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   43865   clinical trials with a EudraCT protocol, of which   7286   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 II, Open-Label,Multicenter, Multi-Cohort Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Patients with Solid Tumors

    Summary
    EudraCT number
    		 2017-000794-37
    Trial protocol
    		 DE   HU   GB   BE   GR   ES  
    Global end of trial date
    25 Jun 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    08 Jan 2021
    First version publication date
    08 Jan 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    WO39760
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03264066
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.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
    25 Jun 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Jun 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main goal of the study was to evaluate the efficacy of cobimetinib plus atezolizumab in participants with advanced solid tumors including the following cohorts: squamous cell carcinoma of the head and neck (SCCHN), urothelial carcinoma (UC), and renal cell carcinoma (RCC).
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 Nov 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Belgium: 7
    Country: Number of subjects enrolled
    United Kingdom: 24
    Country: Number of subjects enrolled
    Hungary: 12
    Country: Number of subjects enrolled
    Korea, Republic of: 24
    Country: Number of subjects enrolled
    United States: 18
    Worldwide total number of subjects
    86
    EEA total number of subjects
    44
    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)
    44
    From 65 to 84 years
    42
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Enrollment took place in 17 investigational sites across the following six countries: Republic of Korea, Belgium, Germany, United Kingdom, Hungary and United States. Seven cohorts were planned in the study. No participants were enrolled in Cohort 7.

    Pre-assignment
    Screening details
    		 Participants with advanced solid tumors were included in the study: squamous cell carcinoma of head and neck (SCCHN), urothelial carcinoma (UC), and renal cell carcinoma (RCC). One subject, who deteriorated after enrollment, did not receive study treatment due to no longer meeting inclusion criteria and is not included here (safety population).

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1 - SCCHN - Treatment Naive
    Arm description
    		 In participants with recurrent or advanced / metastatic squamous cell carcinoma of the head and neck (SSCHN) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg once daily (QD) for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cobimetinib
    Investigational medicinal product code
    Other name
    Cotellic
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab were given a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

    Arm title
    		 Cohort 2 - UC - Treatment Naive
    Arm description
    		 In participants with advanced / metastatic urothelial carcinoma (UC) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab were given a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

    Investigational medicinal product name
    Cobimetinib
    Investigational medicinal product code
    Other name
    Cotellic
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.

    Arm title
    		 Cohort 3 - RCC - Treatment Naive
    Arm description
    		 In participants with metastatic renal cell carcinoma (RCC) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cobimetinib
    Investigational medicinal product code
    Other name
    Cotellic
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab were given a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

    Arm title
    		 Cohort 4 - SCCHN - Previous Treatment Exposure
    Arm description
    		 In participants with SCCHN whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cobimetinib
    Investigational medicinal product code
    Other name
    Cotellic
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab were given a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

    Arm title
    		 Cohort 5 - UC - Previous Treatment Exposure
    Arm description
    		 In participants with UC whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cobimetinib
    Investigational medicinal product code
    Other name
    Cotellic
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab were given a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

    Arm title
    		 Cohort 6 - RCC - Previous Treatment Exposure
    Arm description
    		 In participants with RCC whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cobimetinib
    Investigational medicinal product code
    Other name
    Cotellic
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab were given a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

    Number of subjects in period 1
    		Cohort 1 - SCCHN - Treatment Naive Cohort 2 - UC - Treatment Naive Cohort 3 - RCC - Treatment Naive Cohort 4 - SCCHN - Previous Treatment Exposure Cohort 5 - UC - Previous Treatment Exposure Cohort 6 - RCC - Previous Treatment Exposure
    Started
    20
    19
    17
    20
    7
    3
    Completed
    0
    0
    0
    0
    0
    0
    Not completed
    20
    19
    17
    20
    7
    3
         Adverse event, serious fatal
    12
    11
    8
    10
    6
    1
         Consent withdrawn by subject
    1
    -
    -
    5
    -
    -
         Adverse event, non-fatal
    1
    1
    -
    -
    -
    -
         Progressive Disease
    -
    2
    1
    -
    -
    -
         Study Terminated by Sponsor
    5
    5
    8
    5
    1
    2
         Lost to follow-up
    1
    -
    -
    -
    -
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1 - SCCHN - Treatment Naive
    Reporting group description
    		 In participants with recurrent or advanced / metastatic squamous cell carcinoma of the head and neck (SSCHN) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg once daily (QD) for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group title
    Cohort 2 - UC - Treatment Naive
    Reporting group description
    		 In participants with advanced / metastatic urothelial carcinoma (UC) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group title
    Cohort 3 - RCC - Treatment Naive
    Reporting group description
    		 In participants with metastatic renal cell carcinoma (RCC) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group title
    Cohort 4 - SCCHN - Previous Treatment Exposure
    Reporting group description
    		 In participants with SCCHN whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group title
    Cohort 5 - UC - Previous Treatment Exposure
    Reporting group description
    		 In participants with UC whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group title
    Cohort 6 - RCC - Previous Treatment Exposure
    Reporting group description
    		 In participants with RCC whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group values
    		 Cohort 1 - SCCHN - Treatment Naive Cohort 2 - UC - Treatment Naive Cohort 3 - RCC - Treatment Naive Cohort 4 - SCCHN - Previous Treatment Exposure Cohort 5 - UC - Previous Treatment Exposure Cohort 6 - RCC - Previous Treatment Exposure Total
    Number of subjects
    		 20 19 17 20 7 3 86
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 61.8 ± 10.1 65.3 ± 10.3 60.3 ± 11.5 62.4 ± 6.4 61.4 ± 15.8 68.3 ± 15.0 -
    Sex: Female, Male
    Units: participants
        Male
    		 18 11 11 19 5 1 65
        Female
    		 2 8 6 1 2 2 21

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Cohort 1 - SCCHN - Treatment Naive
    Reporting group description
    		 In participants with recurrent or advanced / metastatic squamous cell carcinoma of the head and neck (SSCHN) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg once daily (QD) for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group title
    Cohort 2 - UC - Treatment Naive
    Reporting group description
    		 In participants with advanced / metastatic urothelial carcinoma (UC) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group title
    Cohort 3 - RCC - Treatment Naive
    Reporting group description
    		 In participants with metastatic renal cell carcinoma (RCC) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group title
    Cohort 4 - SCCHN - Previous Treatment Exposure
    Reporting group description
    		 In participants with SCCHN whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group title
    Cohort 5 - UC - Previous Treatment Exposure
    Reporting group description
    		 In participants with UC whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group title
    Cohort 6 - RCC - Previous Treatment Exposure
    Reporting group description
    		 In participants with RCC whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Subject analysis set title
    Cohort 1 - SCCHN - Treatment Naive
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    In participants with recurrent or advanced / metastatic squamous cell carcinoma of the head and neck (SSCHN) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg once daily (QD) for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

    Subject analysis set title
    Cohort 2 - UC - Treatment Naive
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    In participants with advanced / metastatic urothelial carcinoma (UC) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Subject analysis set title
    Cohort 3 - RCC - Treatment Naive
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    In participants with metastatic renal cell carcinoma (RCC) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Subject analysis set title
    Cohort 4 - SCCHN - Previous Treatment Exposure
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    In participants with SCCHN whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Subject analysis set title
    Cohort 5 - UC - Previous Treatment Exposure
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    In participants with UC whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Subject analysis set title
    Cohort 6 - RCC - Previous Treatment Exposure
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    In participants with RCC whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Subject analysis set title
    Cohorts 1-6
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    In all participants cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Primary: Objective Response Rate (ORR)

    		 Close Top of page
    End point title
    		 Objective Response Rate (ORR) [1]
    End point description
    Objective response rate was defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive tumor assessments ≥4 weeks apart, as determined by the investigators using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). CR was defined as disappearance of all lesions. PR was defined as ≥30% decrease in the sum of diameters of target lesions, in the absence of CR, new lesions, and unequivocal progression in non-target lesions. The intent-to-treat (ITT) population included all participants enrolled in the study.
    End point type
    Primary
    End point timeframe
    Up to approximately 31 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Since all subjects in the study received the same treatments statistical analyses were not planned to be conducted.
    End point values
    		 Cohort 1 - SCCHN - Treatment Naive Cohort 2 - UC - Treatment Naive Cohort 3 - RCC - Treatment Naive Cohort 4 - SCCHN - Previous Treatment Exposure Cohort 5 - UC - Previous Treatment Exposure Cohort 6 - RCC - Previous Treatment Exposure
    Number of subjects analysed
    20
    20
    17
    20
    7
    3
    Units: percentage of participants
        number (confidence interval 95%)
    20.0 (0.00 to 40.03)
    30.0 (7.42 to 52.58)
    17.6 (0.00 to 38.71)
    0 (0.00 to 2.50)
    0 (0.00 to 7.14)
    0 (0.00 to 16.67)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Overall Survival (OS)
    End point description
    Overall survival was defined as the time from enrollment to death from any cause. The ITT population included all participants enrolled in the study. 9.99999: not estimable
    End point type
    Secondary
    End point timeframe
    Up to approximately 31 months
    End point values
    		 Cohort 1 - SCCHN - Treatment Naive Cohort 2 - UC - Treatment Naive Cohort 3 - RCC - Treatment Naive Cohort 4 - SCCHN - Previous Treatment Exposure Cohort 5 - UC - Previous Treatment Exposure Cohort 6 - RCC - Previous Treatment Exposure
    Number of subjects analysed
    20
    20
    17
    20
    7
    3
    Units: months
        median (full range (min-max))
    16.8 (2 to 26)
    18.7 (2 to 26)
    21.7 (1 to 29)
    7.7 (1 to 18)
    5.9 (2 to 12)
    9.99999 (6 to 12)
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS)

    		 Close Top of page
    End point title
    		 Progression-Free Survival (PFS)
    End point description
    PFS was defined as the time from enrollment to the first occurrence of disease progression as determined by the investigator(s), using RECIST v1.1, or to death from any cause, whichever occurs first. Disease progression was defined as ≥20% increase in in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. The ITT population included all participants enrolled in the study.
    End point type
    Secondary
    End point timeframe
    Up to approximately 31 months
    End point values
    		 Cohort 1 - SCCHN - Treatment Naive Cohort 2 - UC - Treatment Naive Cohort 3 - RCC - Treatment Naive Cohort 4 - SCCHN - Previous Treatment Exposure Cohort 5 - UC - Previous Treatment Exposure Cohort 6 - RCC - Previous Treatment Exposure
    Number of subjects analysed
    20
    20
    17
    20
    7
    3
    Units: months
        median (full range (min-max))
    5.5 (2 to 26)
    3.4 (2 to 26)
    3.4 (1 to 28)
    3.6 (0 to 9)
    2.1 (1 to 4)
    2.7 (1 to 4)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

    		 Close Top of page
    End point title
    		 Duration of Response (DOR)
    End point description
    DOR was defined as the time from the first occurrence of a documented, confirmed objective response to disease progression as determined by the investigator, using RECIST v1.1, or to death from any cause, whichever occurs first. Objective response was defined as a complete response (CR) or a partial response (PR) on two consecutive tumor assessments ≥4 weeks apart. CR was defined as disappearance of all lesions. PR was defined as ≥30% decrease in the sum of diameters of target lesions, in the absence of CR, new lesions, and unequivocal progression in non-target lesions. Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. The ITT population included all participants enrolled in the study.
    End point type
    Secondary
    End point timeframe
    Up to approximately 31 months
    End point values
    		 Cohort 1 - SCCHN - Treatment Naive Cohort 2 - UC - Treatment Naive Cohort 3 - RCC - Treatment Naive Cohort 4 - SCCHN - Previous Treatment Exposure Cohort 5 - UC - Previous Treatment Exposure Cohort 6 - RCC - Previous Treatment Exposure
    Number of subjects analysed
    0 [2]
    0 [3]
    0 [4]
    0 [5]
    0 [6]
    0 [7]
    Units: months
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [2] - Median DOR was not estimable due to low number of events.
    [3] - Median DOR was not estimable due to low number of events.
    [4] - Median DOR was not estimable due to low number of events.
    [5] - Median DOR was not estimable due to low number of events.
    [6] - Median DOR was not estimable due to low number of events.
    [7] - Median DOR was not estimable due to low number of events.
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR)

    		 Close Top of page
    End point title
    		 Disease Control Rate (DCR)
    End point description
    DCR was defined as the percentage of participants with a complete response (CR), a partial response (PR), or stable disease at 16 weeks as determined by the investigator using RECIST v1.1. CR was defined as disappearance of all lesions. PR was defined as ≥30% decrease in the sum of diameters of target lesions, in the absence of CR, new lesions, and unequivocal progression in non-target lesions. Stable disease was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for disease progression. Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. The ITT population included all participants enrolled in the study.
    End point type
    Secondary
    End point timeframe
    At 16 weeks
    End point values
    		 Cohort 1 - SCCHN - Treatment Naive Cohort 2 - UC - Treatment Naive Cohort 3 - RCC - Treatment Naive Cohort 4 - SCCHN - Previous Treatment Exposure Cohort 5 - UC - Previous Treatment Exposure Cohort 6 - RCC - Previous Treatment Exposure
    Number of subjects analysed
    20
    20
    17
    20
    7
    3
    Units: percentage of participants
        number (confidence interval 95%)
    50.0 (25.59 to 74.41)
    40.0 (16.03 to 63.97)
    23.5 (0.42 to 46.63)
    25.0 (3.52 to 46.48)
    0 (0.00 to 7.14)
    0 (0.00 to 16.67)
    No statistical analyses for this end point

    Secondary: Number of Participants With Adverse Events

    		 Close Top of page
    End point title
    		 Number of Participants With Adverse Events
    End point description
    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
    End point type
    Secondary
    End point timeframe
    Up to approximately 31 months
    End point values
    		 Cohort 1 - SCCHN - Treatment Naive Cohort 2 - UC - Treatment Naive Cohort 3 - RCC - Treatment Naive Cohort 4 - SCCHN - Previous Treatment Exposure Cohort 5 - UC - Previous Treatment Exposure Cohort 6 - RCC - Previous Treatment Exposure
    Number of subjects analysed
    20
    19
    17
    20
    7
    3
    Units: participants
    20
    19
    17
    20
    7
    3
    No statistical analyses for this end point

    Secondary: Maximum Plasma Concentration (Cmax) of Cobimetinib

    		 Close Top of page
    End point title
    		 Maximum Plasma Concentration (Cmax) of Cobimetinib
    End point description
    Cmax is the maximum (or peak) concentration that a study drug achieves in the body.
    End point type
    Secondary
    End point timeframe
    Day 15 of Cycle 3 (cycle is 28 days): 2-4 hours after cobimetinib dose
    End point values
    		 Cohorts 1-6
    Number of subjects analysed
    33
    Units: nanogram per milliliter (ng/mL)
        geometric mean (geometric coefficient of variation)
    285 ± 56.5
    No statistical analyses for this end point

    Secondary: Minimum Plasma Concentration (Cmin) of Cobimetinib

    		 Close Top of page
    End point title
    		 Minimum Plasma Concentration (Cmin) of Cobimetinib
    End point description
    Cmin is the minimum (or trough) concentration that a study drug achieves in the body.
    End point type
    Secondary
    End point timeframe
    : Day 15 of Cycle 3 (cycle is 28 days): prior to cobimetinib dose
    End point values
    		 Cohorts 1-6
    Number of subjects analysed
    30
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    174 ± 152
    No statistical analyses for this end point

    Secondary: Maximum Serum Concentration (Cmax) of Atezolizumab

    		 Close Top of page
    End point title
    		 Maximum Serum Concentration (Cmax) of Atezolizumab
    End point description
    Cmax is the maximum (or peak) concentration that a study drug achieves in the body.
    End point type
    Secondary
    End point timeframe
    30 minutes following end of atezolizumab infusion on Day 1 of Cycle 1 (each cycle is 28 days) and Day 15 of Cycle 3
    End point values
    		 Cohorts 1-6
    Number of subjects analysed
    40
    Units: micrograms per milliliter (mcg/mL)
        geometric mean (geometric coefficient of variation)
    417000 ± 50.2
    No statistical analyses for this end point

    Secondary: Minimum Serum Concentration (Cmin) of Atezolizumab

    		 Close Top of page
    End point title
    		 Minimum Serum Concentration (Cmin) of Atezolizumab
    End point description
    Cmin is the minimum (or trough) concentration that a study drug achieves in the body.
    End point type
    Secondary
    End point timeframe
    Prior to atezolizumab infusion on Day 1 of Cycles (each cycle is 28 days) 2, 4, 8, 12, and 16, Day 15 of Cycle 3
    End point values
    		 Cohorts 1-6
    Number of subjects analysed
    61
    Units: mcg/mL
        geometric mean (geometric coefficient of variation)
    112000 ± 219
    No statistical analyses for this end point

    Secondary: Number of Participants With Anti-drug Antibodies (ADAs)

    		 Close Top of page
    End point title
    		 Number of Participants With Anti-drug Antibodies (ADAs)
    End point description
    Participants were considered to be ADA positive if they were missing data at baseline but developed an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was at least 4-fold greater (i.e., ≥0.60-titer units) than the titer of the baseline sample (treatment-enhanced ADA response). Participants were considered to be ADA negative if they were missing data at baseline, had a post-baseline ADA result, and all post-baseline samples were negative, or if they were ADA positive at baseline but did not have any post-baseline samples with a titer that was at least 4-fold greater than the titer of the baseline sample (treatment unaffected).
    End point type
    Secondary
    End point timeframe
    Day 1 of Cycles (each cycle is 28 days) 1, 2, 4, 8, 12, and 16; Day 15 of Cycle 3; at atezolizumab treatment discontinuation visit, and <90 days after last atezolizumab infusion (up to approximately 31 months)
    End point values
    		 Cohorts 1-6
    Number of subjects analysed
    75
    Units: participants
    24
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to approximately 31 months
    Adverse event reporting additional description
    The safety population included all enrolled participants who received at least one dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Cohort 1 - SCCHN - Treatment Naive
    Reporting group description
    		 In participants with recurrent or advanced / metastatic squamous cell carcinoma of the head and neck (SSCHN) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg once daily (QD) for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group title
    Cohort 2 - UC - Treatment Naive
    Reporting group description
    		 In participants with advanced / metastatic urothelial carcinoma (UC) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group title
    Cohort 3 - RCC - Treatment Naive
    Reporting group description
    		 In participants with metastatic renal cell carcinoma (RCC) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group title
    Cohort 4 - SCCHN - Previous Treatment Exposure
    Reporting group description
    		 In participants with SCCHN whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group title
    Cohort 5 - UC - Previous Treatment Exposure
    Reporting group description
    		 In participants with UC whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Reporting group title
    Cohort 6 - RCC - Previous Treatment Exposure
    Reporting group description
    		 In participants with RCC whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

    Serious adverse events
    		 Cohort 1 - SCCHN - Treatment Naive Cohort 2 - UC - Treatment Naive Cohort 3 - RCC - Treatment Naive Cohort 4 - SCCHN - Previous Treatment Exposure Cohort 5 - UC - Previous Treatment Exposure Cohort 6 - RCC - Previous Treatment Exposure
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 20 (65.00%)
    9 / 19 (47.37%)
    8 / 17 (47.06%)
    10 / 20 (50.00%)
    4 / 7 (57.14%)
    1 / 3 (33.33%)
         number of deaths (all causes)
    12
    12
    8
    12
    6
    1
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    TUMOUR HAEMORRHAGE
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    HYPOTENSION
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    GASTROSTOMY
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHILLS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FACE OEDEMA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FATIGUE
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GENERAL PHYSICAL HEALTH DETERIORATION
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    DYSPNOEA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    2 / 17 (11.76%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONITIS
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY TRACT OEDEMA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    DEVICE DISLOCATION
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    EJECTION FRACTION DECREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    HUMERUS FRACTURE
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INFUSION RELATED REACTION
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    POSTOPERATIVE RESPIRATORY FAILURE
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    ATRIAL FIBRILLATION
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERICARDITIS
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    ALTERED STATE OF CONSCIOUSNESS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    IMMUNE-MEDIATED ENCEPHALITIS
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    COLITIS
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    2 / 17 (11.76%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DYSPHAGIA
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ENTEROCOLITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTRITIS EROSIVE
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ILEUS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL OBSTRUCTION
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINAL OBSTRUCTION
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINE PERFORATION
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMATOSIS INTESTINALIS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RECTAL HAEMORRHAGE
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    UPPER GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VOMITING
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    IMMUNE-MEDIATED HEPATITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    RASH
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RASH MACULAR
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RASH MACULO-PAPULAR
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    NEPHRITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URINARY RETENTION
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    DEVICE RELATED SEPSIS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ENDOCARDITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PHARYNGITIS STREPTOCOCCAL
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    3 / 20 (15.00%)
    2 / 19 (10.53%)
    2 / 17 (11.76%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 2
    1 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 19 (10.53%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Cohort 1 - SCCHN - Treatment Naive Cohort 2 - UC - Treatment Naive Cohort 3 - RCC - Treatment Naive Cohort 4 - SCCHN - Previous Treatment Exposure Cohort 5 - UC - Previous Treatment Exposure Cohort 6 - RCC - Previous Treatment Exposure
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    20 / 20 (100.00%)
    19 / 19 (100.00%)
    17 / 17 (100.00%)
    19 / 20 (95.00%)
    7 / 7 (100.00%)
    3 / 3 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ADENOCARCINOMA OF COLON
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    CANCER PAIN
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    KERATOACANTHOMA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    TUMOUR HAEMORRHAGE
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Vascular disorders
    FLUSHING
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    HYPERTENSION
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    3 / 20 (15.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    8
    0
    0
    HYPOTENSION
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    2 / 17 (11.76%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    2
    0
    0
    0
    LYMPHOEDEMA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    ORTHOSTATIC HYPOTENSION
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    1 / 20 (5.00%)
    3 / 19 (15.79%)
    2 / 17 (11.76%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    3
    2
    0
    0
    0
    CHEST PAIN
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    CHILLS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    2
    0
    FACE OEDEMA
         subjects affected / exposed
    2 / 20 (10.00%)
    2 / 19 (10.53%)
    2 / 17 (11.76%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    2
    2
    1
    0
    0
    FACIAL PAIN
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    FATIGUE
         subjects affected / exposed
    6 / 20 (30.00%)
    9 / 19 (47.37%)
    5 / 17 (29.41%)
    5 / 20 (25.00%)
    5 / 7 (71.43%)
    0 / 3 (0.00%)
         occurrences all number
    6
    14
    7
    5
    5
    0
    GENERALISED OEDEMA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    1 / 20 (5.00%)
    3 / 19 (15.79%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    3
    0
    1
    0
    0
    LOCALISED OEDEMA
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    MALAISE
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    MUCOSAL INFLAMMATION
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    2 / 17 (11.76%)
    1 / 20 (5.00%)
    1 / 7 (14.29%)
    1 / 3 (33.33%)
         occurrences all number
    1
    1
    2
    1
    1
    1
    OEDEMA
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    2 / 17 (11.76%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    2
    1
    0
    0
    OEDEMA PERIPHERAL
         subjects affected / exposed
    3 / 20 (15.00%)
    2 / 19 (10.53%)
    3 / 17 (17.65%)
    2 / 20 (10.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
         occurrences all number
    3
    2
    3
    2
    2
    0
    PAIN
         subjects affected / exposed
    3 / 20 (15.00%)
    2 / 19 (10.53%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    2
    0
    1
    0
    0
    PERIPHERAL SWELLING
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 19 (10.53%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    PYREXIA
         subjects affected / exposed
    2 / 20 (10.00%)
    7 / 19 (36.84%)
    5 / 17 (29.41%)
    1 / 20 (5.00%)
    4 / 7 (57.14%)
    0 / 3 (0.00%)
         occurrences all number
    2
    9
    9
    1
    4
    0
    SWELLING FACE
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Immune system disorders
    HYPERSENSITIVITY
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Reproductive system and breast disorders
    SCROTAL OEDEMA
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    TESTICULAR SWELLING
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    VAGINAL DISCHARGE
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    VAGINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 19 (10.53%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    COUGH
         subjects affected / exposed
    1 / 20 (5.00%)
    4 / 19 (21.05%)
    2 / 17 (11.76%)
    2 / 20 (10.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    5
    2
    2
    1
    0
    DYSPHONIA
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    2
    0
    0
    DYSPNOEA
         subjects affected / exposed
    0 / 20 (0.00%)
    4 / 19 (21.05%)
    1 / 17 (5.88%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    1
    2
    0
    0
    DYSPNOEA EXERTIONAL
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    EPISTAXIS
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    0
    HAEMOPTYSIS
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    1
    0
    LARYNGEAL OEDEMA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    NASAL CONGESTION
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    NASAL OBSTRUCTION
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    1
    0
    1
    0
    0
    PNEUMONITIS
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    1
    0
    0
    0
    PRODUCTIVE COUGH
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    RALES
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    WHEEZING
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Psychiatric disorders
    ANGER
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    ANXIETY
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    CONFUSIONAL STATE
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 19 (5.26%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    1
    1
    0
    0
    0
    DEPRESSION
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    DISORIENTATION
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    INSOMNIA
         subjects affected / exposed
    3 / 20 (15.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 19 (10.53%)
    1 / 17 (5.88%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    1
    3
    0
    0
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    3 / 19 (15.79%)
    0 / 17 (0.00%)
    2 / 20 (10.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    3
    0
    4
    1
    0
    BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    BLOOD BILIRUBIN INCREASED
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    BLOOD CREATINE PHOSPHOKINASE INCREASED
         subjects affected / exposed
    4 / 20 (20.00%)
    7 / 19 (36.84%)
    3 / 17 (17.65%)
    1 / 20 (5.00%)
    3 / 7 (42.86%)
    0 / 3 (0.00%)
         occurrences all number
    4
    9
    3
    1
    3
    0
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    1 / 20 (5.00%)
    4 / 19 (21.05%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    4
    0
    0
    0
    0
    BLOOD MAGNESIUM DECREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    BLOOD POTASSIUM DECREASED
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    BLOOD PRESSURE DECREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    BLOOD PRESSURE INCREASED
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    BLOOD THYROID STIMULATING HORMONE INCREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    BLOOD URIC ACID INCREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    BRAIN NATRIURETIC PEPTIDE INCREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    C-REACTIVE PROTEIN INCREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    CYTOMEGALOVIRUS TEST POSITIVE
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    EJECTION FRACTION DECREASED
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    2 / 17 (11.76%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    3
    0
    0
    0
    GAMMA-GLUTAMYLTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    HAEMOGLOBIN DECREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    INTERNATIONAL NORMALISED RATIO INCREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    PLATELET COUNT DECREASED
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    0
    1
    0
    PLATELET COUNT INCREASED
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    VITAMIN B12 DECREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    VITAMIN D DECREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    WEIGHT DECREASED
         subjects affected / exposed
    2 / 20 (10.00%)
    3 / 19 (15.79%)
    1 / 17 (5.88%)
    4 / 20 (20.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    3
    3
    1
    5
    0
    1
    Injury, poisoning and procedural complications
    CONTUSION
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    FACE INJURY
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    FALL
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    INFUSION RELATED REACTION
         subjects affected / exposed
    0 / 20 (0.00%)
    3 / 19 (15.79%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    1 / 3 (33.33%)
         occurrences all number
    0
    4
    1
    0
    2
    1
    INJURY
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    LIMB INJURY
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    POST PROCEDURAL SWELLING
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    SKIN LACERATION
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    STRESS FRACTURE
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    WOUND COMPLICATION
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Cardiac disorders
    ATRIAL FIBRILLATION
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    ATRIOVENTRICULAR BLOCK FIRST DEGREE
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    CARDIAC FAILURE CONGESTIVE
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    CORONARY ARTERY DISEASE
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    PERICARDITIS
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    SINUS BRADYCARDIA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    SINUS TACHYCARDIA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    TACHYCARDIA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    VENTRICULAR DYSFUNCTION
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Nervous system disorders
    APHASIA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    CAUDA EQUINA SYNDROME
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    CEREBRAL INFARCTION
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    DIZZINESS
         subjects affected / exposed
    0 / 20 (0.00%)
    4 / 19 (21.05%)
    2 / 17 (11.76%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    2
    1
    0
    0
    DIZZINESS POSTURAL
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    DYSARTHRIA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    DYSGEUSIA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    2
    0
    HEADACHE
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    3 / 20 (15.00%)
    2 / 7 (28.57%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    1
    3
    2
    1
    LETHARGY
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    LUMBAR RADICULOPATHY
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    NEUROPATHY PERIPHERAL
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    PARAESTHESIA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    PRESYNCOPE
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 19 (10.53%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    RESTLESS LEGS SYNDROME
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    SCIATICA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    STATUS EPILEPTICUS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    SYNCOPE
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    1
    0
    0
    TASTE DISORDER
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    8 / 20 (40.00%)
    6 / 19 (31.58%)
    4 / 17 (23.53%)
    2 / 20 (10.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    9
    6
    5
    4
    1
    0
    IRON DEFICIENCY ANAEMIA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    LEUKOCYTOSIS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    LEUKOPENIA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    LYMPH NODE PAIN
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    LYMPHADENITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    LYMPHOPENIA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    NEUTROPENIA
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    7
    0
    0
    0
    0
    1
    THROMBOCYTOPENIA
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    2 / 7 (28.57%)
    1 / 3 (33.33%)
         occurrences all number
    1
    1
    0
    1
    2
    1
    Ear and labyrinth disorders
    HYPOACUSIS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    INNER EAR DISORDER
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    VERTIGO
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Eye disorders
    CATARACT
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    CHORIORETINOPATHY
         subjects affected / exposed
    2 / 20 (10.00%)
    3 / 19 (15.79%)
    2 / 17 (11.76%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    2
    4
    2
    0
    1
    0
    ENTROPION
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    EYELID OEDEMA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    EYELID PTOSIS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    GLAUCOMA
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    LACRIMATION INCREASED
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    MACULAR OEDEMA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    OPTIC NERVE DISORDER
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    PERIORBITAL OEDEMA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    RETINAL OEDEMA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    RETINOPATHY
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    SUBRETINAL FLUID
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    SWELLING OF EYELID
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    TRICHIASIS
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    VISION BLURRED
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    3
    0
    0
    VISUAL IMPAIRMENT
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    0
    VITREOUS FLOATERS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Gastrointestinal disorders
    ABDOMINAL DISCOMFORT
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    ABDOMINAL DISTENSION
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    ABDOMINAL PAIN
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 19 (10.53%)
    2 / 17 (11.76%)
    1 / 20 (5.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
         occurrences all number
    0
    3
    2
    3
    3
    0
    ANAL HAEMORRHAGE
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    ANGULAR CHEILITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    ASCITES
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    CHEILITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    CONSTIPATION
         subjects affected / exposed
    1 / 20 (5.00%)
    5 / 19 (26.32%)
    3 / 17 (17.65%)
    4 / 20 (20.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    7
    3
    4
    2
    0
    DIAPHRAGMATIC HERNIA
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    DIARRHOEA
         subjects affected / exposed
    7 / 20 (35.00%)
    11 / 19 (57.89%)
    9 / 17 (52.94%)
    13 / 20 (65.00%)
    5 / 7 (71.43%)
    2 / 3 (66.67%)
         occurrences all number
    9
    15
    13
    16
    6
    2
    DRY MOUTH
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    0
    DYSPEPSIA
         subjects affected / exposed
    2 / 20 (10.00%)
    4 / 19 (21.05%)
    3 / 17 (17.65%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    4
    3
    0
    0
    0
    DYSPHAGIA
         subjects affected / exposed
    2 / 20 (10.00%)
    2 / 19 (10.53%)
    1 / 17 (5.88%)
    3 / 20 (15.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    3
    1
    3
    0
    0
    FLATULENCE
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    GASTRIC ULCER
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    GASTRITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    0
    1
    0
    GINGIVAL BLEEDING
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    GLOSSITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    GLOSSODYNIA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    HAEMATEMESIS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    HAEMATOCHEZIA
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 19 (10.53%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    HAEMORRHOIDS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    LIP OEDEMA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    LIP PAIN
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    LIP SWELLING
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    MOUTH ULCERATION
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    0
    MUCOUS STOOLS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    NAUSEA
         subjects affected / exposed
    6 / 20 (30.00%)
    3 / 19 (15.79%)
    5 / 17 (29.41%)
    6 / 20 (30.00%)
    4 / 7 (57.14%)
    0 / 3 (0.00%)
         occurrences all number
    6
    3
    5
    8
    5
    0
    OESOPHAGITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    ORAL DISCHARGE
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    ORAL PAIN
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    0
    RECTAL HAEMORRHAGE
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    STOMATITIS
         subjects affected / exposed
    2 / 20 (10.00%)
    5 / 19 (26.32%)
    2 / 17 (11.76%)
    4 / 20 (20.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    3
    5
    2
    4
    0
    1
    TOOTHACHE
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    VOMITING
         subjects affected / exposed
    7 / 20 (35.00%)
    4 / 19 (21.05%)
    3 / 17 (17.65%)
    4 / 20 (20.00%)
    1 / 7 (14.29%)
    1 / 3 (33.33%)
         occurrences all number
    9
    8
    3
    4
    2
    1
    Skin and subcutaneous tissue disorders
    ALOPECIA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    BLISTER
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    DERMATITIS
         subjects affected / exposed
    3 / 20 (15.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    1
    0
    0
    0
    DERMATITIS ACNEIFORM
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 19 (10.53%)
    3 / 17 (17.65%)
    5 / 20 (25.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    3
    5
    3
    0
    DERMATITIS PSORIASIFORM
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    DRY SKIN
         subjects affected / exposed
    3 / 20 (15.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    4 / 20 (20.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    1
    5
    2
    0
    ECZEMA
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    ERYTHEMA
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    INTERTRIGO
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    NIGHT SWEATS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    ONYCHOCLASIS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    PRURITUS
         subjects affected / exposed
    2 / 20 (10.00%)
    3 / 19 (15.79%)
    1 / 17 (5.88%)
    4 / 20 (20.00%)
    3 / 7 (42.86%)
    0 / 3 (0.00%)
         occurrences all number
    2
    3
    2
    4
    6
    0
    RASH
         subjects affected / exposed
    9 / 20 (45.00%)
    9 / 19 (47.37%)
    12 / 17 (70.59%)
    5 / 20 (25.00%)
    5 / 7 (71.43%)
    1 / 3 (33.33%)
         occurrences all number
    10
    11
    14
    6
    7
    1
    RASH ERYTHEMATOUS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    RASH MACULO-PAPULAR
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    RASH PAPULAR
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    RASH PRURITIC
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    SKIN FISSURES
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    2
    0
    0
    0
    1
    STASIS DERMATITIS
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    URTICARIA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    3
    2
    0
    0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    1 / 17 (5.88%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    0
    DYSURIA
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 19 (10.53%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    3 / 7 (42.86%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    3
    0
    HAEMATURIA
         subjects affected / exposed
    0 / 20 (0.00%)
    3 / 19 (15.79%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    0
    0
    2
    0
    NOCTURIA
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    POLLAKIURIA
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    PROTEINURIA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    RENAL FAILURE
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    RENAL IMPAIRMENT
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    URINARY RETENTION
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    3
    0
    URINARY TRACT OBSTRUCTION
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    URINARY TRACT PAIN
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Endocrine disorders
    HYPERTHYROIDISM
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    HYPOTHYROIDISM
         subjects affected / exposed
    3 / 20 (15.00%)
    1 / 19 (5.26%)
    1 / 17 (5.88%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    4
    1
    1
    2
    0
    0
    THYROIDITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    2 / 20 (10.00%)
    2 / 19 (10.53%)
    3 / 17 (17.65%)
    2 / 20 (10.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    2
    3
    3
    2
    1
    0
    BACK PAIN
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    1 / 17 (5.88%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    0
    BONE PAIN
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    FLANK PAIN
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    GROIN PAIN
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    JOINT SWELLING
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    MUSCLE SPASMS
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    1
    0
    1
    0
    0
    MUSCULAR WEAKNESS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    0
    1
    0
    MYALGIA
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 19 (10.53%)
    1 / 17 (5.88%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    1
    1
    0
    0
    MYOSITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    NECK PAIN
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    OSTEONECROSIS OF JAW
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    PAIN IN EXTREMITY
         subjects affected / exposed
    3 / 20 (15.00%)
    2 / 19 (10.53%)
    1 / 17 (5.88%)
    1 / 20 (5.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
         occurrences all number
    3
    2
    1
    1
    2
    0
    SYNOVITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    TRISMUS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Infections and infestations
    BRONCHITIS
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    CANDIDA INFECTION
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    CELLULITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    CONJUNCTIVITIS
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    1
    1
    0
    0
    CYSTITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    CYSTITIS BACTERIAL
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    DEVICE RELATED INFECTION
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    DIVERTICULITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    INFECTION
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    INFLUENZA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    3 / 20 (15.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    4
    0
    1
    1
    0
    0
    NASOPHARYNGITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    ORAL CANDIDIASIS
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    ORAL HERPES
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    OTITIS EXTERNA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    OTITIS MEDIA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    RASH PUSTULAR
         subjects affected / exposed
    2 / 20 (10.00%)
    2 / 19 (10.53%)
    0 / 17 (0.00%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    2
    0
    1
    0
    0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    RHINITIS
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    SKIN INFECTION
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    STAPHYLOCOCCAL INFECTION
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    TONGUE FUNGAL INFECTION
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    TOOTH INFECTION
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    4
    0
    0
    0
    0
    0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 19 (5.26%)
    2 / 17 (11.76%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    2
    1
    0
    0
    URINARY TRACT INFECTION
         subjects affected / exposed
    0 / 20 (0.00%)
    4 / 19 (21.05%)
    2 / 17 (11.76%)
    0 / 20 (0.00%)
    4 / 7 (57.14%)
    0 / 3 (0.00%)
         occurrences all number
    0
    5
    2
    0
    4
    0
    URINARY TRACT INFECTION STAPHYLOCOCCAL
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    VIRAL INFECTION
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Metabolism and nutrition disorders
    CACHEXIA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    DECREASED APPETITE
         subjects affected / exposed
    4 / 20 (20.00%)
    7 / 19 (36.84%)
    3 / 17 (17.65%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    4
    8
    4
    0
    1
    0
    DEHYDRATION
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    2
    0
    0
    0
    HYPERCALCAEMIA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    HYPERGLYCAEMIA
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    HYPERKALAEMIA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    1 / 17 (5.88%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    0
    HYPOALBUMINAEMIA
         subjects affected / exposed
    0 / 20 (0.00%)
    3 / 19 (15.79%)
    6 / 17 (35.29%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    7
    0
    0
    0
    HYPOCALCAEMIA
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    2
    0
    0
    HYPOKALAEMIA
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    2 / 20 (10.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    1
    0
    2
    0
    0
    HYPOMAGNESAEMIA
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 19 (0.00%)
    0 / 17 (0.00%)
    2 / 20 (10.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    2
    1
    0
    HYPONATRAEMIA
         subjects affected / exposed
    0 / 20 (0.00%)
    3 / 19 (15.79%)
    1 / 17 (5.88%)
    1 / 20 (5.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    3
    1
    1
    0
    0
    HYPOPHOSPHATAEMIA
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 19 (10.53%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    1
    2
    0
    0
    1
    0
    IRON DEFICIENCY
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 19 (5.26%)
    0 / 17 (0.00%)
    0 / 20 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Oct 2017
    Guidelines for managing subjects who experienced atezolizumab-associated adverse events were revised to include guidelines for hypophysitis and myocarditis. Adverse events of special interest (AESIs) were updated to include suspected transmission of an infectious agent by the study drug.
    29 Mar 2018
    Additional Cohorts 4-7 (post-CPI progressors and biopsy cohort) were added to the protocol with rationale for the additional cohorts. Tumor specimen biopsies in the cancer-related inclusion criteria were revised to allow more flexibility. Primary analysis was changed from 24 weeks to 16 weeks and sample size adjusted.
    18 Sep 2018
    Updated the lists of risks for atezolizumab and guidelines for managing subjects who experience atezolizumab-associated adverse events to include nephritis. Cobimetinib dose modification was amended to allow for dose re-escalations on a case-by-case basis after discussion with the Medical Monitor or his designee.

    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-Sat Apr 27 22:33:00 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA