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    Clinical Trial Results:
    A Phase 3b, Multicenter, Open-Label Study to Evaluate the Long-Term Safety and Efficacy of LY2127399 in Patients with Rheumatoid Arthritis (RA)

    Summary
    EudraCT number
    		 2010-022208-36
    Trial protocol
    		 HU   DE   LT   ES   IT   BG   PL   GR  
    Global end of trial date
    24 Mar 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Apr 2018
    First version publication date
    09 Apr 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    H9B-MC-BCDP
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01215942
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 13419
    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
    24 Mar 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Mar 2014
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary purpose of this study is to help answer if LY2127399 is safe and effective during long-term treatment in participants with Rheumatoid Arthritis. This study is comprised of 2 periods: Period 1: Unblinded treatment for up to 240 weeks for participants who enroll from Study H9B-MC-BCDO (BCDO) (EU#2010-022206-40) ) or Study H9B-MC-BCDV (BCDV) (EU#2010-022207-22) or up to 168 weeks for participants who enroll from Study H9B-MC-BCDM (BCDM) (EU#2010-022205-17). Period 2: 48-week post-treatment follow-up
    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
    22 Jun 2011
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 12 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 442
    Country: Number of subjects enrolled
    Taiwan: 20
    Country: Number of subjects enrolled
    Slovakia: 12
    Country: Number of subjects enrolled
    Greece: 2
    Country: Number of subjects enrolled
    Ukraine: 33
    Country: Number of subjects enrolled
    Russian Federation: 33
    Country: Number of subjects enrolled
    Colombia: 35
    Country: Number of subjects enrolled
    Sri Lanka: 9
    Country: Number of subjects enrolled
    India: 20
    Country: Number of subjects enrolled
    Malaysia: 4
    Country: Number of subjects enrolled
    Australia: 10
    Country: Number of subjects enrolled
    South Africa: 82
    Country: Number of subjects enrolled
    Korea, Republic of: 17
    Country: Number of subjects enrolled
    Lithuania: 31
    Country: Number of subjects enrolled
    Hungary: 14
    Country: Number of subjects enrolled
    Mexico: 43
    Country: Number of subjects enrolled
    Argentina: 23
    Country: Number of subjects enrolled
    Poland: 78
    Country: Number of subjects enrolled
    Brazil: 9
    Country: Number of subjects enrolled
    Croatia: 4
    Country: Number of subjects enrolled
    Romania: 3
    Country: Number of subjects enrolled
    Bulgaria: 24
    Country: Number of subjects enrolled
    Germany: 4
    Country: Number of subjects enrolled
    Japan: 116
    Country: Number of subjects enrolled
    New Zealand: 18
    Worldwide total number of subjects
    1086
    EEA total number of subjects
    172
    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)
    951
    From 65 to 84 years
    135
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Study consisted of a Treatment Period of up to 240 weeks for participants (pts) who enrolled from Studies H9B-MC-BCDO (BCDO) and H9B-MC-BCDV (BCDV) or up to 168 weeks for pts who enrolled from Study H9-MC-BCDM (BCDM). Discontinued pts were followed in Post-Treatment Follow-Up Period for up to 48 weeks.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 120 mg LY2127399 (LY A)
    Arm description
    		 120 milligrams (mg) LY2127399 administered subcutaneously (SC) every 4 weeks (Q4W). Participants from Studies BCDO, BCDV and BCDM who were on 120 mg LY2127399 SC Q4W immediately prior to Study H9B-MC-BCDP (BCDP) enrollment remained on 120 mg LY2127399 SC Q4W. Participants from Studies BCDO, BCDV and BCDM who were on placebo immediately prior to Study BCDP enrollment were randomized to receive a loading dose of 240 mg LY2127399 SC, 4 weeks later followed by 120 mg LY2127399 SC Q4W for the subsequent treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tabalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    120 milligrams (mg) of LY2127399 Given every 4 weeks for 240 weeks for those participants from Study BCDO or Study BCDV. Participants who had been receiving placebo immediately prior to enrollment will receive a 240 mg loading dose when initiating treatment. Or Given every 4 weeks for 168 weeks for those participants from Study BCDM.

    Arm title
    		 90 mg LY2127399 (LY B)
    Arm description
    		 90 mg LY2127399 administered SC every 2 weeks (Q2W). Participants from Studies BCDO, BCDV and BCDM who were on 90 mg LY2127399 SC Q2W immediately prior to Study BCDP enrollment remained on 90 mg LY2127399 SC Q2W. Participants from Studies BCDO, BCDV and BCDM who were on placebo immediately prior to Study BCDP enrollment were randomized to receive a loading dose of 180 mg LY2127399 SC, 2 weeks later followed by 90 mg LY2127399 SC Q2W for the subsequent treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tabalumab
    Investigational medicinal product code
    LY2127399
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    90 mg LY2127399 Given every 2 weeks for 240 weeks for those participants from Study BCDO or Study BCDV. Participants who had been receiving placebo immediately prior to enrollment will receive a 180 mg loading dose when initiating treatment. Or Given every 2 weeks for 168 weeks for those participants from Study BCDM.

