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    Clinical Trial Results:
    A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study Evaluating the Efficacy and Safety of Baricitinib (LY3009104) in Patients with Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Tumor Necrosis Factor Inhibitors

    Summary
    EudraCT number
    2012-002323-15
    Trial protocol
    IT   PL   BE   GB   AT   DK   ES   NL   GR   HR  
    Global end of trial date
    02 Sep 2014

    Results information
    Results version number
    v2(current)
    This version publication date
    07 Mar 2018
    First version publication date
    26 Mar 2017
    Other versions
    v1
    Version creation reason
    • New data added to full data set
    Revision required

    Trial information

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    Trial identification
    Sponsor protocol code
    14058
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01721044
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Trial Number: 14058 , Trial Alias: I4V-MC-JADW
    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
    02 Sep 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Sep 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to determine whether baricitinib 4 milligram (mg) once daily is superior to placebo in the treatment of participants with moderately to severely active Rheumatoid Arthritis (RA) who have had an inadequate response to a tumor necrosis factor (TNF) inhibitor, despite ongoing treatment with conventional synthetic drugs (DMARDs).
    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
    16 Jan 2013
    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
    Spain: 27
    Country: Number of subjects enrolled
    Switzerland: 7
    Country: Number of subjects enrolled
    Turkey: 3
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    United States: 226
    Country: Number of subjects enrolled
    Argentina: 21
    Country: Number of subjects enrolled
    Australia: 21
    Country: Number of subjects enrolled
    Austria: 16
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    Canada: 8
    Country: Number of subjects enrolled
    Denmark: 6
    Country: Number of subjects enrolled
    France: 24
    Country: Number of subjects enrolled
    Germany: 19
    Country: Number of subjects enrolled
    Greece: 9
    Country: Number of subjects enrolled
    Israel: 30
    Country: Number of subjects enrolled
    Italy: 8
    Country: Number of subjects enrolled
    Japan: 20
    Country: Number of subjects enrolled
    Korea, Republic of: 10
    Country: Number of subjects enrolled
    Mexico: 31
    Country: Number of subjects enrolled
    Netherlands: 2
    Country: Number of subjects enrolled
    Poland: 32
    Worldwide total number of subjects
    527
    EEA total number of subjects
    150
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    411
    From 65 to 84 years
    116
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    No Text Entered

    Pre-assignment
    Screening details
    Participants who did not adequately respond (nonresponders) to study drug were eligible for rescue treatment with baricitinib 4 mg beginning at Week 16. Nonresponders were defined as lack of improvement of at least 20% in both tender joint count and swollen joint count at both Weeks 14 and 16 compared to baseline.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Placebo administered orally (PO) once daily (QD) through Week 24. Participants continued to take background conventional synthetic drug (DMARD) therapy throughout study.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo administered orally once daily through Week 24. Starting at Week 16, participants who are nonresponders will be rescued with baricitinib 4 milligram (mg) orally once daily through Week 24.

    Arm title
    Baricitinib 2 mg
    Arm description
    Baricitinib 2 milligram (mg) administered PO QD through Week 24. Participants continued to take background DMARD therapy throughout study.
    Arm type
    Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    Other name
    LY3009104, INCB 028050
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Baricitinib 2 mg administered orally once daily through Week 24. Starting at Week 16, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily through Week 24.

    Arm title
    Baricitinib 4 mg
    Arm description
    Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background DMARD therapy throughout study.
    Arm type
    Experimental

    Investigational medicinal product name
    Baricitinib
    Investigational medicinal product code
    Other name
    LY3009104, INCB 028050
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Baricitinib 4 mg administered orally once daily through Week 24. Starting at Week 16, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily through Week 24.

    Number of subjects in period 1
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Started
    176
    174
    177
    Rescue week 16-24
    56 [1]
    38 [2]
    33 [3]
    Completed
    144
    157
    158
    Not completed
    32
    17
    19
         Protocol deviation
    1
    -
    -
         Physician decision
    1
    -
    2
         Lack of efficacy
    16
    4
    4
         Adverse event, serious fatal
    -
    -
    1
         Adverse event, non-fatal
    7
    7
    10
         Consent withdrawn by subject
    7
    6
    1
         Lost to follow-up
    -
    -
    1
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Nonresponders were eligible for rescue treatment with baricitinib 4 mg beginning at Week 16. Nonresponders were defined as lack of improvement of at least 20% in both tender joint count and swollen joint count at both Weeks 14 and 16 compared to baseline.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Nonresponders were eligible for rescue treatment with baricitinib 4 mg beginning at Week 16. Nonresponders were defined as lack of improvement of at least 20% in both tender joint count and swollen joint count at both Weeks 14 and 16 compared to baseline.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Nonresponders were eligible for rescue treatment with baricitinib 4 mg beginning at Week 16. Nonresponders were defined as lack of improvement of at least 20% in both tender joint count and swollen joint count at both Weeks 14 and 16 compared to baseline.
    Period 2
    Period 2 title
    Follow Up
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    Baricitinib 2 mg
    Arm description
    No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    Baricitinib 4 mg
    Arm description
    Includes participants who were rescued to baricitinib 4 mg. No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 2 [4]
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Started
    19
    9
    20
    Completed
    19
    9
    20
    Notes
    [4] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Includes participants who entered the post-treatment follow-up period

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo administered orally (PO) once daily (QD) through Week 24. Participants continued to take background conventional synthetic drug (DMARD) therapy throughout study.

