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    Clinical Trial Results:
    A Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab versus Docetaxel and Placebo in the Treatment of Stage IV Non-Small Cell Lung Cancer Following Disease Progression after One Prior Platinum-Based Therapy

    Summary
    EudraCT number
    2010-021297-11
    Trial protocol
    DE   NL   ES   IT   NO   AT   SE   GR   GB   HU  
    Global end of trial date
    10 Aug 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    28 Jul 2017
    First version publication date
    28 Jul 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    13852
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01168973
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Trial Number: 13852 , Trial Alias: I4T-MC-JVBA
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, United States, 46285
    Public contact
    Eli Lilly and Company, Available Mon - Fri 9 AM - 5 PM EST, 1 877-285-4559,
    Scientific contact
    Eli Lilly and Company, Available Mon - Fri 9 AM - 5 PM EST, 1 877-CTLilly,
    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
    10 Aug 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Aug 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of the study is to compare the survival of participants who receive chemotherapy and ramucirumab versus chemotherapy alone as second line treatment for NSCLC after prior first line platinum-based chemotherapy.
    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
    03 Dec 2010
    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
    United States: 308
    Country: Number of subjects enrolled
    Taiwan: 27
    Country: Number of subjects enrolled
    Greece: 44
    Country: Number of subjects enrolled
    Spain: 50
    Country: Number of subjects enrolled
    Israel: 22
    Country: Number of subjects enrolled
    Russian Federation: 61
    Country: Number of subjects enrolled
    Italy: 54
    Country: Number of subjects enrolled
    Switzerland: 26
    Country: Number of subjects enrolled
    India: 55
    Country: Number of subjects enrolled
    France: 45
    Country: Number of subjects enrolled
    Puerto Rico: 3
    Country: Number of subjects enrolled
    Netherlands: 31
    Country: Number of subjects enrolled
    Korea, Republic of: 62
    Country: Number of subjects enrolled
    Turkey: 45
    Country: Number of subjects enrolled
    Austria: 20
    Country: Number of subjects enrolled
    United Kingdom: 38
    Country: Number of subjects enrolled
    Hungary: 13
    Country: Number of subjects enrolled
    Mexico: 31
    Country: Number of subjects enrolled
    Canada: 19
    Country: Number of subjects enrolled
    Argentina: 33
    Country: Number of subjects enrolled
    Brazil: 7
    Country: Number of subjects enrolled
    Poland: 63
    Country: Number of subjects enrolled
    Romania: 77
    Country: Number of subjects enrolled
    Norway: 13
    Country: Number of subjects enrolled
    Germany: 82
    Country: Number of subjects enrolled
    New Zealand: 7
    Country: Number of subjects enrolled
    Sweden: 17
    Worldwide total number of subjects
    1253
    EEA total number of subjects
    547
    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)
    798
    From 65 to 84 years
    453
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Participants who died, due to any cause, or were alive at the end of the study but off study drug were considered to have completed the study.

    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, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Ramucirumab and Docetaxel
    Arm description
    On Day 1 of each 21-day cycle, participants received ramucirumab drug product (DP) followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met. • Ramucirumab DP: 10 milligrams per kilogram (mg/kg) administered intravenously. • Docetaxel: 75 milligrams per square meter (mg/m^2) (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.
    Arm type
    Experimental

    Investigational medicinal product name
    Ramucirumab
    Investigational medicinal product code
    Other name
    IMC 1121B, LY3009806
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    10 milligrams per kilogram (mg/kg) administered intravenously (IV) on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    75 milligrams per square meter (mg/m^2) (60 mg/m^2 for the countries of Korea and Taiwan only with protocol amendment dated 22 May 2012) administered IV on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

    Arm title
    Placebo and Docetaxel
    Arm description
    On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met. • Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously. • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.
    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
    Administered IV on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    75 milligrams per square meter (mg/m^2) (60 mg/m^2 for the countries of Korea and Taiwan only with protocol amendment dated 22 May 2012) administered IV on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

