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    Clinical Trial Results:
    A Randomized, Multicenter, Open-Label, Phase 3 Study of Nivolumab plus Ipilimumab or Nivolumab in Combination with Oxaliplatin plus Fluoropyrimidine versus Oxaliplatin plus Fluoropyrimidine in Subjects with Previously Untreated Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

    Summary
    EudraCT number
    		 2016-001018-76
    Trial protocol
    		 ES   GR   PL   HU   DE   PT   FR   CZ   GB   IT  
    Global end of trial date
    06 Jun 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    22 Jun 2025
    First version publication date
    22 Jun 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CA209-649
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussée de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    Global Submission Management, Clinical Trials, Bristol-Myers Squibb International Corporation, mg-gsm-ct@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, mg-gsm-ct@bms.com
    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 Jun 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Jun 2024
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To compare OS in subjects with advanced or metastatic GC or GEJ cancer with PD-L1 CPS ≥ 5 To compare PFS, as assessed by BICR in subjects with advanced or metastatic GC or GEJ cancer with PD-L1 CPS ≥ 5
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    12 Oct 2016
    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
    Argentina: 93
    Country: Number of subjects enrolled
    Australia: 53
    Country: Number of subjects enrolled
    Brazil: 76
    Country: Number of subjects enrolled
    Canada: 81
    Country: Number of subjects enrolled
    Chile: 162
    Country: Number of subjects enrolled
    China: 273
    Country: Number of subjects enrolled
    Colombia: 37
    Country: Number of subjects enrolled
    Czechia: 24
    Country: Number of subjects enrolled
    France: 73
    Country: Number of subjects enrolled
    Germany: 97
    Country: Number of subjects enrolled
    Greece: 46
    Country: Number of subjects enrolled
    Hong Kong: 7
    Country: Number of subjects enrolled
    Hungary: 31
    Country: Number of subjects enrolled
    Israel: 35
    Country: Number of subjects enrolled
    Italy: 64
    Country: Number of subjects enrolled
    Japan: 151
    Country: Number of subjects enrolled
    Korea, Republic of: 22
    Country: Number of subjects enrolled
    Mexico: 35
    Country: Number of subjects enrolled
    Peru: 51
    Country: Number of subjects enrolled
    Poland: 74
    Country: Number of subjects enrolled
    Portugal: 24
    Country: Number of subjects enrolled
    Romania: 74
    Country: Number of subjects enrolled
    Russian Federation: 24
    Country: Number of subjects enrolled
    Singapore: 24
    Country: Number of subjects enrolled
    Spain: 48
    Country: Number of subjects enrolled
    Taiwan: 8
    Country: Number of subjects enrolled
    Türkiye: 37
    Country: Number of subjects enrolled
    United Kingdom: 45
    Country: Number of subjects enrolled
    United States: 262
    Worldwide total number of subjects
    2031
    EEA total number of subjects
    555
    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)
    1248
    From 65 to 84 years
    775
    85 years and over
    8

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 2031 Participants Randomized and 1991 Treated

    Period 1
    Period 1 title
    Pre-Treatment
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX)
    Arm description
    		 Nivolumab + Xelox: Nivolumab 360 mg IV over 30 minutes on Day 1 of each treatment cycle, every 3 weeks + Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks Nivolumab + Folfox: Nivolumab 240 mg IV over 30 minutes on Day 1 of each treatment cycle, every 2 weeks + Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg (10 mg/mL)

    Investigational medicinal product name
    Leucovorin (Folfox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg (50 mg/mL)

    Investigational medicinal product name
    Fluorouracil (Folfox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    2500 mg (50 mg/ mL)

    Investigational medicinal product name
    capecitabine (xelox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg and 500 mg tablets

    Investigational medicinal product name
    oxaliplatin (xelox and folfox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg (5 mg/mL)

    Arm title
    		 Arm 2: Chemotherapy (XELOX or FOLFOX)
    Arm description
    		 Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. This chemotherapy group consists of the two comparison chemotherapy sub-groups. Arm 2a (792 participants) is the comparison group to Arm 1 and Arm 2b (404 participants) is the comparison group to Arm 3. Some participants were counted in both Arm 2a and Arm 2b.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    oxaliplatin (xelox and folfox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg (5 mg/mL)

    Investigational medicinal product name
    Leucovorin (Folfox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg (50 mg/mL)

    Investigational medicinal product name
    Fluorouracil (Folfox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    2500 mg (50 mg/ mL)

    Investigational medicinal product name
    capecitabine (xelox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg and 500 mg tablets

    Arm title
    		 Arm 3: Nivolumab + Ipilimumab
    Arm description
    		 1 mg/kg nivolumab administered IV over 30 minutes followed by ipilimumab 3 mg/kg administered IV over 30 minutes on Day 1 of each treatment cycle every 3 weeks for 4 doses (Cycles 1 to 4), followed by nivolumab 240 mg administered IV over 30 minutes on Day 1 of each treatment cycle every 2 weeks (Cycle 5 and beyond). Arm is closed to enrollment as of 05-June-2018.
    Arm type
    		 Experimental

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg (10 mg/mL)

    Investigational medicinal product name
    ipilimumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 mg (5 mg/mL)

    Number of subjects in period 1
    		Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX) Arm 2: Chemotherapy (XELOX or FOLFOX) Arm 3: Nivolumab + Ipilimumab
    Started
    789
    833
    409
    Completed
    782
    806
    403
    Not completed
    7
    27
    6
         withdrew consent
    2
    20
    3
         request to discontinue study treatment
    -
    2
    -
         Adverse event unrelated to study drug
    -
    2
    1
         Other reasons
    1
    2
    2
         no longer meets study criteria
    4
    -
    -
         Disease Progression
    -
    1
    -
    Period 2
    Period 2 title
    Treatment
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX)
    Arm description
    		 Nivolumab + Xelox: Nivolumab 360 mg IV over 30 minutes on Day 1 of each treatment cycle, every 3 weeks + Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks Nivolumab + Folfox: Nivolumab 240 mg IV over 30 minutes on Day 1 of each treatment cycle, every 2 weeks + Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg (10 mg/mL)

    Investigational medicinal product name
    Leucovorin (Folfox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg (50 mg/mL)

    Investigational medicinal product name
    Fluorouracil (Folfox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    2500 mg (50 mg/ mL)

    Investigational medicinal product name
    capecitabine (xelox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg and 500 mg tablets

    Investigational medicinal product name
    oxaliplatin (xelox and folfox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg (5 mg/mL)

    Arm title
    		 Arm 2: Chemotherapy (XELOX or FOLFOX)
    Arm description
    		 Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. This chemotherapy group consists of the two comparison chemotherapy sub-groups. Arm 2a (792 participants) is the comparison group to Arm 1 and Arm 2b (404 participants) is the comparison group to Arm 3. Some participants were counted in both Arm 2a and Arm 2b.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Leucovorin (Folfox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg (50 mg/mL)

    Investigational medicinal product name
    Fluorouracil (Folfox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    2500 mg (50 mg/ mL)

    Investigational medicinal product name
    capecitabine (xelox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg and 500 mg tablets

    Investigational medicinal product name
    oxaliplatin (xelox and folfox)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg (5 mg/mL)

    Arm title
    		 Arm 3: Nivolumab + Ipilimumab
    Arm description
    		 1 mg/kg nivolumab administered IV over 30 minutes followed by ipilimumab 3 mg/kg administered IV over 30 minutes on Day 1 of each treatment cycle every 3 weeks for 4 doses (Cycles 1 to 4), followed by nivolumab 240 mg administered IV over 30 minutes on Day 1 of each treatment cycle every 2 weeks (Cycle 5 and beyond). Arm is closed to enrollment as of 05-June-2018.
    Arm type
    		 Experimental

