    0 / 237 (0.00%)
    0 / 238 (0.00%)
    1 / 237 (0.42%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    hydrosalpinx
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed [6]
    0 / 237 (0.00%)
    1 / 238 (0.42%)
    0 / 237 (0.00%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    ovarian cyst
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed [7]
    1 / 237 (0.42%)
    0 / 238 (0.00%)
    0 / 237 (0.00%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    Respiratory, thoracic and mediastinal disorders
    bronchitis chronic
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    pleural effusion
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    pleurisy
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    pulmonary embolism
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    pulmonary hypertension
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    Psychiatric disorders
    major depression
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    Injury, poisoning and procedural complications
    ankle fracture
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    2 / 252 (0.79%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    device use issue
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    femur fracture
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    fibula fracture
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    foot fracture
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    tendon rupture
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    Cardiac disorders
    acute myocardial infarction
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    arteriosclerosis coronary artery
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    atrial fibrillation
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    coronary artery disease
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    myocardial ischaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    pericarditis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    Nervous system disorders
    cerebrovascular accident
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    leukopenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    neutropenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    Gastrointestinal disorders
    abdominal adhesions
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    abdominal pain lower
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    epiploic appendagitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    gastric ulcer
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    gastritis erosive
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    haematochezia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    haemorrhoidal haemorrhage
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    obstructive pancreatitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    upper gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    Hepatobiliary disorders
    bile duct stone
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    cholecystitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    cholecystitis chronic
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cholelithiasis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    cutaneous lupus erythematosus
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    dermatitis bullous
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    Renal and urinary disorders
    lupus nephritis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    2 / 255 (0.78%)
    1 / 252 (0.40%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ureterolithiasis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    osteoarthritis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    osteonecrosis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    spinal stenosis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    systemic lupus erythematosus
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    1 / 255 (0.39%)
    4 / 252 (1.59%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    1 / 20 (5.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 4
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    anal abscess
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    appendicitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    arthritis bacterial
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    atypical pneumonia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    bronchitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    covid-19
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    covid-19 pneumonia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    escherichia urinary tract infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    1 / 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
    gastroenteritis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    herpes zoster
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    1 / 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
    infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    laryngitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    pneumonia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    4 / 255 (1.57%)
    2 / 252 (0.79%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 5
    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
    pyelonephritis acute
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    tubo-ovarian abscess
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed [8]
    0 / 237 (0.00%)
    1 / 238 (0.42%)