    Number of subjects in period 1
    Ramucirumab and Docetaxel Placebo and Docetaxel
    Started
    628
    625
    Received any quantity of any study drug
    624
    621
    Completed
    15
    14
    Not completed
    613
    611
         Adverse event, serious fatal
    42
    45
         Consent withdrawn by subject
    90
    53
         Physician decision
    37
    19
         Protocol Criterion Not Met and Deviation
    7
    9
         Adverse event, non-fatal
    94
    55
         Progressive Disease
    341
    429
         Sponsor Decision
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Ramucirumab and Docetaxel
    Reporting group description
    On Day 1 of each 21-day cycle, participants received ramucirumab drug product (DP) followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met. • Ramucirumab DP: 10 milligrams per kilogram (mg/kg) administered intravenously. • Docetaxel: 75 milligrams per square meter (mg/m^2) (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

    Reporting group title
    Placebo and Docetaxel
    Reporting group description
    On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met. • Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously. • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

    Reporting group values
    Ramucirumab and Docetaxel Placebo and Docetaxel Total
    Number of subjects
    628 625 1253
    Age Categorical
    Units:
        Between 18 and 65 years
    391 407 798
        >=65 years
    237 218 455
    Gender, Male/Female
    Units:
        Female
    209 210 419
        Male
    419 415 834
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    43 53 96
        Not Hispanic or Latino
    387 380 767
        Unknown or Not Reported
    198 192 390
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    9 20 29
        Asian
    74 86 160
        Native Hawaiian or Other Pacific Islander
    1 0 1
        Black or African American
    17 16 33
        White
    526 503 1029
        More than one race
    0 0 0
        Unknown or Not Reported
    1 0 1

    End points

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    End points reporting groups
    Reporting group title
    Ramucirumab and Docetaxel
    Reporting group description
    On Day 1 of each 21-day cycle, participants received ramucirumab drug product (DP) followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met. • Ramucirumab DP: 10 milligrams per kilogram (mg/kg) administered intravenously. • Docetaxel: 75 milligrams per square meter (mg/m^2) (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

    Reporting group title
    Placebo and Docetaxel
    Reporting group description
    On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met. • Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously. • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

    Primary: Overall survival

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    End point title
    Overall survival [1]
    End point description
    Overall survival was the time from randomization until the date of death from any cause. Participants who were alive at the end of the follow-up period (or lost to follow‑up) were censored on the last date the participant was known to be alive.
    End point type
    Primary
    End point timeframe
    Randomization to date of death from any cause (up to 34 months)
    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: Per the protocol, this study was considered complete when the final analysis of the primary endpoint was performed. After the primary analysis, only ramucirumab participants who were on study therapy and experiencing ongoing clinical benefit (that is, no disease progression) continued to receive their current study therapy in the extension period. Hence no additional analyses of OS will be conducted after the primary since only a small subset of participants were being followed.
    End point values
    Ramucirumab and Docetaxel Placebo and Docetaxel
    Number of subjects analysed
    628
    625
    Units: months
        median (confidence interval 95%)
    10.5 (9.5 to 11.2)
    9.1 (8.4 to 10)
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS) Time

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    End point title
    Progression-Free Survival (PFS) Time
    End point description
    PFS time was the time from randomization until the date of objectively determined progressive disease (PD) or death due to any cause, whichever occurred first. According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), PD was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions was also considered progression. Participants without objectively determined PD who were alive at the end of the follow-up period (or lost to follow‑up) were censored on the date of the participant's last complete radiographic tumor assessment; if no baseline or post-baseline radiologic assessment was available, the participant was censored at the date of randomization.
    End point type
    Secondary
    End point timeframe
    Randomization to measured PD or date of death from any cause (up to 29 months)
    End point values
    Ramucirumab and Docetaxel Placebo and Docetaxel
    Number of subjects analysed
    628
    625
    Units: months
        median (confidence interval 95%)
    4.5 (4.2 to 5.3)
    3 (2.8 to 3.9)
    No statistical analyses for this end point

    Secondary: Percentage of participants achieving an objective response (objective response rate)

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    End point title
    Percentage of participants achieving an objective response (objective response rate)
    End point description
    Participants achieved an objective response if they had a best overall response of partial response (PR) or complete response (CR). According to RECIST v1.1, PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter; CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels [if tumor markers were initially above the upper limit of normal (ULN)]. The percentage of participants who achieved an objective response=(number of participants with CR or PR)/(number of participants assessed)*100.
    End point type
    Secondary
    End point timeframe
    Baseline to measured PD (up to 29 months)
    End point values
    Ramucirumab and Docetaxel Placebo and Docetaxel
    Number of subjects analysed
    628
    625
    Units: percentage of participants
        number (confidence interval 95%)
    22.9 (19.7 to 26.4)
    13.6 (11 to 16.5)
    No statistical analyses for this end point

    Secondary: Percentage of participants achieving disease control (Disease Control Rate)

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    End point title
    Percentage of participants achieving disease control (Disease Control Rate)
    End point description
    Participants achieved disease control if they had a best overall response of PR, CR or stable disease (SD). According to RECIST v1.1, PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter; CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the ULN). SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. The percentage of participants who achieved disease control=(number of participants with CR, PR, or SD)/(number of participants assessed)*100.
    End point type
    Secondary
    End point timeframe
    Baseline to measured PD (up to 29 months)
    End point values
    Ramucirumab and Docetaxel Placebo and Docetaxel
    Number of subjects analysed
    628
    625
    Units: percentage of participants
        number (confidence interval 95%)
    64 (60.1 to 67.8)
    52.6 (48.6 to 56.6)
    No statistical analyses for this end point

    Secondary: Maximum Improvement on Lung Cancer Symptom Scale (LCSS)

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    End point title
    Maximum Improvement on Lung Cancer Symptom Scale (LCSS)
    End point description
    The LCSS consisted of 9 items: 6 items focused on lung cancer symptoms [loss of appetite, fatigue, cough, dyspnea (shortness of breath), hemoptysis (blood in sputum), and pain] and 3 items were global items (symptom distress, interference with activity level, and global quality of life). Participant responses to each item were measured using visual analogue scales (VAS) with 100-mm lines. A higher score for any item represented a higher level of symptoms/problems. The Average Symptom Burden Index (ASBI) was the mean of the 6 symptom items of the LCSS, and the Total LCSS was the mean of all 9 LCSS items. ASBI and Total LCSS were not computed for a participant if he/she had 1 or more missing values for the 6 and 9 items, respectively. Maximum improvement in LCSS scores, ASBI, and Total LCSS score was the largest decrease from baseline for each variable, which was the smallest (most negative or smallest positive) non-missing value among all change from baseline values for each variable.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 21 of each cycle, and 30 days following the last infusion (up to Cycle 38, 21 days/cycle) Population: Randomized participants grouped according to assigned treatment at randomization, with a baseline and at least 1 post-baseline LCSS Score.
    End point values
    Ramucirumab and Docetaxel Placebo and Docetaxel
    Number of subjects analysed
    476
    477
    Units: mm
    arithmetic mean (standard deviation)
        Loss of Appetite (n=473, 471)
    -10.9 ( 26.11 )
    -11 ( 26.22 )
        Fatigue (n=473, 472)
    -12.1 ( 23.86 )
    -12 ( 27.29 )
        Cough (n=476, 473)
    -13.8 ( 24.28 )
    -14.3 ( 26.28 )
        Dyspnea (n=472, 477)
    -11 ( 23.01 )
    -10.5 ( 24.31 )
        Hemoptysis (n=475, 475)
    -1.4 ( 8.89 )
    -1.1 ( 8.79 )
        Pain (n=476, 475)
    -11.3 ( 23.62 )
    -11.5 ( 24.85 )
        Symptom Distress (n=474, 472)
    -10.7 ( 23.37 )
    -12.2 ( 26.25 )
        Interference With Activity Level (n=474, 472)
    -8.5 ( 24.13 )
    -7.9 ( 24.95 )
        Global Quality of Life (n=467, 469)
    -10.4 ( 22.68 )
    -8.9 ( 23.23 )
        ASBI (n=455, 456)
    -6.1 ( 13.75 )
    -6.9 ( 14.5 )
        Total LCSS (n=446, 446)
    -5.2 ( 13.75 )
    -6.4 ( 14.66 )
    No statistical analyses for this end point

    Secondary: Change from baseline to 30-Day follow-Up visit on European Quality of Life Questionnaire-5 Dimension (EQ-5D) Health State Scores

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    End point title
    Change from baseline to 30-Day follow-Up visit on European Quality of Life Questionnaire-5 Dimension (EQ-5D) Health State Scores
    End point description
    The EQ-5D is a quality-of-life instrument that consists of 2 parts. The first part (Health State Index score) allowed participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a scale from 1 to 3 (no problem, some problems, and extreme problems, respectively). These combinations of attributes were converted into a weighted Health State Index score according to a United Kingdom population-based algorithm; the possible values for the Health State Index score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). The second part of the EQ-5D was a VAS that allowed participants to rate their present health condition. Possible EQ-5D VAS scores ranged from 0 (worst imaginable health state) to 100 (best imaginable health state).
    End point type
    Secondary
    End point timeframe
    Baseline, 30 days following last infusion (up to Cycle 38, 21 days/cycle) Population: Randomized participants grouped according to their assigned treatment at randomization, who had an EQ-5D assessment at a baseline and 30 days post treatment.
    End point values
    Ramucirumab and Docetaxel Placebo and Docetaxel
    Number of subjects analysed
    272 [2]
    272 [3]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Health State Index Score (n=266, 272)
    -0.14 ( 0.308 )
    -0.126 ( 0.294 )
        Health State VAS Score (n=272, 254)
    -5.9 ( 21.02 )
    -6.1 ( 20.31 )
    Notes
    [2] - Participants who had an EQ-5D assessment at a baseline and 30 days post treatment.
    [3] - Participants who had an EQ-5D assessment at a baseline and 30 days post treatment.
    No statistical analyses for this end point

    Secondary: Maximum and Minimum Serum Concentrations (Cmax and Cmin) of Ramucirumab

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    End point title
    Maximum and Minimum Serum Concentrations (Cmax and Cmin) of Ramucirumab [4]
    End point description
    Participants assigned to the ramucirumab and docetaxel arm at randomization, who had evaluable ramucirumab pharmacokinetic (PK) data to calculate Cmax and Cmin.
    End point type
    Secondary
    End point timeframe
    Prior to infusion and 1 hour following infusion for Cycles 3 and 5 (21 days/cycle)
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is analyzing the ramucirumab PK data; not applicable for placebo arm.
    End point values
    Ramucirumab and Docetaxel
    Number of subjects analysed
    594 [5]
    Units: micrograms per milliliter (mcg/mL)
    geometric mean (geometric coefficient of variation)
        Cmax at Cycle 3
    262 ( 30 )
        Cmin at Cycle 3
    28.3 ( 65 )
        Cmax at Cycle 5
    237 ( 38 )
        Cmin at Cycle 5
    38.4 ( 63 )
    Notes
    [5] - Participants who had evaluable ramucirumab PK data calculate Cmax and Cmin.
    No statistical analyses for this end point

    Secondary: Number of Participants with anti-Ramucirumab antibodies

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    End point title
    Number of Participants with anti-Ramucirumab antibodies
    End point description
    The number of participants who had treatment-emergent or follow-up emergent anti-drug antibodies (ADA) is reported. Participants with treatment-emergent ADA were defined as participants who had any sample from baseline through Cycle 5 pre-infusion that was a 4-fold increase (2 dilution increase) in immunogenicity titer over the baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). Participants with follow-up emergent ADA were defined as participants who had any sample during 30 days post last infusion that was a 4-fold increase (2 dilution increase) in immunogenicity titer over the baseline titer. Population: Randomized participants who received any quantity of study treatment, grouped by the treatment they actually received, who had a baseline and at least 1 post-baseline ADA assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, prior to infusion for Cycles 3 and 5, and 30 days following last infusion (up to Cycle 38, 21 days/cycle)
    End point values
    Ramucirumab and Docetaxel Placebo and Docetaxel
    Number of subjects analysed
    599 [6]
    598 [7]
    Units: participants
    number (not applicable)
        Treatment-Emergent ADA (n=599, 598)
    9
    16
        Follow-Up Emergent ADA (n=506, 481)
    9
    16
    Notes
    [6] - Participants who had a baseline and at least 1 post-baseline ADA assessment.
    [7] - Participants who had a baseline and at least 1 post-baseline ADA assessment.
    No statistical analyses for this end point