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg (10 mg/mL)

    Investigational medicinal product name
    ipilimumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 mg (5 mg/mL)

    Number of subjects in period 2
    		Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX) Arm 2: Chemotherapy (XELOX or FOLFOX) Arm 3: Nivolumab + Ipilimumab
    Started
    782
    806
    403
    Completed
    623
    653
    319
    Not completed
    159
    153
    84
         Adverse event, serious fatal
    122
    94
    68
         Participant withdrew consent
    20
    40
    8
         Other reasons
    12
    12
    5
         Lost to follow-up
    5
    7
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX)
    Reporting group description
    		 Nivolumab + Xelox: Nivolumab 360 mg IV over 30 minutes on Day 1 of each treatment cycle, every 3 weeks + Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks Nivolumab + Folfox: Nivolumab 240 mg IV over 30 minutes on Day 1 of each treatment cycle, every 2 weeks + Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks

    Reporting group title
    Arm 2: Chemotherapy (XELOX or FOLFOX)
    Reporting group description
    		 Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. This chemotherapy group consists of the two comparison chemotherapy sub-groups. Arm 2a (792 participants) is the comparison group to Arm 1 and Arm 2b (404 participants) is the comparison group to Arm 3. Some participants were counted in both Arm 2a and Arm 2b.

    Reporting group title
    Arm 3: Nivolumab + Ipilimumab
    Reporting group description
    		 1 mg/kg nivolumab administered IV over 30 minutes followed by ipilimumab 3 mg/kg administered IV over 30 minutes on Day 1 of each treatment cycle every 3 weeks for 4 doses (Cycles 1 to 4), followed by nivolumab 240 mg administered IV over 30 minutes on Day 1 of each treatment cycle every 2 weeks (Cycle 5 and beyond). Arm is closed to enrollment as of 05-June-2018.

    Reporting group values
    		 Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX) Arm 2: Chemotherapy (XELOX or FOLFOX) Arm 3: Nivolumab + Ipilimumab Total
    Number of subjects
    		 789 833 409 2031
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 473 517 258 1248
        From 65-84 years
    		 314 310 151 775
        85 years and over
    		 2 6 0 8
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 60.3 ( 11.9 ) 59.8 ( 12.1 ) 59.4 ( 11.7 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 249 246 131 626
        Male
    		 540 587 278 1405
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 12 13 1 26
        Asian
    		 186 200 124 510
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        Black or African American
    		 7 11 6 24
        White
    		 556 570 264 1390
        More than one race
    		 0 0 0 0
        Unknown or Not Reported
    		 28 39 14 81

    End points

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    End points reporting groups
    Reporting group title
    Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX)
    Reporting group description
    		 Nivolumab + Xelox: Nivolumab 360 mg IV over 30 minutes on Day 1 of each treatment cycle, every 3 weeks + Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks Nivolumab + Folfox: Nivolumab 240 mg IV over 30 minutes on Day 1 of each treatment cycle, every 2 weeks + Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks

    Reporting group title
    Arm 2: Chemotherapy (XELOX or FOLFOX)
    Reporting group description
    		 Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. This chemotherapy group consists of the two comparison chemotherapy sub-groups. Arm 2a (792 participants) is the comparison group to Arm 1 and Arm 2b (404 participants) is the comparison group to Arm 3. Some participants were counted in both Arm 2a and Arm 2b.

    Reporting group title
    Arm 3: Nivolumab + Ipilimumab
    Reporting group description
    		 1 mg/kg nivolumab administered IV over 30 minutes followed by ipilimumab 3 mg/kg administered IV over 30 minutes on Day 1 of each treatment cycle every 3 weeks for 4 doses (Cycles 1 to 4), followed by nivolumab 240 mg administered IV over 30 minutes on Day 1 of each treatment cycle every 2 weeks (Cycle 5 and beyond). Arm is closed to enrollment as of 05-June-2018.
    Reporting group title
    Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX)
    Reporting group description
    		 Nivolumab + Xelox: Nivolumab 360 mg IV over 30 minutes on Day 1 of each treatment cycle, every 3 weeks + Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks Nivolumab + Folfox: Nivolumab 240 mg IV over 30 minutes on Day 1 of each treatment cycle, every 2 weeks + Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks

    Reporting group title
    Arm 2: Chemotherapy (XELOX or FOLFOX)
    Reporting group description
    		 Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. This chemotherapy group consists of the two comparison chemotherapy sub-groups. Arm 2a (792 participants) is the comparison group to Arm 1 and Arm 2b (404 participants) is the comparison group to Arm 3. Some participants were counted in both Arm 2a and Arm 2b.

    Reporting group title
    Arm 3: Nivolumab + Ipilimumab
    Reporting group description
    		 1 mg/kg nivolumab administered IV over 30 minutes followed by ipilimumab 3 mg/kg administered IV over 30 minutes on Day 1 of each treatment cycle every 3 weeks for 4 doses (Cycles 1 to 4), followed by nivolumab 240 mg administered IV over 30 minutes on Day 1 of each treatment cycle every 2 weeks (Cycle 5 and beyond). Arm is closed to enrollment as of 05-June-2018.

    Subject analysis set title
    Arm 2a: Chemotherapy (XELOX or FOLFOX)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. This arm is a subgroup of the chemotherapy group that acts as a comparison group to Arm 1.

    Subject analysis set title
    Arm 2b: Chemotherapy (XELOX or FOLFOX)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. Comparison group to Arm 3.

    Subject analysis set title
    Arm 2b: Chemotherapy (XELOX or FOLFOX)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. This arm is a subgroup of the chemotherapy group that acts as a comparison group to Arm 3.

    Subject analysis set title
    Arm 1: Nivo + Chem (PD-L1 CPS ≥ 5)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All Randomized Subjects with PD-L1 CPS ≥ 5

    Subject analysis set title
    Arm 2a: Chemo (PD-L1 CPS ≥ 5)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All Randomized Subjects with PD-L1 CPS ≥ 5

    Subject analysis set title
    Nivo + Chem (PD-L1 CPS ≥ 10)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All randomized subjects with PD-L1 CPS ≥ 10

    Subject analysis set title
    Nivo + Chem (PD-L1 CPS ≥ 1)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All Randomized Subjects with PD-L1 CPS ≥ 1

    Subject analysis set title
    Arm 2a: Chemotherapy (PD-L1 CPS ≥ 10)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All randomized subjects with PD-L1 CPS ≥ 10

    Subject analysis set title
    Arm 2a: Chemotherapy (PD-L1 CPS ≥ 1)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All randomized subjects with PD-L1 CPS ≥ 1

    Primary: Overall Survival (OS) in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS ≥ 5

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    End point title
    		 Overall Survival (OS) in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS ≥ 5
    End point description
    Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS (combined positive score) ≥ 5. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
    End point type
    Primary
    End point timeframe
    From the date of randomization up to the date of death, up to approximately 17 months
    End point values
    		 Arm 1: Nivo + Chem (PD-L1 CPS ≥ 5) Arm 2a: Chemo (PD-L1 CPS ≥ 5)
    Number of subjects analysed
    402
    441
    Units: Months
        median (confidence interval 95%)
    14.39 (13.11 to 16.23)
    11.14 (10.05 to 12.12)
    Statistical analysis title
    		 OS for PD-L1 CPS ≥ 5
    Comparison groups
    Arm 1: Nivo + Chem (PD-L1 CPS ≥ 5) v Arm 2a: Chemo (PD-L1 CPS ≥ 5)
    Number of subjects included in analysis
    843
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 0.81

    Primary: Progression Free Survival (PFS) in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS ≥ 5