    0 / 237 (0.00%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    viral myocarditis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    viral pericarditis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    Metabolism and nutrition disorders
    dehydration
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    hypoalbuminaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    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
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
    [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
    [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
    [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
    [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
    [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
    [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo 2 mg Baricitinib 4 mg Baricitinib Placebo Maximum Extended Enrollment (MEE) 2 mg Baricitinib (MEE) 4 mg Baricitinib (MEE)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    129 / 253 (50.99%)
    144 / 255 (56.47%)
    144 / 252 (57.14%)
    17 / 21 (80.95%)
    14 / 20 (70.00%)
    17 / 20 (85.00%)
    Vascular disorders
    hypertension
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    10 / 253 (3.95%)
    17 / 255 (6.67%)
    17 / 252 (6.75%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    1 / 20 (5.00%)
         occurrences all number
    10
    18
    18
    0
    1
    1
    General disorders and administration site conditions
    chest discomfort
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    0 / 255 (0.00%)
    4 / 252 (1.59%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    4
    4
    0
    0
    Reproductive system and breast disorders
    prostatitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed [9]
    0 / 16 (0.00%)
    1 / 17 (5.88%)
    0 / 15 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    cough
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    7 / 253 (2.77%)
    5 / 255 (1.96%)
    7 / 252 (2.78%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    7
    5
    7
    2
    0
    1
    Psychiatric disorders
    insomnia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    8 / 253 (3.16%)
    4 / 255 (1.57%)
    5 / 252 (1.98%)
    1 / 21 (4.76%)
    2 / 20 (10.00%)
    0 / 20 (0.00%)
         occurrences all number
    8
    4
    6
    1
    2
    0
    Investigations
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    7 / 253 (2.77%)
    6 / 255 (2.35%)
    2 / 252 (0.79%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    2 / 20 (10.00%)
         occurrences all number
    7
    8
    5
    1
    0
    2
    blood creatine phosphokinase increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 253 (1.19%)
    8 / 255 (3.14%)
    14 / 252 (5.56%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    4
    9
    20
    0
    0
    0
    hepatic enzyme increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    2 / 252 (0.79%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    1
    0
    2
    3
    0
    1
    weight increased
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    7 / 253 (2.77%)
    5 / 255 (1.96%)
    3 / 252 (1.19%)
    2 / 21 (9.52%)
    1 / 20 (5.00%)
    1 / 20 (5.00%)
         occurrences all number
    9
    5
    3
    4
    1
    1
    Nervous system disorders
    dizziness
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    4 / 253 (1.58%)
    1 / 255 (0.39%)
    5 / 252 (1.98%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    3 / 20 (15.00%)
         occurrences all number
    4
    1
    6
    0
    1
    4
    headache
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    25 / 253 (9.88%)
    16 / 255 (6.27%)
    20 / 252 (7.94%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    1 / 20 (5.00%)
         occurrences all number
    26
    19
    23
    3
    1
    1
    hypoaesthesia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 255 (0.39%)
    2 / 252 (0.79%)
    0 / 21 (0.00%)
    2 / 20 (10.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    2
    0
    4
    0
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    4 / 253 (1.58%)
    4 / 255 (1.57%)
    13 / 252 (5.16%)
    3 / 21 (14.29%)
    2 / 20 (10.00%)
    2 / 20 (10.00%)
         occurrences all number
    4
    6
    16
    4
    2
    2
    iron deficiency anaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    4 / 255 (1.57%)
    0 / 252 (0.00%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    2 / 20 (10.00%)
         occurrences all number
    0
    4
    0
    2
    0
    2
    lymphopenia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    10 / 253 (3.95%)
    11 / 255 (4.31%)
    9 / 252 (3.57%)
    3 / 21 (14.29%)
    1 / 20 (5.00%)
    1 / 20 (5.00%)
         occurrences all number
    13
    14
    10
    3
    1
    1
    Gastrointestinal disorders
    abdominal discomfort
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    2 / 255 (0.78%)
    3 / 252 (1.19%)
    1 / 21 (4.76%)
    2 / 20 (10.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    2
    4
    1
    4
    0
    diarrhoea
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    10 / 253 (3.95%)
    10 / 255 (3.92%)
    10 / 252 (3.97%)
    1 / 21 (4.76%)
    2 / 20 (10.00%)
    1 / 20 (5.00%)
         occurrences all number
    12
    12
    12
    1
    2
    1
    gastritis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    4 / 255 (1.57%)
    2 / 252 (0.79%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    4
    2
    2
    0
    0
    mouth ulceration
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    2 / 255 (0.78%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    2 / 20 (10.00%)