    Other pre-specified: Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died

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    End point title
    Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died
    End point description
    Data presented are the number of participants who experienced at least 1 TEAE, Grade 3, 4, or 5 TEAE, treatment-emergent serious adverse event (SAE), TEAE leading to discontinuation of study treatment (ramucirumab/placebo or docetaxel), and TEAE leading to death. Clinically significant events were defined as treatment-emergent SAEs and other non-serious adverse events (AEs) regardless of causality. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. Safety population: Randomized participants who received any quantity of study drug, grouped by the treatment they actually received.
    End point type
    Other pre-specified
    End point timeframe
    First infusion up to 30 days following last infusion (up to Cycle 38, 21 days/cycle)
    End point values
    Ramucirumab and Docetaxel Placebo and Docetaxel
    Number of subjects analysed
    627 [8]
    618 [9]
    Units: participants
    number (not applicable)
        At least 1 TEAE
    613
    594
        At least 1 Grade 3, 4, or 5 TEAE
    495
    444
        At least 1 treatment-emergent SAE
    269
    262
        TEAE leading to study drug discontinuation
    58
    32
        TEAE leading to death
    34
    35
        Deaths While On Treatment
    428
    451
        Deaths During 30 Days Post Last Dose
    53
    58
    Notes
    [8] - Participants who received any quantity of study drug, grouped by treatment they actually received.
    [9] - Participants who received any quantity of study drug, grouped by treatment they actually received.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Randomization through 30 days following last infusion (up to Cycle 38, 21 days/cycle)
    Adverse event reporting additional description
    Safety Population: All randomized participants who received any quantity of study treatment, grouped by the treatment they actually received. Three participants randomized to placebo and docetaxel received 1 dose of ramucirumab in error.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Ramucirumab and Docetaxel
    Reporting group description
    On Day 1 of each 21-day cycle, participants received ramucirumab DP followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met. • Ramucirumab DP: 10 mg/kg administered intravenously. • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

    Reporting group title
    Placebo and Docetaxel
    Reporting group description
    On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met. • Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously. • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

    Serious adverse events
    Ramucirumab and Docetaxel Placebo and Docetaxel
    Total subjects affected by serious adverse events
         subjects affected / exposed
    284 / 627 (45.30%)
    281 / 618 (45.47%)
         number of deaths (all causes)
    34
    41
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Intracranial tumour haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphangiosis carcinomatosa
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant ascites
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant pleural effusion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    5 / 618 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to bone
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to central nervous system
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    3 / 618 (0.49%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to liver
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to meninges
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to spine
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    3 / 618 (0.49%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metastatic neoplasm
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metastatic pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    5 / 627 (0.80%)
    7 / 618 (1.13%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion malignant
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestine carcinoma
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour associated fever
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour compression
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour necrosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm rupture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Deep vein thrombosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    1 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 627 (0.48%)
    4 / 618 (0.65%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iliac artery occlusion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jugular vein thrombosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery aneurysm
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superior vena cava syndrome
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Venous thrombosis limb
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Hospitalisation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung lobectomy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adverse drug reaction
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 627 (0.48%)
    4 / 618 (0.65%)
         occurrences causally related to treatment / all
    11 / 11
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    5 / 627 (0.80%)
    3 / 618 (0.49%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 5
    0 / 3
    Disease progression
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    12 / 627 (1.91%)
    6 / 618 (0.97%)
         occurrences causally related to treatment / all
    14 / 18
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    5 / 627 (0.80%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    4 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal inflammation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multi-organ failure
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    3 / 618 (0.49%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral swelling
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    10 / 627 (1.59%)
    10 / 618 (1.62%)
         occurrences causally related to treatment / all
    3 / 10
    1 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Immune system disorders
    Anaphylactic shock
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug hypersensitivity
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    1 / 2
    0 / 2
    Acute respiratory failure
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    6 / 618 (0.97%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Aspiration
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atelectasis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catarrh
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    5 / 627 (0.80%)
    4 / 618 (0.65%)
         occurrences causally related to treatment / all
    2 / 7
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cough
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    11 / 627 (1.75%)
    26 / 618 (4.21%)
         occurrences causally related to treatment / all
    2 / 12
    3 / 32
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    7 / 627 (1.12%)
    6 / 618 (0.97%)
         occurrences causally related to treatment / all
    7 / 9
    3 / 7
         deaths causally related to treatment / all
    1 / 2
    0 / 2
    Haemothorax
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiccups
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrothorax
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    3 / 618 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infiltration
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oropharyngeal pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    9 / 627 (1.44%)
    21 / 618 (3.40%)
         occurrences causally related to treatment / all
    0 / 10
    4 / 23
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumomediastinum
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Pneumothorax
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    5 / 627 (0.80%)
    3 / 618 (0.49%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    3 / 618 (0.49%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 3
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Pneumothorax spontaneous
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary bulla
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary congestion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    8 / 627 (1.28%)
    12 / 618 (1.94%)
         occurrences causally related to treatment / all
    4 / 8
    8 / 13
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    Pulmonary haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 627 (0.64%)
    4 / 618 (0.65%)
         occurrences causally related to treatment / all
    2 / 4
    1 / 5
         deaths causally related to treatment / all
    2 / 4
    1 / 3
    Pulmonary oedema
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory acidosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory arrest
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Respiratory failure
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 627 (0.48%)
    9 / 618 (1.46%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 10
         deaths causally related to treatment / all
    0 / 2
    1 / 5
    Respiratory tract haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Tachypnoea
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    7 / 627 (1.12%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    3 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conversion disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Echolalia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mania
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood alkaline phosphatase increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diagnostic aspiration
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test abnormal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    9 / 627 (1.44%)
    3 / 618 (0.49%)
         occurrences causally related to treatment / all
    10 / 10
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transaminases increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 627 (0.48%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax traumatic
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 627 (0.48%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pubis fracture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suture related complication
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic arthropathy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Tracheo-oesophageal fistula
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Arrhythmia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    6 / 627 (0.96%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial tachycardia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    2 / 2
    0 / 1
    Cardiac failure
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac tamponade
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 2
    1 / 2
    Coronary artery occlusion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pericardial effusion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    6 / 618 (0.97%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    3 / 618 (0.49%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Tachycardia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular arrhythmia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Aphasia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain oedema
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral ischaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cognitive disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Convulsion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 627 (0.48%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiplegia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Ivth nerve paralysis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lethargy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine with aura
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuralgia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraparesis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peroneal nerve palsy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radicular syndrome
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Senile dementia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stupor
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 627 (0.64%)
    4 / 618 (0.65%)
         occurrences causally related to treatment / all
    3 / 4
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxic encephalopathy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tremor
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vocal cord paresis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    10 / 627 (1.59%)
    14 / 618 (2.27%)
         occurrences causally related to treatment / all
    15 / 16
    11 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    86 / 627 (13.72%)
    51 / 618 (8.25%)
         occurrences causally related to treatment / all
    104 / 104
    55 / 56
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    5 / 627 (0.80%)
    10 / 618 (1.62%)
         occurrences causally related to treatment / all
    6 / 6
    14 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    30 / 627 (4.78%)
    27 / 618 (4.37%)
         occurrences causally related to treatment / all
    37 / 38
    33 / 33
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 627 (0.48%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Diplopia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal vein thrombosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 627 (0.48%)
    7 / 618 (1.13%)
         occurrences causally related to treatment / all
    0 / 3
    2 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal fistula
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal inflammation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Diarrhoea
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    13 / 627 (2.07%)
    9 / 618 (1.46%)
         occurrences causally related to treatment / all
    12 / 13
    5 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticular perforation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    3 / 618 (0.49%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Gastrointestinal inflammation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gingival bleeding
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileal fistula
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus paralytic
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestinal obstruction
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    7 / 627 (1.12%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    5 / 8
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic colitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal fistula
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Oesophageal pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal perforation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal perforation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomatitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    14 / 627 (2.23%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    16 / 16
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subileus
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Vomiting
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    6 / 627 (0.96%)
    8 / 618 (1.29%)
         occurrences causally related to treatment / all
    5 / 6
    4 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatitis acute
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jaundice
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Hyperhidrosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pruritus
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psoriasis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous emphysema
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urticaria
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute prerenal failure
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure acute
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 627 (0.64%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    5 / 8
    1 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flank pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pathological fracture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    3 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis perforated
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary tract infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    6 / 618 (0.97%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis moraxella
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopneumonia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Candida infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 627 (0.48%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis staphylococcal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related sepsis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 627 (0.48%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Empyema
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lobar pneumonia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    7 / 627 (1.12%)
    8 / 618 (1.29%)
         occurrences causally related to treatment / all
    4 / 7
    3 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Localised infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 627 (0.48%)
    5 / 618 (0.81%)
         occurrences causally related to treatment / all
    1 / 6
    4 / 5
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Neutropenic infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic sepsis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Oral candidiasis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral herpes
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paronychia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic abscess
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 627 (0.48%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    3 / 618 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    37 / 627 (5.90%)
    41 / 618 (6.63%)
         occurrences causally related to treatment / all
    18 / 43
    7 / 48
         deaths causally related to treatment / all
    2 / 3
    1 / 6
    Pneumonia bacterial
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia escherichia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia pneumococcal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia staphylococcal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia streptococcal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Postoperative wound infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 627 (0.48%)
    3 / 618 (0.49%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 627 (0.48%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    3 / 3
    2 / 2
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    Septic shock
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    3 / 618 (0.49%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Staphylococcal sepsis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stenotrophomonas sepsis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Upper respiratory tract infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    4 / 618 (0.65%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Decreased appetite
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    15 / 627 (2.39%)
    15 / 618 (2.43%)
         occurrences causally related to treatment / all
    14 / 17
    11 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to thrive
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 627 (0.32%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    2 / 618 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 627 (0.00%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 627 (0.16%)