    Number of subjects in period 1
    		120 mg LY2127399 (LY A) 90 mg LY2127399 (LY B)
    Started
    414
    672
    One dose of study drug
    414
    672
    Completed treatment period Wk 240
    0 [1]
    0 [2]
    Entered Post-treatment follow-up
    368
    591
    Completed
    283
    445
    Not completed
    131
    227
         Consent withdrawn by subject
    83
    140
         Physician decision
    1
    2
         Death
    2
    5
         Lost to follow-up
    15
    17
         Sponsor decision
    28
    61
         Investigator site close
    2
    2
    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: No patients completed the 240-week (participants from BCDO and BCDV) or 168-week (participants from BCDM) Treatment Period before termination of the study. Participants who discontinued treatment were followed in post-treatment follow-up, however not all participants who discontinued treatment entered post-treatment follow-up period.
    [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: No patients completed the 240-week (participants from BCDO and BCDV) or 168-week (participants from BCDM)Treatment Period before termination of the study. Participants who discontinued treatment were followed in post-treatment follow-up, however not all participants who discontinued treatment entered post-treatment follow-up period.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    120 mg LY2127399 (LY A)
    Reporting group description
    		 120 milligrams (mg) LY2127399 administered subcutaneously (SC) every 4 weeks (Q4W). Participants from Studies BCDO, BCDV and BCDM who were on 120 mg LY2127399 SC Q4W immediately prior to Study H9B-MC-BCDP (BCDP) enrollment remained on 120 mg LY2127399 SC Q4W. Participants from Studies BCDO, BCDV and BCDM who were on placebo immediately prior to Study BCDP enrollment were randomized to receive a loading dose of 240 mg LY2127399 SC, 4 weeks later followed by 120 mg LY2127399 SC Q4W for the subsequent treatment.

    Reporting group title
    90 mg LY2127399 (LY B)
    Reporting group description
    		 90 mg LY2127399 administered SC every 2 weeks (Q2W). Participants from Studies BCDO, BCDV and BCDM who were on 90 mg LY2127399 SC Q2W immediately prior to Study BCDP enrollment remained on 90 mg LY2127399 SC Q2W. Participants from Studies BCDO, BCDV and BCDM who were on placebo immediately prior to Study BCDP enrollment were randomized to receive a loading dose of 180 mg LY2127399 SC, 2 weeks later followed by 90 mg LY2127399 SC Q2W for the subsequent treatment.

    Reporting group values
    		 120 mg LY2127399 (LY A) 90 mg LY2127399 (LY B) Total
    Number of subjects
    		 414 672 1086
    Age categorical
    Units: Subjects
    Gender, Male/Female
    Units:
        Female
    		 339 538 877
        Male
    		 75 134 209
    Region of Enrollment
    Units: Subjects
        United States
    		 148 294 442
        Taiwan
    		 7 13 20
        Slovakia
    		 9 3 12
        Greece
    		 2 0 2
        Ukraine
    		 12 21 33
        Russian Federation
    		 12 21 33
        Colombia
    		 13 22 35
        Sri Lanka
    		 4 5 9
        India
    		 13 7 20
        Malaysia
    		 1 3 4
        Australia
    		 1 9 10
        South Africa
    		 23 59 82
        Korea, Republic of
    		 8 9 17
        Lithuania
    		 16 15 31
        Hungary
    		 4 10 14
        Mexico
    		 18 25 43
        Argentina
    		 9 14 23
        Poland
    		 42 36 78
        Brazil
    		 5 4 9
        Croatia
    		 1 3 4
        Romania
    		 1 2 3
        Bulgaria
    		 12 12 24
        Germany
    		 2 2 4
        Japan
    		 44 72 116
        New Zealand
    		 7 11 18
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 17 36 53
        Asian
    		 82 125 207
        Native Hawaiian or Other Pacific Islander
    		 1 1 2
        Black or African American
    		 24 43 67
        White
    		 285 450 735
        More than one race
    		 5 13 18
        Unknown or Not Reported
    		 0 4 4
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 52 100 152
        Not Hispanic or Latino
    		 218 365 583
        Unknown or Not Reported
    		 144 207 351
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 52.9 ( 10.9 ) 52.4 ( 11.7 ) -

    End points

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    End points reporting groups
    Reporting group title
    120 mg LY2127399 (LY A)
    Reporting group description
    		 120 milligrams (mg) LY2127399 administered subcutaneously (SC) every 4 weeks (Q4W). Participants from Studies BCDO, BCDV and BCDM who were on 120 mg LY2127399 SC Q4W immediately prior to Study H9B-MC-BCDP (BCDP) enrollment remained on 120 mg LY2127399 SC Q4W. Participants from Studies BCDO, BCDV and BCDM who were on placebo immediately prior to Study BCDP enrollment were randomized to receive a loading dose of 240 mg LY2127399 SC, 4 weeks later followed by 120 mg LY2127399 SC Q4W for the subsequent treatment.

    Reporting group title
    90 mg LY2127399 (LY B)
    Reporting group description
    		 90 mg LY2127399 administered SC every 2 weeks (Q2W). Participants from Studies BCDO, BCDV and BCDM who were on 90 mg LY2127399 SC Q2W immediately prior to Study BCDP enrollment remained on 90 mg LY2127399 SC Q2W. Participants from Studies BCDO, BCDV and BCDM who were on placebo immediately prior to Study BCDP enrollment were randomized to receive a loading dose of 180 mg LY2127399 SC, 2 weeks later followed by 90 mg LY2127399 SC Q2W for the subsequent treatment.

    Subject analysis set title
    LY A
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    120 mg LY2127399 administered SC Q4W (LY A). All Week 16 responders from Studies BCDO and BCDV who were randomized to 120 mg LY2127399 SC Q4W at Week 0 of Studies BCDO and BCDV.

