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    Clinical Trial Results:
    Phase 3 Study of Pemetrexed, Cisplatin, and Radiotherapy Followed by Consolidation Pemetrexed versus Etoposide, Cisplatin, and Radiotherapy Followed by Consolidation Cytotoxic Chemotherapy of Choice in Patients with Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer Other than Predominantly Squamous Cell Histology

    Summary
    EudraCT number
    		 2008-001170-32
    Trial protocol
    		 PT   HU   ES   NL   BE   FR   DE   GB   IE  
    Global end of trial date
    06 Nov 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    08 Jun 2016
    First version publication date
    08 Jun 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    H3E-MC-JMIG
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00686959
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Alias : H3E-MC-JMIG, Trial ID: 11514
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon - Fri 9 AM - 5 PM EST , Eli Lilly and Company, 1 877-CTLilly,
    Scientific contact
    Available Mon - Fri 9 AM - 5 PM EST , Eli Lilly and Company, 1 877-285-4559,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    06 Nov 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    06 Nov 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Nov 2014
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To compare the overall survival of patients with locally advanced, Stage III NSCLC of predominantly nonsquamous histology (hereafter simply referred to as nonsquamous) treated with pemetrexed plus cisplatin and concurrent TRT, followed by consolidation chemotherapy with pemetrexed (Arm A) versus etoposide plus cisplatin and concurrent TRT, followed by consolidation with cytotoxic chemotherapy of choice (Arm B).
    Protection of trial subjects
    This study was conducted in accordance with International Code of 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
    		 Thoracic Radiation Therapy (TRT) Arm A: Pemetrexed + Cisplatin and TRT: Beginning on Day 1 of chemotherapy, once daily fractions (2 Gray [Gy] per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions. Arm B: Etoposide + Cisplatin and TRT: Beginning on Day 1 of chemotherapy, once daily fractions (2 Gray [Gy] per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Sep 2008
    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
    Netherlands: 46
    Country: Number of subjects enrolled
    Portugal: 18
    Country: Number of subjects enrolled
    Spain: 65
    Country: Number of subjects enrolled
    United Kingdom: 19
    Country: Number of subjects enrolled
    Belgium: 44
    Country: Number of subjects enrolled
    France: 22
    Country: Number of subjects enrolled
    Germany: 37
    Country: Number of subjects enrolled
    Greece: 16
    Country: Number of subjects enrolled
    Argentina: 3
    Country: Number of subjects enrolled
    United States: 134
    Country: Number of subjects enrolled
    Canada: 26
    Country: Number of subjects enrolled
    Turkey: 7
    Country: Number of subjects enrolled
    Ireland: 1
    Country: Number of subjects enrolled
    China: 61
    Country: Number of subjects enrolled
    Taiwan: 25
    Country: Number of subjects enrolled
    Brazil: 16
    Country: Number of subjects enrolled
    Korea, Republic of: 11
    Country: Number of subjects enrolled
    Australia: 17
    Country: Number of subjects enrolled
    Mexico: 2
    Country: Number of subjects enrolled
    India: 28
    Worldwide total number of subjects
    598
    EEA total number of subjects
    268
    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)
    426
    From 65 to 84 years
    172
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Overall study with two reporting groups. There were 598 participants randomized (Arm A = 301; Arm B = 297), of those participants who were randomized 555 received at least on dose of study drug (Arm A = 283; Arm B = 272) Study completion includes death due to any cause.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Pemetrexed + Cisplatin and Thoracic Radiation Therapy (TRT)
    Arm description
    		 Participants were treated with pemetrexed plus Cisplatin and concurrent TRT ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for up to four 21-day cycles
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pemetrexed
    Investigational medicinal product code
    LY231514
    Other name
    Alimta
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pemetrexed: 500 milligrams per meter squared (mg/m^2), intravenous (IV) on Day 1 of each 21-day cycle for 3 cycles.

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cisplatin: 75 mg/m^2, IV on Day 1 of each 21-day cycle x 3 cycles.

