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    Clinical Trial Results:
    A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Tabalumab in Combination with Bortezomib and Dexamethasone in Patients with Previously Treated Multiple Myeloma

    Summary
    EudraCT number
    		 2011-005103-32
    Trial protocol
    		 GB   ES   GR   PL   DE   NL   IT  
    Global end of trial date
    29 Jul 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
    H9S-MC-JDCG
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01602224
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 14199
    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
    29 Jul 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Jul 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to evaluate an investigational drug called tabalumab in participants with Multiple Myeloma (MM) who have tried at least one other therapy in the past. Tabalumab will be given in combination with standard doses of two other drugs that are often used to treat MM. Study doctors will collect information about the effectiveness and side effects of this therapy.
    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
    12 Jun 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Brazil: 11
    Country: Number of subjects enrolled
    Canada: 4
    Country: Number of subjects enrolled
    France: 12
    Country: Number of subjects enrolled
    Germany: 4
    Country: Number of subjects enrolled
    Greece: 22
    Country: Number of subjects enrolled
    Italy: 12
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 23
    Country: Number of subjects enrolled
    Mexico: 6
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    Poland: 24
    Country: Number of subjects enrolled
    Spain: 21
    Country: Number of subjects enrolled
    Taiwan: 18
    Country: Number of subjects enrolled
    Turkey: 17
    Country: Number of subjects enrolled
    United States: 29
    Country: Number of subjects enrolled
    United Kingdom: 16
    Worldwide total number of subjects
    220
    EEA total number of subjects
    112
    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)
    99
    From 65 to 84 years
    119
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Completers are defined as participants who died or had disease progression or completed treatment or did not complete treatment and were followed for survival data.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 100 mg Tabalumab+Dexamethasone+Bortezomib
    Arm description
    		 Tabalumab 100 milligram (mg) administered once intravenously (IV) over 30 minutes on Day 1 every 21 days for 8 cycles. Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles. Bortezomib 1.3 milligram per square meter (mg/m^2) administered once subcutaneously (SQ) on Days 1, 4, 8 and 11 every 21 days for 8 cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles.

    Investigational medicinal product name
    Bortezomib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.

    Investigational medicinal product name
    100 mg Tabalumab
    Investigational medicinal product code
    Other name
    LY2127399
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Tabalumab 100 mg administered once IV over 30 minutes on Day 1 every 21 days for 8 cycles. Dexamethasone 20 mg administered orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles.

    Arm title
    		 300 mg Tabalumab+Dexamethasone+Bortezomib
    Arm description
    		 Tabalumab 300 mg administered once IV over 30 minutes on Day 1 every 21 days for 8 cycles. Dexamethasone 20 mg administered orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles. Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles.

    Investigational medicinal product name
    Bortezomib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.

    Investigational medicinal product name
    300 mg Tabalumab
    Investigational medicinal product code
    Other name
    LY2127399
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Tabalumab 300 mg administered once IV over 30 minutes on Day 1 every 21 days for 8 cycles. Dexamethasone 20 mg administered orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles.

    Arm title
    		 Placebo Comparator: Placebo + Dexamethasone + Bortezomib
    Arm description
    		 Placebo administered once IV on Day 1 every 21 days for 8 cycles. Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles. Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo administered once IV on Day 1 every 21 days for 8 cycles.

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles.

    Investigational medicinal product name
    Bortezomib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.

    Number of subjects in period 1
    		100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib Placebo Comparator: Placebo + Dexamethasone + Bortezomib
    Started
    74
    74
    72
    Received at Least 1 Dose of Study Drug
    73
    74
    72
    Completed
    66
    66
    66
    Not completed
    8
    8
    6
         Consent withdrawn by subject
    5
    3
    3
         Adverse event, non-fatal
    -
    1
    -
         Investigator Decison
    1
    -
    -
         Sponsor Decision
    2
    3
    2
         Lost to follow-up
    -
    -
    1
         Protocol deviation
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    100 mg Tabalumab+Dexamethasone+Bortezomib
    Reporting group description
    		 Tabalumab 100 milligram (mg) administered once intravenously (IV) over 30 minutes on Day 1 every 21 days for 8 cycles. Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles. Bortezomib 1.3 milligram per square meter (mg/m^2) administered once subcutaneously (SQ) on Days 1, 4, 8 and 11 every 21 days for 8 cycles.

    Reporting group title
    300 mg Tabalumab+Dexamethasone+Bortezomib
    Reporting group description
    		 Tabalumab 300 mg administered once IV over 30 minutes on Day 1 every 21 days for 8 cycles. Dexamethasone 20 mg administered orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles. Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.

    Reporting group title
    Placebo Comparator: Placebo + Dexamethasone + Bortezomib
    Reporting group description
    		 Placebo administered once IV on Day 1 every 21 days for 8 cycles. Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles. Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.

