Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44393   clinical trials with a EudraCT protocol, of which   7405   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 3, randomized, placebo-controlled, double-blind clinical study of pembrolizumab (MK-3475) with or without lenvatinib (E7080/MK-7902) to evaluate the safety and efficacy of pembrolizumab and lenvatinib as 1L intervention in a PD-L1 selected population of participants with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) (LEAP-010)

    Summary
    EudraCT number
    		 2019-003717-34
    Trial protocol
    		 ES   PL   HU   DE   FR   GB   IT  
    Global end of trial date
    31 Mar 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Apr 2026
    First version publication date
    02 Apr 2026
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    7902-010
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04199104
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme LLC
    Sponsor organisation address
    126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.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
    31 Mar 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 May 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Mar 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This is a study of pembrolizumab (MK-3475) with or without lenvatinib (E7080/MK-7902) as a first line intervention in a PD-L1 selected population with participants with recurrent or metastatic head and neck squamous cell carcinoma. Hypotheses include: - Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR). - Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR. - Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to overall survival (OS).
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Feb 2020
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 61 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 16
    Country: Number of subjects enrolled
    Brazil: 34
    Country: Number of subjects enrolled
    Canada: 12
    Country: Number of subjects enrolled
    China: 57
    Country: Number of subjects enrolled
    France: 31
    Country: Number of subjects enrolled
    Germany: 20
    Country: Number of subjects enrolled
    Hungary: 24
    Country: Number of subjects enrolled
    Italy: 19
    Country: Number of subjects enrolled
    Japan: 47
    Country: Number of subjects enrolled
    Korea, Republic of: 14
    Country: Number of subjects enrolled
    Mexico: 19
    Country: Number of subjects enrolled
    Peru: 26
    Country: Number of subjects enrolled
    Poland: 24
    Country: Number of subjects enrolled
    Russian Federation: 20
    Country: Number of subjects enrolled
    Spain: 14
    Country: Number of subjects enrolled
    Taiwan: 24
    Country: Number of subjects enrolled
    Türkiye: 42
    Country: Number of subjects enrolled
    United Kingdom: 20
    Country: Number of subjects enrolled
    United States: 48
    Worldwide total number of subjects
    511
    EEA total number of subjects
    132
    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)
    265
    From 65 to 84 years
    245
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Adult participants with recurrent or metastatic head and neck squamous cell carcinoma were enrolled. 511 participants were randomized 1:1 to Arm 1 (Pembrolizumab + Lenvatinib) and Arm 2 (Pembrolizumab + Placebo).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Pembrolizumab + Lenvatinib
    Arm description
    		 Participants were administered Pembrolizumab 200mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) plus Lenvatinib 20 mg orally once a day (QD)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475 Keytruda®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab 200 mg, every 3 weeks (Q3W) by intravenous (IV) infusion for up to 35 3-week cycles

    Investigational medicinal product name
    Lenvatinib
    Investigational medicinal product code
    Other name
    E7080 MK-7902 LENVIMA®
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Lenvatinib, 20 mg (two 10-mg oral capsules) administered once daily (QD)

    Arm title
    		 Pembrolizumab + Placebo
    Arm description
    		 Participants were administered Pembrolizumab 200mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) plus lenvatinib-matching placebo orally once a day (QD)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475 Keytruda®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab 200 mg, every 3 weeks (Q3W) by intravenous (IV) infusion for up to 35 3-week cycles

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Lenvatinib-matching placebo, oral capsules, administered QD

    Number of subjects in period 1
    		Pembrolizumab + Lenvatinib Pembrolizumab + Placebo
    Started
    256
    255
    Treated
    254
    253
    Received second course
    3
    3
    Completed
    0
    0
    Not completed
    256
    255
         Consent withdrawn by subject
    5
    5
         Death
    182
    163
         Sponsor Decision
    68
    85
         Lost to follow-up
    1
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Pembrolizumab + Lenvatinib
    Reporting group description
    		 Participants were administered Pembrolizumab 200mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) plus Lenvatinib 20 mg orally once a day (QD)