    Subject analysis set title
    LY B
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    90 mg LY2127399 administered SC Q2W (LY B). All Week 16 responders from Studies BCDO and BCDV who were randomized to 90 mg LY2127399 SC Q2W at Week 0 of Studies BCDO and BCDV.

    Subject analysis set title
    NR LY A to LY B
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    90 mg LY2127399 administered SC Q2W. All Week 16 non-responders (NR) from Studies BCDO and BCDV who were randomized to 120 mg LY2127399 SC Q4W at Week 0 of Studies BCDO and BCDV and assigned to 90 mg LY2127399 SC Q2W at Week 16 of Studies BCDO and BCDV.

    Subject analysis set title
    NR LY B to LY B
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    90 mg LY2127399 administered SC Q2W. All Week 16 NR from Studies BCDO and BCDV who were randomized to 90 mg LY2127399 SC Q2W at Week 0 of Studies BCDO and BCDV and continued to receive 90 mg LY2127399 SC Q2W at Week 16 of Studies BCDO and BCDV.

    Subject analysis set title
    NR Placebo to LY B
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    90 mg LY2127399 administered SC Q2W. All Week 16 NR from Studies BCDO and BCDV who were randomized to placebo SC Q2W at Week 0 of Studies BCDO and BCDV and assigned to 90 mg LY2127399 SC Q2W at Week 16 of Studies BCDO and BCDV.

    Subject analysis set title
    Placebo to LY A
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    120 mg LY2127399 administered SC Q4W (240 mg LY2127399 loading dose at Week 0). All Week 16 responders from Studies BCDO and BCDV who were randomized to placebo SC Q2W at Week 0 of Studies BCDO and BCDV and were randomized to receive 120 mg LY2127399 SC Q4W in Study BCDP.

    Subject analysis set title
    Placebo to LY B
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    90 mg LY2127399 administered SC Q2W (180 mg LY2127399 loading dose at Week 0). All Week 16 responders from Studies BCDO and BCDV who were randomized to placebo SC Q2W at Week 0 of Studies BCDO and BCDV and were randomized to receive 90 mg LY2127399 SC Q2W in Study BCDP.

    Primary: Percentage of Participants Developing Anti-LY2127399 Antibodies

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    End point title
    		 Percentage of Participants Developing Anti-LY2127399 Antibodies [1]
    End point description
    Participants with treatment-emergent anti-LY2127399 antibodies were participants who had any samples from baseline up to and through Week 72 that was a 4-fold increase (2-dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). Baseline is defined as the last non-missing observation on or prior to the date of the first injection of LY2127399 in preceding studies or Study BCDP. Percentage of participants with anti-LY2127399 antibodies=(number of participants with treatment-emergent anti-LY2127399 antibodies / number of participants assessed)*100. Analysis Population Description: All participants from Studies BCDO and BCDV with an evaluable baseline anti-LY2127399 antibodies result and a post-baseline anti-LY2127399 antibodies result. Participants missing an evaluable baseline result with a negative post-baseline results were included.
    End point type
    Primary
    End point timeframe
    Baseline through Weeks 4, 24, 48 and 72
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The study was terminated early due to insufficient efficacy; no statistical analyses were conducted.
    End point values
    		 LY A LY B NR LY A to LY B NR LY B to LY B NR Placebo to LY B Placebo to LY A Placebo to LY B
    Number of subjects analysed
    291
    292
    88
    88
    67
    97
    102
    Units: percentage of participants
    number (not applicable)
        Week 4 (n=291, 292, 88, 88, 67, 97, 102)
    1.7
    0.3
    3.4
    1.1
    1.5
    2.1
    1
        Week 24 (n= 267, 280, 75, 72, 56, 90, 95)
    0.7
    0.7
    1.3
    1.4
    0
    1.1
    0
        Week 48 (n= 156, 157, 50, 39, 31, 54, 62)
    0
    0.6
    0
    0
    0
    0
    0
        Week 72 (n= 61, 68, 27, 17, 16, 22, 22)
    0
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI) During Treatment Period

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    End point title
    		 Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI) During Treatment Period [2]
    End point description
    A TEAE was defined as an event that first occurred or worsened in severity on or after the date of the first injection and prior to study termination. AESI are infection, injection site reactions, malignancy, major adverse cardiovascular events (MACE), allergy and hypersensitivity, depression, suicide/self-injury and pregnancy. MACE were defined as 1 of the adjudicated events: cardiovascular death, Myocardial infarction (MI), stroke, hospitalization for unstable angina, hospitalization for heart failure, coronary revascularization procedure, peripheral revascularization procedure, cardiogenic shock due to MI, resuscitated sudden death, serious arrhythmia, hospitalization for hypertension, peripheral arterial event. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
    End point type
    Primary
    End point timeframe
    up to 84.4 weeks during treatment period
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The study was terminated early due to insufficient efficacy; no statistical analyses were conducted.
    End point values
    		 120 mg LY2127399 (LY A) 90 mg LY2127399 (LY B)
    Number of subjects analysed
    414
    672
    Units: participants
    number (not applicable)
        TEAE
    259
    422
        SAE
    30
    57
        Infection
    127
    266
        Injection Site Reaction
    15
    30
        Malignancy
    0
    7
        Major Adverse Cardiovascular Events (MACE)
    4
    6
        Allergy and Hypersensitivity
    13
    23
        Depression
    7
    10
        Suicide/Self-injury
    1
    0
        Pregnancy
    1
    2
    No statistical analyses for this end point