    Reporting group title
    Baricitinib 2 mg
    Reporting group description
    Baricitinib 2 milligram (mg) administered PO QD through Week 24. Participants continued to take background DMARD therapy throughout study.

    Reporting group title
    Baricitinib 4 mg
    Reporting group description
    Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background DMARD therapy throughout study.

    Reporting group values
    Placebo Baricitinib 2 mg Baricitinib 4 mg Total
    Number of subjects
    176 174 177 527
    Age categorical
    Units: Subjects
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    56 ± 10.7 55.1 ± 11.1 55.9 ± 11.3 -
    Gender, Male/Female
    Units: Participants
        Female
    145 137 149 431
        Male
    31 37 28 96
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    9 12 11 32
        Asian
    11 9 12 32
        Native Hawaiian or Other Pacific Islander
    0 0 0 0
        Black or African American
    8 9 7 24
        White
    147 144 144 435
        More than one race
    1 0 0 1
        Unknown or Not Reported
    0 0 3 3
    Region of Enrollment
    Units: Subjects
        Argentina
    9 5 7 21
        Australia
    8 9 4 21
        Austria
    5 3 8 16
        Belgium
    1 1 1 3
        Canada
    1 4 3 8
        Denmark
    2 3 1 6
        France
    7 10 7 24
        Germany
    8 5 6 19
        Greece
    4 3 2 9
        Israel
    9 8 13 30
        Italy
    2 3 3 8
        Japan
    6 6 8 20
        Mexico
    9 12 10 31
        Netherlands
    0 1 1 2
        Poland
    10 13 9 32
        Korea, Republic of
    4 3 3 10
        Spain
    10 7 10 27
        Switzerland
    1 2 4 7
        Turkey
    1 1 1 3
        United Kingdom
    2 1 1 4
        United States
    77 74 75 226
    Duration of Rheumatoid Arthritis
    Time from Symptom Onset of Rheumatoid Arthritis
    Units: Years
        arithmetic mean (standard deviation)
    14 ± 9.6 13.7 ± 8 14.3 ± 9.4 -
    Tender Joint Count of 68 Evaluable Joints
    N-obs: 174, 174, 177 and 525, respectively. Tender joint count based on 68 joints.
    Units: Number of Joints
        arithmetic mean (standard deviation)
    28.3 ± 16.4 31 ± 16.3 28.1 ± 15.6 -
    Swollen Joint Count of 66 Evaluable Joints
    N-obs: 174,174,177 and 525, respectively. Swollen joint count based on 66 joints.
    Units: Number of Joints
        arithmetic mean (standard deviation)
    17.2 ± 10.8 18.6 ± 12.3 16.3 ± 8.9 -
    High Sensitivity C-Reactive Protein (hsCRP)
    Units: milligrams/liter (mg/L)
        arithmetic mean (standard deviation)
    20.64 ± 25.26 19.87 ± 22.48 19.76 ± 24.84 -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo administered orally (PO) once daily (QD) through Week 24. Participants continued to take background conventional synthetic drug (DMARD) therapy throughout study.

    Reporting group title
    Baricitinib 2 mg
    Reporting group description
    Baricitinib 2 milligram (mg) administered PO QD through Week 24. Participants continued to take background DMARD therapy throughout study.

    Reporting group title
    Baricitinib 4 mg
    Reporting group description
    Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background DMARD therapy throughout study.
    Reporting group title
    Placebo
    Reporting group description
    No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.

    Reporting group title
    Baricitinib 2 mg
    Reporting group description
    No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.

    Reporting group title
    Baricitinib 4 mg
    Reporting group description
    Includes participants who were rescued to baricitinib 4 mg. No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.

    Subject analysis set title
    PK population 2mg Baricitinib
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All randomized participants who received at least 1 dose of 2 mg baricitinib with evaluable PK data.

    Subject analysis set title
    PK population 4mg Baricitinib
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All randomized participants who received at least 1 dose of 4 mg baricitinib with evaluable PK data.