    Reporting group title
    Pembrolizumab + Placebo
    Reporting group description
    		 Participants were administered Pembrolizumab 200mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) plus lenvatinib-matching placebo orally once a day (QD)

    Reporting group values
    		 Pembrolizumab + Lenvatinib Pembrolizumab + Placebo Total
    Number of subjects
    		 256 255 511
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 124 141 265
        From 65-84 years
    		 132 113 245
        85 years and over
    		 0 1 1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 64.0 ( 8.8 ) 62.7 ( 9.6 ) -
    Sex: Female, Male
    Units:
        Female
    		 37 42 79
        Male
    		 219 213 432
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 2 7 9
        Asian
    		 67 80 147
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 2 2 4
        White
    		 168 147 315
        More than one race
    		 17 19 36
        Unknown or Not Reported
    		 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 33 42 75
        Not Hispanic or Latino
    		 205 199 404
        Unknown or Not Reported
    		 18 14 32
    Programmed Cell Death Ligand 1 (PD-L1) Tumor Expression
    Participants were assessed for their PD- L1 tumor expression level by immunohistochemistry assay using tumor tissue from a newly obtained biopsy. PD-L1 expression analyses were restricted to only tumor cells with TPS (tumor proportion scoring) <50% vs ≥50%.
    Units: Subjects
        <50%
    		 192 191 383
        >=50%
    		 64 64 128
    Human Papilloma Virus (HPV) Status
    HPV status for oropharynx cancer as determined by immunohistochemistry (positive or negative); HPV status for participants without oropharynx cancer (eg, cancers of the oral cavity, hypopharynx and larynx) is considered HPV negative.
    Units: Subjects
        Positive
    		 57 58 115
        Negative
    		 199 197 396
    Eastern Cooperative Oncology Group (ECOG Status of 0 vs 1)
    Participants were stratified on basis of their ECOG status of 0 vs 1. The ECOG status 0 meant fully active, able to carry on all pre-disease performance without restriction, whereas an ECOG status 1 meant restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature.
    Units: Subjects
        ECOG 0
    		 122 115 237
        ECOG 1
    		 134 140 274

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Pembrolizumab + Lenvatinib
    Reporting group description
    		 Participants were administered Pembrolizumab 200mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) plus Lenvatinib 20 mg orally once a day (QD)

    Reporting group title
    Pembrolizumab + Placebo
    Reporting group description
    		 Participants were administered Pembrolizumab 200mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) plus lenvatinib-matching placebo orally once a day (QD)

    Primary: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

    		 Close Top of page
    End point title
    		 Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
    End point description
    ORR is defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a CR or PR based on modified RECIST 1.1 is presented. Participants were included in the treatment group to which they were randomized.
    End point type
    Primary
    End point timeframe
    Up to ~ 37 months
    End point values
    		 Pembrolizumab + Lenvatinib Pembrolizumab + Placebo
    Number of subjects analysed
    256
    255
    Units: Percentage of participants
        number (confidence interval 95%)
    46.9 (40.6 to 53.2)
    27.5 (22.1 to 33.4)
    Statistical analysis title
    		 Point Estimate of Objective Response Rate
    Comparison groups
    Pembrolizumab + Lenvatinib v Pembrolizumab + Placebo
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0000019
    Method
    		 Miettinen and Nurminen method
    Parameter type
    		 point estimate
    Point estimate
    19.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.2
         upper limit
    		 27.3

    Primary: Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR).