    Primary: Change from Baseline in Absolute B Cell Counts

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    End point title
    		 Change from Baseline in Absolute B Cell Counts [3]
    End point description
    Cell-surface marker cluster designation (CD) 3 negative, CD20 positive (CD3-CD20+) defines total mature B cells. B-lymphocyte antigen CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B cells. Baseline B cell count is the average of the values on or prior to the date of first injection of study treatment in preceding studies, including unscheduled visits. A positive or negative change indicated an increase or decrease, respectively, in B cell count. Analysis Population Description: All participants from Studies BCDO and BCDV with an evaluable baseline anti-LY2127399 antibodies result and a post-baseline anti-LY2127399 antibodies result. Participants missing an evaluable baseline result with a negative post-baseline results were included.
    End point type
    Primary
    End point timeframe
    Baseline, Week 48
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The study was terminated early due to insufficient efficacy; no statistical analyses were conducted.
    End point values
    		 LY A LY B NR LY A to LY B NR LY B to LY B NR Placebo to LY B Placebo to LY A Placebo to LY B
    Number of subjects analysed
    302
    305
    90
    88
    70
    102
    105
    Units: cells/microliter (cells/µL)
        arithmetic mean (standard deviation)
    -111.68 ( 155.59 )
    -121.3 ( 132.68 )
    -134.68 ( 130.21 )
    -110.92 ( 125.3 )
    -99.67 ( 126.55 )
    -75.92 ( 126.55 )
    -104.67 ( 143.24 )
    No statistical analyses for this end point

    Primary: Change from Baseline in Serum Immunoglobulin (Ig) Levels

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    End point title
    		 Change from Baseline in Serum Immunoglobulin (Ig) Levels [4]
    End point description
    Immunoglobulins (Ig), or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Change from baseline serum immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels are reported. A negative change indicated a decrease in Ig levels. Baseline is defined as the last non-missing observation on or prior to the date of the first injection of LY2127399 in preceding studies or Study BCDP. Analysis Population Description: All participants from Studies BCDO and BCDV with an evaluable serum Ig data. LOCF was used to impute missing post-baseline values.
    End point type
    Primary
    End point timeframe
    Baseline, Week 48
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The study was terminated early due to insufficient efficacy; no statistical analyses were conducted.
    End point values
    		 LY A LY B NR LY A to LY B NR LY B to LY B NR Placebo to LY B Placebo to LY A Placebo to LY B
    Number of subjects analysed
    306
    307
    90
    91
    71
    104
    105
    Units: grams/liter (g/L)
    arithmetic mean (standard deviation)
        IgA
    -0.402 ( 0.58 )
    -0.424 ( 0.604 )
    -0.499 ( 0.681 )
    -0.465 ( 0.501 )
    -0.298 ( 0.376 )
    -0.3 ( 0.59 )
    -0.407 ( 0.481 )
        IgG
    -1.465 ( 2.112 )
    -1.366 ( 2.166 )
    -1.321 ( 2.071 )
    -1.196 ( 2.276 )
    -1.42 ( 1.651 )
    -1.376 ( 2.295 )
    -1.415 ( 2.163 )
        IgM
    -0.346 ( 0.372 )
    -0.332 ( 0.465 )
    -0.422 ( 0.505 )
    -0.387 ( 0.267 )
    -0.287 ( 0.228 )
    -0.256 ( 0.289 )
    -0.267 ( 0.298 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants with American College of Rheumatology 20% Response (ACR20)

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    End point title
    		 Percentage of Participants with American College of Rheumatology 20% Response (ACR20)
    End point description
    ACR Responder Index is a Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responders: had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). Baseline is defined as the last non-missing observation on or prior to the date of the first injection of LY2127399 in preceding studies or Study BCDP. Percentage of participants achieving ACR20 response=(number of ACR20 responders / number of participants treated) * 100. All participants who discontinue study treatment for any reason were defined as NR at that time point and going forward.
    End point type
    Secondary
    End point timeframe
    Baseline through Weeks 12, 24 and 48
    End point values
    		 LY A LY B NR LY A to LY B NR LY B to LY B NR Placebo to LY B Placebo to LY A Placebo to LY B
    Number of subjects analysed
    308 [5]
    308 [6]
    91 [7]
    92 [8]
    72 [9]
    105 [10]
    106 [11]
    Units: percentage of participants
    number (not applicable)
        Week 12
    41.9
    46.1
    30.8
    21.7
    25
    8.6
    4.7
        Week 24
    37.3
    37
    29.7
    16.3
    27.8
    6.7
    9.4
        Week 48
    14
    15.9
    18.7
    7.6
    16.7
    6.7
    5.7
    Notes
    [5] - All participants from Studies BCDO and BCDV with evaluable ACR20 responder data.
    [6] - All participants from Studies BCDO and BCDV with evaluable ACR20 responder data.
    [7] - All participants from Studies BCDO and BCDV with evaluable ACR20 responder data.
    [8] - All participants from Studies BCDO and BCDV with evaluable ACR20 responder data.
    [9] - All participants from Studies BCDO and BCDV with evaluable ACR20 responder data.
    [10] - All participants from Studies BCDO and BCDV with evaluable ACR20 responder data.
    [11] - All participants from Studies BCDO and BCDV with evaluable ACR20 responder data.
    No statistical analyses for this end point