    Primary: Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response

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    End point title
    Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response
    End point description
    ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. ACR20 Responder is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity using visual analog scale (VAS), Health Assessment Questionnaire – Disability Index (HAQ-DI), pain due to arthritis, and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and participants who discontinue study or drug or are rescued before analysis timepoint are deemed non-responders. Analysis Population Description: Modified Intent-to-Treat (mITT) population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using non-responder imputation (NRI).
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    176
    174
    177
    Units: Percentage of Participants
        number (not applicable)
    27.3
    48.9
    55.4
    Statistical analysis title
    Primary Outcome Statisical Analysis
    Comparison groups
    Placebo v Baricitinib 4 mg
    Number of subjects included in analysis
    353
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    Regression, Logistic
    Confidence interval
         sides
    2-sided
         lower limit
    -
         upper limit
    -

    Secondary: Change from Baseline in HAQ-DI Score

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    End point title
    Change from Baseline in HAQ-DI Score
    End point description
    The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate the HAQ-DI score, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. Analysis Population Description: mITT population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using modified baseline observation carried forward (mBOCF).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    176
    174
    177
    Units: Units on a Scale
        arithmetic mean (standard deviation)
    -0.2 ± 0.5
    -0.38 ± 0.51
    -0.42 ± 0.49
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Disease Activity Score Based on a 28-Joint Count (DAS28) High Sensitivity C-Reactive Protein (hsCRP)

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    End point title
    Change from Baseline in the Disease Activity Score Based on a 28-Joint Count (DAS28) High Sensitivity C-Reactive Protein (hsCRP)
    End point description
    DAS28 consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), high sensitivity C-reactive protein (hsCRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using following formula: DAS28-hsCRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*Patient's Global VAS+0.96. Total scores ranged from 1.0-9.4, where lower scores indicated less disease activity. Analysis Population Description: mITT population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mBOCF.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    174
    174
    177
    Units: Units on a Scale
        arithmetic mean (standard deviation)
    -0.85 ± 1.19
    -1.53 ± 1.34
    -1.81 ± 1.43
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Score ≤3.3

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    End point title
    Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Score ≤3.3
    End point description
    SDAI is a tool for measurement of disease activity in RA that integrates TJC28, SJC28, acute phase response using C-reactive protein (milligrams per liter), Participant's Global Assessment of Disease Activity using VAS centimeters (cm), and Physician's Global Assessment of Disease Activity using VAS (cm). The SDAI is calculated by summing the values of the 5 components. Lower scores indicated less disease activity. An index-based definition of remission occurs with an SDAI score ≤3.3. Analysis Population Description: mITT population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    176
    174
    177
    Units: Percent of Participants
        number (not applicable)
    1.7
    2.3
    5.1
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving ACR20 Response

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    End point title
    Percentage of Participants Achieving ACR20 Response
    End point description
    ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. ACR20 Responder is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity using VAS, Patient's Global Assessment of Disease Activity using VAS, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis time point are deemed non-responders. Analysis Population Description: mITT population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    176
    174
    177
    Units: Percentage of Participants
        number (not applicable)
    27.3
    44.8
    46.3
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving American Col0lege of Rheumatology 50% (ACR50) Response

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    End point title
    Percentage of Participants Achieving American Col0lege of Rheumatology 50% (ACR50) Response
    End point description
    ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. ACR50 Responder is a participant who has at least 50% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis time point are deemed non-responders. Analysis Population Description: mITT population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
    End point type
    Secondary
    End point timeframe
    Week 12 and Week 24
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    176
    174
    177
    Units: Percentage of Participants
    number (not applicable)
        Week 12
    8
    20.1
    28.2
        Week 24
    13.1
    23
    29.4
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response

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    End point title
    Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
    End point description
    ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in RA. ACR70 Responder is a participant who has at least 70% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis time point are deemed non-responders. Analysis Population Description: mITT population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
    End point type
    Secondary
    End point timeframe
    Week 12 and Week 24
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    176
    174
    177
    Units: Percentage of Participants
    number (not applicable)
        Week 12
    2.3
    12.6
    11.3
        Week 24
    3.4
    13.2
    16.9
    No statistical analyses for this end point

    Secondary: Change from Baseline in DAS28 - Erythrocyte Sedimentation Rate (ESR)

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    End point title
    Change from Baseline in DAS28 - Erythrocyte Sedimentation Rate (ESR)
    End point description
    DAS28 consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), ESR (millimeters per hour), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using following formula: DAS28-ESR=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.70*natural log(ESR)+0.014*Patient's Global VAS. Total scores ranged from 1.0-9.4, where lower scores indicated less disease activity. Analysis Population Description: mITT population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using modified last observation carried forward (mLOCF).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    168
    169
    173
    Units: Units on a Scale
        arithmetic mean (standard deviation)
    -0.92 ± 1.21
    -1.52 ± 1.37
    -1.8 ± 1.44
    No statistical analyses for this end point