    		 Close Top of page
    End point title
    		 Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR).
    End point description
    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD. Participants were included in the treatment group to which they were randomized.
    End point type
    Primary
    End point timeframe
    Up to ~ 37 months
    End point values
    		 Pembrolizumab + Lenvatinib Pembrolizumab + Placebo
    Number of subjects analysed
    256
    255
    Units: Months
        median (confidence interval 95%)
    7.0 (5.6 to 8.0)
    2.8 (2.6 to 4.1)
    Statistical analysis title
    		 Hazard Ratio of Progression Free Survival
    Comparison groups
    Pembrolizumab + Lenvatinib v Pembrolizumab + Placebo
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0001129
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 0.83

    Primary: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Overall Survival (OS)
    End point description
    OS is the time from randomization to death due to any cause. Participants were included in the treatment group to which they were randomized.
    End point type
    Primary
    End point timeframe
    Up to ~ 37 months
    End point values
    		 Pembrolizumab + Lenvatinib Pembrolizumab + Placebo
    Number of subjects analysed
    256
    255
    Units: Months
        median (confidence interval 95%)
    15.0 (13.2 to 17.0)
    17.9 (13.8 to 21.6)
    Statistical analysis title
    		 Hazard Ratio of Overall Survival
    Comparison groups
    Pembrolizumab + Lenvatinib v Pembrolizumab + Placebo
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8819584
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.45

    Secondary: Duration of Response (DOR)

    		 Close Top of page
    End point title
    		 Duration of Response (DOR)
    End point description
    For all randomized participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. Participants were included in the treatment group to which they were randomized. A value of 9999 indicates the endpoint was not reached.
    End point type
    Secondary
    End point timeframe
    Up to ~ 37 months
    End point values
    		 Pembrolizumab + Lenvatinib Pembrolizumab + Placebo
    Number of subjects analysed
    120
    70
    Units: Months
        median (confidence interval 95%)
    10.1 (8.3 to 13.9)
    9999 (11.9 to 9999)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Experienced an Adverse Event (AE)

    		 Close Top of page
    End point title
    		 Percentage of Participants Who Experienced an Adverse Event (AE)
    End point description
    An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Safety analyses were conducted in the all-participants-as-treated (APaT) population, which consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Up to ~ 61 months
    End point values
    		 Pembrolizumab + Lenvatinib Pembrolizumab + Placebo
    Number of subjects analysed
    254
    253
    Units: Percentage of Participants
        number (not applicable)
    99.21
    96.84
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Discontinued Study Drug Due to an AE

    		 Close Top of page
    End point title
    		 Percentage of Participants Who Discontinued Study Drug Due to an AE
    End point description
    An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Safety analyses were conducted in the APaT population, which consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Up to ~ 46 months
    End point values
    		 Pembrolizumab + Lenvatinib Pembrolizumab + Placebo
    Number of subjects analysed
    254
    253
    Units: Percentage of Participants
        number (not applicable)
    46.9
    15.8
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to ~ 61 months
    Adverse event reporting additional description
    All-cause mortality includes all randomized participants (n=511). Adverse events (AEs) include all randomized participants who received ≥1 dose of study drug. Cancer disease progression was not an AE unless study related. MedDRA terms neoplasm progression, malignant neoplasm progression & disease progression unrelated to study drug were excluded.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    28.0
    Reporting groups
    Reporting group title
    Pembrolizumab + Lenvatinib (First Course)
    Reporting group description
    		 -

    Reporting group title
    Pembrolizumab + Placebo (Second Course)
    Reporting group description
    		 -

    Reporting group title
    Pembrolizumab + Lenvatinib (Second Course)
    Reporting group description
    		 -

    Reporting group title
    Pembrolizumab + Placebo (First Course)
    Reporting group description
    		 -