    Secondary: Change from Baseline in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP)

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    End point title
    		 Change from Baseline in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP)
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, 240 weeks
    End point values
    		 LY A LY B NR LY A to LY B NR LY B to LY B NR Placebo to LY B Placebo to LY A Placebo to LY B
    Number of subjects analysed
    0 [12]
    0 [13]
    0 [14]
    0 [15]
    0 [16]
    0 [17]
    0 [18]
    Units: NA
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Notes
    [12] - No participants were analyzed due to early termination of the study.
    [13] - No participants were analyzed due to early termination of the study.
    [14] - No participants were analyzed due to early termination of the study.
    [15] - No participants were analyzed due to early termination of the study.
    [16] - No participants were analyzed due to early termination of the study.
    [17] - No participants were analyzed due to early termination of the study.
    [18] - No participants were analyzed due to early termination of the study.
    No statistical analyses for this end point

    Secondary: Percentage of Participants with DAS28-Based European League Against Rheumatism (EULAR-28) Response

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    End point title
    		 Percentage of Participants with DAS28-Based European League Against Rheumatism (EULAR-28) Response
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline through 240 weeks
    End point values
    		 LY A LY B NR LY A to LY B NR LY B to LY B NR Placebo to LY B Placebo to LY A Placebo to LY B
    Number of subjects analysed
    0 [19]
    0 [20]
    0 [21]
    0 [22]
    0 [23]
    0 [24]
    0 [25]
    Units: NA
        number (not applicable)
    Notes
    [19] - No participants were analyzed due to early termination of the study.
    [20] - No participants were analyzed due to early termination of the study.
    [21] - No participants were analyzed due to early termination of the study.
    [22] - No participants were analyzed due to early termination of the study.
    [23] - No participants were analyzed due to early termination of the study.
    [24] - No participants were analyzed due to early termination of the study.
    [25] - No participants were analyzed due to early termination of the study.
    No statistical analyses for this end point

    Secondary: Change from Baseline in Tender Joint Count (68 Joint Count)

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    End point title
    		 Change from Baseline in Tender Joint Count (68 Joint Count)
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, 240 weeks
    End point values
    		 LY A LY B NR LY A to LY B NR LY B to LY B NR Placebo to LY B Placebo to LY A Placebo to LY B
    Number of subjects analysed
    0 [26]
    0 [27]
    0 [28]
    0 [29]
    0 [30]
    0 [31]
    0 [32]
    Units: NA
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Notes
    [26] - No participants were analyzed due to early termination of the study.
    [27] - No participants were analyzed due to early termination of the study.
    [28] - No participants were analyzed due to early termination of the study.
    [29] - No participants were analyzed due to early termination of the study.
    [30] - No participants were analyzed due to early termination of the study.
    [31] - No participants were analyzed due to early termination of the study.
    [32] - No participants were analyzed due to early termination of the study.
    No statistical analyses for this end point

    Secondary: Change from Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores

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    End point title
    		 Change from Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, 240 weeks
    End point values
    		 LY A LY B NR LY A to LY B NR LY B to LY B NR Placebo to LY B Placebo to LY A Placebo to LY B
    Number of subjects analysed
    0 [33]
    0 [34]
    0 [35]
    0 [36]
    0 [37]
    0 [38]
    0 [39]
    Units: NA
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Notes
    [33] - No participants were analyzed due to early termination of the study.
    [34] - No participants were analyzed due to early termination of the study.
    [35] - No participants were analyzed due to early termination of the study.
    [36] - No participants were analyzed due to early termination of the study.
    [37] - No participants were analyzed due to early termination of the study.
    [38] - No participants were analyzed due to early termination of the study.
    [39] - No participants were analyzed due to early termination of the study.
    No statistical analyses for this end point

    Secondary: Change from Baseline in Swollen Joint Count (66 joint count)

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    End point title
    		 Change from Baseline in Swollen Joint Count (66 joint count)
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, 240 weeks
    End point values
    		 LY A LY B NR LY A to LY B NR LY B to LY B NR Placebo to LY B Placebo to LY A Placebo to LY B
    Number of subjects analysed
    0 [40]
    0 [41]
    0 [42]
    0 [43]
    0 [44]
    0 [45]
    0 [46]
    Units: NA
        number (not applicable)
    Notes
    [40] - No participants were analyzed due to early termination of the study.
    [41] - No participants were analyzed due to early termination of the study.
    [42] - No participants were analyzed due to early termination of the study.
    [43] - No participants were analyzed due to early termination of the study.
    [44] - No participants were analyzed due to early termination of the study.
    [45] - No participants were analyzed due to early termination of the study.
    [46] - No participants were analyzed due to early termination of the study.
    No statistical analyses for this end point

    Secondary: Change from Baseline in Participant's Assessment of Pain [Visual Analog Scale (VAS)]

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    End point title
    		 Change from Baseline in Participant's Assessment of Pain [Visual Analog Scale (VAS)]
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, 240 weeks
    End point values
    		 LY A LY B NR LY A to LY B NR LY B to LY B NR Placebo to LY B Placebo to LY A Placebo to LY B
    Number of subjects analysed
    0 [47]
    0 [48]
    0 [49]
    0 [50]
    0 [51]
    0 [52]
    0 [53]
    Units: mm
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Notes
    [47] - No participants were analyzed due to early termination of the study.
    [48] - No participants were analyzed due to early termination of the study.
    [49] - No participants were analyzed due to early termination of the study.
    [50] - No participants were analyzed due to early termination of the study.
    [51] - No participants were analyzed due to early termination of the study.
    [52] - No participants were analyzed due to early termination of the study.
    [53] - No participants were analyzed due to early termination of the study.
    No statistical analyses for this end point

    Secondary: Change from Baseline in Participant's Global Assessment of Disease Activity (VAS)

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    End point title
    		 Change from Baseline in Participant's Global Assessment of Disease Activity (VAS)
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, 240 weeks
    End point values
    		 LY A LY B NR LY A to LY B NR LY B to LY B NR Placebo to LY B Placebo to LY A Placebo to LY B
    Number of subjects analysed
    0 [54]
    0 [55]
    0 [56]
    0 [57]
    0 [58]
    0 [59]
    0 [60]
    Units: Millimeter (mm)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Notes
    [54] - No participants were analyzed due to early termination of the study.
    [55] - No participants were analyzed due to early termination of the study.
    [56] - No participants were analyzed due to early termination of the study.
    [57] - No participants were analyzed due to early termination of the study.
    [58] - No participants were analyzed due to early termination of the study.
    [59] - No participants were analyzed due to early termination of the study.
    [60] - No participants were analyzed due to early termination of the study.
    No statistical analyses for this end point

    Secondary: Change from Baseline in Physician's Global Assessment of Disease Activity (VAS)

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    End point title
    		 Change from Baseline in Physician's Global Assessment of Disease Activity (VAS)
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, 240 weeks
    End point values
    		 LY A LY B NR LY A to LY B NR LY B to LY B NR Placebo to LY B Placebo to LY A Placebo to LY B
    Number of subjects analysed
    0 [61]
    0 [62]
    0 [63]
    0 [64]
    0 [65]
    0 [66]
    0 [67]
    Units: mm
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Notes
    [61] - No participants were analyzed due to early termination of the study.
    [62] - No participants were analyzed due to early termination of the study.
    [63] - No participants were analyzed due to early termination of the study.
    [64] - No participants were analyzed due to early termination of the study.
    [65] - No participants were analyzed due to early termination of the study.
    [66] - No participants were analyzed due to early termination of the study.
    [67] - No participants were analyzed due to early termination of the study.
    No statistical analyses for this end point

    Secondary: Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)

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    End point title
    		 Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, 240 weeks
    End point values
    		 LY A LY B NR LY A to LY B NR LY B to LY B NR Placebo to LY B Placebo to LY A Placebo to LY B
    Number of subjects analysed
    0 [68]
    0 [69]
    0 [70]
    0 [71]
    0 [72]
    0 [73]
    0 [74]
    Units: NA
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Notes
    [68] - No participants were analyzed due to early termination of the study.
    [69] - No participants were analyzed due to early termination of the study.
    [70] - No participants were analyzed due to early termination of the study.
    [71] - No participants were analyzed due to early termination of the study..
    [72] - No participants were analyzed due to early termination of the study.
    [73] - No participants were analyzed due to early termination of the study.
    [74] - No participants were analyzed due to early termination of the study.
    No statistical analyses for this end point

    Secondary: Change from Baseline in CRP

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    End point title
    		 Change from Baseline in CRP
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, 240 weeks
    End point values
    		 LY A LY B NR LY A to LY B NR LY B to LY B NR Placebo to LY B Placebo to LY A Placebo to LY B
    Number of subjects analysed
    0 [75]
    0 [76]
    0 [77]
    0 [78]
    0 [79]
    0 [80]
    0 [81]
    Units: NA
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Notes
    [75] - No participants were analyzed due to early termination of the study.
    [76] - No participants were analyzed due to early termination of the study.
    [77] - No participants were analyzed due to early termination of the study.
    [78] - No participants were analyzed due to early termination of the study.
    [79] - No participants were analyzed due to early termination of the study.
    [80] - No participants were analyzed due to early termination of the study.
    [81] - No participants were analyzed due to early termination of the study.
    No statistical analyses for this end point

    Secondary: American College of Rheumatology Percent Improvement (ACR-N)

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    End point title
    		 American College of Rheumatology Percent Improvement (ACR-N)
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline through 240 weeks
    End point values
    		 LY A LY B NR LY A to LY B NR LY B to LY B NR Placebo to LY B Placebo to LY A Placebo to LY B
    Number of subjects analysed
    0 [82]
    0 [83]
    0 [84]
    0 [85]
    0 [86]
    0 [87]
    0 [88]
    Units: NA
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Notes
    [82] - No participants were analyzed due to early termination of the study.
    [83] - No participants were analyzed due to early termination of the study.
    [84] - No participants were analyzed due to early termination of the study.
    [85] - No participants were analyzed due to early termination of the study.
    [86] - No participants were analyzed due to early termination of the study.
    [87] - No participants were analyzed due to early termination of the study.
    [88] - No participants were analyzed due to early termination of the study.
    No statistical analyses for this end point

    Other pre-specified: Number of Participants Who Died During Treatment Period and Post-Treatment Follow-Up Period