    Arm title
    		 Etoposide + Csiplatin and TRT
    Arm description
    		 Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etoposide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Etoposide: 50 mg/m^2, IV on Days 1 to 5 and Days 29 to 33

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cisplatin: 50 mg/m^2, IV on Days1, 8, 29, and 36

    Number of subjects in period 1
    		Pemetrexed + Cisplatin and Thoracic Radiation Therapy (TRT) Etoposide + Csiplatin and TRT
    Started
    301
    297
    Received at Least One Dose of Study Drug
    283
    272
    Entered Consolidation Phase
    229
    202
    Completed
    177
    180
    Not completed
    124
    117
         Participants censored (no death events)
    124
    117

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Pemetrexed + Cisplatin and Thoracic Radiation Therapy (TRT)
    Reporting group description
    		 Participants were treated with pemetrexed plus Cisplatin and concurrent TRT ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for up to four 21-day cycles

    Reporting group title
    Etoposide + Csiplatin and TRT
    Reporting group description
    		 Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles

    Reporting group values
    		 Pemetrexed + Cisplatin and Thoracic Radiation Therapy (TRT) Etoposide + Csiplatin and TRT Total
    Number of subjects
    		 301 297 598
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 215 211 426
        From 65-84 years
    		 86 86 172
        85 years and over
    		 0 0 0
    Gender categorical
    Units: Subjects
        Female
    		 124 119 243
        Male
    		 177 178 355
    Race/ Ethnicity
    Units: Subjects
        African
    		 15 12 27
        Caucasian
    		 217 204 421
        East Asian
    		 54 68 122
        Hispanic
    		 5 4 9
        Native American
    		 1 1 2
        West Asian
    		 6 6 12
        Missing (unknown)
    		 3 2 5
    Eastern Cooperative Oncology Group (ECOG) Performance Status
    0=Fully active, able to carry on all pre-disease performance without restriction 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, such as, light housework, office work
    Units: Subjects
        ECOG 0
    		 148 145 293
        ECOG 1
    		 152 149 301
        Missing
    		 1 3 4
    Disease Stage
    Stage means how big the tumor is and how far it has spread. Stages range from 0 (not spread) to IV (spread throughout the body). Stage IIIA - the cancer has spread to nearby tissue or spread to far away lymph nodes; Stage IIIB - cancer spread to opposite side of chest, more than one tumor within same lobe of lung.
    Units: Subjects
        Stage IIIA
    		 140 142 282
        Stage IIIB
    		 161 152 313
        Missing
    		 0 3 3
    Histology
    Units: Subjects
        Adenocarcinoma
    		 226 226 452
        Large Cell Carcinoma
    		 16 21 37
        Other
    		 59 48 107
        Missing
    		 0 2 2
    Smoking Status
    Smoking history: moderate smoker means </= 15 pack year (PY); heavy smoker means > 15PY.
    Units: Subjects
        Never Smoked
    		 50 58 108
        Moderate Smoker
    		 42 38 80
        Heavy Smoker
    		 190 183 373
        Missing
    		 19 18 37
    Baseline Positron Emmission Tomography (PET) Scan
    Participant had a baseline PET scan for staging
    Units: Subjects
        Yes
    		 250 241 491
        No
    		 51 56 107

    End points

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    End points reporting groups
    Reporting group title
    Pemetrexed + Cisplatin and Thoracic Radiation Therapy (TRT)
    Reporting group description
    		 Participants were treated with pemetrexed plus Cisplatin and concurrent TRT ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for up to four 21-day cycles

    Reporting group title
    Etoposide + Csiplatin and TRT
    Reporting group description
    		 Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles

    Primary: Overall Survival

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    End point title
    		 Overall Survival
    End point description
    Overall survival (OS) time is from baseline to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participant was known to be alive prior to the data cut-off date. OS was summarized using Kaplan-Meier estimates.
    End point type
    Primary
    End point timeframe
    Baseline to Date of Death from Any Cause (Up to 71.4 Months)
    End point values
    		 Pemetrexed + Cisplatin and Thoracic Radiation Therapy (TRT) Etoposide + Csiplatin and TRT
    Number of subjects analysed
    301
    297
    Units: Months
        median (confidence interval 95%)
    26.81 (20.4 to 30.92)
    24.97 (22.18 to 29.83)
    Statistical analysis title
    		 Overall Survival
    Statistical analysis description
    All randomized participants. Arm A had 124 participants censored and Arm B had 117 participants censored.
    Comparison groups
    Pemetrexed + Cisplatin and Thoracic Radiation Therapy (TRT) v Etoposide + Csiplatin and TRT
    Number of subjects included in analysis
    598
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.831
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.2

    Secondary: Progression Free Survival

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    End point title
    		 Progression Free Survival
    End point description
    Progression-free survival (PFS) time is from baseline to the first date of documented objective progressive disease (PD) or death from any cause. For participants who were not known to have died or to have had objective PD as of the data inclusion cut-off date for a particular analysis, PFS was censored at the date of the last objective progression-free disease assessments.
    End point type
    Secondary
    End point timeframe
    Baseline to Measured Progressive Disease or Death from Any Cause (Up to 66.6 Months)
    End point values
    		 Pemetrexed + Cisplatin and Thoracic Radiation Therapy (TRT) Etoposide + Csiplatin and TRT
    Number of subjects analysed
    301
    297
    Units: Months
        median (confidence interval 95%)
    11.37 (10.25 to 13.21)
    9.76 (8.38 to 11.73)
    No statistical analyses for this end point

    Secondary: Objective Response Rate (Complete Response [CR] + Partial Response [PR])

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    End point title
    		 Objective Response Rate (Complete Response [CR] + Partial Response [PR])
    End point description
    Overall response rate (ORR) is the best response of CR or PR as classified by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) guidelines. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.
    End point type
    Secondary
    End point timeframe
    Baseline to Measured Progressive Disease (Up to 7 Months)
    End point values
    		 Pemetrexed + Cisplatin and Thoracic Radiation Therapy (TRT) Etoposide + Csiplatin and TRT
    Number of subjects analysed
    301
    297
    Units: Percentage of participants
        number (confidence interval 95%)
    35.9 (30.46 to 41.58)
    33 (27.67 to 38.66)
    No statistical analyses for this end point

    Secondary: Survival Rates at 1, 2, and 3 Years

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    End point title
    		 Survival Rates at 1, 2, and 3 Years
    End point description
    The probability that survival time is at least 1, 2, or 3 years was summarized using Kaplan-Meier estimates.
    End point type
    Secondary
    End point timeframe
    Baseline to Date of Death from Any Cause (Up to 71.4 Months)
    End point values
    		 Pemetrexed + Cisplatin and Thoracic Radiation Therapy (TRT) Etoposide + Csiplatin and TRT
    Number of subjects analysed
    301
    297
    Units: Probabliity of survival
    number (confidence interval 95%)
        1 year (12months)
    0.76 (0.7 to 0.8)
    0.77 (0.72 to 0.81)
        2 years (24 months)
    0.52 (0.46 to 0.58)
    0.52 (0.46 to 0.58)
        3 years (36 months)
    0.4 (0.34 to 0.46)
    0.37 (0.31 to 0.43)
    No statistical analyses for this end point

    Secondary: First Site of Disease Failure in Terms of Relapse

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    End point title
    		 First Site of Disease Failure in Terms of Relapse
    End point description
    The percentage of participants with first sites of disease failure in terms of relapse within the radiation treatment field, inside the thorax, (outside of the radiation field), or distant disease are presented. Results were summarized using Kaplan-Meier estimates. Some participants relapsed in more than 1 location/site and appear in more than a single category.
    End point type
    Secondary
    End point timeframe
    Baseline to Relapse (Up to 66.6 Months)
    End point values
    		 Pemetrexed + Cisplatin and Thoracic Radiation Therapy (TRT) Etoposide + Csiplatin and TRT
    Number of subjects analysed
    166 [1]
    190 [2]
    Units: Percentage of participants
    number (confidence interval 95%)
        Relapsed within the radiation treatment field
    37.3 (30 to 45.2)
    45.8 (38.6 to 53.2)
        Relapsed inside thorax, outside radiation field
    20.5 (14.6 to 27.4)
    16.3 (11.4 to 22.4)
        Relapsed distant disease
    50 (42.2 to 57.8)
    45.8 (38.6 to 53.2)
    Notes
    [1] - All randomized participants with objective PD
    [2] - All randomized participants with objective PD
    No statistical analyses for this end point