    Secondary: Change from Baseline in Clinical Disease Activity Index Score

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    End point title
    Change from Baseline in Clinical Disease Activity Index Score
    End point description
    The Clinical Disease Activity Index (CDAI) is a tool for measurement of disease activity in RA that does not require a laboratory component and was scored by the investigative site. It integrates TJC28, SJC28, Patient's Global Assessment of Disease Activity using visual analog scale (cm), and Physician's Global Assessment of Disease Activity using visual analog scale (cm). The CDAI is calculated by summing the values of the 4 components. Lower scores indicated less disease activity. Analysis Population Description: mITT population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    170
    169
    171
    Units: Units on a Scale
        arithmetic mean (standard deviation)
    -12.19 ± 16.96
    -17.17 ± 16.96
    -20.3 ± 16.29
    No statistical analyses for this end point

    Secondary: Change from Baseline in Measures of SDAI Score

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    End point title
    Change from Baseline in Measures of SDAI Score
    End point description
    The SDAI is a tool for measurement of disease activity in RA that integrates TJC28, SJC28, acute phase response using C-reactive protein (milligrams per liter), Patient's Global Assessment of Disease Activity using visual analog scale (cm), and Physician's Global Assessment of Disease Activity using visual analog scale (cm). The SDAI is calculated by summing the values of the 5 components. Lower scores indicated less disease activity. Analysis Population Description: mITT population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    170
    169
    171
    Units: Units on a Scale
        arithmetic mean (standard deviation)
    -12.07 ± 17.5
    -17.8 ± 17.5
    -21.26 ± 17.01
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving ACR/EULAR Remission – Boolean Remission

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    End point title
    Percentage of Participants Achieving ACR/EULAR Remission – Boolean Remission
    End point description
    The ACR/EULAR definitions of RA remission includes a Boolean-based definition. The Boolean-based definition of remission occurs when all 4 of the following criteria are met at the same visit: TJC28 ≤1, SJC28 ≤1, acute phase response using C-reactive protein (milligrams per deciliter) ≤1, Patient's Global Assessment of Disease Activity using VAS (cm) ≤1. Analysis Population Description: mITT population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    176
    174
    177
    Units: Percentage of Participants
        number (not applicable)
    1.1
    4
    6.8
    No statistical analyses for this end point

    Secondary: Change from Baseline in Duration of Morning Joint Stiffness

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    End point title
    Change from Baseline in Duration of Morning Joint Stiffness
    End point description
    Participants reported the duration of their morning joint stiffness (MJS) in hours and minutes. The participants were asked about their duration of morning joint stiffness on the day prior to the study visit to capture actual symptoms, since the participant may have had an atypical morning routine on that day. If morning joint stiffness duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses. A decrease in duration of morning joint stiffness indicated an improvement in the participant's condition. Analysis Population Description: mITT population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    172
    172
    175
    Units: Minutes
        median (confidence interval 95%)
    -8 (-15 to 0)
    -25.5 (-40 to -15)
    -27 (-40 to -15)
    No statistical analyses for this end point

    Secondary: Change from Baseline in Worst Tiredness numeric rating scale (NRS)

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    End point title
    Change from Baseline in Worst Tiredness numeric rating scale (NRS)
    End point description
    A participant-administered, single-item, 11-point horizontal scale anchored at 0 and 10, with 0 representing (no tiredness) and 10 representing (as bad as you can imagine). Participants rate their tiredness by selecting the one number that describes their worst level of tiredness during the past 24 hours. Total scores ranged from 0-10. Analysis Population Description: mITT population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    172
    172
    175
    Units: Units on a Scale
        arithmetic mean (standard deviation)
    -1.1 ± 2.3
    -1.8 ± 2.7
    -2 ± 2.6
    No statistical analyses for this end point

    Secondary: Change from Baseline in Worst Joint Pain NRS

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    End point title
    Change from Baseline in Worst Joint Pain NRS
    End point description
    Participant-administered, single-item, 11-point horizontal scale anchored at 0 and 10, with 0 representing (no joint pain) and 10 representing (pain as bad as you can imagine). Participants rate their joint pain by selecting the one number that describes their worst level of joint pain during the past 24 hours. Total scores ranged from 0-10. Analysis Population Description: mITT population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    172
    172
    175
    Units: Units on a Scale
        arithmetic mean (standard deviation)
    -1.2 ± 2.4
    -2.1 ± 2.5
    -2.5 ± 2.7
    No statistical analyses for this end point