    Serious adverse events
    		 Pembrolizumab + Lenvatinib (First Course) Pembrolizumab + Placebo (Second Course) Pembrolizumab + Lenvatinib (Second Course) Pembrolizumab + Placebo (First Course)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    155 / 254 (61.02%)
    2 / 3 (66.67%)
    1 / 3 (33.33%)
    92 / 253 (36.36%)
         number of deaths (all causes)
    185
    0
    1
    167
         number of deaths resulting from adverse events
    41
    0
    0
    23
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Oral haemangioma
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leiomyoma
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infected neoplasm
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 253 (0.79%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma stage 0
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oropharyngeal squamous cell carcinoma
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    10 / 254 (3.94%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    8 / 253 (3.16%)
         occurrences causally related to treatment / all
    11 / 14
    0 / 0
    0 / 0
    3 / 9
         deaths causally related to treatment / all
    3 / 5
    0 / 0
    0 / 0
    1 / 2
    Vascular disorders
    Arterial haemorrhage
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    3 / 254 (1.18%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    3 / 254 (1.18%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular occlusion
         subjects affected / exposed
    0 / 254 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    6 / 254 (2.36%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 253 (1.19%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 6
    0 / 0
    0 / 0
    0 / 3
    Pyrexia
         subjects affected / exposed
    3 / 254 (1.18%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 253 (0.79%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Malaise
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Prostatitis
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Aspiration
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Apnoea
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Acute respiratory failure
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acquired tracheo-oesophageal fistula
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngeal stenosis
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated lung disease
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    3 / 254 (1.18%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Autoimmune lung disease
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopleural fistula
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchial obstruction
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    5 / 254 (1.97%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Oropharyngeal fistula
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oropharyngeal pain
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngeal haemorrhage
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumomediastinum
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    3 / 254 (1.18%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    6 / 253 (2.37%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 0
    6 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 253 (0.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstructive airways disorder
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 253 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pulmonary haemorrhage
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Respiratory failure
         subjects affected / exposed
    3 / 254 (1.18%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Tracheal fistula
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alcohol withdrawal syndrome
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device occlusion
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device dislocation
         subjects affected / exposed
    4 / 254 (1.57%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Weight decreased
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood urea increased
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Concussion
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoradionecrosis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tracheal obstruction
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiation necrosis
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stoma site haemorrhage
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrostomy tube site complication
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound complication
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Tracheo-oesophageal fistula
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Bradyarrhythmia
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    4 / 254 (1.57%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Cardiac arrest
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cardiovascular disorder
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiovascular insufficiency
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Coronary artery stenosis
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral infarction
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Autonomic dysreflexia
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic hyperosmolar coma
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral sensorimotor neuropathy
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 254 (1.18%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile bone marrow aplasia
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    5 / 254 (1.97%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    4 / 5
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    7 / 254 (2.76%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    6 / 253 (2.37%)
         occurrences causally related to treatment / all
    3 / 8
    0 / 0
    0 / 0
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated enterocolitis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Enterocolitis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal stenosis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mouth haemorrhage
         subjects affected / exposed
    3 / 254 (1.18%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral pain