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    End point title
    		 Number of Participants Who Died During Treatment Period and Post-Treatment Follow-Up Period
    End point description
    Analysis Population Description: All enrolled participants.
    End point type
    Other pre-specified
    End point timeframe
    Up to 84.4 weeks during treatment period and discontinuation from study treatment up to 48 weeks during follow-up period
    End point values
    		 120 mg LY2127399 (LY A) 90 mg LY2127399 (LY B)
    Number of subjects analysed
    414
    672
    Units: participants
    number (not applicable)
        Treatment Period (n=414, 672)
    2
    4
        Post-Treatment Follow-Up Period (n=368, 591
    0
    1
    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
    H9B-MC-BCDP
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.0
    Reporting groups
    Reporting group title
    120 mg LY2127399 (LY A) Treatment Period
    Reporting group description
    		 120 mg LY2127399 administered subcutaneous (SC) every 4 weeks (Q4W). Participants from Studies BCDO, BCDV and BCDM who were on 120 mg LY2127399 SC Q4W immediately prior to Study BCDP enrollment remained on 120 mg LY2127399 SC Q4W. Participants from Studies BCDO, BCDV and BCDM who were on placebo immediately prior to Study BCDP enrollment were randomized to receive a loading dose of 240 mg LY2127399 SC, 4 weeks later followed by 120 mg LY2127399 SC Q4W for the subsequent treatment.

    Reporting group title
    90 mg LY2127399 (LY B) Treatment Period
    Reporting group description
    		 90 mg LY2127399 administered SC every 2 weeks (Q2W). Participants from Studies BCDO, BCDV and BCDM who were on 90 mg LY2127399 SC Q2W immediately prior to Study BCDP enrollment remained on 90 mg LY2127399 SC Q2W. Participants from Studies BCDO, BCDV and BCDM who were on placebo immediately prior to Study BCDP enrollment were randomized to receive a loading dose of 180 mg LY2127399 SC, 2 weeks later followed by 90 mg LY2127399 SC Q2W for the subsequent treatment.

    Reporting group title
    120 mg LY2127399 (LY A) Follow-Up Period
    Reporting group description
    		 The Post-Treatment Follow-Up Period was defined as the time after study treatment discontinuation visit up to 48 weeks following the last injection of study treatment. Includes Participants who were previously enrolled in Studies BCDO, BCDV and BCDM and who received 120 mg LY2127399 SC Q4W during Study BCDP treatment period.

    Reporting group title
    90 mg LY2127399 (LY B) Follow-Up Period
    Reporting group description
    		 The Post-Treatment Follow-Up Period was defined as the time after study treatment discontinuation visit up to 48 weeks following the last injection of study treatment. Includes Participants who were previously enrolled in Studies BCDO, BCDV and BCDM and who received 90 mg LY2127399 SC Q2W during Study BCDP treatment period.

    Serious adverse events
    		 120 mg LY2127399 (LY A) Treatment Period 90 mg LY2127399 (LY B) Treatment Period 120 mg LY2127399 (LY A) Follow-Up Period 90 mg LY2127399 (LY B) Follow-Up Period
    Total subjects affected by serious adverse events
         subjects affected / exposed
    30 / 414 (7.25%)
    57 / 672 (8.48%)
    15 / 368 (4.08%)
    28 / 591 (4.74%)
         number of deaths (all causes)
    2
    4
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    basal cell carcinoma
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    2 / 672 (0.30%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cervix carcinoma stage 0
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed [1]
    0 / 339 (0.00%)
    1 / 538 (0.19%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    colon adenoma
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    colon cancer metastatic
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    invasive ductal breast carcinoma
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    prostate cancer
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed [2]
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 67 (0.00%)
    1 / 118 (0.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    squamous cell carcinoma
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    squamous cell carcinoma of skin
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ureteric cancer
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    uterine leiomyoma
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed [3]
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 301 (0.00%)
    1 / 473 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    aortic stenosis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    arterial haemorrhage
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    arteriosclerosis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    deep vein thrombosis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hypertension
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hypotension
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    abortion spontaneous
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed [4]
    0 / 339 (0.00%)
    1 / 538 (0.19%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pregnancy
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed [5]
    0 / 339 (0.00%)
    1 / 538 (0.19%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    chest pain
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    non-cardiac chest pain
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    2 / 672 (0.30%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ulcer haemorrhage
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    uterine polyp
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed [6]
    0 / 339 (0.00%)
    1 / 538 (0.19%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    asthma
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    atelectasis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    interstitial lung disease
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    lung infiltration
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pleural effusion
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pulmonary embolism
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    2 / 672 (0.30%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    sleep apnoea syndrome
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    depression
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    schizoaffective disorder bipolar type
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    accidental overdose
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    chest injury
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    fall
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    femur fracture
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    2 / 591 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    fibula fracture
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    foot fracture
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    humerus fracture
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    2 / 672 (0.30%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    meniscus injury
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pelvic fracture
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    spinal compression fracture
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    traumatic arthritis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    upper limb fracture
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    vascular pseudoaneurysm
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    acute myocardial infarction
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    arteriosclerosis coronary artery
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    atrial fibrillation
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    3 / 414 (0.72%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cardiac failure acute
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    cardiac failure congestive
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    2 / 414 (0.48%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    coronary artery disease
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    2 / 672 (0.30%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    left ventricular dysfunction
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    palpitations
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    supraventricular tachycardia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    cerebrovascular accident
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ischaemic stroke
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    lumbar radiculopathy
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    transient ischaemic attack
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    vertebral artery dissection
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    diabetic retinal oedema
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    diabetic retinopathy
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    maculopathy
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    abdominal adhesions
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    abdominal pain upper
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    colon dysplasia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    duodenal ulcer
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    duodenal ulcer perforation
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    dyspepsia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastritis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    haemorrhoids
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    nausea
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pancreatitis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    small intestinal obstruction
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    2 / 672 (0.30%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    vomiting
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    cholecystitis chronic
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cholelithiasis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hepatic function abnormal
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    non-alcoholic steatohepatitis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    2 / 591 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    skin ulcer
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    renal failure acute
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    hyperthyroidism
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    arthritis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    back pain
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    bunion
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    bursitis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    intervertebral disc protrusion
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    neuropathic arthropathy
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    osteoarthritis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    2 / 672 (0.30%)
    1 / 368 (0.27%)
    3 / 591 (0.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    osteonecrosis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    rheumatoid arthritis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    2 / 414 (0.48%)
    5 / 672 (0.74%)
    2 / 368 (0.54%)
    3 / 591 (0.51%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    spondylolisthesis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    synovial cyst
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    abscess limb
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    appendicitis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    bacterial pyelonephritis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    bronchiolitis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    campylobacter gastroenteritis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cellulitis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cellulitis staphylococcal
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cholecystitis infective
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    clostridium difficile colitis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    diverticulitis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastroenteritis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    infected bunion
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    influenza
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    klebsiella infection
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pelvic inflammatory disease
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed [7]
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 301 (0.00%)
    1 / 473 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pneumocystis jiroveci pneumonia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    1 / 672 (0.15%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pyelonephritis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    sepsis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    2 / 414 (0.48%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    septic shock
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    sinusitis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    soft tissue infection
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    staphylococcal bacteraemia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    staphylococcal infection
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    subcutaneous abscess
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    urosepsis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    1 / 672 (0.15%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    wound infection
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    dehydration
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 414 (0.24%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    diabetes mellitus
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    1 / 368 (0.27%)
    0 / 591 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hypercalcaemia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 414 (0.00%)
    0 / 672 (0.00%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    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.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: 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 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.
    [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
    [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
    [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
    [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: 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
    		 120 mg LY2127399 (LY A) Treatment Period 90 mg LY2127399 (LY B) Treatment Period 120 mg LY2127399 (LY A) Follow-Up Period 90 mg LY2127399 (LY B) Follow-Up Period
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    130 / 414 (31.40%)
    251 / 672 (37.35%)
    47 / 368 (12.77%)
    71 / 591 (12.01%)
    Nervous system disorders
    headache
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    11 / 414 (2.66%)
    9 / 672 (1.34%)
    1 / 368 (0.27%)
    3 / 591 (0.51%)
         occurrences all number
    11
    11
    1
    3
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    6 / 414 (1.45%)
    15 / 672 (2.23%)
    3 / 368 (0.82%)
    4 / 591 (0.68%)
         occurrences all number
    6
    15
    3
    4
    General disorders and administration site conditions
    injection site reaction
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    7 / 414 (1.69%)
    16 / 672 (2.38%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences all number
    10
    44
    0
    9
    Respiratory, thoracic and mediastinal disorders
    cough
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    10 / 414 (2.42%)
    13 / 672 (1.93%)
    0 / 368 (0.00%)
    1 / 591 (0.17%)
         occurrences all number
    11
    14
    0
    1
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    16 / 414 (3.86%)
    25 / 672 (3.72%)
    3 / 368 (0.82%)
    2 / 591 (0.34%)
         occurrences all number
    19
    27
    3
    2
    pain in extremity
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    9 / 414 (2.17%)
    6 / 672 (0.89%)
    2 / 368 (0.54%)
    2 / 591 (0.34%)
         occurrences all number
    9
    7
    2
    2
    rheumatoid arthritis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    26 / 414 (6.28%)
    59 / 672 (8.78%)
    10 / 368 (2.72%)
    15 / 591 (2.54%)
         occurrences all number
    33
    65
    10
    21
    Infections and infestations
    bronchitis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    15 / 414 (3.62%)
    30 / 672 (4.46%)
    5 / 368 (1.36%)
    13 / 591 (2.20%)
         occurrences all number
    15
    36
    7
    13
    influenza
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    6 / 414 (1.45%)
    18 / 672 (2.68%)
    3 / 368 (0.82%)
    3 / 591 (0.51%)
         occurrences all number
    6
    19
    3
    3
    nasopharyngitis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    21 / 414 (5.07%)
    38 / 672 (5.65%)
    12 / 368 (3.26%)
    12 / 591 (2.03%)
         occurrences all number
    32
    44
    17
    14
    sinusitis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    17 / 414 (4.11%)
    23 / 672 (3.42%)
    3 / 368 (0.82%)
    11 / 591 (1.86%)
         occurrences all number
    19
    26
    3
    12
    upper respiratory tract infection
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    23 / 414 (5.56%)
    73 / 672 (10.86%)
    8 / 368 (2.17%)
    11 / 591 (1.86%)
         occurrences all number
    36
    89
    8
    11
    urinary tract infection
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    16 / 414 (3.86%)
    17 / 672 (2.53%)
    2 / 368 (0.54%)
    5 / 591 (0.85%)
         occurrences all number
    19
    22
    2
    7

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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.
    Study BCDP was terminated early due to insufficient efficacy observed in Studies BCDM and BCDV. 4 participants enrolled from Study BCDM were included in TEAE, SAE, AESI and death summary but not in summary of other primary or secondary measures.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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