    Secondary: Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Scores

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    End point title
    Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Scores
    End point description
    The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale is a brief 13-item, symptom-specific questionnaire that specifically assesses the participant's self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0 (Not at all) to 4 (Very much) for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue. Analysis Population Description: mITT population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    170
    170
    174
    Units: Units on a Scale
    arithmetic mean (standard deviation)
        Week 12
    5.9 ± 10.5
    8.8 ± 10
    8.5 ± 9.9
        Week 24
    6.6 ± 10.7
    8.8 ± 10.4
    9.7 ± 10.7
    No statistical analyses for this end point

    Secondary: Change from Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute)

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    End point title
    Change from Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute)
    End point description
    The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and 2 component scores (mental [MCS] and physical [PCS]). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status. Analysis Population Description: mITT population includes all randomized participants who received at least 1 dose of the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    168
    168
    174
    Units: Units on a Scale
    arithmetic mean (standard deviation)
        Week 12 MCS
    1.6 ± 10.7
    3.4 ± 9.7
    2.4 ± 10
        Week 24 MCS
    2.5 ± 10.8
    3.2 ± 11.5
    3.3 ± 10.6
        Week 12 PCS
    3.3 ± 8
    6.3 ± 8.8
    6.4 ± 8.8
        Week 24 PCS
    2.4 ± 8.2
    6.4 ± 8.9
    7 ± 9.3
    No statistical analyses for this end point

    Secondary: Change from Baseline in European Quality of Life-5 Dimensions-5 Level Scores

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    End point title
    Change from Baseline in European Quality of Life-5 Dimensions-5 Level Scores
    End point description
    EQ-5D-5L is a standardized measure of health status. The first component is a descriptive system of the respondent’s health comprised of the 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1. A higher score indicates better health state. The second component is a self-perceived health score which is assessed using a VAS that ranged from 0 to 100 millimeter (mm), where 0 mm indicated the worst health you can imagine and 100 mm indicated the best health you can imagine. Population Description: mITT population. Missing data were imputed using mLOCF.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    168
    168
    173
    Units: Units on a Scale
    arithmetic mean (standard deviation)
        Index Score (US Algorithm) Wk 12 (N=168,168,173)
    0.035 ± 0.167
    0.08 ± 0.152
    0.128 ± 0.148
        Index Score (US Algorithm) Wk 24 (N=167,168,173)
    0.042 ± 0.166
    0.082 ± 0.17
    0.128 ± 0.157
        Index Score (UK Algorithm) Wk 12 (N=168,168,173)
    0.052 ± 0.25
    0.116 ± 0.224
    0.191 ± 0.224
        Index Score (UK Algorithm) Wk 24 (N=167,168,173)
    0.064 ± 0.245
    0.122 ± 0.25
    0.192 ± 0.237
        Self-Perceived Health Wk 12 (N=168,168,173)
    4.1 ± 29
    14.1 ± 24.2
    10.3 ± 27.3
        Self-Perceived Health Wk 24 (N=167,168,173)
    3.8 ± 27.8
    11.4 ± 26.5
    13.3 ± 29
    No statistical analyses for this end point

    Secondary: Percentage Change from Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores

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    End point title
    Percentage Change from Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores
    End point description
    The WPAI-RA participant questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. Using 6 questions, it yields four types of scores: absenteeism (work time missed), presenteeism (impairment at work), work productivity loss (overall work impairment), and activity impairment, with outcomes expressed as impairment percentages. Percentage work time missed absenteeism: Q2/(Q2+Q4)*100, Percentage impairment while working presenteeism: Q5/10*100; Percentage overall work impairment work productivity loss: Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))x(Q5/10)]*100; Percentage activity impairment activity impairment: Q6/10*100. Higher numbers indicate greater impairment and less productivity, that is, worse outcomes. Population: mITT population includes all randomized participants who received at least 1 dose of the study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24
    End point values
    Placebo Baricitinib 2 mg Baricitinib 4 mg
    Number of subjects analysed
    176
    174
    177
    Units: Percentage of Impairment
    arithmetic mean (standard deviation)
        Absenteeism Week 12 (n=39, 57, 46)
    3.2 ± 23.8
    -6.7 ± 26.6
    -6.5 ± 22.1
        Absenteeism Week 24 (n=22, 37, 38)
    0.9 ± 12.4
    -1.9 ± 31.4
    -2.3 ± 29.5
        Presenteeism Week 12 (n=37, 54, 43)
    -4.1 ± 26.4
    12 ± 24
    -10.5 ± 24
        Presenteeism Week 24 (n=21, 35, 34)
    -7.1 ± 30.5
    -11.4 ± 24.9
    -15.6 ± 25.4
        Work Productivity Loss Week 12 (n=37, 54, 43)
    -4.2 ± 27.8
    -13.7 ± 26.7
    -12.3 ± 24.8
        Work Productivity Loss Week 24 (n=21, 35, 34)
    -6 ± 33.4
    -13.2 ± 27.6
    -14.8 ± 32.4
        Activity Impairment Week 12 (n=157, 162, 165)
    -10.4 ± 22.8
    -16 ± 25.5
    -18.1 ± 24.8
        Activity Impairment Week 24 (n= 91, 119, 125)
    -15.7 ± 25.5
    -20.8 ± 23.7
    -25.8 ± 25.2
    No statistical analyses for this end point