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic mass
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Salivary duct inflammation
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 253 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    3 / 254 (1.18%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    2 / 3
    0 / 0
    0 / 0
    0 / 1
    Vomiting
         subjects affected / exposed
    4 / 254 (1.57%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangitis acute
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertransaminasaemia
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver injury
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug eruption
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrotic syndrome
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia of malignancy
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Hypopituitarism
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue swelling
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scleroderma
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis of jaw
         subjects affected / exposed
    3 / 254 (1.18%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematoma muscle
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fistula
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Trismus
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal infection
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Abscess neck
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    3 / 254 (1.18%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 253 (1.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 253 (0.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Catheter site infection
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fournier's gangrene
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perirectal abscess
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Necrotising soft tissue infection
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perineal abscess
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumococcal infection
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    21 / 254 (8.27%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    13 / 253 (5.14%)
         occurrences causally related to treatment / all
    5 / 25
    0 / 0
    0 / 0
    0 / 14
         deaths causally related to treatment / all
    1 / 4
    0 / 0
    0 / 0
    0 / 3
    Pneumonia acinetobacter
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia necrotising
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Rash pustular
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    7 / 254 (2.76%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    4 / 253 (1.58%)
         occurrences causally related to treatment / all
    2 / 8
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    Respiratory tract infection
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Skin infection
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stoma site infection
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tracheitis
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 254 (1.18%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    5 / 254 (1.97%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    3 / 5
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    4 / 254 (1.57%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    6 / 6
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fulminant type 1 diabetes mellitus
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    3 / 254 (1.18%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 253 (0.79%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 254 (0.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 253 (0.79%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 254 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Pembrolizumab + Lenvatinib (First Course) Pembrolizumab + Placebo (Second Course) Pembrolizumab + Lenvatinib (Second Course) Pembrolizumab + Placebo (First Course)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    245 / 254 (96.46%)
    2 / 3 (66.67%)
    3 / 3 (100.00%)
    222 / 253 (87.75%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    117 / 254 (46.06%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    25 / 253 (9.88%)
         occurrences all number
    208
    0
    0
    42
    Hypotension
         subjects affected / exposed
    15 / 254 (5.91%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    7 / 253 (2.77%)
         occurrences all number
    16
    0
    1
    8
    General disorders and administration site conditions
    Mucosal inflammation
         subjects affected / exposed
    26 / 254 (10.24%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    7 / 253 (2.77%)
         occurrences all number
    36
    0
    0
    10
    Fatigue
         subjects affected / exposed
    80 / 254 (31.50%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    43 / 253 (17.00%)
         occurrences all number
    92
    0
    1
    46
    Asthenia
         subjects affected / exposed
    26 / 254 (10.24%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    25 / 253 (9.88%)
         occurrences all number
    32
    0
    1
    30
    Pyrexia
         subjects affected / exposed
    21 / 254 (8.27%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    20 / 253 (7.91%)
         occurrences all number
    23
    0
    0
    25
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    40 / 254 (15.75%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    24 / 253 (9.49%)
         occurrences all number
    47
    0
    1
    26
    Dysphonia
         subjects affected / exposed
    23 / 254 (9.06%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    4 / 253 (1.58%)
         occurrences all number
    26
    0
    0
    4
    Dyspnoea
         subjects affected / exposed
    26 / 254 (10.24%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    15 / 253 (5.93%)
         occurrences all number
    34
    0
    0
    15
    Haemoptysis
         subjects affected / exposed
    10 / 254 (3.94%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    10 / 253 (3.95%)
         occurrences all number
    18
    0
    1
    12
    Oropharyngeal pain
         subjects affected / exposed