    1 / 618 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 627 (0.64%)
    3 / 618 (0.49%)
         occurrences causally related to treatment / all
    3 / 4
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 627 (0.48%)
    0 / 618 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Ramucirumab and Docetaxel Placebo and Docetaxel
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    601 / 627 (95.85%)
    583 / 618 (94.34%)
    Investigations
    Neutrophil count decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    112 / 627 (17.86%)
    89 / 618 (14.40%)
         occurrences all number
    281
    193
    Platelet count decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    36 / 627 (5.74%)
    9 / 618 (1.46%)
         occurrences all number
    104
    20
    Weight decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    67 / 627 (10.69%)
    49 / 618 (7.93%)
         occurrences all number
    84
    56
    White blood cell count decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    58 / 627 (9.25%)
    50 / 618 (8.09%)
         occurrences all number
    148
    219
    Vascular disorders
    Hypertension
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    67 / 627 (10.69%)
    29 / 618 (4.69%)
         occurrences all number
    129
    107
    Nervous system disorders
    Dizziness
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    43 / 627 (6.86%)
    46 / 618 (7.44%)
         occurrences all number
    54
    52
    Dysgeusia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    69 / 627 (11.00%)
    46 / 618 (7.44%)
         occurrences all number
    83
    55
    Headache
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    66 / 627 (10.53%)
    65 / 618 (10.52%)
         occurrences all number
    88
    78
    Paraesthesia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    38 / 627 (6.06%)
    36 / 618 (5.83%)
         occurrences all number
    49
    46
    Peripheral sensory neuropathy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    74 / 627 (11.80%)
    60 / 618 (9.71%)
         occurrences all number
    121
    102
    Blood and lymphatic system disorders
    Anaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    135 / 627 (21.53%)
    174 / 618 (28.16%)
         occurrences all number
    306
    399
    Leukopenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    79 / 627 (12.60%)
    68 / 618 (11.00%)
         occurrences all number
    259
    151
    Neutropenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    228 / 627 (36.36%)
    188 / 618 (30.42%)
         occurrences all number
    547
    415
    Thrombocytopenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    51 / 627 (8.13%)
    27 / 618 (4.37%)
         occurrences all number
    114
    48
    General disorders and administration site conditions
    Asthenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    72 / 627 (11.48%)
    65 / 618 (10.52%)
         occurrences all number
    178
    127
    Fatigue
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    287 / 627 (45.77%)
    260 / 618 (42.07%)
         occurrences all number
    623
    524
    Mucosal inflammation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    103 / 627 (16.43%)
    43 / 618 (6.96%)
         occurrences all number
    167
    53
    Oedema peripheral
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    107 / 627 (17.07%)
    55 / 618 (8.90%)
         occurrences all number
    149
    86
    Pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    35 / 627 (5.58%)
    33 / 618 (5.34%)
         occurrences all number
    40
    37
    Pyrexia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    100 / 627 (15.95%)
    79 / 618 (12.78%)
         occurrences all number
    148
    114
    Eye disorders
    Lacrimation increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    85 / 627 (13.56%)
    29 / 618 (4.69%)
         occurrences all number
    100
    31
    Gastrointestinal disorders
    Abdominal pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    56 / 627 (8.93%)
    35 / 618 (5.66%)
         occurrences all number
    69
    41
    Constipation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    107 / 627 (17.07%)
    110 / 618 (17.80%)
         occurrences all number
    135
    132
    Diarrhoea
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    200 / 627 (31.90%)
    175 / 618 (28.32%)
         occurrences all number
    338
    226
    Dyspepsia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    37 / 627 (5.90%)
    18 / 618 (2.91%)
         occurrences all number
    47
    25
    Nausea
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    170 / 627 (27.11%)
    173 / 618 (27.99%)
         occurrences all number
    236
    256
    Stomatitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    143 / 627 (22.81%)
    81 / 618 (13.11%)
         occurrences all number
    245
    104
    Vomiting
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    88 / 627 (14.04%)
    86 / 618 (13.92%)
         occurrences all number
    117
    119
    Respiratory, thoracic and mediastinal disorders
    Cough
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    137 / 627 (21.85%)
    131 / 618 (21.20%)
         occurrences all number
    194
    169
    Dysphonia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    38 / 627 (6.06%)
    23 / 618 (3.72%)
         occurrences all number
    49
    23
    Dyspnoea
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    150 / 627 (23.92%)
    148 / 618 (23.95%)
         occurrences all number
    220
    207
    Epistaxis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    116 / 627 (18.50%)
    41 / 618 (6.63%)
         occurrences all number
    149
    45
    Haemoptysis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    36 / 627 (5.74%)
    31 / 618 (5.02%)
         occurrences all number
    38
    37
    Oropharyngeal pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    49 / 627 (7.81%)
    30 / 618 (4.85%)
         occurrences all number
    65
    39
    Productive cough
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    40 / 627 (6.38%)
    34 / 618 (5.50%)
         occurrences all number
    61
    41
    Skin and subcutaneous tissue disorders
    Alopecia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    163 / 627 (26.00%)
    156 / 618 (25.24%)
         occurrences all number
    192
    176
    Nail discolouration
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    41 / 627 (6.54%)
    27 / 618 (4.37%)
         occurrences all number
    45
    27
    Rash
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    44 / 627 (7.02%)
    36 / 618 (5.83%)
         occurrences all number
    56
    51
    Psychiatric disorders
    Insomnia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    69 / 627 (11.00%)
    54 / 618 (8.74%)
         occurrences all number
    78
    55
    Musculoskeletal and connective tissue disorders
    Arthralgia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    71 / 627 (11.32%)
    51 / 618 (8.25%)
         occurrences all number
    110
    86
    Back pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    73 / 627 (11.64%)
    56 / 618 (9.06%)
         occurrences all number
    113
    83
    Bone pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    31 / 627 (4.94%)
    36 / 618 (5.83%)
         occurrences all number
    40
    57
    Myalgia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    79 / 627 (12.60%)
    65 / 618 (10.52%)
         occurrences all number
    123
    110
    Pain in extremity
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    50 / 627 (7.97%)
    26 / 618 (4.21%)
         occurrences all number
    60
    31
    Metabolism and nutrition disorders
    Decreased appetite
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    189 / 627 (30.14%)
    163 / 618 (26.38%)
         occurrences all number
    290
    221
    Dehydration
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    39 / 627 (6.22%)
    24 / 618 (3.88%)
         occurrences all number
    47
    31
    Hyperglycaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    39 / 627 (6.22%)
    25 / 618 (4.05%)
         occurrences all number
    83
    49

    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.
    Three participants randomized to placebo and docetaxel received 1 dose of ramucirumab in error. They are included in the placebo and docetaxel arm in the ITT population and are included in the ramucirumab and docetaxel arm in the Safety population.
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