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    End point title
    		 Progression Free Survival (PFS) in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS ≥ 5
    End point description
    Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented PD or death due to any cause. PD is determined by blinded independent committee review (BICR) per RECIST1.1 criteria in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS ≥ 5. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
    End point type
    Primary
    End point timeframe
    From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 10 months)
    End point values
    		 Arm 1: Nivo + Chem (PD-L1 CPS ≥ 5) Arm 2a: Chemo (PD-L1 CPS ≥ 5)
    Number of subjects analysed
    366
    376
    Units: Months
        median (confidence interval 95%)
    8.31 (7.03 to 9.40)
    6.14 (5.55 to 6.93)
    Statistical analysis title
    		 PFS for PD-L1 CPS ≥ 5
    Comparison groups
    Arm 1: Nivo + Chem (PD-L1 CPS ≥ 5) v Arm 2a: Chemo (PD-L1 CPS ≥ 5)
    Number of subjects included in analysis
    742
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 0.82

    Secondary: OS in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy

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    End point title
    		 OS in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy [1]
    End point description
    Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS ≥ 1, 10, and all randomized participants. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
    End point type
    Secondary
    End point timeframe
    From the date of randomization up to the date of death, up to approximately 17 months
    Notes
    [1] - 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: No further statistical analysis done at this time
    End point values
    		 Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX) Arm 2a: Chemotherapy (XELOX or FOLFOX) Nivo + Chem (PD-L1 CPS ≥ 10) Nivo + Chem (PD-L1 CPS ≥ 1) Arm 2a: Chemotherapy (PD-L1 CPS ≥ 10) Arm 2a: Chemotherapy (PD-L1 CPS ≥ 1)
    Number of subjects analysed
    697
    727
    316
    561
    355
    607
    Units: Months
    median (confidence interval 95%)
        All Randomized
    13.73 (12.42 to 14.49)
    11.63 (10.94 to 12.52)
    15.01 (13.63 to 16.66)
    13.80 (12.42 to 14.82)
    10.94 (9.89 to 11.96)
    11.37 (10.74 to 12.25)
    No statistical analyses for this end point

    Secondary: PFS in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy

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    End point title
    		 PFS in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy [2]
    End point description
    Progression free survival (PFS), defined as the time from randomization to the date of the first documented progressive disease (PD) or death due to any cause, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy by BICR per RECIST1.1 in participants with PD-L1 CPS ≥ 10, 1, or all randomized subjects. Progreessive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
    End point type
    Secondary
    End point timeframe
    From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 10 months)
    Notes
    [2] - 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: No further statistical analysis done at this time
    End point values
    		 Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX) Arm 2a: Chemotherapy (XELOX or FOLFOX) Nivo + Chem (PD-L1 CPS ≥ 10) Nivo + Chem (PD-L1 CPS ≥ 1) Arm 2a: Chemotherapy (PD-L1 CPS ≥ 10) Arm 2a: Chemotherapy (PD-L1 CPS ≥ 1)
    Number of subjects analysed
    614
    598
    285
    506
    307
    510
    Units: Months
    median (confidence interval 95%)
        All Randomized
    7.75 (7.10 to 8.57)
    6.93 (6.67 to 7.16)
    8.41 (7.00 to 9.79)
    7.52 (7.03 to 8.51)
    5.82 (5.45 to 6.90)
    6.93 (6.21 to 7.06)
    No statistical analyses for this end point

    Secondary: Objective Response Rate in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy

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    End point title
    		 Objective Response Rate in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy [3]
    End point description
    Objective response rate (ORR) as assessed by BICR in participants with PD-L1 CPS ≥ 10, 5, 1, or all randomized participants. ORR is a percentage of participants determined by the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of measurable participants with target lesion at baseline. BOR is defined as the best response designation as determined by the BICR, recorded between the date of randomization and the date of objectively documented progression (per RECIST 1.1 as determined by the BICR) or the date of subsequent anti-cancer therapy, whichever occurs first. CR is defined as the disappearance of all target lesions. PR is define as at 30% decrease in the sum of diameters of target lesions. The 806 chemotherapy treated participants are split into two separate arms (Arm 2a and Arm 2b) to act as comparison groups to the other treatment arms.
    End point type
    Secondary
    End point timeframe
    From randomization to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (up to approximately 43 months)
    Notes
    [3] - 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: No further statistical analysis done at this time
    End point values
    		 Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX) Arm 2a: Chemotherapy (XELOX or FOLFOX) Arm 1: Nivo + Chem (PD-L1 CPS ≥ 5) Arm 2a: Chemo (PD-L1 CPS ≥ 5) Nivo + Chem (PD-L1 CPS ≥ 10) Nivo + Chem (PD-L1 CPS ≥ 1) Arm 2a: Chemotherapy (PD-L1 CPS ≥ 10) Arm 2a: Chemotherapy (PD-L1 CPS ≥ 1)
    Number of subjects analysed
    789
    792
    473
    482
    375
    641
    393
    656
    Units: Percentage of Participants
    number (confidence interval 95%)
        All randomized participants
    46.9 (43.4 to 50.4)
    46.9 (43.4 to 50.4)
    50.1 (45.5 to 54.7)
    38.2 (33.8 to 42.7)
    48.8 (43.6 to 54.0)
    48.8 (44.9 to 52.8)
    37.7 (32.9 to 42.7)
    38.0 (34.2 to 41.8)
    No statistical analyses for this end point

    Secondary: Time to Symptom Deterioration (TTSD) in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy

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    End point title
    		 Time to Symptom Deterioration (TTSD) in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy [4]
    End point description
    TTSD is defined as the the time from randomization until a clinically meaningful decline from baseline in Gastric Cancer Subscale (GaCS) score. A clinically meaningful deterioration is defined as a reduction of 8.2 points in the GaCS score. Subjects who do not deteriorate will be censored at the time of their last GACS assessment. Subjects without baseline GaCS assessment will be censored on the randomization date. Those with baseline GaCS, who do not have any GaCS assessments after randomization will be censored on the day after randomization. Here "99999" means NA
    End point type
    Secondary
    End point timeframe
    From randomization until a clinically meaningful decline from baseline in GaCS score
    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: No further statistical analysis done at this time
    End point values
    		 Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX)
    Number of subjects analysed
    194
    Units: Months
        median (confidence interval 95%)
    99999 (22.64 to 99999)
    No statistical analyses for this end point

    Secondary: OS in participants treated with Nivolumab plus Ipilimumab vs Chemotherapy

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    End point title
    		 OS in participants treated with Nivolumab plus Ipilimumab vs Chemotherapy [5]
    End point description
    Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Ipilimumab vs Chemotherapy with PD-L1 CPS (combined positive score) ≥ 1, 5, 10, and all randomized participants. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
    End point type
    Secondary
    End point timeframe
    From the date of randomization up to the date of death, up to approximately 14 months
    Notes
    [5] - 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: No further statistical analysis done at this time
    End point values
    		 Arm 3: Nivolumab + Ipilimumab Arm 2b: Chemotherapy (XELOX or FOLFOX)
    Number of subjects analysed
    409
    404
    Units: Months
    median (confidence interval 95%)
        All randomized participants
    11.73 (9.56 to 13.54)
    11.83 (10.97 to 12.71)
        Participants with CPS ≥ 1
    11.73 (9.49 to 13.54)
    11.47 (10.48 to 12.65)
        Participants with CPS ≥ 5
    11.24 (9.17 to 13.40)
    11.63 (10.05 to 12.71)
        Participants with CPS ≥ 10
    11.63 (9.26 to 13.54)
    11.33 (9.92 to 12.65)
    No statistical analyses for this end point

    Secondary: PFS in participants treated with Nivolumab plus Ipilimumab vs Chemotherapy

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    End point title
    		 PFS in participants treated with Nivolumab plus Ipilimumab vs Chemotherapy [6]
    End point description
    Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented PD or death due to any cause. PD is determined by blinded independent committee review (BICR) per RECIST1.1 criteria in participants treated with Nivolumab plus Ipilumab vs Chemotherapy with PD-L1 CPS ≥ 10, 5, 1 or all randomized participants. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
    End point type
    Secondary
    End point timeframe
    From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 9 months)
    Notes
    [6] - 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: No further statistical analysis done at this time
    End point values
    		 Arm 3: Nivolumab + Ipilimumab Arm 2b: Chemotherapy (XELOX or FOLFOX)
    Number of subjects analysed
    409
    404
    Units: Months
    median (confidence interval 95%)
        All randomized participants
    2.83 (2.63 to 3.58)
    7.06 (6.87 to 8.21)
        PD-L1 CPS ≥ 1
    2.79 (2.60 to 3.91)
    6.93 (5.98 to 7.26)
        PD-L1 CPS ≥ 5
    2.83 (2.60 to 4.04)
    6.28 (5.59 to 7.06)
        PD-L1 CPS ≥ 10
    2.89 (2.63 to 4.24)
    6.28 (5.52 to 7.13)
    No statistical analyses for this end point

    Secondary: Objective Response Rate in participants treated with Nivolumab plus Ipilimumab vs Chemotherapy

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    End point title
    		 Objective Response Rate in participants treated with Nivolumab plus Ipilimumab vs Chemotherapy [7]
    End point description
    Objective response rate (ORR) as assessed by BICR in participants with PD-L1 CPS ≥ 10, 5, 1, or all randomized participants. ORR is a percentage of participants determined by the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of measurable participants with target lesion at baseline. BOR is defined as the best response designation as determined by the BICR, recorded between the date of randomization and the date of objectively documented progression (per RECIST 1.1 as determined by the BICR) or the date of subsequent anti-cancer therapy, whichever occurs first. CR is defined as the disappearance of all target lesions. PR is define as at 30% decrease in the sum of diameters of target lesions. The 806 chemotherapy treated participants are split into two separate arms (Arm 2a and Arm 2b) to act as comparison groups to the other treatment arms.
    End point type
    Secondary
    End point timeframe
    From randomization to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (up to approximately 43 months)
    Notes
    [7] - 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: No further statistical analysis done at this time
    End point values
    		 Arm 3: Nivolumab + Ipilimumab Arm 2b: Chemotherapy (XELOX or FOLFOX)
    Number of subjects analysed
    409
    404
    Units: Percentage of Participants
    number (confidence interval 95%)
        Participants with CPS ≥ 1
    21.7 (17.4 to 26.6)
    37.3 (32.0 to 42.9)
        Participants with CPS ≥ 5
    23.1 (17.8 to 29.0)
    37.7 (31.5 to 44.1)
        Participants with CPS ≥ 10
    24.3 (18.3 to 31.2)
    35.9 (29.2 to 43.0)
        All randomized participants
    20.8 (17.0 to 25.0)
    34.9 (30.3 to 39.8)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All-cause mortality: from date of randomization to study completion (up to approximately 5 years). Serious Adverse events and other adverse events: from date of first dose to 100 days post last dose (up to approximately 5 years).
    Adverse event reporting additional description
    The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX)
    Reporting group description
    		 Nivolumab + Xelox: Nivolumab 360 mg IV over 30 minutes on Day 1 of each treatment cycle, every 3 weeks + Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks Nivolumab + Folfox: Nivolumab 240 mg IV over 30 minutes on Day 1 of each treatment cycle, every 2 weeks + Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks

    Reporting group title
    Arm 3: Nivolumab + Ipilimumab
    Reporting group description
    		 1 mg/kg nivolumab administered IV over 30 minutes followed by ipilimumab 3 mg/kg administered IV over 30 minutes on Day 1 of each treatment cycle every 3 weeks for 4 doses (Cycles 1 to 4), followed by nivolumab 240 mg administered IV over 30 minutes on Day 1 of each treatment cycle every 2 weeks (Cycle 5 and beyond). Arm is closed to enrollment as of 05-June-2018.

    Reporting group title
    Arm 2: Chemotherapy (XELOX or FOLFOX)
    Reporting group description
    		 Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. This chemotherapy group consists of the two comparison chemotherapy sub-groups. Arm 2a (792 participants) is the comparison group to Arm 1 and Arm 2b (404 participants) is the comparison group to Arm 3. Some participants were counted in both Arm 2a and Arm 2b.

    Serious adverse events
    		 Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX) Arm 3: Nivolumab + Ipilimumab Arm 2: Chemotherapy (XELOX or FOLFOX)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    529 / 782 (67.65%)
    307 / 403 (76.18%)
    474 / 806 (58.81%)
         number of deaths (all causes)
    691
    361
    741
         number of deaths resulting from adverse events
    301
    133
    286
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastatic gastric cancer
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastasis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to meninges
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Metastases to liver
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    3 / 782 (0.38%)
    0 / 403 (0.00%)
    4 / 806 (0.50%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    248 / 782 (31.71%)
    112 / 403 (27.79%)
    246 / 806 (30.52%)
         occurrences causally related to treatment / all
    1 / 262
    0 / 114
    0 / 250
         deaths causally related to treatment / all
    1 / 238
    0 / 97
    0 / 232
    Laryngeal squamous cell carcinoma
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric neoplasm
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    2 / 782 (0.26%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cancer pain
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    2 / 782 (0.26%)
    2 / 403 (0.50%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neoplasm malignant
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Neoplasm progression
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal adenocarcinoma
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Oesophageal cancer metastatic
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Second primary malignancy
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour associated fever
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    3 / 782 (0.38%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour necrosis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour obstruction
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour ulceration
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Obstructive shock
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Axillary vein thrombosis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Capillary leak syndrome
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Deep vein thrombosis
         subjects affected / exposed
    2 / 782 (0.26%)
    3 / 403 (0.74%)
    3 / 806 (0.37%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    6 / 782 (0.77%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Jugular vein thrombosis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral venous disease
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Shock haemorrhagic
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Subclavian artery stenosis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic venous thrombosis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Euthanasia
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 782 (0.13%)
    3 / 403 (0.74%)
    5 / 806 (0.62%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 3
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Malaise
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    3 / 806 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inflammation
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Catheter site haemorrhage
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Complication associated with device
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 782 (0.13%)
    2 / 403 (0.50%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    Disease progression
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Effusion
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Face oedema
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    3 / 782 (0.38%)
    6 / 403 (1.49%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    3 / 3
    2 / 6
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Gait disturbance
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    5 / 782 (0.64%)
    3 / 403 (0.74%)
    7 / 806 (0.87%)
         occurrences causally related to treatment / all
    0 / 5
    1 / 3
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Generalised oedema
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Catheter site extravasation
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ulcer haemorrhage
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    2 / 782 (0.26%)
    2 / 403 (0.50%)
    3 / 806 (0.37%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    0 / 3
    Pyrexia
         subjects affected / exposed
    22 / 782 (2.81%)
    9 / 403 (2.23%)
    11 / 806 (1.36%)
         occurrences causally related to treatment / all
    8 / 24
    11 / 13
    3 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral swelling
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Performance status decreased
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    3 / 782 (0.38%)
    0 / 403 (0.00%)
    4 / 806 (0.50%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    3 / 782 (0.38%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    2 / 782 (0.26%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    1 / 2
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    4 / 782 (0.51%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    3 / 4
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Contrast media allergy
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaphylactic reaction
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Malignant pleural effusion
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laryngeal haemorrhage
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    3 / 782 (0.38%)
    2 / 403 (0.50%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    4 / 4
    2 / 2
    2 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    Immune-mediated lung disease
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hiccups
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mediastinal effusion
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Bronchospasm
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asphyxia
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    Dyspnoea
         subjects affected / exposed
    0 / 782 (0.00%)
    2 / 403 (0.50%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    14 / 782 (1.79%)
    10 / 403 (2.48%)
    18 / 806 (2.23%)
         occurrences causally related to treatment / all
    1 / 14
    1 / 10
    2 / 19
         deaths causally related to treatment / all
    0 / 5
    0 / 3
    1 / 2
    Pulmonary hypertension
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    5 / 782 (0.64%)
    2 / 403 (0.50%)
    3 / 806 (0.37%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 3
    0 / 2
    0 / 1
    Restrictive pulmonary disease
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oropharyngeal discomfort
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    5 / 782 (0.64%)
    6 / 403 (1.49%)
    6 / 806 (0.74%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Pneumonitis
         subjects affected / exposed
    19 / 782 (2.43%)
    7 / 403 (1.74%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    22 / 22
    9 / 9
    0 / 1
         deaths causally related to treatment / all
    4 / 4
    1 / 1
    0 / 0
    Pneumothorax
         subjects affected / exposed
    3 / 782 (0.38%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pulmonary artery thrombosis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis aspiration
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicide attempt
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Mental status changes
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Eating disorder
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bipolar disorder
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Stent malfunction
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device occlusion
         subjects affected / exposed
    3 / 782 (0.38%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device leakage
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device dislocation
         subjects affected / exposed
    3 / 782 (0.38%)
    2 / 403 (0.50%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device breakage
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Autoimmune hepatitis
         subjects affected / exposed
    0 / 782 (0.00%)
    6 / 403 (1.49%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    6 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Bile duct stone
         subjects affected / exposed
    3 / 782 (0.38%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bile duct stenosis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute hepatic failure
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Hepatitis acute
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    1 / 782 (0.13%)
    5 / 403 (1.24%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    6 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    3 / 782 (0.38%)
    5 / 403 (1.24%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    3 / 4
    4 / 5
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Hepatic failure
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Hepatic cyst ruptured
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    1 / 782 (0.13%)
    3 / 403 (0.74%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    5 / 782 (0.64%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholangitis acute
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    3 / 782 (0.38%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Biliary obstruction
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis toxic
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Portal hypertension
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Liver injury
         subjects affected / exposed
    0 / 782 (0.00%)
    3 / 403 (0.74%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    7 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Liver disorder
         subjects affected / exposed
    2 / 782 (0.26%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatorenal failure
         subjects affected / exposed
    0 / 782 (0.00%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    Jaundice
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated hepatitis
         subjects affected / exposed
    3 / 782 (0.38%)
    3 / 403 (0.74%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated hepatic disorder
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 782 (0.00%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    6 / 782 (0.77%)
    2 / 403 (0.50%)
    4 / 806 (0.50%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Suspected drug-induced liver injury
         subjects affected / exposed
    0 / 782 (0.00%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Biliary cyst
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Lipase increased
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 782 (0.13%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Amylase increased
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    6 / 782 (0.77%)
    2 / 403 (0.50%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood corticotrophin decreased
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    0 / 782 (0.00%)
    2 / 403 (0.50%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram ST segment elevation
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical condition abnormal
         subjects affected / exposed
    2 / 782 (0.26%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis C virus test positive
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Liver function test increased
         subjects affected / exposed
    0 / 782 (0.00%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    3 / 782 (0.38%)
    0 / 403 (0.00%)
    3 / 806 (0.37%)
         occurrences causally related to treatment / all
    5 / 5
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    3 / 782 (0.38%)
    1 / 403 (0.25%)
    4 / 806 (0.50%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 1
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Anastomotic stenosis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal stoma complication
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    3 / 782 (0.38%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis radiation
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Procedural complication
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Soft tissue injury
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Heat stroke
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    3 / 782 (0.38%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    6 / 782 (0.77%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    7 / 7
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    11 / 782 (1.41%)
    0 / 403 (0.00%)
    6 / 806 (0.74%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 0
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Synovial rupture
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular access malfunction
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Afferent loop syndrome
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Microvillous inclusion disease
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyloric stenosis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Tracheo-oesophageal fistula
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    4 / 782 (0.51%)
    1 / 403 (0.25%)
    4 / 806 (0.50%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    Angina pectoris
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Atrial fibrillation
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    2 / 782 (0.26%)
    1 / 403 (0.25%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    Autoimmune myocarditis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    2 / 782 (0.26%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    Cardiac failure
         subjects affected / exposed
    0 / 782 (0.00%)
    2 / 403 (0.50%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    2 / 2
    0 / 1
    Cardiac failure acute
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Cardiac failure congestive
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    2 / 782 (0.26%)
    3 / 403 (0.74%)
    5 / 806 (0.62%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 5
    Pericardial effusion
         subjects affected / exposed
    3 / 782 (0.38%)
    1 / 403 (0.25%)
    3 / 806 (0.37%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Supraventricular extrasystoles
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachyarrhythmia
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial injury
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Epilepsy
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalitis autoimmune
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic hyperosmolar coma
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aphasia
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    2 / 782 (0.26%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    Cerebellar syndrome
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Central nervous system lesion
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain stem infarction
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    3 / 782 (0.38%)
    1 / 403 (0.25%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    Seizure
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuritis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Facial paresis
         subjects affected / exposed
    0 / 782 (0.00%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intracranial pressure increased
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Immune-mediated neuropathy
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokinesia
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Guillain-Barre syndrome
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Transient ischaemic attack
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    9 / 782 (1.15%)
    2 / 403 (0.50%)
    4 / 806 (0.50%)
         occurrences causally related to treatment / all
    1 / 9
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    2 / 782 (0.26%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Embolic stroke
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    28 / 782 (3.58%)
    13 / 403 (3.23%)
    17 / 806 (2.11%)
         occurrences causally related to treatment / all
    13 / 33
    1 / 16
    4 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood loss anaemia
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    20 / 782 (2.56%)
    1 / 403 (0.25%)
    10 / 806 (1.24%)
         occurrences causally related to treatment / all
    17 / 21
    0 / 1
    6 / 10
         deaths causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Febrile bone marrow aplasia
         subjects affected / exposed
    2 / 782 (0.26%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone marrow failure
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune thrombocytopenia
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombotic microangiopathy
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Neutropenia
         subjects affected / exposed
    4 / 782 (0.51%)
    0 / 403 (0.00%)
    3 / 806 (0.37%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Splenic haematoma
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    4 / 782 (0.51%)
    2 / 403 (0.50%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    3 / 4
    1 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Myelosuppression
         subjects affected / exposed
    4 / 782 (0.51%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    3 / 4
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ocular vasculitis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Visual impairment
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal adhesions
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal distension
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    6 / 782 (0.77%)
    11 / 403 (2.73%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    6 / 6
    15 / 15
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    3 / 782 (0.38%)
    2 / 403 (0.50%)
    3 / 806 (0.37%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cyclic vomiting syndrome
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    21 / 782 (2.69%)
    13 / 403 (3.23%)
    14 / 806 (1.74%)
         occurrences causally related to treatment / all
    17 / 22
    10 / 15
    13 / 16
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal obstruction
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Autoimmune colitis
         subjects affected / exposed
    2 / 782 (0.26%)
    3 / 403 (0.74%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    0 / 782 (0.00%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    13 / 782 (1.66%)
    9 / 403 (2.23%)
    23 / 806 (2.85%)
         occurrences causally related to treatment / all
    0 / 15
    1 / 12
    0 / 24
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Abdominal pain
         subjects affected / exposed
    12 / 782 (1.53%)
    4 / 403 (0.99%)
    13 / 806 (1.61%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 4
    1 / 14
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    2 / 782 (0.26%)
    2 / 403 (0.50%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    15 / 782 (1.92%)
    6 / 403 (1.49%)
    9 / 806 (1.12%)
         occurrences causally related to treatment / all
    1 / 16
    0 / 6
    0 / 10
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    Duodenal perforation
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 782 (0.13%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    4 / 782 (0.51%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    4 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    3 / 782 (0.38%)
    4 / 403 (0.99%)
    11 / 806 (1.36%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 5
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    Gastric perforation
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    3 / 806 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric stenosis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal fistula
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    13 / 782 (1.66%)
    4 / 403 (0.99%)
    9 / 806 (1.12%)
         occurrences causally related to treatment / all
    2 / 14
    0 / 4
    2 / 10
         deaths causally related to treatment / all
    1 / 3
    0 / 1
    0 / 0
    Gastrointestinal inflammation
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Gastrointestinal necrosis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal obstruction
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal perforation
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal stenosis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Intestinal stenosis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Intestinal obstruction
         subjects affected / exposed
    3 / 782 (0.38%)
    2 / 403 (0.50%)
    7 / 806 (0.87%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated enterocolitis
         subjects affected / exposed
    1 / 782 (0.13%)
    11 / 403 (2.73%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    13 / 13
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Large intestinal haemorrhage
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Ileus
         subjects affected / exposed
    4 / 782 (0.51%)
    1 / 403 (0.25%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoperitoneum
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 782 (0.00%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestinal stenosis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malabsorption
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant gastrointestinal obstruction
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    8 / 782 (1.02%)
    7 / 403 (1.74%)
    10 / 806 (1.24%)
         occurrences causally related to treatment / all
    7 / 11
    1 / 7
    8 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    4 / 782 (0.51%)
    6 / 403 (1.49%)
    6 / 806 (0.74%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Obstructive pancreatitis
         subjects affected / exposed
    0 / 782 (0.00%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal compression
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal fistula
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal haemorrhage
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal obstruction
         subjects affected / exposed
    4 / 782 (0.51%)
    4 / 403 (0.99%)
    3 / 806 (0.37%)
         occurrences causally related to treatment / all
    0 / 5
    1 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal pain
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal stenosis
         subjects affected / exposed
    3 / 782 (0.38%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal ulcer haemorrhage
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    29 / 782 (3.71%)
    11 / 403 (2.73%)
    23 / 806 (2.85%)
         occurrences causally related to treatment / all
    14 / 36
    0 / 13
    20 / 28
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    17 / 782 (2.17%)
    13 / 403 (3.23%)
    10 / 806 (1.24%)
         occurrences causally related to treatment / all
    1 / 20
    3 / 15
    2 / 10
         deaths causally related to treatment / all
    0 / 2
    1 / 3
    0 / 0
    Thrombosis mesenteric vessel
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
    Subileus
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    4 / 782 (0.51%)
    0 / 403 (0.00%)
    5 / 806 (0.62%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Retroperitoneal haematoma
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prepyloric stenosis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Peritoneal adhesions
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 782 (0.13%)
    3 / 403 (0.74%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant ascites
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug eruption
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eczema asteatotic
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    2 / 782 (0.26%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic skin ulcer
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin lesion
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Toxic epidermal necrolysis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 782 (0.00%)
    3 / 403 (0.74%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pemphigoid
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    6 / 782 (0.77%)
    9 / 403 (2.23%)
    4 / 806 (0.50%)
         occurrences causally related to treatment / all
    1 / 6
    4 / 10
    1 / 5
         deaths causally related to treatment / all
    0 / 4
    0 / 1
    0 / 0
    Cystitis noninfective
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 782 (0.00%)
    2 / 403 (0.50%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ureteric dilatation
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    3 / 806 (0.37%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Prerenal failure
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephritis
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Hypophysitis
         subjects affected / exposed
    1 / 782 (0.13%)
    4 / 403 (0.99%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Adrenal insufficiency
         subjects affected / exposed
    3 / 782 (0.38%)
    4 / 403 (0.99%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    3 / 3
    3 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Autoimmune thyroiditis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypopituitarism
         subjects affected / exposed
    3 / 782 (0.38%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypothalamo-pituitary disorder
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated hypophysitis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Secondary adrenocortical insufficiency
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thyroiditis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    4 / 782 (0.51%)
    1 / 403 (0.25%)
    4 / 806 (0.50%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone lesion
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fistula
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mixed connective tissue disease
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    0 / 782 (0.00%)
    3 / 403 (0.74%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteolysis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Bronchitis viral
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Biliary tract infection
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    4 / 782 (0.51%)
    3 / 403 (0.74%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Amoebic colitis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal sepsis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal infection
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal abscess
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 782 (0.13%)
    2 / 403 (0.50%)
    3 / 806 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chorioretinitis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    2 / 782 (0.26%)
    1 / 403 (0.25%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Diarrhoea infectious
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endophthalmitis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enteritis infectious
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Giardiasis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis C
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes simplex reactivation
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Lung abscess
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    2 / 782 (0.26%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestine infection
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 782 (0.13%)
    2 / 403 (0.50%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Herpes virus infection
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphangitis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mycobacterium avium complex infection
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenic infection
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal candidiasis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Peritonitis
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis bacterial
         subjects affected / exposed
    2 / 782 (0.26%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    30 / 782 (3.84%)
    14 / 403 (3.47%)
    21 / 806 (2.61%)
         occurrences causally related to treatment / all
    6 / 35
    0 / 15
    2 / 21
         deaths causally related to treatment / all
    1 / 7
    0 / 2
    0 / 4
    Pneumonia bacterial
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia klebsiella
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tuberculous pleurisy
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    12 / 782 (1.53%)
    3 / 403 (0.74%)
    8 / 806 (0.99%)
         occurrences causally related to treatment / all
    1 / 12
    1 / 3
    0 / 8
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    0 / 2
    Septic shock
         subjects affected / exposed
    1 / 782 (0.13%)
    2 / 403 (0.50%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 2
    0 / 1
    Sialoadenitis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 782 (0.00%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stoma site infection
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Streptococcal bacteraemia
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psoas abscess
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 782 (0.38%)
    6 / 403 (1.49%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular device infection
         subjects affected / exposed
    3 / 782 (0.38%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    3 / 782 (0.38%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Haematological infection
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spontaneous bacterial peritonitis
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Failure to thrive
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    8 / 782 (1.02%)
    3 / 403 (0.74%)
    7 / 806 (0.87%)
         occurrences causally related to treatment / all
    3 / 9
    0 / 3
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Electrolyte imbalance
         subjects affected / exposed
    2 / 782 (0.26%)
    1 / 403 (0.25%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Decreased appetite
         subjects affected / exposed
    7 / 782 (0.90%)
    6 / 403 (1.49%)
    9 / 806 (1.12%)
         occurrences causally related to treatment / all
    5 / 10
    2 / 6
    10 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Gout
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 782 (0.00%)
    2 / 403 (0.50%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Hypernatraemia
         subjects affected / exposed
    1 / 782 (0.13%)
    0 / 403 (0.00%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 782 (0.13%)
    3 / 403 (0.74%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 782 (0.13%)
    2 / 403 (0.50%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    3 / 782 (0.38%)
    2 / 403 (0.50%)
    5 / 806 (0.62%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 2
    4 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    4 / 782 (0.51%)
    3 / 403 (0.74%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypophagia
         subjects affected / exposed
    0 / 782 (0.00%)
    0 / 403 (0.00%)
    1 / 806 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoproteinaemia
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    2 / 806 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Metabolic acidosis
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Type 1 diabetes mellitus
         subjects affected / exposed
    0 / 782 (0.00%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 782 (0.13%)
    1 / 403 (0.25%)
    0 / 806 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX) Arm 3: Nivolumab + Ipilimumab Arm 2: Chemotherapy (XELOX or FOLFOX)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    763 / 782 (97.57%)
    369 / 403 (91.56%)
    756 / 806 (93.80%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    26 / 782 (3.32%)
    21 / 403 (5.21%)
    21 / 806 (2.61%)
         occurrences all number
    31
    29
    24
    Hypertension
         subjects affected / exposed
    48 / 782 (6.14%)
    17 / 403 (4.22%)
    42 / 806 (5.21%)
         occurrences all number
    66
    25
    61
    General disorders and administration site conditions
    Malaise
         subjects affected / exposed
    40 / 782 (5.12%)
    19 / 403 (4.71%)
    41 / 806 (5.09%)
         occurrences all number
    54
    23
    47
    Mucosal inflammation
         subjects affected / exposed
    77 / 782 (9.85%)
    7 / 403 (1.74%)
    47 / 806 (5.83%)
         occurrences all number
    127
    10
    64
    Oedema peripheral
         subjects affected / exposed
    93 / 782 (11.89%)
    44 / 403 (10.92%)
    67 / 806 (8.31%)
         occurrences all number
    122
    46
    70
    Pyrexia
         subjects affected / exposed
    143 / 782 (18.29%)
    93 / 403 (23.08%)
    95 / 806 (11.79%)
         occurrences all number
    219
    129
    127
    Fatigue
         subjects affected / exposed
    273 / 782 (34.91%)
    103 / 403 (25.56%)
    235 / 806 (29.16%)
         occurrences all number
    403
    129
    341
    Asthenia
         subjects affected / exposed
    119 / 782 (15.22%)
    48 / 403 (11.91%)
    130 / 806 (16.13%)
         occurrences all number
    169
    56
    192
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    48 / 782 (6.14%)
    4 / 403 (0.99%)
    13 / 806 (1.61%)
         occurrences all number
    57
    4
    15
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    102 / 782 (13.04%)
    51 / 403 (12.66%)
    64 / 806 (7.94%)
         occurrences all number
    138
    64
    76
    Dyspnoea
         subjects affected / exposed
    66 / 782 (8.44%)
    37 / 403 (9.18%)
    49 / 806 (6.08%)
         occurrences all number
    82
    50
    53
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    61 / 782 (7.80%)
    36 / 403 (8.93%)
    69 / 806 (8.56%)
         occurrences all number
    65
    38
    74
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    120 / 782 (15.35%)
    76 / 403 (18.86%)
    88 / 806 (10.92%)
         occurrences all number
    177
    94
    128
    Amylase increased
         subjects affected / exposed
    91 / 782 (11.64%)
    48 / 403 (11.91%)
    45 / 806 (5.58%)
         occurrences all number
    133
    62
    56
    Aspartate aminotransferase increased
         subjects affected / exposed
    165 / 782 (21.10%)
    81 / 403 (20.10%)
    115 / 806 (14.27%)
         occurrences all number
    282
    103
    176
    Blood bilirubin increased
         subjects affected / exposed
    83 / 782 (10.61%)
    30 / 403 (7.44%)
    62 / 806 (7.69%)
         occurrences all number
    169
    32
    96
    Blood alkaline phosphatase increased
         subjects affected / exposed
    107 / 782 (13.68%)
    47 / 403 (11.66%)
    69 / 806 (8.56%)
         occurrences all number
    144
    58
    109
    Blood creatinine increased
         subjects affected / exposed
    42 / 782 (5.37%)
    35 / 403 (8.68%)
    22 / 806 (2.73%)
         occurrences all number
    65
    53
    36
    Lipase increased
         subjects affected / exposed
    107 / 782 (13.68%)
    52 / 403 (12.90%)
    72 / 806 (8.93%)
         occurrences all number
    149
    66
    87
    Neutrophil count decreased
         subjects affected / exposed
    171 / 782 (21.87%)
    19 / 403 (4.71%)
    140 / 806 (17.37%)
         occurrences all number
    492
    25
    335
    Platelet count decreased
         subjects affected / exposed
    175 / 782 (22.38%)
    21 / 403 (5.21%)
    132 / 806 (16.38%)
         occurrences all number
    338
    25
    238
    Weight decreased
         subjects affected / exposed
    139 / 782 (17.77%)
    60 / 403 (14.89%)
    128 / 806 (15.88%)
         occurrences all number
    171
    65
    134
    White blood cell count decreased
         subjects affected / exposed
    124 / 782 (15.86%)
    16 / 403 (3.97%)
    92 / 806 (11.41%)
         occurrences all number
    338
    23
    228
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    67 / 782 (8.57%)
    12 / 403 (2.98%)
    31 / 806 (3.85%)
         occurrences all number
    85
    14
    43
    Nervous system disorders
    Hypoaesthesia
         subjects affected / exposed
    45 / 782 (5.75%)
    6 / 403 (1.49%)
    42 / 806 (5.21%)
         occurrences all number
    68
    6
    51
    Headache
         subjects affected / exposed
    89 / 782 (11.38%)
    33 / 403 (8.19%)
    53 / 806 (6.58%)
         occurrences all number
    134
    47
    75
    Dysgeusia
         subjects affected / exposed
    48 / 782 (6.14%)
    10 / 403 (2.48%)
    43 / 806 (5.33%)
         occurrences all number
    53
    11
    45
    Dizziness
         subjects affected / exposed
    57 / 782 (7.29%)
    16 / 403 (3.97%)
    59 / 806 (7.32%)
         occurrences all number
    75
    18
    73
    Peripheral sensory neuropathy
         subjects affected / exposed
    146 / 782 (18.67%)
    13 / 403 (3.23%)
    129 / 806 (16.00%)
         occurrences all number
    205
    14
    202
    Paraesthesia
         subjects affected / exposed
    72 / 782 (9.21%)
    7 / 403 (1.74%)
    78 / 806 (9.68%)
         occurrences all number
    102
    8
    117
    Neuropathy peripheral
         subjects affected / exposed
    241 / 782 (30.82%)
    7 / 403 (1.74%)
    211 / 806 (26.18%)
         occurrences all number
    356
    8
    320
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    172 / 782 (21.99%)
    10 / 403 (2.48%)
    161 / 806 (19.98%)
         occurrences all number
    298
    12
    286
    Neutropenia
         subjects affected / exposed
    221 / 782 (28.26%)
    18 / 403 (4.47%)
    205 / 806 (25.43%)
         occurrences all number
    503
    28
    415
    Anaemia
         subjects affected / exposed
    312 / 782 (39.90%)
    132 / 403 (32.75%)
    279 / 806 (34.62%)
         occurrences all number
    511
    179
    387
    Leukopenia
         subjects affected / exposed
    76 / 782 (9.72%)
    9 / 403 (2.23%)
    65 / 806 (8.06%)
         occurrences all number
    203
    19
    128
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    56 / 782 (7.16%)
    26 / 403 (6.45%)
    43 / 806 (5.33%)
         occurrences all number
    63
    31
    44
    Abdominal pain upper
         subjects affected / exposed
    75 / 782 (9.59%)
    37 / 403 (9.18%)
    77 / 806 (9.55%)
         occurrences all number
    97
    44
    98
    Abdominal pain
         subjects affected / exposed
    159 / 782 (20.33%)
    66 / 403 (16.38%)
    134 / 806 (16.63%)
         occurrences all number
    209
    83
    169
    Vomiting
         subjects affected / exposed
    248 / 782 (31.71%)
    72 / 403 (17.87%)
    234 / 806 (29.03%)
         occurrences all number
    488
    114
    442
    Stomatitis
         subjects affected / exposed
    68 / 782 (8.70%)
    13 / 403 (3.23%)
    57 / 806 (7.07%)
         occurrences all number
    97
    14
    73
    Nausea
         subjects affected / exposed
    386 / 782 (49.36%)
    101 / 403 (25.06%)
    364 / 806 (45.16%)
         occurrences all number
    765
    137
    643
    Diarrhoea
         subjects affected / exposed
    310 / 782 (39.64%)
    112 / 403 (27.79%)
    287 / 806 (35.61%)
         occurrences all number
    523
    171
    503
    Constipation
         subjects affected / exposed
    201 / 782 (25.70%)
    77 / 403 (19.11%)
    177 / 806 (21.96%)
         occurrences all number
    310
    89
    223
    Dysphagia
         subjects affected / exposed
    64 / 782 (8.18%)
    32 / 403 (7.94%)
    65 / 806 (8.06%)
         occurrences all number
    73
    34
    74
    Skin and subcutaneous tissue disorders
    Rash maculo-papular
         subjects affected / exposed
    28 / 782 (3.58%)
    41 / 403 (10.17%)
    7 / 806 (0.87%)
         occurrences all number
    36
    46
    9
    Rash
         subjects affected / exposed
    90 / 782 (11.51%)
    77 / 403 (19.11%)
    22 / 806 (2.73%)
         occurrences all number
    109
    100
    24
    Pruritus
         subjects affected / exposed
    79 / 782 (10.10%)
    72 / 403 (17.87%)
    19 / 806 (2.36%)
         occurrences all number
    97
    84
    21
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    108 / 782 (13.81%)
    0 / 403 (0.00%)
    98 / 806 (12.16%)
         occurrences all number
    137
    0
    123
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    82 / 782 (10.49%)
    54 / 403 (13.40%)
    13 / 806 (1.61%)
         occurrences all number
    90
    67
    20
    Hyperthyroidism
         subjects affected / exposed
    30 / 782 (3.84%)
    26 / 403 (6.45%)
    2 / 806 (0.25%)
         occurrences all number
    34
    28
    6
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    43 / 782 (5.50%)
    9 / 403 (2.23%)
    21 / 806 (2.61%)
         occurrences all number
    50
    12
    21
    Back pain
         subjects affected / exposed
    87 / 782 (11.13%)
    38 / 403 (9.43%)
    69 / 806 (8.56%)
         occurrences all number
    102
    43
    81
    Arthralgia
         subjects affected / exposed
    74 / 782 (9.46%)
    30 / 403 (7.44%)
    42 / 806 (5.21%)
         occurrences all number
    94
    33
    47
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    72 / 782 (9.21%)
    53 / 403 (13.15%)
    51 / 806 (6.33%)
         occurrences all number
    110
    75
    61
    Hypokalaemia
         subjects affected / exposed
    93 / 782 (11.89%)
    37 / 403 (9.18%)
    74 / 806 (9.18%)
         occurrences all number
    136
    55
    101
    Hypocalcaemia
         subjects affected / exposed
    53 / 782 (6.78%)
    21 / 403 (5.21%)
    37 / 806 (4.59%)
         occurrences all number
    84
    32
    50
    Hypoalbuminaemia
         subjects affected / exposed
    109 / 782 (13.94%)
    62 / 403 (15.38%)
    72 / 806 (8.93%)
         occurrences all number
    176
    81
    92
    Decreased appetite
         subjects affected / exposed
    237 / 782 (30.31%)
    111 / 403 (27.54%)
    226 / 806 (28.04%)
         occurrences all number
    345
    137
    315
    Hyperglycaemia
         subjects affected / exposed
    82 / 782 (10.49%)
    37 / 403 (9.18%)
    64 / 806 (7.94%)
         occurrences all number
    161
    70
    119

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Oct 2016
    • Provided reference to the newly-updated Nivolumab Investigator Brochure Version 15 in order to ensure the latest safety information is available, including updated algorithms for the management of side effects and contraception language • Clarified some study inclusion/exclusion criteria and procedures • Provided additional guidance on the implementation of RECIST 1.1 criteria
    07 Dec 2016
    • Added a new randomization arm, nivolumab-plus-chemotherapy (XELOX or FOLFOX) to the study • Added Blinded Independent Central Review (BICR) of tumor images • Clarified some study procedures, including limiting the treatment period with nivolumab to 2 years • Added safety recommendations for subjects receiving capecitabine
    10 May 2017
    • Modified inclusion value for albumin to 3.0 g/dL. • Added clarification for traditional Chinese medicines. • Clarified that PDL1 result must be evaluable in order to be randomized and that tumor sample must be submitted on positively charged slides if not sent as a tumor block. • Added instructions for the administration of nivolumab and chemotherapy when administered on the same day. • Specified that capecitabine should be taken with food. • Clarified that outcome research assessments schedule is independent of dosing schedule, and removed some wording that was leading to confusion regarding the safety visits schedule and treatment beyond disease progression.
    05 Jan 2018
    • Change the primary population to all comers in nivolumab in combination with oxaliplatin and fluoropyrimidine, • Add ORR by Blinded Independent Central Review (BICR) and PFS by BICR as primary endpoints in the nivolumab in combination with oxaliplatin and fluoropyrimidine and oxaliplatin plus fluoropyrimidine arms. • Clarify distal esophageal adenocarcinoma is eligible in the inclusion criteria. • Removal of the 28 day screening window, amylase and lipase removal from mandatory tests, clarification of procedures • Correction of minor formatting and typographical errors
    29 May 2018
    • Added that randomization of an additional 300 subjects beyond the originally planned 1349 subjects across the 3 study arms will allow for more robust analysis of the treatment effect of nivolumab in combination with ipilimumab or chemotherapy across different PD-L1 cutoffs in 1L GC/GEJ cancer.
    11 Jun 2018
    • Per recommendation of the Data Monitoring Committee (DMC), as of 05-June-2018, the nivolumab plus ipilimumab arm is now closed. Subjects randomized to this arm prior to or on 05-June-2018 will continue to receive treatment with study drugs per protocol, and the study data will remain blinded until planned primary analysis.
    14 Sep 2018
    • Incorporates the combined positive score (CPS) for PD-L1 expression into CA209649; the primary population is now subjects with PD-L1expression ≥5 by CPS rather than by the tumor proportion score (TPS) for subjects with nivolumab in combination with oxaliplatin and fluoropyrimidine compared to oxaliplatin and fluoropyrimidine. • The planned analysis of overall survival (OS) for nivolumab plus ipilimumab arm is changed to a secondary objective. • Objective response rate (ORR) has been changed to a secondary endpoint. • The primary, secondary, and exploratory objectives have been updated to reflect changes in subject population definition. • Second disease progression (PFS2) and time to secondary subsequent therapy (TSST) have been added as exploratory analyses. Information on subsequent treatment will be collected during follow-up period. • Statistical assumptions and considerations revised to reflect changes in study population and revised objectives. • Biomarker sampling has been adjusted based on new knowledge in this area of clinical research.
    15 Nov 2018
     Based on recent internal data, added approximately 356 subjects into randomization, in total of approximately 2005 subjects will be randomized to keep sample size for primary analyses of PFS and OS in PD-L1 CPS ≥5 subjects for nivolumab in combination with chemotherapy vs chemotherapy.
    16 Sep 2019
     Based on the data from the Keynote 062 study, PFS and OS Kaplan-Meier curves separation observed delay, the timing of PFS and OS analyses are updated with minimum follow up 12 and 24 months. In addition, to reduce variability of efficacy results, PFS population was expanded to all randomized subjects with PD-L1 CPS  5.  Per Amendment 29, a 480 mg Q4W nivolumab dosing option for subjects who receive nivolumab alone after treatment with nivolumab in combination with ipilimumab or FOLFOX/XELOX is allowed.
    11 May 2022
    The primary purpose for this amendment is to incorporate changes from the approved Administrative Letters 12, 13, 14/15, 16, and 17 into the global protocol. Additional revisions include updates related to study governance considerations.

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

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