    28 / 254 (11.02%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    9 / 253 (3.56%)
         occurrences all number
    33
    0
    0
    9
    Pneumonitis
         subjects affected / exposed
    11 / 254 (4.33%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    10 / 253 (3.95%)
         occurrences all number
    12
    0
    1
    10
    Productive cough
         subjects affected / exposed
    17 / 254 (6.69%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    7 / 253 (2.77%)
         occurrences all number
    18
    0
    0
    7
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    25 / 254 (9.84%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    12 / 253 (4.74%)
         occurrences all number
    27
    0
    0
    13
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    36 / 254 (14.17%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    22 / 253 (8.70%)
         occurrences all number
    49
    0
    0
    29
    Amylase increased
         subjects affected / exposed
    15 / 254 (5.91%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    14 / 253 (5.53%)
         occurrences all number
    22
    0
    0
    21
    Aspartate aminotransferase increased
         subjects affected / exposed
    37 / 254 (14.57%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    23 / 253 (9.09%)
         occurrences all number
    58
    0
    0
    36
    Blood alkaline phosphatase increased
         subjects affected / exposed
    13 / 254 (5.12%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    20 / 253 (7.91%)
         occurrences all number
    15
    0
    0
    25
    Blood bilirubin increased
         subjects affected / exposed
    17 / 254 (6.69%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    7 / 253 (2.77%)
         occurrences all number
    20
    0
    0
    10
    Blood creatinine increased
         subjects affected / exposed
    26 / 254 (10.24%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    7 / 253 (2.77%)
         occurrences all number
    28
    0
    0
    9
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    17 / 254 (6.69%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    7 / 253 (2.77%)
         occurrences all number
    22
    0
    0
    7
    Lipase increased
         subjects affected / exposed
    32 / 254 (12.60%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    18 / 253 (7.11%)
         occurrences all number
    40
    0
    0
    33
    Lymphocyte count decreased
         subjects affected / exposed
    30 / 254 (11.81%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    23 / 253 (9.09%)
         occurrences all number
    59
    0
    0
    45
    Platelet count decreased
         subjects affected / exposed
    33 / 254 (12.99%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    8 / 253 (3.16%)
         occurrences all number
    47
    0
    0
    13
    Weight decreased
         subjects affected / exposed
    65 / 254 (25.59%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    41 / 253 (16.21%)
         occurrences all number
    74
    0
    0
    43
    White blood cell count decreased
         subjects affected / exposed
    16 / 254 (6.30%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    11 / 253 (4.35%)
         occurrences all number
    34
    0
    0
    17
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    3 / 254 (1.18%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    4 / 253 (1.58%)
         occurrences all number
    3
    0
    1
    4
    Nervous system disorders
    Headache
         subjects affected / exposed
    32 / 254 (12.60%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    16 / 253 (6.32%)
         occurrences all number
    37
    0
    0
    16
    Dizziness
         subjects affected / exposed
    13 / 254 (5.12%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    8 / 253 (3.16%)
         occurrences all number
    18
    0
    0
    8
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    66 / 254 (25.98%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    52 / 253 (20.55%)
         occurrences all number
    102
    1
    0
    75
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    1 / 254 (0.39%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 253 (0.40%)
         occurrences all number
    1
    1
    0
    1
    Ear pain
         subjects affected / exposed
    7 / 254 (2.76%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    3 / 253 (1.19%)
         occurrences all number
    7
    0
    1
    3
    Gastrointestinal disorders
    Salivary gland pain
         subjects affected / exposed
    0 / 254 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 253 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Oral pain
         subjects affected / exposed
    30 / 254 (11.81%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    7 / 253 (2.77%)
         occurrences all number
    35
    0
    0
    8
    Nausea
         subjects affected / exposed
    62 / 254 (24.41%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    26 / 253 (10.28%)
         occurrences all number
    83
    0
    0
    28
    Flatulence
         subjects affected / exposed
    2 / 254 (0.79%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 253 (0.40%)
         occurrences all number
    2
    0
    1
    1
    Dysphagia
         subjects affected / exposed
    36 / 254 (14.17%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    14 / 253 (5.53%)
         occurrences all number
    40
    0
    0
    15
    Dyspepsia
         subjects affected / exposed
    14 / 254 (5.51%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 253 (1.19%)
         occurrences all number
    22
    0
    0
    3
    Dry mouth
         subjects affected / exposed
    18 / 254 (7.09%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    18 / 253 (7.11%)
         occurrences all number
    19
    0
    0
    19
    Diarrhoea
         subjects affected / exposed
    73 / 254 (28.74%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    34 / 253 (13.44%)
         occurrences all number
    117
    0
    1
    46
    Constipation
         subjects affected / exposed
    57 / 254 (22.44%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    47 / 253 (18.58%)
         occurrences all number
    74
    0
    0
    57