    Secondary: Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of Baricitinib

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    End point title
    Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of Baricitinib
    End point description
    Analysis Population Description: All randomized participants who received at least 1 dose of study drug with evaluable PK data.
    End point type
    Secondary
    End point timeframe
    Week 0 (Baseline): 15 min. post-dose, 1 hour post-dose. Week 4 (Day 28 ±2 days): 2 to 4 hours post-dose. Week 8 (Day 56 ±3 days): 4 to 6 hours post-dose. Week 12 (Day 84 ±3 days): Pre-dose. Week 24 (Day 168 ±5 days): Pre-dose.
    End point values
    PK population 2mg Baricitinib PK population 4mg Baricitinib
    Number of subjects analysed
    185
    210
    Units: nanomoles/Liter (nmol/L)
        geometric mean (geometric coefficient of variation)
    65.6 ± 21.4
    130 ± 19.3
    No statistical analyses for this end point

    Secondary: Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib

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    End point title
    Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib
    End point description
    Analysis Population Description: All randomized participants who received at least 1 dose of study drug with evaluable PK data.
    End point type
    Secondary
    End point timeframe
    Week 0 (Baseline): 15 min. post-dose, 1 hour post-dose. Week 4 (Day 28 ±2 days): 2 to 4 hours post-dose. Week 8 (Day 56 ±3 days): 4 to 6 hours post-dose. Week 12 (Day 84 ±3 days): Pre-dose. Week 24 (Day 168 ±5 days): Pre-dose.
    End point values
    PK population 2mg Baricitinib PK population 4mg Baricitinib
    Number of subjects analysed
    185
    210
    Units: nanomoles*hour/Liter (nmol*h/L)
        geometric mean (geometric coefficient of variation)
    615 ± 43.1
    1140 ± 38.7
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Entire Study
    Adverse event reporting additional description
    I4V-MC-JADW
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo administered orally (PO) once daily (QD) through Week 24. Participants continued to take background conventional synthetic drug (DMARD) therapy throughout study.

    Reporting group title
    Baricitinib 2 mg
    Reporting group description
    Baricitinib 2 milligram (mg) administered PO QD through Week 24. Participants continued to take background DMARD therapy throughout study.

    Reporting group title
    Baricitinib 4 mg
    Reporting group description
    Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background DMARD therapy throughout study.

    Reporting group title
    Rescue (Weeks 16-24)
    Reporting group description
    Baricitinib 4 mg administered PO QD Weeks 16-24 only. Participants continued to take background DMARD therapy throughout study.

    Reporting group title
    Placebo - Follow Up
    Reporting group description
    No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.

    Reporting group title
    Baricitinib 2 mg - Follow Up
    Reporting group description
    No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.

    Reporting group title
    Baricitinib 4 mg - Follow Up
    Reporting group description
    Includes participants who were rescued to baricitinib 4 mg. No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.

    Serious adverse events
    Placebo Baricitinib 2 mg Baricitinib 4 mg Rescue (Weeks 16-24) Placebo - Follow Up Baricitinib 2 mg - Follow Up Baricitinib 4 mg - Follow Up
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 176 (7.95%)
    8 / 174 (4.60%)
    19 / 177 (10.73%)
    2 / 127 (1.57%)
    0 / 19 (0.00%)
    1 / 9 (11.11%)
    0 / 20 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    Vascular disorders
    hypertension
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 176 (1.14%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hypertensive crisis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    peripheral arterial occlusive disease
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    1 / 174 (0.57%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    peripheral embolism
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    1 / 174 (0.57%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    medical device complication
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    confusional state
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    delirium
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    accident at work
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    acetabulum fracture
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    alcohol poisoning
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    bone contusion
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cardiac contusion
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    concussion
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    1 / 174 (0.57%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    facial bones fracture
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    fall
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    fractured sacrum
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hand fracture
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    laceration
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ligament sprain
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    1 / 174 (0.57%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    lower limb fracture
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    muscle rupture
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    1 / 127 (0.79%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    road traffic accident
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    1 / 174 (0.57%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    spinal fracture
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ulna fracture
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    blood alkaline phosphatase increased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    blood creatine phosphokinase increased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hepatic enzyme increased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    weight decreased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    coronary artery disease
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    2 / 177 (1.13%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    myocardial infarction
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    tachycardia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    asthma
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    1 / 174 (0.57%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pleuritic pain
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pneumonia aspiration
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    1 / 174 (0.57%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pulmonary mass
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    haemorrhagic anaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    iron deficiency anaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    leukocytosis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    thrombocytopenia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    basilar artery thrombosis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    carpal tunnel syndrome
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    1 / 174 (0.57%)
    0 / 177 (0.00%)
    1 / 127 (0.79%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    headache
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    transient global amnesia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    vertebral artery thrombosis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    motion sickness
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    vertigo positional
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    diverticulum intestinal haemorrhagic
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    1 / 9 (11.11%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    inguinal hernia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    oral disorder
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    1 / 174 (0.57%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    renal failure
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    cholecystitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    1 / 174 (0.57%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    osteoarthritis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    1 / 174 (0.57%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    rheumatoid arthritis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    3 / 176 (1.70%)
    0 / 174 (0.00%)
    2 / 177 (1.13%)
    1 / 127 (0.79%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    synovitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    electrolyte imbalance
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hyperglycaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    malnutrition
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    campylobacter gastroenteritis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    1 / 174 (0.57%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cellulitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 176 (1.14%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastroenteritis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastroenteritis viral
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    herpes zoster
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    intervertebral discitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    1 / 174 (0.57%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    osteomyelitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    1 / 174 (0.57%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    1 / 174 (0.57%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    tooth infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    upper respiratory tract infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    1 / 174 (0.57%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 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
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    2 / 177 (1.13%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    vulval abscess
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed [1]
    0 / 145 (0.00%)
    0 / 137 (0.00%)
    1 / 149 (0.67%)
    0 / 113 (0.00%)
    0 / 16 (0.00%)
    0 / 9 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    Placebo Baricitinib 2 mg Baricitinib 4 mg Rescue (Weeks 16-24) Placebo - Follow Up Baricitinib 2 mg - Follow Up Baricitinib 4 mg - Follow Up
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    79 / 176 (44.89%)
    105 / 174 (60.34%)
    102 / 177 (57.63%)
    6 / 127 (4.72%)
    2 / 19 (10.53%)
    3 / 9 (33.33%)
    1 / 20 (5.00%)
    Vascular disorders
    hypertension
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    4 / 176 (2.27%)
    7 / 174 (4.02%)
    9 / 177 (5.08%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    4
    7
    9
    0
    0
    0
    0
    General disorders and administration site conditions
    fatigue
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    5 / 176 (2.84%)
    6 / 174 (3.45%)
    3 / 177 (1.69%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    5
    6
    4
    0
    0
    0
    0
    pyrexia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    7 / 174 (4.02%)
    3 / 177 (1.69%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    8
    3
    0
    0
    0
    0
    Psychiatric disorders
    insomnia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    1 / 9 (11.11%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    contusion
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    4 / 176 (2.27%)
    4 / 174 (2.30%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    4
    4
    1
    0
    0
    0
    0
    Investigations
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    0 / 174 (0.00%)
    4 / 177 (2.26%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    6
    0
    0
    0
    0