    Reporting group values
    		 100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib Placebo Comparator: Placebo + Dexamethasone + Bortezomib Total
    Number of subjects
    		 74 74 72 220
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 37 30 32 99
        From 65-84 years
    		 36 43 40 119
        85 years and over
    		 1 1 0 2
    Age Continuous
    Units: years
        median (standard deviation)
    		 63.2 ± 11.01 65.7 ± 9.11 65.4 ± 9.50 -
    Gender categorical
    Units: Subjects
        Female
    		 44 37 32 113
        Male
    		 30 37 40 107
    Sex: Female, Male
    Units: Subjects
        Female
    		 44 37 32 113
        Male
    		 30 37 40 107
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 4 3 5 12
        Not Hispanic or Latino
    		 39 50 35 124
        Unknown or Not Reported
    		 31 21 32 84
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 3 1 2 6
        Asian
    		 14 18 13 45
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        Black or African American
    		 1 2 2 5
        White
    		 56 53 53 162
        More than one race
    		 0 0 0 0
        Unknown or Not Reported
    		 0 0 2 2
    Region of Enrollment
    Units: Subjects
        United States
    		 11 9 9 29
        United Kingdom
    		 5 7 4 16
        Spain
    		 8 5 8 21
        Greece
    		 6 7 9 22
        Canada
    		 2 2 0 4
        South Korea
    		 6 9 8 23
        Netherlands
    		 0 0 1 1
        Turkey
    		 6 7 4 17
        Taiwan
    		 7 6 5 18
        Brazil
    		 4 2 5 11
        Poland
    		 4 13 7 24
        Italy
    		 7 2 3 12
        Mexico
    		 3 1 2 6
        France
    		 3 3 6 12
        Germany
    		 2 1 1 4

    End points

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    End points reporting groups
    Reporting group title
    100 mg Tabalumab+Dexamethasone+Bortezomib
    Reporting group description
    		 Tabalumab 100 milligram (mg) administered once intravenously (IV) over 30 minutes on Day 1 every 21 days for 8 cycles. Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles. Bortezomib 1.3 milligram per square meter (mg/m^2) administered once subcutaneously (SQ) on Days 1, 4, 8 and 11 every 21 days for 8 cycles.

    Reporting group title
    300 mg Tabalumab+Dexamethasone+Bortezomib
    Reporting group description
    		 Tabalumab 300 mg administered once IV over 30 minutes on Day 1 every 21 days for 8 cycles. Dexamethasone 20 mg administered orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles. Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.

    Reporting group title
    Placebo Comparator: Placebo + Dexamethasone + Bortezomib
    Reporting group description
    		 Placebo administered once IV on Day 1 every 21 days for 8 cycles. Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles. Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.

    Primary: Progression Free Survival (PFS)

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    End point title
    		 Progression Free Survival (PFS)
    End point description
    PFS is defined as the time from date of first dose to the first observation of disease progression or death due to any cause. If a participant does not have a complete baseline disease assessment, then the PFS time is censored at the enrollment date, regardless of whether or not objectively determined disease progression (Increase of > 25% from lowest response in serum M component, urine M component, bone marrow plasma cell percentage, development of bone lesions) or death has been observed for the participant. If a participant is not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time is censored at the last complete objective progression-free disease assessment date.
    End point type
    Primary
    End point timeframe
    Baseline up to Objective Disease Progression or Death From Any Cause (9 months)
    End point values
    		 100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib Placebo Comparator: Placebo + Dexamethasone + Bortezomib
    Number of subjects analysed
    74 [1]
    74 [2]
    72 [3]
    Units: months
        median (confidence interval 95%)
    6.6 (5.6 to 8.5)
    7.5 (5.8 to 9.3)
    7.6 (6.5 to 9.3)
    Notes
    [1] - All randomized participants.
    [2] - All randomized participants.
    [3] - All randomized participants.
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    300 mg Tabalumab+Dexamethasone+Bortezomib v Placebo Comparator: Placebo + Dexamethasone + Bortezomib v 100 mg Tabalumab+Dexamethasone+Bortezomib
    Number of subjects included in analysis
    220
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0187
    Method
    		 nominal one-sided p-value
    Confidence interval

    Secondary: Overall Survival

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    End point title
    		 Overall Survival
    End point description
    Overall survival is the duration from enrollment to death from any cause. For participants who were alive, overall survival was censored at the last contact. 9999 is the equivalent for N/A as medians were not reached for the timeframe.
    End point type
    Secondary
    End point timeframe
    Baseline to Death From Any Cause (19 months)
    End point values
    		 100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib Placebo Comparator: Placebo + Dexamethasone + Bortezomib
    Number of subjects analysed
    74 [4]
    74 [5]
    72 [6]
    Units: months
        median (confidence interval 95%)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    Notes
    [4] - Medians were not reached for timeframe, no data to report.
    [5] - Medians were not reached for timeframe, no data to report.
    [6] - Medians were not reached for timeframe, no data to report.
    No statistical analyses for this end point

    Secondary: Time to First Skeletal-Related Event (SRE)

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    End point title
    		 Time to First Skeletal-Related Event (SRE)
    End point description
    Time to first SRE is defined as time from randomization to any one of the following related to multiple myeloma: New Pathological Fracture, Spinal Cord Compression, Surgery to the Bone, Radiation to the Bone collected until participant death, study closure or lost to follow up. Participants not known to have had an SRE at the time of the analysis were censored at the date of their last complete documented assessment for SRE. 9999 is the equivalent for N/A as medians were not reached for the timeframe.
    End point type
    Secondary
    End point timeframe
    Baseline to Date of First Skeletal Related Event (19 months)
    End point values
    		 100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib Placebo Comparator: Placebo + Dexamethasone + Bortezomib
    Number of subjects analysed
    74 [7]
    74 [8]
    72 [9]
    Units: months
        median (confidence interval 95%)
    9999 (9999 to 9999)
    9999 (19.8 to 9999)
    9999 (9999 to 9999)
    Notes
    [7] - Medians were not reached for timeframe, no data to report.
    [8] - Medians were not reached for timeframe, no data to report.
    [9] - Medians were not reached for timeframe, no data to report.
    No statistical analyses for this end point

    Secondary: Number of Participants with >30% Reduction in Brief Pain Inventory (BPI) - Worst Pain Score

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    End point title
    		 Number of Participants with >30% Reduction in Brief Pain Inventory (BPI) - Worst Pain Score
    End point description
    BPI is assessed by 7 questions rated "0" for "no pain" and higher numbers indicated more pain.
    End point type
    Secondary
    End point timeframe
    Baseline through End of Treatment (19 months)
    End point values
    		 100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib Placebo Comparator: Placebo + Dexamethasone + Bortezomib
    Number of subjects analysed
    74 [10]
    74 [11]
    72 [12]
    Units: Participants
        number (not applicable)
    37
    30
    30
    Notes
    [10] - All randomized participants.
    [11] - All randomized participants.
    [12] - All randomized participants.
    No statistical analyses for this end point

    Secondary: Time to Progression (TTP)

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    End point title
    		 Time to Progression (TTP)
    End point description
    Time to progression is defined as the time from the date of randomization to the date of first observed objective progression or death due to study disease. Time to progression will be censored as for PFS for those participants not known to have progressed or that died from other causes.
    End point type
    Secondary
    End point timeframe
    Baseline to Objective Disease Progression or Death (9 months)
    End point values
    		 100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib Placebo Comparator: Placebo + Dexamethasone + Bortezomib
    Number of subjects analysed
    74 [13]
    74 [14]
    72 [15]
    Units: months
        median (confidence interval 95%)
    6.6 (5.9 to 9.3)
    8.2 (6.4 to 11.2)
    8.1 (6.9 to 9.5)
    Notes
    [13] - All randomized participants.
    [14] - All randomized participants.
    [15] - All randomized participants.
    No statistical analyses for this end point

    Secondary: Duration of Response (DoR)

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    End point title
    		 Duration of Response (DoR)
    End point description
    DOR is measured from the date of first evidence of a confirmed response to the date of objective progression or the date of death due to any cause, whichever is earlier. If a responder is not known to have died or have objective progression as of the data inclusion cutoff date, the DOR time will be censored at the last complete objective progression-free disease assessment date.
    End point type
    Secondary
    End point timeframe
    Time from Response to Objective Disease Progression (38 months)
    End point values
    		 100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib Placebo Comparator: Placebo + Dexamethasone + Bortezomib
    Number of subjects analysed
    43 [16]
    44 [17]
    44 [18]
    Units: months
        median (confidence interval 95%)
    7.9 (6.0 to 11.6)
    8.6 (6.5 to 10.7)
    7.7 (5.8 to 13.1)
    Notes
    [16] - All randomized participants who received at least 1 dose of study drug and had a response.
    [17] - All randomized participants who received at least 1 dose of study drug and had a response.
    [18] - All randomized participants who received at least 1 dose of study drug and had a response.
    No statistical analyses for this end point

    Secondary: Time to Next Treatment (TNT)

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    End point title
    		 Time to Next Treatment (TNT)
    End point description
    TNT is defined as the time from the date of randomization to the date of initiation of the first poststudy treatment course of anticancer therapy or death from any cause. Time to next treatment will be censored at the date of the last visit for participant who did not initiate additional anticancer therapy.
    End point type
    Secondary
    End point timeframe
    Baseline to Initiation of New Cancer Treatment or Death From Any Cause (18 Months)
    End point values
    		 100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib Placebo Comparator: Placebo + Dexamethasone + Bortezomib
    Number of subjects analysed
    74 [19]
    74 [20]
    72 [21]
    Units: months
        median (confidence interval 95%)
    10.1 (7.0 to 11.9)
    9.9 (6.8 to 14.8)
    11.7 (7.8 to 17.5)
    Notes
    [19] - All randomized participants.
    [20] - All randomized participants.
    [21] - All randomized participants.
    No statistical analyses for this end point

    Secondary: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Tabalumab

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    End point title
    		 Pharmacokinetics (PK): Maximum Concentration (Cmax) of Tabalumab [22]
    End point description
    Maximum Concentration (Cmax) of Tabalumab. Baseline, Cycle 1: Day 1 pre to LY2127399 dose, post Bortezomib (BTZ) dose, 2 hours post dose (hrs pd), Day 4:pre BTZ dose, Day 8:Pre BTZ dose, Day 11: pre BTZ dose, BTZ pd Cycle 2 Day 1 pre LY2127399 dose, BTZ pd, Day 4: anytime, Day 8 anytime, Day 11 anytime Cycle 3 - completion of study: Day 1 pre LY2127399 dose, BTZ pd with week 6-10 considered Steady State
    End point type
    Secondary
    End point timeframe
    See Outcome Measure description for time frame
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only arms that received tabalumab were reported.
    End point values
    		 100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib
    Number of subjects analysed
    68 [23]
    71 [24]
    Units: micrograms per milliliter
    geometric mean (geometric coefficient of variation)
        Cycle 1
    38.0 ± 39
    103 ± 43
        Cycle 2
    47.9 ± 51
    131 ± 40
        Steady State (Cycle 6-10)
    69.0 ± 51
    189 ± 54
    Notes
    [23] - All randomized participants with evaluable PK data.
    [24] - All randomized participants with evaluable PK data.
    No statistical analyses for this end point

    Secondary: PK: Time to Maximum Plasma Concentration (Tmax) of Tabalumab

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    End point title
    		 PK: Time to Maximum Plasma Concentration (Tmax) of Tabalumab [25]
    End point description
    Baseline, Cycle 1: Day 1 pre to LY2127399 dose, post BTZ dose, 2 hours post dose (hrs pd), Day 4:pre BTZ dose, Day 8:Pre BTZ dose, Day 11: pre BTZ dose, BTZ pd Cycle 2 Day 1 pre LY2127399 dose, BTZ pd, Day 4: anytime, Day 8 anytime, Day 11 anytime Cycle 3 - completion of study: Day 1 pre LY2127399 dose, BTZ pd with week 6-10 considered Steady State
    End point type
    Secondary
    End point timeframe
    See Outcome Measure description for time frame
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only arms that received tabalumab were reported.
    End point values
    		 100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib
    Number of subjects analysed
    73 [26]
    74 [27]
    Units: hours
    arithmetic mean (confidence interval 95%)
        Cycle 1
    1.5 (0.75 to 503.75)
    1.58 (0.92 to 162.58)
        Cycle 2
    0.92 (0.47 to 503.77)
    0.76 (0.5 to 503.58)
        Steady State (Cycle 6-10)
    0.75 (0.338 to 9.92)
    0.73 (0 to 1.75)
    Notes
    [26] - All randomized participants with evaluable PK data.
    [27] - All randomized participants with evaluable PK data.
    No statistical analyses for this end point

    Secondary: PK: Area Under the Curve Over the Dosing Interval (AUC-T) for Tabalumab

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    End point title
    		 PK: Area Under the Curve Over the Dosing Interval (AUC-T) for Tabalumab [28]
    End point description
    Baseline, Cycle 1: Day 1 pre to LY2127399 dose, post BTZ dose, 2 hours post dose (hrs pd), Day 4:pre BTZ dose, Day 8:Pre BTZ dose, Day 11: pre BTZ dose, BTZ pd Cycle 2 Day 1 pre LY2127399 dose, BTZ pd, Day 4: anytime, Day 8 anytime, Day 11 anytime Cycle 3 - completion of study: Day 1 pre LY2127399 dose, BTZ pd with week 6-10 considered Steady State
    End point type
    Secondary
    End point timeframe
    See Outcome Measure description for time frame
    Notes
    [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only arms that received tabalumab were reported.
    End point values
    		 100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib
    Number of subjects analysed
    68 [29]
    63 [30]
    Units: micrograms times hour per milliliter
    geometric mean (geometric coefficient of variation)
        Cycle 1
    7790 ± 42
    2220 ± 44
        Cycle 2
    11600 ± 36
    35400 ± 49
        Steady State (Cycle 6-10)
    25300 ± 57
    70100 ± 52
    Notes
    [29] - All randomized participants with evaluable PK data.
    [30] - All randomized participants with evaluable PK data.
    No statistical analyses for this end point

    Secondary: Number of Participants Developing Anti-tabalumab Antibodies

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    End point title
    		 Number of Participants Developing Anti-tabalumab Antibodies
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline through Cycle 8
    End point values
    		 100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib Placebo Comparator: Placebo + Dexamethasone + Bortezomib
    Number of subjects analysed
    0 [31]
    0 [32]
    0 [33]
    Units: Participants
        number (not applicable)
    Notes
    [31] - Zero participants analyzed due to insufficient sample collection.
    [32] - Zero participants analyzed due to insufficient sample collection.
    [33] - Zero participants analyzed due to insufficient sample collection.
    No statistical analyses for this end point

    Secondary: Participants with Best Overall Response (BOR) in Each Category

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    End point title
    		 Participants with Best Overall Response (BOR) in Each Category
    End point description
    Stringent Complete Response-Complete Response and normal free light chain ration and no clonal cells in bone marrow Complete Response- no monoclonal protein (mp) in blood, no serum or urine mp, less than 5% plasma cells in bone marrow Very Good Partial Response-more than 90% decrease in mp and urine protein Partial Response- over 50% decrease in serum mp Stable Disease- less than 25 percent decrease of monoclonal protein Progressive Disease- 25% increase compared to lowest value of serum mp, urine mp, no measurable mp
    End point type
    Secondary
    End point timeframe
    Baseline to Objective Disease Progression or Initiation of New Cancer Treatment (28 Months)
    End point values
    		 100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib Placebo Comparator: Placebo + Dexamethasone + Bortezomib
    Number of subjects analysed
    74 [34]
    74 [35]
    72 [36]
    Units: participants
    number (not applicable)
        Stringent Complete Response
    1
    0
    2
        Complete Response
    10
    4
    4
        Very Good Partial Response
    10
    16
    9
        Partial Response
    23
    23
    29
        Minimal Response
    6
    8
    6
        Stable Disease
    14
    10
    12
        Progressive Disease
    6
    7
    6
    Notes
    [34] - All randomized participants.
    [35] - All randomized participants.
    [36] - All randomized participants.
    No statistical analyses for this end point

    Secondary: Number of Participants with a Given Best Objective Myeloma Response (Quality of Response [QoR])

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    End point title
    		 Number of Participants with a Given Best Objective Myeloma Response (Quality of Response [QoR]) [37]
    End point description
    Quality of response was classified into ordered categories of sCR, CR, VGPR, PR, MR, SD, or PD, according to the International Uniform Response Criteria for Multiple Myeloma, that is, sCR > CR > VGPR > PR > MR > SD > PD. The quality of response was evaluated as an ordinal outcome using a logistic regression model. Independent variables in the analysis include treatment, baseline stratification factors of ISS risk category (high risk, low risk), number of lines of prior therapy (1, >1), baseline disease assessment method (SPEP/UPEP, SFLC), response to prior bortezomib therapy (bortezomib naïve or ≥PR lasting 6 months or longer, MR or PR lasting less than 6 months), and C – 1 threshold effects, where C is the number of response categories analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline to Objective Disease Progression or Initiation of New Cancer Treatment ( 28 Months)
    Notes
    [37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The logistic regression model comparing the 2 tabalumab arms is able to identify a trend for improved response in 1 cohort over another.
    End point values
    		 100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib
    Number of subjects analysed
    74 [38]
    74 [39]
    Units: odds ratio
        number (not applicable)
    1.84
    1.98
    Notes
    [38] - All randomized participants.
    [39] - All randomized participants.
    No statistical analyses for this end point

    Secondary: Overall Response Rate (ORR)

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    End point title
    		 Overall Response Rate (ORR)
    End point description
    Overall Response Rate (ORR) is the proportion of participants that had a response.
    End point type
    Secondary
    End point timeframe
    Baseline to Objective Disease Progression or Initiation of New Cancer Treatment (28 Months)
    End point values
    		 100 mg Tabalumab+Dexamethasone+Bortezomib 300 mg Tabalumab+Dexamethasone+Bortezomib Placebo Comparator: Placebo + Dexamethasone + Bortezomib
    Number of subjects analysed
    74 [40]
    74 [41]
    72 [42]
    Units: percentage of participants
        number (not applicable)
    58.1
    59.5
    61.1
    Notes
    [40] - All randomized participants who had a partial response or greater.
    [41] - All randomized participants who had a partial response or greater.
    [42] - All randomized participants who had a partial response or greater.
    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
    H9S-MC-JDCG
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Placebo Comparator: Placebo + Dexamethasone + Bortezomib
    Reporting group description
    		 Placebo administered once IV on Day 1 every 21 days for 8 cycles. Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles. Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.

    Reporting group title
    300 mg Tabalumab+Dexame thasone+Bortezomib
    Reporting group description
    		 Tabalumab 300 mg administered once IV over 30 minutes on Day 1 every 21 days for 8 cycles. Dexamethasone 20 mg administered orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles. Bortezomib 1.3 mg/m^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles.

    Reporting group title
    100 mg Tabalumab+Dexame thasone+Bortezomib
    Reporting group description
    		 Tabalumab 100 milligram (mg) administered once intravenously (IV) over 30 minutes on Day 1 every 21 days for 8 cycles. Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles. Bortezomib 1.3 milligram per square meter (mg/m^2) administered once subcutaneously (SQ) on Days 1, 4, 8 and 11 every 21 days for 8 cycles.

    Serious adverse events
    		 Placebo Comparator: Placebo + Dexamethasone + Bortezomib 300 mg Tabalumab+Dexame thasone+Bortezomib 100 mg Tabalumab+Dexame thasone+Bortezomib
    Total subjects affected by serious adverse events
         subjects affected / exposed
    26 / 72 (36.11%)
    35 / 74 (47.30%)
    33 / 73 (45.21%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    acute myeloid leukaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    colorectal cancer
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    hepatic neoplasm
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    plasma cell leukaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    plasma cell myeloma
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    2 / 74 (2.70%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    deep vein thrombosis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    haemorrhage
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    hypotension
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    hypovolaemic shock
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    orthostatic hypotension
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    shock haemorrhagic
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    disease progression
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    fatigue
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    general physical health deterioration
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 74 (1.35%)
    2 / 73 (2.74%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    localised oedema
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    multi-organ failure
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 74 (1.35%)
    2 / 73 (2.74%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    oedema peripheral
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    pyrexia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 72 (2.78%)
    2 / 74 (2.70%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    acute respiratory failure
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    chronic obstructive pulmonary disease
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    dyspnoea
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    interstitial lung disease
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    pleural effusion
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    pneumonitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    platelet count decreased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 74 (1.35%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    renal function test abnormal
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    troponin increased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    fall
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 74 (1.35%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    femur fracture
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    humerus fracture
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    injury
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    multiple fractures
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    subdural haemorrhage
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    thoracic vertebral fracture
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    traumatic haemorrhage
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    left ventricle outflow tract obstruction
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    acute coronary syndrome
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    acute myocardial infarction
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    angina pectoris
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    atrial fibrillation
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    cardiac arrest
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    cardiac failure
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ventricular dysfunction
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Nervous system disorders
    altered state of consciousness
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    autonomic neuropathy
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ischaemic stroke
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    loss of consciousness
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    2 / 73 (2.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    neuropathy peripheral
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    peripheral sensory neuropathy
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 72 (2.78%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 72 (2.78%)
    2 / 74 (2.70%)
    2 / 73 (2.74%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    febrile neutropenia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    3 / 73 (4.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    leukopenia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    neutropenia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    thrombocytopenia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 74 (1.35%)
    3 / 73 (4.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Gastrointestinal disorders
    colitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    constipation
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 74 (1.35%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    diarrhoea
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    2 / 74 (2.70%)
    3 / 73 (4.11%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    gastric perforation
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ileus paralytic
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    intestinal ischaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    large intestinal haemorrhage
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    melaena
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    nausea
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    upper gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    vomiting
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    cholecystitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    cholecystitis acute
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Renal and urinary disorders
    haematuria
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    incontinence
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    renal failure
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 72 (2.78%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    renal failure acute
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    5 / 72 (6.94%)
    4 / 74 (5.41%)
    3 / 73 (4.11%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 4
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    back pain
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    bone pain
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    muscular weakness
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    musculoskeletal pain
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    pathological fracture
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    bacteraemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    2 / 73 (2.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    brain abscess
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    bronchopneumonia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    2 / 73 (2.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    cellulitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    cytomegalovirus colitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    diverticulitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    helicobacter infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    herpes zoster
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    2 / 74 (2.70%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    2 / 74 (2.70%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    infectious colitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    influenza
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    lobar pneumonia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 74 (1.35%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    lower respiratory tract infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    otitis media
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    pneumococcal sepsis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    pneumocystis jiroveci pneumonia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    5 / 72 (6.94%)
    3 / 74 (4.05%)
    9 / 73 (12.33%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 3
    7 / 11
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    pneumonia haemophilus
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    respiratory syncytial virus infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    respiratory tract infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    2 / 74 (2.70%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    sepsis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    5 / 74 (6.76%)
    2 / 73 (2.74%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 4
    0 / 1
    septic shock
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    4 / 73 (5.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    sinusitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    soft tissue infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    2 / 74 (2.70%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    upper respiratory tract infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    2 / 74 (2.70%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    2 / 73 (2.74%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    wound infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    decreased appetite
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    2 / 74 (2.70%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    dehydration
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    1 / 74 (1.35%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    diabetes mellitus
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    hyperglycaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    hypovolaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    0 / 74 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Comparator: Placebo + Dexamethasone + Bortezomib 300 mg Tabalumab+Dexame thasone+Bortezomib 100 mg Tabalumab+Dexame thasone+Bortezomib
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    69 / 72 (95.83%)
    72 / 74 (97.30%)
    71 / 73 (97.26%)
    Vascular disorders
    orthostatic hypotension
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    5 / 72 (6.94%)
    4 / 74 (5.41%)
    3 / 73 (4.11%)
         occurrences all number
    6
    5
    4
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    9 / 72 (12.50%)
    6 / 74 (8.11%)
    7 / 73 (9.59%)
         occurrences all number
    9
    6
    11
    face oedema
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 72 (2.78%)
    4 / 74 (5.41%)
    1 / 73 (1.37%)
         occurrences all number
    2
    4
    2
    fatigue
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    26 / 72 (36.11%)
    27 / 74 (36.49%)
    28 / 73 (38.36%)
         occurrences all number
    47
    49
    38
    injection site erythema
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    2 / 74 (2.70%)
    4 / 73 (5.48%)
         occurrences all number
    1
    5
    4
    injection site reaction
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    3 / 72 (4.17%)
    3 / 74 (4.05%)
    6 / 73 (8.22%)
         occurrences all number
    7
    5
    13
    oedema
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    4 / 72 (5.56%)
    4 / 74 (5.41%)
    1 / 73 (1.37%)
         occurrences all number
    25
    35
    5
    oedema peripheral
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    8 / 72 (11.11%)
    15 / 74 (20.27%)
    14 / 73 (19.18%)
         occurrences all number
    27
    69
    57
    pain
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 72 (2.78%)
    3 / 74 (4.05%)
    6 / 73 (8.22%)
         occurrences all number
    3
    3
    7
    pyrexia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    6 / 72 (8.33%)
    10 / 74 (13.51%)
    11 / 73 (15.07%)
         occurrences all number
    8
    13
    13
    Reproductive system and breast disorders
    benign prostatic hyperplasia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed [1]
    1 / 40 (2.50%)
    0 / 37 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    0
    2
    Respiratory, thoracic and mediastinal disorders
    cough
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    13 / 72 (18.06%)
    16 / 74 (21.62%)
    8 / 73 (10.96%)
         occurrences all number
    18
    17
    9
    dyspnoea
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    11 / 72 (15.28%)
    8 / 74 (10.81%)
    9 / 73 (12.33%)
         occurrences all number
    16
    8
    10
    epistaxis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    3 / 74 (4.05%)
    4 / 73 (5.48%)
         occurrences all number
    1
    3
    8
    Psychiatric disorders
    depression
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    4 / 72 (5.56%)
    5 / 74 (6.76%)
    1 / 73 (1.37%)
         occurrences all number
    4
    5
    1
    insomnia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    11 / 72 (15.28%)
    15 / 74 (20.27%)
    12 / 73 (16.44%)
         occurrences all number
    24
    19
    12
    Investigations
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    6 / 74 (8.11%)
    8 / 73 (10.96%)
         occurrences all number
    2
    6
    11
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    6 / 74 (8.11%)
    7 / 73 (9.59%)
         occurrences all number
    1
    6
    9
    blood alkaline phosphatase increased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    4 / 74 (5.41%)
    3 / 73 (4.11%)
         occurrences all number
    0
    5
    5
    blood cholesterol increased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    6 / 72 (8.33%)
    2 / 74 (2.70%)
    5 / 73 (6.85%)
         occurrences all number
    10
    6
    12
    lymphocyte count decreased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    5 / 74 (6.76%)
    1 / 73 (1.37%)
         occurrences all number
    1
    13
    1
    neutrophil count decreased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    2 / 74 (2.70%)
    4 / 73 (5.48%)
         occurrences all number
    5
    3
    8
    platelet count decreased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    8 / 72 (11.11%)
    7 / 74 (9.46%)
    16 / 73 (21.92%)
         occurrences all number
    15
    10
    46
    weight decreased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    5 / 72 (6.94%)
    8 / 74 (10.81%)
    5 / 73 (6.85%)
         occurrences all number
    5
    11
    7
    weight increased
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    3 / 72 (4.17%)
    3 / 74 (4.05%)
    4 / 73 (5.48%)
         occurrences all number
    5
    3
    4
    Injury, poisoning and procedural complications
    contusion
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 72 (2.78%)
    5 / 74 (6.76%)
    3 / 73 (4.11%)
         occurrences all number
    3
    5
    3
    Cardiac disorders
    atrial fibrillation
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    3 / 72 (4.17%)
    2 / 74 (2.70%)
    4 / 73 (5.48%)
         occurrences all number
    3
    2
    4
    Nervous system disorders
    dizziness
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    16 / 72 (22.22%)
    15 / 74 (20.27%)
    6 / 73 (8.22%)
         occurrences all number
    23
    20
    7
    dysgeusia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 72 (2.78%)
    3 / 74 (4.05%)
    5 / 73 (6.85%)
         occurrences all number
    2
    4
    5
    headache
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    5 / 72 (6.94%)
    3 / 74 (4.05%)
    9 / 73 (12.33%)
         occurrences all number
    9
    4
    10
    hypoaesthesia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    4 / 73 (5.48%)
         occurrences all number
    1
    0
    5
    neuralgia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    7 / 72 (9.72%)
    9 / 74 (12.16%)
    1 / 73 (1.37%)
         occurrences all number
    10
    12
    1
    neuropathy peripheral
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    13 / 72 (18.06%)
    11 / 74 (14.86%)
    17 / 73 (23.29%)
         occurrences all number
    25
    16
    20
    paraesthesia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    5 / 72 (6.94%)
    8 / 74 (10.81%)
    8 / 73 (10.96%)
         occurrences all number
    6
    11
    12
    peripheral sensory neuropathy
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    17 / 72 (23.61%)
    19 / 74 (25.68%)
    10 / 73 (13.70%)
         occurrences all number
    31
    32
    16
    tremor
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    4 / 73 (5.48%)
         occurrences all number
    1
    0
    4
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    17 / 72 (23.61%)
    13 / 74 (17.57%)
    25 / 73 (34.25%)
         occurrences all number
    24
    25
    52
    neutropenia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    6 / 72 (8.33%)
    4 / 74 (5.41%)
    6 / 73 (8.22%)
         occurrences all number
    6
    11
    8
    thrombocytopenia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    23 / 72 (31.94%)
    8 / 74 (10.81%)
    16 / 73 (21.92%)
         occurrences all number
    60
    26
    34
    Eye disorders
    vision blurred
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    4 / 72 (5.56%)
    1 / 74 (1.35%)
    2 / 73 (2.74%)
         occurrences all number
    4
    1
    2
    Gastrointestinal disorders
    abdominal distension
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    5 / 72 (6.94%)
    5 / 74 (6.76%)
    8 / 73 (10.96%)
         occurrences all number
    8
    5
    13
    abdominal pain
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    5 / 72 (6.94%)
    6 / 74 (8.11%)
    5 / 73 (6.85%)
         occurrences all number
    6
    6
    8
    abdominal pain upper
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    3 / 72 (4.17%)
    4 / 74 (5.41%)
    5 / 73 (6.85%)
         occurrences all number
    4
    4
    5
    constipation
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    23 / 72 (31.94%)
    26 / 74 (35.14%)
    19 / 73 (26.03%)
         occurrences all number
    30
    32
    31
    diarrhoea
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    21 / 72 (29.17%)
    27 / 74 (36.49%)
    28 / 73 (38.36%)
         occurrences all number
    27
    40
    44
    dyspepsia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    8 / 72 (11.11%)
    7 / 74 (9.46%)
    5 / 73 (6.85%)
         occurrences all number
    10
    9
    5
    nausea
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    14 / 72 (19.44%)
    11 / 74 (14.86%)
    15 / 73 (20.55%)
         occurrences all number
    18
    12
    19
    stomatitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    3 / 72 (4.17%)
    5 / 74 (6.76%)
    1 / 73 (1.37%)
         occurrences all number
    3
    5
    2
    toothache
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    0 / 74 (0.00%)
    4 / 73 (5.48%)
         occurrences all number
    1
    0
    4
    vomiting
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    9 / 72 (12.50%)
    5 / 74 (6.76%)
    6 / 73 (8.22%)
         occurrences all number
    9
    8
    7
    Skin and subcutaneous tissue disorders
    erythema
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    5 / 74 (6.76%)
    1 / 73 (1.37%)
         occurrences all number
    0
    8
    1
    pruritus
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    5 / 74 (6.76%)
    1 / 73 (1.37%)
         occurrences all number
    0
    6
    1
    rash
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 72 (2.78%)
    7 / 74 (9.46%)
    7 / 73 (9.59%)
         occurrences all number
    6
    16
    16
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    3 / 72 (4.17%)
    7 / 74 (9.46%)
    5 / 73 (6.85%)
         occurrences all number
    4
    7
    5
    back pain
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    13 / 72 (18.06%)
    12 / 74 (16.22%)
    7 / 73 (9.59%)
         occurrences all number
    16
    14
    10
    muscular weakness
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    6 / 72 (8.33%)
    4 / 74 (5.41%)
    6 / 73 (8.22%)
         occurrences all number
    9
    5
    7
    musculoskeletal chest pain
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    4 / 72 (5.56%)
    0 / 74 (0.00%)
    7 / 73 (9.59%)
         occurrences all number
    4
    0
    8
    musculoskeletal pain
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    4 / 72 (5.56%)
    4 / 74 (5.41%)
    4 / 73 (5.48%)
         occurrences all number
    5
    5
    4
    myalgia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    5 / 72 (6.94%)
    3 / 74 (4.05%)
    6 / 73 (8.22%)
         occurrences all number
    7
    3
    7
    pain in extremity
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    11 / 72 (15.28%)
    10 / 74 (13.51%)
    6 / 73 (8.22%)
         occurrences all number
    11
    14
    11
    Infections and infestations
    herpes zoster
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    4 / 72 (5.56%)
    6 / 74 (8.11%)
    4 / 73 (5.48%)
         occurrences all number
    5
    7
    4
    nasopharyngitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    2 / 72 (2.78%)
    4 / 74 (5.41%)
    3 / 73 (4.11%)
         occurrences all number
    2
    4
    5
    pneumonia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    3 / 72 (4.17%)
    3 / 74 (4.05%)
    6 / 73 (8.22%)
         occurrences all number
    3
    4
    7
    respiratory tract infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    3 / 74 (4.05%)
    8 / 73 (10.96%)
         occurrences all number
    0
    4
    14
    sinusitis
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    0 / 72 (0.00%)
    4 / 74 (5.41%)
    3 / 73 (4.11%)
         occurrences all number
    0
    4
    3
    upper respiratory tract infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    20 / 72 (27.78%)
    18 / 74 (24.32%)
    11 / 73 (15.07%)
         occurrences all number
    27
    31
    17
    urinary tract infection
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    5 / 72 (6.94%)
    4 / 74 (5.41%)
    8 / 73 (10.96%)
         occurrences all number
    5
    4
    12
    Metabolism and nutrition disorders
    decreased appetite
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    8 / 72 (11.11%)
    12 / 74 (16.22%)
    12 / 73 (16.44%)
         occurrences all number
    10
    13
    13
    dehydration
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    5 / 72 (6.94%)
    1 / 74 (1.35%)
    3 / 73 (4.11%)
         occurrences all number
    7
    1
    5
    hyperglycaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    7 / 72 (9.72%)
    5 / 74 (6.76%)
    5 / 73 (6.85%)
         occurrences all number
    11
    10
    11
    hyperkalaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    5 / 72 (6.94%)
    1 / 74 (1.35%)
    3 / 73 (4.11%)
         occurrences all number
    7
    1
    3
    hypocalcaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    1 / 72 (1.39%)
    7 / 74 (9.46%)
    7 / 73 (9.59%)
         occurrences all number
    1
    9
    12
    hypokalaemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    3 / 72 (4.17%)
    7 / 74 (9.46%)
    7 / 73 (9.59%)
         occurrences all number
    3
    8
    12
    hyponatraemia
    alternative dictionary used: MedDRA 17.0
         subjects affected / exposed
    3 / 72 (4.17%)
    4 / 74 (5.41%)
    3 / 73 (4.11%)
         occurrences all number
    4
    4
    3
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male subjects. The number of subjects exposed has been adjusted accordingly.

    More information

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

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

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