         occurrences all number
    1
    2
    1
    0
    0
    2
    nausea
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    5 / 253 (1.98%)
    11 / 255 (4.31%)
    12 / 252 (4.76%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    2 / 20 (10.00%)
         occurrences all number
    5
    13
    14
    0
    1
    2
    toothache
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    5 / 255 (1.96%)
    3 / 252 (1.19%)
    2 / 21 (9.52%)
    1 / 20 (5.00%)
    1 / 20 (5.00%)
         occurrences all number
    1
    5
    3
    2
    1
    2
    Hepatobiliary disorders
    hepatic function abnormal
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 253 (0.00%)
    3 / 255 (1.18%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    2 / 20 (10.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    3
    0
    0
    2
    2
    Skin and subcutaneous tissue disorders
    urticaria
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 253 (1.19%)
    3 / 255 (1.18%)
    4 / 252 (1.59%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    3
    3
    4
    3
    0
    1
    Endocrine disorders
    hypothyroidism
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    1 / 255 (0.39%)
    0 / 252 (0.00%)
    0 / 21 (0.00%)
    2 / 20 (10.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    1
    0
    0
    2
    0
    Infections and infestations
    covid-19
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    9 / 253 (3.56%)
    16 / 255 (6.27%)
    13 / 252 (5.16%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    9
    16
    13
    0
    0
    0
    gingivitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 255 (0.00%)
    1 / 252 (0.40%)
    0 / 21 (0.00%)
    2 / 20 (10.00%)
    1 / 20 (5.00%)
         occurrences all number
    1
    0
    1
    0
    4
    1
    herpes zoster
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    8 / 253 (3.16%)
    9 / 255 (3.53%)
    16 / 252 (6.35%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    8
    9
    18
    0
    0
    1
    nasopharyngitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    17 / 253 (6.72%)
    19 / 255 (7.45%)
    18 / 252 (7.14%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    24
    21
    24
    0
    0
    1
    upper respiratory tract infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    17 / 253 (6.72%)
    21 / 255 (8.24%)
    19 / 252 (7.54%)
    5 / 21 (23.81%)
    9 / 20 (45.00%)
    7 / 20 (35.00%)
         occurrences all number
    19
    30
    27
    11
    17
    8
    urinary tract infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    25 / 253 (9.88%)
    32 / 255 (12.55%)
    37 / 252 (14.68%)
    2 / 21 (9.52%)
    3 / 20 (15.00%)
    1 / 20 (5.00%)
         occurrences all number
    38
    41
    47
    2
    3
    1
    vulvitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed [10]
    0 / 237 (0.00%)
    0 / 238 (0.00%)
    0 / 237 (0.00%)
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Metabolism and nutrition disorders
    hyperlipidaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    2 / 255 (0.78%)
    6 / 252 (2.38%)
    3 / 21 (14.29%)
    4 / 20 (20.00%)
    3 / 20 (15.00%)
         occurrences all number
    1
    2
    6
    4
    4
    3
    hypertriglyceridaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    4 / 253 (1.58%)
    9 / 255 (3.53%)
    3 / 252 (1.19%)
    5 / 21 (23.81%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    5
    9
    3
    5
    0
    1
    hyperuricaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 253 (0.40%)
    2 / 255 (0.78%)
    2 / 252 (0.79%)
    2 / 21 (9.52%)
    3 / 20 (15.00%)
    4 / 20 (20.00%)
         occurrences all number
    2
    2
    2
    3
    3
    4
    Notes
    [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
    [10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Dec 2018
    - Modified logistic regression analyses; - Clarified the definition of post-menopausal; - Data from types of chest imaging other than x-ray can be accepted for tuberculosis screening; - Arterial thromboembolic events (ATEs) adjudicated by a blinded clinical event committee; - Analysis Methods were revised; - Language was revised for missing data imputation; - Subgroup analysis has been removed from the protocol.
    20 Apr 2020
    - Participant number and statistical analysis was revised to account for COVID-19 affected participants; - Protocol updated to include provisions put into place in order to assure the safety of trial participants and minimizing risks to trial integrity during the COVID-19 pandemic; - Schedule of activities was clarified; - Analysis of British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) endpoint was included in the protocol to supplement efficacy analyses; - Updated to clarify that while most concomitant medications should remain stable during the trial, reductions in dose for safety are permitted; - Updated to clarify that prohibited use of corticosteroids for SLE requires discontinuation from study drug, while use of prohibited doses of corticosteroids for other reasons may not require discontinuation of study drug; - An interim analysis has been added to assess the likelihood of trial failure time prior to trial conclusion in order to minimize participant exposure to an ineffective drug.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    One investigational site with seven participants was excluded from analysis due to confirmed misconduct. Study terminated due to insufficient evidence to support a positive benefit: risk ratio.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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