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    5 / 177 (2.82%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    7
    0
    0
    0
    0
    blood creatine phosphokinase increased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    4 / 174 (2.30%)
    6 / 177 (3.39%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    4
    8
    0
    0
    0
    0
    weight increased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    4 / 174 (2.30%)
    3 / 177 (1.69%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    4
    3
    0
    0
    0
    0
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 176 (1.14%)
    4 / 174 (2.30%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    2
    4
    1
    0
    0
    0
    0
    lymphopenia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    1 / 9 (11.11%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    cough
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    6 / 176 (3.41%)
    2 / 174 (1.15%)
    5 / 177 (2.82%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    6
    2
    5
    0
    0
    0
    0
    oropharyngeal pain
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 176 (1.14%)
    5 / 174 (2.87%)
    5 / 177 (2.82%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    1 / 9 (11.11%)
    0 / 20 (0.00%)
         occurrences all number
    2
    6
    5
    0
    0
    1
    0
    Nervous system disorders
    headache
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    11 / 176 (6.25%)
    17 / 174 (9.77%)
    12 / 177 (6.78%)
    3 / 127 (2.36%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    12
    17
    12
    3
    0
    0
    0
    Eye disorders
    episcleritis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    1 / 19 (5.26%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Gastrointestinal disorders
    abdominal pain
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    4 / 176 (2.27%)
    5 / 174 (2.87%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    4
    5
    0
    0
    0
    0
    0
    abdominal pain upper
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    7 / 174 (4.02%)
    4 / 177 (2.26%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    7
    4
    0
    0
    0
    0
    constipation
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    4 / 176 (2.27%)
    4 / 174 (2.30%)
    3 / 177 (1.69%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    5
    4
    3
    0
    0
    0
    0
    diarrhoea
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    12 / 176 (6.82%)
    10 / 174 (5.75%)
    7 / 177 (3.95%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    12
    10
    7
    0
    0
    0
    0
    gastritis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    2 / 174 (1.15%)
    4 / 177 (2.26%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    2
    4
    0
    0
    0
    0
    gastrooesophageal reflux disease
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    4 / 176 (2.27%)
    3 / 174 (1.72%)
    2 / 177 (1.13%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    4
    3
    2
    0
    0
    0
    0
    nausea
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    5 / 176 (2.84%)
    7 / 174 (4.02%)
    10 / 177 (5.65%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    6
    9
    10
    0
    0
    0
    0
    vomiting
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 176 (1.14%)
    4 / 174 (2.30%)
    4 / 177 (2.26%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    2
    5
    4
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    rash
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 176 (1.14%)
    5 / 174 (2.87%)
    2 / 177 (1.13%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    2
    5
    2
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    8 / 176 (4.55%)
    3 / 174 (1.72%)
    5 / 177 (2.82%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    10
    4
    6
    0
    0
    0
    0
    back pain
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    6 / 176 (3.41%)
    8 / 174 (4.60%)
    6 / 177 (3.39%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    6
    8
    6
    0
    0
    0
    0
    muscle spasms
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 176 (1.14%)
    3 / 174 (1.72%)
    4 / 177 (2.26%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    2
    3
    4
    0
    0
    0
    0
    myalgia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    5 / 174 (2.87%)
    4 / 177 (2.26%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    6
    4
    0
    0
    0
    0
    neck pain
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    4 / 176 (2.27%)
    2 / 174 (1.15%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    4
    2
    1
    0
    0
    0
    0
    pain in extremity
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    4 / 174 (2.30%)
    1 / 177 (0.56%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    6
    2
    0
    0
    0
    0
    rheumatoid arthritis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    7 / 176 (3.98%)
    5 / 174 (2.87%)
    8 / 177 (4.52%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    8
    6
    10
    0
    0
    0
    0
    Metabolism and nutrition disorders
    hypercholesterolaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 176 (1.14%)
    1 / 174 (0.57%)
    7 / 177 (3.95%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    2
    1
    7
    0
    0
    0
    0
    hyperlipidaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    3 / 174 (1.72%)
    5 / 177 (2.82%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    3
    5
    0
    0
    0
    0
    Infections and infestations
    bronchitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    6 / 176 (3.41%)
    6 / 174 (3.45%)
    10 / 177 (5.65%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    7
    7
    12
    0
    0
    0
    0
    cervicitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed [2]
    0 / 145 (0.00%)
    0 / 137 (0.00%)
    0 / 149 (0.00%)
    0 / 113 (0.00%)
    0 / 16 (0.00%)
    0 / 9 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    conjunctivitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    0 / 174 (0.00%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    1 / 19 (5.26%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    gastroenteritis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    3 / 176 (1.70%)
    4 / 174 (2.30%)
    6 / 177 (3.39%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    3
    4
    7
    0
    0
    0
    0
    herpes zoster
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    2 / 174 (1.15%)
    6 / 177 (3.39%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    2
    6
    0
    0
    0
    0
    influenza
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 176 (1.14%)
    4 / 174 (2.30%)
    8 / 177 (4.52%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    2
    4
    10
    0
    0
    0
    0
    nasopharyngitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    7 / 176 (3.98%)
    12 / 174 (6.90%)
    9 / 177 (5.08%)
    4 / 127 (3.15%)
    1 / 19 (5.26%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    7
    13
    10
    5
    1
    0
    0
    pharyngitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 176 (0.00%)
    4 / 174 (2.30%)
    5 / 177 (2.82%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    4
    5
    0
    0
    0
    0
    rhinitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    5 / 174 (2.87%)
    0 / 177 (0.00%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    5
    0
    0
    0
    0
    0
    sinusitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 176 (0.57%)
    8 / 174 (4.60%)
    4 / 177 (2.26%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    8
    4
    0
    0
    0
    0
    upper respiratory tract infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    8 / 176 (4.55%)
    15 / 174 (8.62%)
    9 / 177 (5.08%)
    0 / 127 (0.00%)
    0 / 19 (0.00%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    8
    17
    11
    0
    0
    0
    0
    urinary tract infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    6 / 176 (3.41%)
    7 / 174 (4.02%)
    8 / 177 (4.52%)
    0 / 127 (0.00%)
    1 / 19 (5.26%)
    0 / 9 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    6
    10
    10
    0
    1
    0
    0
    vulvovaginal candidiasis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed [3]
    0 / 145 (0.00%)
    3 / 137 (2.19%)
    0 / 149 (0.00%)
    0 / 113 (0.00%)
    0 / 16 (0.00%)
    0 / 9 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    0
    Notes
    [2] - 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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
    [3] - 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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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