    Secondary: Percentage of Participants With a Post Baseline Swallowing Diary Score >=4

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    End point title
    		 Percentage of Participants With a Post Baseline Swallowing Diary Score >=4
    End point description
    Participants were provided with a swallowing diary to record issues with swallowing using a 5-point categorical scale: (1) no problems; (2) mild soreness; (3) swallowing solids with some difficulty; (4) inability to swallow solids; and (5) inability to swallow liquids. Participants rated swallowing over the previous 24 hours. The percentage of participants was calculated by dividing the number of with a post baseline swallowing diary score >=4 by total number of participants analyzed, multiplied by 100.
    End point type
    Secondary
    End point timeframe
    Baseline through 30 Days Post Study
    End point values
    		 Pemetrexed + Cisplatin and Thoracic Radiation Therapy (TRT) Etoposide + Csiplatin and TRT
    Number of subjects analysed
    284 [3]
    269 [4]
    Units: Percentage of participants
        number (confidence interval 95%)
    33.8 (26.7 to 37.5)
    29 (21.3 to 31.7)
    Notes
    [3] - All randomized participants with at least one post baseline swallowing diary score
    [4] - All randomized participants with at least one post baseline swallowing diary score
    No statistical analyses for this end point

    Secondary: Adverse Events: The Number of Deaths Per Treatment Group

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    End point title
    		 Adverse Events: The Number of Deaths Per Treatment Group
    End point description
    The number of deaths that occurred while on study drug, the number of deaths due to adverse events (AEs) while on study drug, and the number of deaths due to the study disease (that is, disease progression) while on study drug are presented. In addition, the number of deaths within 30 days of treatment discontinuation, the number of deaths due to AEs within 30 days of treatment discontinuation, and the number of deaths due to study disease within 30 days of treatment discontinuation are presented. For both the deaths due to AEs that occurred on study and for deaths due to AEs that occurred within 30 days of treatment discontinuation, the causality (events assess as possibly related [poss related] to study drug per investigator judgement) is also presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
    End point type
    Secondary
    End point timeframe
    Baseline through 30 Days Post Study
    End point values
    		 Pemetrexed + Cisplatin and Thoracic Radiation Therapy (TRT) Etoposide + Csiplatin and TRT
    Number of subjects analysed
    283 [5]
    272 [6]
    Units: Participants
    number (not applicable)
        On study drug (total)
    12
    6
        On study drug: Due to AE
    10
    4
        On study drug: Due to AE possibly related
    5
    3
        On study drug: Due to study disease
    2
    0
        Within 30 Days of Discontinuation (disc) (total)
    10
    6
        Within 30 Days of Disc: Due to AE
    5
    4
        Within 30 Days of Disc: Due to AE poss related
    2
    0
        Within 30 Days of Disc: Due to study disease
    5
    2
    Notes
    [5] - All randomized participants who received at least one dose of study drug.
    [6] - All randomized participants who received at least one dose of study drug.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Entire Study
    Adverse event reporting additional description
    H3E-MC-JMIG
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Pemetrexed + Cisplatin
    Reporting group description
    		 -

    Reporting group title
    Etoposide + Cisplatin
    Reporting group description
    		 -

    Serious adverse events
    		 Pemetrexed + Cisplatin Etoposide + Cisplatin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    134 / 283 (47.35%)
    145 / 272 (53.31%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    lung infiltration malignant
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    malignant melanoma in situ
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    metastases to central nervous system
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 283 (1.06%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    paraneoplastic syndrome
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    thyroid cancer
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tumour haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    tumour pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    deep vein thrombosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    embolism arterial
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypotension
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypovolaemic shock
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    jugular vein thrombosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         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 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peripheral ischaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    phlebitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    superior vena cava syndrome
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thrombophlebitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thrombosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    vena cava thrombosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    chest pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 283 (1.06%)
    5 / 272 (1.84%)
         occurrences causally related to treatment / all
    0 / 5
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    death
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    fatigue
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 283 (1.06%)
    4 / 272 (1.47%)
         occurrences causally related to treatment / all
    2 / 4
    3 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    malaise
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    mucosal inflammation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    multi-organ failure
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    non-cardiac chest pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pyrexia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    11 / 283 (3.89%)
    4 / 272 (1.47%)
         occurrences causally related to treatment / all
    2 / 14
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    drug hypersensitivity
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    acute respiratory distress syndrome
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    acute respiratory failure
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 1
    aspiration
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    atelectasis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bronchial secretion retention
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bronchopleural fistula
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    chronic obstructive pulmonary disease
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cough
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dyspnoea
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 283 (1.06%)
    3 / 272 (1.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haemoptysis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypoxia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pleural effusion
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 283 (1.06%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia aspiration
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    6 / 283 (2.12%)
    3 / 272 (1.10%)
         occurrences causally related to treatment / all
    4 / 19
    0 / 19
         deaths causally related to treatment / all
    2 / 2
    0 / 0
    pneumothorax
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 283 (1.06%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pulmonary embolism
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 283 (1.06%)
    10 / 272 (3.68%)
         occurrences causally related to treatment / all
    0 / 10
    2 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pulmonary haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    respiratory failure
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 283 (1.06%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    2 / 4
    1 / 1
         deaths causally related to treatment / all
    2 / 3
    1 / 1
    Psychiatric disorders
    confusional state
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    delirium
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    depression
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hallucination
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    blood creatinine increased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haemoglobin decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neutrophil count decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    platelet count decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    3 / 272 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    weight decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    4 / 283 (1.41%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    2 / 13
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    white blood cell count decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    fall
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fracture
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hip fracture
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lumbar vertebral fracture
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    radiation fibrosis - lung
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    radiation oesophagitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    7 / 283 (2.47%)
    13 / 272 (4.78%)
         occurrences causally related to treatment / all
    6 / 18
    8 / 20
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    radiation pneumonitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    7 / 283 (2.47%)
    5 / 272 (1.84%)
         occurrences causally related to treatment / all
    3 / 19
    1 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    radiation skin injury
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    stoma site pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tracheal haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    aplasia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tracheo-oesophageal fistula
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    atrial fibrillation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    4 / 283 (1.41%)
    3 / 272 (1.10%)
         occurrences causally related to treatment / all
    3 / 11
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cardiac arrest
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    cardiac failure
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cardio-respiratory arrest
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    coronary artery disease
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    endocarditis noninfective
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    myocardial infarction
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    pericardial effusion
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pericarditis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    supraventricular tachycardia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    cerebral infarction
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 11
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    cerebrovascular accident
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    convulsion
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dizziness
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    epilepsy
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    intracranial pressure increased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    loss of consciousness
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    migraine
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    paraplegia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peripheral sensory neuropathy
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    spinal cord compression
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    syncope
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    transient ischaemic attack
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 283 (1.06%)
    5 / 272 (1.84%)
         occurrences causally related to treatment / all
    4 / 6
    3 / 22
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    febrile neutropenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    12 / 283 (4.24%)
    24 / 272 (8.82%)
         occurrences causally related to treatment / all
    13 / 14
    23 / 25
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    leukopenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    4 / 283 (1.41%)
    6 / 272 (2.21%)
         occurrences causally related to treatment / all
    4 / 6
    9 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lymphopenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neutropenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    8 / 283 (2.83%)
    13 / 272 (4.78%)
         occurrences causally related to treatment / all
    8 / 21
    15 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pancytopenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thrombocytopenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    5 / 272 (1.84%)
         occurrences causally related to treatment / all
    1 / 4
    5 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    tinnitus
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    abdominal pain upper
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    anal fistula
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    aorto-oesophageal fistula
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    constipation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diarrhoea
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    6 / 283 (2.12%)
    5 / 272 (1.84%)
         occurrences causally related to treatment / all
    4 / 15
    4 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dyspepsia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dysphagia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    4 / 283 (1.41%)
    5 / 272 (1.84%)
         occurrences causally related to treatment / all
    1 / 8
    4 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    enteritis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    eructation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastric perforation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    gastritis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastrointestinal angiodysplasia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastrointestinal ulcer
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haematemesis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    ileus
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    intra-abdominal haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    large intestine perforation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lower gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    nausea
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    8 / 283 (2.83%)
    7 / 272 (2.57%)
         occurrences causally related to treatment / all
    8 / 27
    6 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    odynophagia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oesophageal pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oesophageal perforation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         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 17.1
         subjects affected / exposed
    26 / 283 (9.19%)
    29 / 272 (10.66%)
         occurrences causally related to treatment / all
    21 / 63
    19 / 89
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oesophagitis ulcerative
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pancreatitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    small intestinal obstruction
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    vomiting
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    14 / 283 (4.95%)
    8 / 272 (2.94%)
         occurrences causally related to treatment / all
    13 / 23
    6 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatobiliary disorders
    cholecystitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    renal failure
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    2 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    renal failure acute
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    3 / 272 (1.10%)
         occurrences causally related to treatment / all
    2 / 3
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    renal impairment
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    inappropriate antidiuretic hormone secretion
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    muscle spasms
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    osteoporosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    atypical pneumonia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    bacteraemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         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 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bronchopneumonia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    device related infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diverticulitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastroenteritis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    infectious colitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    influenza
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    laryngitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lobar pneumonia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    1 / 7
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lower respiratory tract infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    3 / 272 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neutropenic infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (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 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    oral candidiasis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumocystis jirovecii pneumonia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    18 / 283 (6.36%)
    18 / 272 (6.62%)
         occurrences causally related to treatment / all
    10 / 30
    6 / 32
         deaths causally related to treatment / all
    1 / 2
    2 / 4
    pneumonia bacterial
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia haemophilus
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia necrotising
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    pseudomembranous colitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pseudomonas infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pulmonary tuberculosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    respiratory tract infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    4 / 283 (1.41%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    2 / 6
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sepsis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    4 / 272 (1.47%)
         occurrences causally related to treatment / all
    0 / 2
    4 / 5
         deaths causally related to treatment / all
    0 / 1
    2 / 2
    septic shock
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    upper respiratory tract infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    varicella
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    0 / 272 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    decreased appetite
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 283 (1.06%)
    3 / 272 (1.10%)
         occurrences causally related to treatment / all
    5 / 8
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dehydration
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    7 / 283 (2.47%)
    6 / 272 (2.21%)
         occurrences causally related to treatment / all
    7 / 15
    2 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyperglycaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    3 / 272 (1.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypokalaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypomagnesaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 283 (0.00%)
    2 / 272 (0.74%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyponatraemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 283 (0.71%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypovolaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 283 (0.35%)
    1 / 272 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Pemetrexed + Cisplatin Etoposide + Cisplatin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    279 / 283 (98.59%)
    269 / 272 (98.90%)
    Vascular disorders
    hypotension
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 283 (1.06%)
    16 / 272 (5.88%)
         occurrences all number
    6
    40
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    64 / 283 (22.61%)
    35 / 272 (12.87%)
         occurrences all number
    249
    101
    chest pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    40 / 283 (14.13%)
    32 / 272 (11.76%)
         occurrences all number
    154
    71
    fatigue
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    139 / 283 (49.12%)
    131 / 272 (48.16%)
         occurrences all number
    685
    472
    mucosal inflammation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    31 / 283 (10.95%)
    23 / 272 (8.46%)
         occurrences all number
    73
    64
    oedema peripheral
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    24 / 283 (8.48%)
    12 / 272 (4.41%)
         occurrences all number
    61
    28
    pyrexia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    56 / 283 (19.79%)
    42 / 272 (15.44%)
         occurrences all number
    76
    60
    Respiratory, thoracic and mediastinal disorders
    cough
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    105 / 283 (37.10%)
    84 / 272 (30.88%)
         occurrences all number
    430
    273
    dyspnoea
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    93 / 283 (32.86%)
    53 / 272 (19.49%)
         occurrences all number
    308
    142
    hiccups
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    31 / 283 (10.95%)
    17 / 272 (6.25%)
         occurrences all number
    84
    33
    oropharyngeal pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    17 / 283 (6.01%)
    24 / 272 (8.82%)
         occurrences all number
    43
    41
    pneumonitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    23 / 283 (8.13%)
    8 / 272 (2.94%)
         occurrences all number
    59
    23
    Psychiatric disorders
    anxiety
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    17 / 283 (6.01%)
    12 / 272 (4.41%)
         occurrences all number
    61
    35
    insomnia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    52 / 283 (18.37%)
    42 / 272 (15.44%)
         occurrences all number
    175
    126
    Investigations
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    21 / 283 (7.42%)
    11 / 272 (4.04%)
         occurrences all number
    84
    25
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    20 / 283 (7.07%)
    9 / 272 (3.31%)
         occurrences all number
    63
    18
    blood creatinine increased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    26 / 283 (9.19%)
    16 / 272 (5.88%)
         occurrences all number
    67
    32
    haemoglobin decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    48 / 283 (16.96%)
    43 / 272 (15.81%)
         occurrences all number
    218
    155
    neutrophil count decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    32 / 283 (11.31%)
    31 / 272 (11.40%)
         occurrences all number
    115
    76
    platelet count decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    24 / 283 (8.48%)
    33 / 272 (12.13%)
         occurrences all number
    74
    78
    weight decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    69 / 283 (24.38%)
    61 / 272 (22.43%)
         occurrences all number
    257
    204
    white blood cell count decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    47 / 283 (16.61%)
    43 / 272 (15.81%)
         occurrences all number
    212
    131
    Injury, poisoning and procedural complications
    radiation oesophagitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    16 / 283 (5.65%)
    18 / 272 (6.62%)
         occurrences all number
    50
    42
    radiation pneumonitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    22 / 283 (7.77%)
    16 / 272 (5.88%)
         occurrences all number
    52
    29
    radiation skin injury
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    45 / 283 (15.90%)
    37 / 272 (13.60%)
         occurrences all number
    159
    81
    Nervous system disorders
    dizziness
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    50 / 283 (17.67%)
    45 / 272 (16.54%)
         occurrences all number
    152
    96
    dysgeusia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    31 / 283 (10.95%)
    22 / 272 (8.09%)
         occurrences all number
    122
    60
    headache
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    36 / 283 (12.72%)
    34 / 272 (12.50%)
         occurrences all number
    92
    67
    neuropathy peripheral
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    14 / 283 (4.95%)
    25 / 272 (9.19%)
         occurrences all number
    35
    64
    peripheral sensory neuropathy
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    23 / 283 (8.13%)
    21 / 272 (7.72%)
         occurrences all number
    80
    61
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    88 / 283 (31.10%)
    94 / 272 (34.56%)
         occurrences all number
    336
    312
    leukopenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    63 / 283 (22.26%)
    71 / 272 (26.10%)
         occurrences all number
    267
    237
    lymphopenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    62 / 283 (21.91%)
    47 / 272 (17.28%)
         occurrences all number
    297
    170
    neutropenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    92 / 283 (32.51%)
    123 / 272 (45.22%)
         occurrences all number
    252
    359
    thrombocytopenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    39 / 283 (13.78%)
    53 / 272 (19.49%)
         occurrences all number
    116
    132
    Ear and labyrinth disorders
    tinnitus
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    15 / 283 (5.30%)
    8 / 272 (2.94%)
         occurrences all number
    40
    27
    Gastrointestinal disorders
    abdominal pain upper
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    35 / 283 (12.37%)
    8 / 272 (2.94%)
         occurrences all number
    94
    13
    constipation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    112 / 283 (39.58%)
    129 / 272 (47.43%)
         occurrences all number
    312
    284
    diarrhoea
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    55 / 283 (19.43%)
    63 / 272 (23.16%)
         occurrences all number
    88
    104
    dyspepsia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    43 / 283 (15.19%)
    37 / 272 (13.60%)
         occurrences all number
    148
    95
    dysphagia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    140 / 283 (49.47%)
    110 / 272 (40.44%)
         occurrences all number
    567
    317
    nausea
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    175 / 283 (61.84%)
    144 / 272 (52.94%)
         occurrences all number
    532
    365
    odynophagia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    24 / 283 (8.48%)
    23 / 272 (8.46%)
         occurrences all number
    103
    56
    oesophagitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    119 / 283 (42.05%)
    99 / 272 (36.40%)
         occurrences all number
    470
    253
    stomatitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    26 / 283 (9.19%)
    12 / 272 (4.41%)
         occurrences all number
    50
    23
    vomiting
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    110 / 283 (38.87%)
    95 / 272 (34.93%)
         occurrences all number
    244
    173
    Skin and subcutaneous tissue disorders
    alopecia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    24 / 283 (8.48%)
    103 / 272 (37.87%)
         occurrences all number
    110
    389
    dry skin
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    12 / 283 (4.24%)
    15 / 272 (5.51%)
         occurrences all number
    52
    43
    erythema
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    17 / 283 (6.01%)
    13 / 272 (4.78%)
         occurrences all number
    50
    29
    pruritus
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    18 / 283 (6.36%)
    11 / 272 (4.04%)
         occurrences all number
    55
    19
    rash
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    45 / 283 (15.90%)
    40 / 272 (14.71%)
         occurrences all number
    110
    93
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    13 / 283 (4.59%)
    17 / 272 (6.25%)
         occurrences all number
    33
    30
    back pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    26 / 283 (9.19%)
    21 / 272 (7.72%)
         occurrences all number
    94
    51
    myalgia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    15 / 283 (5.30%)
    11 / 272 (4.04%)
         occurrences all number
    41
    17
    pain in extremity
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    11 / 283 (3.89%)
    14 / 272 (5.15%)
         occurrences all number
    26
    30
    Infections and infestations
    pneumonia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    17 / 283 (6.01%)
    12 / 272 (4.41%)
         occurrences all number
    36
    21
    upper respiratory tract infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    15 / 283 (5.30%)
    11 / 272 (4.04%)
         occurrences all number
    29
    18
    Metabolism and nutrition disorders
    decreased appetite
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    104 / 283 (36.75%)
    88 / 272 (32.35%)
         occurrences all number
    366
    228
    dehydration
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    19 / 283 (6.71%)
    24 / 272 (8.82%)
         occurrences all number
    31
    38
    hyperglycaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    16 / 283 (5.65%)
    8 / 272 (2.94%)
         occurrences all number
    57
    25
    hypokalaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    20 / 283 (7.07%)
    32 / 272 (11.76%)
         occurrences all number
    43
    49
    hypomagnesaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    22 / 283 (7.77%)
    32 / 272 (11.76%)
         occurrences all number
    84
    84
    hyponatraemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    19 / 283 (6.71%)
    22 / 272 (8.09%)
         occurrences all number
    52
    55

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Jan 2009
    Amendment (a): Change to inclusion/exclusion criteria
    22 Jul 2009
    Amendment (b): Change to inclusion/exclusion criteria
    30 Jul 2010
    Amendment (c): Change to inclusion/exclusion criteria
    03 Oct 2011
    Amendment (e): Scientific values of the study

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    02 Sep 2012
    Enrollment was stopped for futility at a point when 598 (99.7%) participants targeted for accrual had been enrolled. The result of the futility analysis suggested that Arm A would not meet the primary endpoint of improvement in Overall Survival over Arm B. No new safety issues were identified during the study and participants who had been randomized and were on active treatment at the time of enrollment closure were allowed to continue with their assigned study therapy.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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