    Bowel movement irregularity
         subjects affected / exposed
    0 / 254 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 253 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vomiting
         subjects affected / exposed
    33 / 254 (12.99%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    14 / 253 (5.53%)
         occurrences all number
    48
    0
    0
    16
    Stomatitis
         subjects affected / exposed
    52 / 254 (20.47%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    12 / 253 (4.74%)
         occurrences all number
    74
    0
    0
    12
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    15 / 254 (5.91%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    8 / 253 (3.16%)
         occurrences all number
    15
    0
    0
    8
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    36 / 254 (14.17%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 253 (0.79%)
         occurrences all number
    51
    0
    0
    2
    Pruritus
         subjects affected / exposed
    29 / 254 (11.42%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    30 / 253 (11.86%)
         occurrences all number
    35
    0
    0
    43
    Rash
         subjects affected / exposed
    34 / 254 (13.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    26 / 253 (10.28%)
         occurrences all number
    47
    0
    0
    29
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    13 / 254 (5.12%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    7 / 253 (2.77%)
         occurrences all number
    20
    0
    0
    11
    Proteinuria
         subjects affected / exposed
    66 / 254 (25.98%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    16 / 253 (6.32%)
         occurrences all number
    125
    0
    0
    17
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    19 / 254 (7.48%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    10 / 253 (3.95%)
         occurrences all number
    23
    0
    0
    10
    Hypothyroidism
         subjects affected / exposed
    125 / 254 (49.21%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    43 / 253 (17.00%)
         occurrences all number
    151
    0
    0
    52
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    40 / 254 (15.75%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    18 / 253 (7.11%)
         occurrences all number
    51
    1
    0
    25
    Musculoskeletal chest pain
         subjects affected / exposed
    8 / 254 (3.15%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    3 / 253 (1.19%)
         occurrences all number
    8
    0
    1
    5
    Neck pain
         subjects affected / exposed
    18 / 254 (7.09%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    9 / 253 (3.56%)
         occurrences all number
    18
    0
    0
    10
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    13 / 254 (5.12%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    13 / 253 (5.14%)
         occurrences all number
    18
    0
    0
    17
    Pneumonia
         subjects affected / exposed
    26 / 254 (10.24%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    12 / 253 (4.74%)
         occurrences all number
    27
    0
    0
    13
    COVID-19
         subjects affected / exposed
    17 / 254 (6.69%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    14 / 253 (5.53%)
         occurrences all number
    18
    0
    0
    14
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    57 / 254 (22.44%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    23 / 253 (9.09%)
         occurrences all number
    70
    0
    1
    25
    Hypercalcaemia
         subjects affected / exposed
    12 / 254 (4.72%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    18 / 253 (7.11%)
         occurrences all number
    15
    0
    0
    20
    Hyperglycaemia
         subjects affected / exposed
    16 / 254 (6.30%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    12 / 253 (4.74%)
         occurrences all number
    25
    0
    0
    13
    Hypoalbuminaemia
         subjects affected / exposed
    34 / 254 (13.39%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    24 / 253 (9.49%)
         occurrences all number
    47
    0
    0
    26
    Hyperkalaemia
         subjects affected / exposed
    18 / 254 (7.09%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    7 / 253 (2.77%)
         occurrences all number
    20
    1
    0
    8
    Hypokalaemia
         subjects affected / exposed
    22 / 254 (8.66%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    9 / 253 (3.56%)
         occurrences all number
    29
    0
    0
    11
    Hypomagnesaemia
         subjects affected / exposed
    22 / 254 (8.66%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    11 / 253 (4.35%)
         occurrences all number
    31
    0
    0
    14
    Hyponatraemia
         subjects affected / exposed
    47 / 254 (18.50%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    29 / 253 (11.46%)
         occurrences all number
    75
    0
    0
    38
    Hypophosphataemia
         subjects affected / exposed
    14 / 254 (5.51%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    4 / 253 (1.58%)
         occurrences all number
    16
    0
    0
    4

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Jul 2020
    Amendment 02: Primary reason for amendment was to incorporate Health Authority feedback, amend exclusion criteria, and provide program-level corrections and clarifications.
    26 Jul 2021
    Amendment 03: Primary reason for amendment was to update the dose modification and toxicity management guidelines for immune-related Adverse Events (irAEs).
    23 Aug 2022
    Amendment 04: Primary reason for amendment was to address an entity name and address change.
    04 Dec 2023
    Amendment 05: Primary reason for amendment was to terminate the study based on interim analysis results and incorporate instructions for discontinuation of study intervention, appropriate measures for safety follow-up of ongoing study participants, and plan for analysis of study data going forward.
    11 Oct 2024
    Amendment 06: Primary reason for amendment was to correct standard text inadvertently removed in Amendment 05.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 02 12:55:39 CEST 2026 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA