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    Clinical Trial Results:
    AG-013736 (Axitinib) for the Treatment of Metastatic Renal Cell Cancer

    Summary
    EudraCT number
    		 2010-018585-23
    Trial protocol
    		 BG  
    Global end of trial date
    29 Apr 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 May 2022
    First version publication date
    06 May 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    A4061051
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00920816
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.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
    09 Jul 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Apr 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Compare the progression-free survival (PFS) of treatment-naïve subjects with metastatic renal cell carcinoma (mRCC) receiving AG-013736 versus sorafenib. Estimate the PFS of previously-treated Asian subjects with mRCC receiving AG-013736 versus sorafenib.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Aug 2009
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 3 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Bosnia and Herzegovina: 11
    Country: Number of subjects enrolled
    Bulgaria: 2
    Country: Number of subjects enrolled
    Chile: 29
    Country: Number of subjects enrolled
    India: 35
    Country: Number of subjects enrolled
    Malaysia: 6
    Country: Number of subjects enrolled
    Mexico: 11
    Country: Number of subjects enrolled
    Philippines: 14
    Country: Number of subjects enrolled
    Romania: 14
    Country: Number of subjects enrolled
    Russian Federation: 58
    Country: Number of subjects enrolled
    South Africa: 1
    Country: Number of subjects enrolled
    Ukraine: 61
    Country: Number of subjects enrolled
    United States: 29
    Country: Number of subjects enrolled
    Taiwan: 6
    Worldwide total number of subjects
    277
    EEA total number of subjects
    16
    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)
    213
    From 65 to 84 years
    63
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 First-line subjects included all treatment-naive subjects with metastatic renal cell cancer (mRCC) from global and second-line subjects included all previously-treated Asian subjects with mRCC.

    Pre-assignment
    Screening details
    		 All China subjects were excluded from safety analysis due to inability to obtain timely approval to use data in accordance with Human Genetic Resources Administration of China (HGRAC) regulation.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Axitinib (First-line Subjects)
    Arm description
    		 Subjects (excluding subjects from China) with no prior systemic first-line therapy received axitinib (AG-013736) tablet at a starting dose of 5 milligram (mg) orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Axitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg

    Arm title
    		 Sorafenib (First-line Subjects)
    Arm description
    		 Subjects (excluding subjects from China) with no prior systemic first-line therapy received sorafenib tablet at a starting dose of 400 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sorafenib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    400 mg

    Arm title
    		 Axitinib (Second-line Subjects)
    Arm description
    		 Asian subjects (excluding subjects from China) with prior systemic first-line therapy containing sunitinib or cytokine received axitinib (AG-013736) tablet at a starting dose of 5 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Axitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg

    Arm title
    		 Sorafenib (Second-line Subjects)
    Arm description
    		 Asian subjects (excluding subjects from China) with prior systemic first-line therapy containing sunitinib or cytokine received sorafenib tablet at a starting dose of 400 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sorafenib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg

    Number of subjects in period 1
    		Axitinib (First-line Subjects) Sorafenib (First-line Subjects) Axitinib (Second-line Subjects) Sorafenib (Second-line Subjects)
    Started
    173
    88
    11
    5
    Completed
    0
    0
    0
    0
    Not completed
    173
    88
    11
    5
         Global deterioration of health status
    2
    -
    -
    -
         Subject refused treatment
    11
    5
    1
    -
         Adverse event
    1
    1
    1
    -
         Subject died
    116
    63
    8
    3
         Unspecified
    26
    15
    1
    2
         Objective progression or relapse
    6
    2
    -
    -
         Lost to follow-up
    11
    2
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Axitinib (First-line Subjects)
    Reporting group description
    		 Subjects (excluding subjects from China) with no prior systemic first-line therapy received axitinib (AG-013736) tablet at a starting dose of 5 milligram (mg) orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.

    Reporting group title
    Sorafenib (First-line Subjects)
    Reporting group description
    		 Subjects (excluding subjects from China) with no prior systemic first-line therapy received sorafenib tablet at a starting dose of 400 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.

    Reporting group title
    Axitinib (Second-line Subjects)
    Reporting group description
    		 Asian subjects (excluding subjects from China) with prior systemic first-line therapy containing sunitinib or cytokine received axitinib (AG-013736) tablet at a starting dose of 5 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.

    Reporting group title
    Sorafenib (Second-line Subjects)
    Reporting group description
    		 Asian subjects (excluding subjects from China) with prior systemic first-line therapy containing sunitinib or cytokine received sorafenib tablet at a starting dose of 400 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.

    Reporting group values
    		 Axitinib (First-line Subjects) Sorafenib (First-line Subjects) Axitinib (Second-line Subjects) Sorafenib (Second-line Subjects) Total
    Number of subjects
    		 173 88 11 5 277
    Age Categorical
    Units: Subjects
        18-64 years
    		 126 72 10 5 213
        >=65 years
    		 47 16 1 0 64
    Sex: Female, Male
    Units: Subjects
        Male
    		 122 69 8 3 202
        Female
    		 51 19 3 2 75

    End points

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    End points reporting groups
    Reporting group title
    Axitinib (First-line Subjects)
    Reporting group description
    		 Subjects (excluding subjects from China) with no prior systemic first-line therapy received axitinib (AG-013736) tablet at a starting dose of 5 milligram (mg) orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.

    Reporting group title
    Sorafenib (First-line Subjects)
    Reporting group description
    		 Subjects (excluding subjects from China) with no prior systemic first-line therapy received sorafenib tablet at a starting dose of 400 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.

    Reporting group title
    Axitinib (Second-line Subjects)
    Reporting group description
    		 Asian subjects (excluding subjects from China) with prior systemic first-line therapy containing sunitinib or cytokine received axitinib (AG-013736) tablet at a starting dose of 5 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.

    Reporting group title
    Sorafenib (Second-line Subjects)
    Reporting group description
    		 Asian subjects (excluding subjects from China) with prior systemic first-line therapy containing sunitinib or cytokine received sorafenib tablet at a starting dose of 400 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.

    Subject analysis set title
    Axitinib (First-line Subjects): PCD
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects with no prior systemic first-line therapy received axitinib (AG-013736) tablet at a starting dose of 5 milligram (mg) orally twice daily, dose adjustment was done based on the tolerability, as per investigator's discretion. Study medication was administered in cycles of 4 weeks.

    Subject analysis set title
    Sorafenib (First-line Subjects): PCD
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects with no prior systemic first-line therapy received sorafenib tablet at a starting dose of 400 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator's discretion. Study medication was administered in cycles of 4 weeks.

    Subject analysis set title
    Axitinib (Second-line Subjects): PCD
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All Asian subjects with prior systemic first-line therapy containing sunitinib or cytokine received axitinib (AG-013736) tablet at a starting dose of 5 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator's discretion. Study medication was administered in cycles of 4 weeks.

    Subject analysis set title
    Sorafenib (Second-line Subjects): PCD
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All Asian subjects with prior systemic first-line therapy containing sunitinib or cytokine received sorafenib tablet at a starting dose of 400 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator's discretion. Study medication was administered in cycles of 4 weeks.

    Primary: Progression Free Survival (PFS): First-Line Subjects

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    End point title
    		 Progression Free Survival (PFS): First-Line Subjects
    End point description
    Time in months from randomisation to first documentation of objective tumour progression or death due to any cause. PFS calculated as (first event date minus date of randomisation plus 1)/30.4. Tumour progression determined from oncologic assessment data (where it meets criteria for progressive disease [PD]), or from adverse event (AE) data (where outcome was "Death"). Progression using Response Evaluation Criteria in Solid Tumours (RECIST) is >= 20 percent (%) increase in sum of longest diameter of target lesions; measurable increase in non-target lesion; appearance of new lesions. Full analysis set (FAS) included all previously-treated Asian subjects who were randomised, with study drug assignment designated according to initial randomisation, regardless of whether subjects received study drug, or received a different drug from that to which they were randomised.
    End point type
    Primary
    End point timeframe
    Baseline until disease progression or death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 107)
    End point values
    		 Axitinib (First-line Subjects): PCD Sorafenib (First-line Subjects): PCD
    Number of subjects analysed
    192
    96
    Units: months
        median (confidence interval 95%)
    10.1 (7.2 to 12.1)
    6.5 (4.7 to 8.3)
    Statistical analysis title
    		 Axitinib vs Sorafenib: First line, PCD
    Statistical analysis description
    First-line subjects: hazard ratio was stratified by eastern cooperative oncology group (ECOG) performance status (0 versus 1).
    Comparison groups
    Axitinib (First-line Subjects): PCD v Sorafenib (First-line Subjects): PCD
    Number of subjects included in analysis
    288
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.767
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.559
         upper limit
    		 1.053

    Primary: Progression Free Survival (PFS): Second-Line Subjects

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    End point title
    		 Progression Free Survival (PFS): Second-Line Subjects
    End point description
    Time in months from randomisation to first documentation of objective tumour progression or death due to any cause. PFS calculated as (first event date minus date of randomisation plus 1)/30.4. Tumour progression determined from oncologic assessment data (where it meets criteria for progressive disease [PD]), or from adverse event (AE) data (where outcome was "Death"). Progression using Response Evaluation Criteria in Solid Tumours (RECIST) is >= 20% increase in sum of longest diameter of target lesions; measurable increase in non-target lesion; appearance of new lesions. FAS included all previously-treated Asian subjects who were randomised, with study drug assignment designated according to initial randomisation, regardless of whether subjects received study drug, or received a different drug from that to which they were randomised.
    End point type
    Primary
    End point timeframe
    Baseline until disease progression or death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 103)
    End point values
    		 Axitinib (Second-line Subjects): PCD Sorafenib (Second-line Subjects): PCD
    Number of subjects analysed
    135
    69
    Units: months
        median (confidence interval 95%)
    6.5 (4.7 to 9.1)
    4.8 (3.0 to 6.5)
    Statistical analysis title
    		 Axitinib vs Sorafenib: Second line, PCD
    Statistical analysis description
    Second-line subjects: hazard ratio was stratified by eastern cooperative oncology group (ECOG) performance status (0 versus 1) and prior treatment (sunitinib versus cytokine-containing regimen).
    Comparison groups
    Axitinib (Second-line Subjects): PCD v Sorafenib (Second-line Subjects): PCD
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.731
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.506
         upper limit
    		 1.058

    Secondary: Percentage of Subjects With Objective Response (OR): First-Line Subjects

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    End point title
    		 Percentage of Subjects With Objective Response (OR): First-Line Subjects
    End point description
    Percentage of subjects with OR based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30% decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent. FAS included all previously-treated Asian subjects who were randomised, with study drug assignment designated according to initial randomisation, regardless of whether subjects received study drug, or received a different drug from that to which they were randomised.
    End point type
    Secondary
    End point timeframe
    Baseline until disease progression or death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 107)
    End point values
    		 Axitinib (First-line Subjects): PCD Sorafenib (First-line Subjects): PCD
    Number of subjects analysed
    192
    96
    Units: percentage of subjects
        number (confidence interval 95%)
    32.3 (25.7 to 39.4)
    14.6 (8.2 to 23.3)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Objective Response (OR): Second-Line Subjects

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    End point title
    		 Percentage of Subjects With Objective Response (OR): Second-Line Subjects
    End point description
    Percentage of subjects with OR based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30% decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent. FAS included all previously-treated Asian subjects who were randomised, with study drug assignment designated according to initial randomisation, regardless of whether subjects received study drug, or received a different drug from that to which they were randomised.
    End point type
    Secondary
    End point timeframe
    Baseline until disease progression or death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 103)
    End point values
    		 Axitinib (Second-line Subjects): PCD Sorafenib (Second-line Subjects): PCD
    Number of subjects analysed
    135
    69
    Units: percentage of subjects
        number (confidence interval 95%)
    23.7 (16.8 to 31.8)
    10.1 (4.2 to 19.8)
    No statistical analyses for this end point

    Secondary: Duration of Response (DR): First-Line Subjects

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    End point title
    		 Duration of Response (DR): First-Line Subjects
    End point description
    Time in months from the first documentation of objective tumour response that is subsequently confirmed to objective tumour progression or death due to any cause. Duration of tumour response was calculated as (the date of the first documentation of objective tumour progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of subjects with a confirmed objective tumour response. DR was calculated for the subgroup of subjects from the FAS treatment-naive population, with a confirmed objective tumour response (CR or PR). '99999' signifies that upper limit of CI was not estimable because subjects were still responding to medication as the study was ongoing at the time of primary completion analysis and this analysis was final.
    End point type
    Secondary
    End point timeframe
    Baseline until disease progression or death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 107)
    End point values
    		 Axitinib (First-line Subjects): PCD Sorafenib (First-line Subjects): PCD
    Number of subjects analysed
    62
    14
    Units: months
        median (confidence interval 95%)
    14.7 (11.0 to 99999)
    14.3 (11.3 to 99999)
    No statistical analyses for this end point

    Secondary: Duration of Response (DR): Second-Line Subjects

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    End point title
    		 Duration of Response (DR): Second-Line Subjects
    End point description
    Time in months from the first documentation of objective tumour response that is subsequently confirmed to objective tumour progression or death due to any cause. Duration of tumour response was calculated as (the date of the first documentation of objective tumour progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of subjects with a confirmed objective tumour response. DR was calculated for the subgroup of subjects from the FAS previously-treated population, with a confirmed objective tumour response (CR or PR). '99999' signifies that median and upper limit of CI was not estimable because subjects were still responding to medication as the study was ongoing at the time of primary completion analysis and this analysis was final.
    End point type
    Secondary
    End point timeframe
    Baseline until disease progression or death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 103)
    End point values
    		 Axitinib (Second-line Subjects): PCD Sorafenib (Second-line Subjects): PCD
    Number of subjects analysed
    32
    7
    Units: months
        median (confidence interval 95%)
    99999 (12.5 to 99999)
    8.7 (4.1 to 99999)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS): First-Line Subjects

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    End point title
    		 Overall Survival (OS): First-Line Subjects
    End point description
    Time in months from date of randomisation to date of death due to any cause. OS was calculated as (the death date minus the date of randomisation plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the subject current status was death). FAS included all treatment-naive subjects who were randomised, with study drug assignment designated according to initial randomisation, regardless of whether subjects received study drug, or received a different drug from that to which they were randomised. "99999" signifies that median and upper limit of the CI was not reachable as data was not matured at the time of the analysis as the study was ongoing at the time of primary completion analysis and this analysis was final.
    End point type
    Secondary
    End point timeframe
    Baseline until death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 107)
    End point values
    		 Axitinib (First-line Subjects): PCD Sorafenib (First-line Subjects): PCD
    Number of subjects analysed
    192
    96
    Units: months
        median (confidence interval 95%)
    99999 (18.1 to 99999)
    99999 (18.1 to 99999)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS): Second-Line Subjects

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    End point title
    		 Overall Survival (OS): Second-Line Subjects
    End point description
    Time in months from date of randomisation to date of death due to any cause. OS was calculated as (the death date minus the date of randomisation plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the subject current status was death). FAS included all treatment-naive subjects who were randomised, with study drug assignment designated according to initial randomisation, regardless of whether subjects received study drug, or received a different drug from that to which they were randomised. "99999" signifies that upper limit of the CI was not reachable as data was not matured at the time of the analysis as the study was ongoing at the time of primary completion analysis and this analysis was final.
    End point type
    Secondary
    End point timeframe
    Baseline until death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 103)
    End point values
    		 Axitinib (Second-line Subjects): PCD Sorafenib (Second-line Subjects): PCD
    Number of subjects analysed
    135
    69
    Units: months
        median (confidence interval 95%)
    17.2 (14.8 to 99999)
    18.1 (12.1 to 99999)
    No statistical analyses for this end point

    Other pre-specified: Functional Assessment of Cancer Therapy Kidney Symptom Index-15 (FKSI-15): First-Line Subjects

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    End point title
    		 Functional Assessment of Cancer Therapy Kidney Symptom Index-15 (FKSI-15): First-Line Subjects
    End point description
    FKSI-15 questionnaires (lack of energy, side effects, pain, weight loss, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria, sleep) was used to assess quality of life (QoL) for those diagnosed with renal cell cancer. Questions answered on 5-point Likert scale: 0 to 4 (0= not at all, 1= little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score 0 to 60; higher scores=better health states (Individual questions may be reversed coded, as appropriate). FAS treatment-naive population. Here ‘Number of subjects analysed’ signifies those subjects who were evaluable for this endpoint and ‘n’ signifies those subjects evaluated for this endpoint at specific time points for each group respectively.
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C23, end of treatment (up to Week 107), follow-up (28 days after last dose)
    End point values
    		 Axitinib (First-line Subjects): PCD Sorafenib (First-line Subjects): PCD
    Number of subjects analysed
    183
    95
    Units: units on a scale
    arithmetic mean (standard deviation)
        C1 D1 (n= 183, 95)
    43.869 ( 8.117 )
    43.865 ( 6.723 )
        C2 D1 (n= 176, 90)
    43.328 ( 7.630 )
    43.969 ( 6.286 )
        C3 D1 (n= 164, 84)
    43.366 ( 7.192 )
    43.345 ( 6.878 )
        C4 D1 (n= 156, 81)
    42.932 ( 7.566 )
    42.926 ( 7.324 )
        C5 D1 (n= 153, 77)
    43.211 ( 7.578 )
    44.022 ( 6.714 )
        C6 D1 (n= 141, 72)
    42.787 ( 8.098 )
    42.344 ( 6.685 )
        C7 D1 (n= 139, 65)
    42.474 ( 7.926 )
    43.446 ( 6.931 )
        C8 D1 (n= 131, 60)
    42.534 ( 7.510 )
    44.077 ( 6.986 )
        C9 D1 (n= 126, 59)
    42.778 ( 8.229 )
    44.051 ( 7.234 )
        C10 D1 (n= 122, 55)
    43.120 ( 7.966 )
    44.018 ( 6.751 )
        C11 D1 (n= 114, 48)
    43.264 ( 7.837 )
    45.000 ( 6.130 )
        C12 D1 (n= 105, 44)
    43.962 ( 7.243 )
    45.318 ( 6.440 )
        C13 D1 (n= 99, 44)
    44.141 ( 7.289 )
    45.787 ( 6.526 )
        C14 D1 (n= 95, 37)
    43.789 ( 7.985 )
    45.459 ( 6.535 )
        C15 D1 (n= 85, 37)
    44.176 ( 8.055 )
    45.514 ( 5.914 )
        C16 D1 (n= 82, 33)
    44.232 ( 7.515 )
    46.000 ( 5.651 )
        C17 D1 (n= 78, 30)
    43.897 ( 8.456 )
    46.400 ( 6.262 )
        C18 D1 (n= 71, 28)
    43.761 ( 8.019 )
    45.357 ( 6.983 )
        C19 D1 (n= 57, 24)
    43.737 ( 7.413 )
    45.583 ( 7.366 )
        C20 D1 (n= 45, 21)
    43.733 ( 7.605 )
    44.333 ( 7.066 )
        C21 D1 (n= 36, 18)
    45.417 ( 6.240 )
    43.500 ( 7.687 )
        C22 D1 (n= 23, 12)
    47.000 ( 5.985 )
    45.833 ( 5.937 )
        C23 D1 (n= 14, 7)
    47.571 ( 6.357 )
    45.714 ( 6.651 )
        End of treatment (n= 72, 42)
    39.052 ( 9.109 )
    39.524 ( 8.896 )
        Follow-up (n= 41, 26)
    39.683 ( 11.132 )
    40.038 ( 9.897 )
    No statistical analyses for this end point

    Other pre-specified: Functional Assessment of Cancer Therapy Kidney Symptom Index-15 (FKSI-15): Second-Line Subjects

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    End point title
    		 Functional Assessment of Cancer Therapy Kidney Symptom Index-15 (FKSI-15): Second-Line Subjects
    End point description
    FKSI-15 questionnaires (lack of energy, side effects, pain, weight loss, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria, sleep) was used to assess quality of life (QoL) for those diagnosed with renal cell cancer. Questions answered on 5-point Likert scale: 0 to 4 (0= not at all, 1= little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score 0 to 60; higher scores=better health states (Individual questions may be reversed coded, as appropriate). FAS previously-treated Asian population. Here ‘Number of subjects analysed’ signifies those subjects who were evaluable for this endpoint and ‘n’ signifies those subjects evaluated for this endpoint at specific time points for each group respectively.
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C21, end of treatment (up to Week 103), follow-up (28 days after last dose)
    End point values
    		 Axitinib (Second-line Subjects): PCD Sorafenib (Second-line Subjects): PCD
    Number of subjects analysed
    134
    69
    Units: units on a scale
    arithmetic mean (standard deviation)
        C1 D1 (n= 134, 69)
    46.753 ( 6.692 )
    47.470 ( 7.450 )
        C2 D1 (n= 127, 66)
    46.217 ( 7.028 )
    45.045 ( 7.478 )
        C3 D1 (n= 124, 57)
    45.968 ( 7.237 )
    45.684 ( 7.756 )
        C4 D1 (n= 116, 53)
    45.060 ( 8.040 )
    45.792 ( 7.762 )
        C5 D1 (n= 111, 48)
    45.775 ( 7.797 )
    46.125 ( 7.491 )
        C6 D1 (n= 108, 41)
    45.407 ( 7.274 )
    46.341 ( 7.213 )
        C7 D1 (n= 100, 38)
    45.709 ( 8.263 )
    45.053 ( 7.843 )
        C8 D1 (n= 89, 37)
    45.169 ( 7.609 )
    45.676 ( 9.357 )
        C9 D1 (n= 82, 33)
    45.829 ( 7.442 )
    45.970 ( 8.487 )
        C10 D1 (n= 74, 27)
    45.608 ( 8.299 )
    46.148 ( 8.156 )
        C11 D1 (n= 66, 22)
    45.833 ( 7.599 )
    47.227 ( 6.611 )
        C12 D1 (n= 59, 22)
    45.797 ( 6.967 )
    48.091 ( 6.414 )
        C13 D1 (n= 55, 20)
    46.727 ( 7.307 )
    47.600 ( 5.762 )
        C14 D1 (n= 50, 15)
    47.740 ( 7.094 )
    49.133 ( 5.235 )
        C15 D1 (n= 44, 13)
    48.023 ( 6.297 )
    49.308 ( 4.111 )
        C16 D1 (n= 38, 12)
    48.184 ( 6.186 )
    50.500 ( 3.989 )
        C17 D1 (n= 33, 10)
    47.909 ( 6.866 )
    49.000 ( 5.869 )
        C18 D1 (n= 29, 8)
    48.138 ( 6.791 )
    49.125 ( 5.139 )
        C19 D1 (n= 22, 7)
    48.636 ( 5.206 )
    48.571 ( 7.458 )
        C20 D1 (n= 21, 6)
    48.810 ( 6.478 )
    50.500 ( 4.637 )
        C21 D1 (n= 16, 6)
    50.188 ( 5.588 )
    50.000 ( 5.177 )
        End of treatment (n= 37, 27)
    41.432 ( 9.188 )
    42.889 ( 8.846 )
        Follow-up (n= 13, 12)
    35.385 ( 7.795 )
    38.583 ( 11.556 )
    No statistical analyses for this end point

    Other pre-specified: Functional Assessment of Cancer Therapy Kidney Symptom Index -Disease Related Symptoms (FKSI-DRS): First-Line Subjects

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    End point title
    		 Functional Assessment of Cancer Therapy Kidney Symptom Index -Disease Related Symptoms (FKSI-DRS): First-Line Subjects
    End point description
    FKSI-DRS: subset of FKSI which is FACT–Kidney Symptom Index questionnaire used to assess QoL for subjects diagnosed with renal cell cancer. FKSI contains 15 questions and FKSI-DRS 9 questions (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, hematuria) each ranging from 0 (not at all) to 4 (very much). FKSI-DRS total score 0 to 36; higher scores associated with better health states (Individual questions may be reversed coded, as appropriate). FAS treatment-naive population. Here ‘Number of subjects analysed’ signifies those subjects who were evaluable for this endpoint and ‘n’ signifies those subjects evaluated for this endpoint at specific time points for each group respectively.
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C23, end of treatment (up to Week 107), follow-up (28 days after last dose)
    End point values
    		 Axitinib (First-line Subjects): PCD Sorafenib (First-line Subjects): PCD
    Number of subjects analysed
    183
    95
    Units: units on a scale
    arithmetic mean (standard deviation)
        C1 D1 (n= 183, 95)
    28.691 ( 5.392 )
    29.653 ( 4.699 )
        C2 D1 (n= 176, 90)
    28.728 ( 4.581 )
    29.963 ( 3.817 )
        C3 D1 (n= 164, 84)
    29.171 ( 4.093 )
    29.750 ( 4.095 )
        C4 D1 (n= 156, 81)
    28.577 ( 4.305 )
    29.642 ( 4.244 )
        C5 D1 (n= 153, 77)
    29.020 ( 4.257 )
    30.255 ( 3.668 )
        C6 D1 (n= 141, 72)
    28.574 ( 4.674 )
    29.153 ( 4.009 )
        C7 D1 (n= 139, 65)
    28.568 ( 4.548 )
    29.523 ( 4.051 )
        C8 D1 (n= 131, 60)
    28.557 ( 4.308 )
    30.296 ( 3.890 )
        C9 D1 (n= 126, 59)
    28.817 ( 4.665 )
    30.186 ( 4.392 )
        C10 D1 (n= 122, 55)
    29.057 ( 4.484 )
    30.364 ( 4.143 )
        C11 D1 (n= 114, 48)
    29.146 ( 4.207 )
    30.688 ( 3.926 )
        C12 D1 (n= 105, 44)
    29.648 ( 3.752 )
    30.727 ( 3.896 )
        C13 D1 (n= 99, 44)
    29.545 ( 4.056 )
    31.483 ( 3.602 )
        C14 D1 (n= 95, 37)
    29.579 ( 4.186 )
    31.027 ( 3.790 )
        C15 D1 (n= 85, 37)
    29.859 ( 4.438 )
    30.730 ( 3.724 )
        C16 D1 (n= 82, 33)
    29.683 ( 4.242 )
    31.515 ( 3.242 )
        C17 D1 (n= 78, 30)
    29.564 ( 4.695 )
    31.567 ( 3.884 )
        C18 D1 (n= 71, 28)
    29.380 ( 4.752 )
    31.107 ( 4.425 )
        C19 D1 (n= 57, 24)
    29.737 ( 4.414 )
    31.417 ( 3.911 )
        C20 D1 (n= 45, 21)
    29.844 ( 4.527 )
    30.762 ( 4.122 )
        C21 D1 (n= 36, 18)
    30.889 ( 3.115 )
    30.056 ( 4.372 )
        C22 D1 (n= 23, 12)
    31.696 ( 3.081 )
    31.000 ( 3.275 )
        C23 D1 (n= 14, 7)
    31.357 ( 3.388 )
    31.143 ( 4.413 )
        End of treatment (n= 72, 42)
    26.556 ( 5.487 )
    26.786 ( 5.982 )
        Follow-up (n= 41, 26)
    26.805 ( 6.373 )
    26.769 ( 6.095 )
    No statistical analyses for this end point

    Other pre-specified: Functional Assessment of Cancer Therapy Kidney Symptom Index -Disease Related Symptoms (FKSI-DRS): Second-Line Subjects

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    End point title
    		 Functional Assessment of Cancer Therapy Kidney Symptom Index -Disease Related Symptoms (FKSI-DRS): Second-Line Subjects
    End point description
    FKSI-DRS: subset of FKSI which is FACT–Kidney Symptom Index questionnaire used to assess QoL for subjects diagnosed with renal cell cancer. FKSI contains 15 questions and FKSI-DRS 9 questions (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, hematuria) each ranging from 0 (not at all) to 4 (very much). FKSI-DRS total score 0 to 36; higher scores associated with better health states (Individual questions may be reversed coded, as appropriate). FAS previously-treated Asian population. Here ‘Number of subjects analysed’ signifies those subjects who were evaluable for this endpoint and ‘n’ signifies those subjects evaluated for this endpoint at specific time points for each group respectively.
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C21, end of treatment (up to Week 103), follow-up (28 days after last dose)
    End point values
    		 Axitinib (Second-line Subjects): PCD Sorafenib (Second-line Subjects): PCD
    Number of subjects analysed
    134
    69
    Units: units on a scale
    arithmetic mean (standard deviation)
        C1 D1 (n= 134, 69)
    31.020 ( 3.986 )
    31.489 ( 4.538 )
        C2 D1 (n= 127, 66)
    30.600 ( 3.892 )
    30.682 ( 3.895 )
        C3 D1 (n= 124, 57)
    30.645 ( 3.681 )
    30.965 ( 3.803 )
        C4 D1 (n= 116, 53)
    30.103 ( 4.558 )
    30.679 ( 3.980 )
        C5 D1 (n= 111, 48)
    30.676 ( 4.271 )
    31.063 ( 3.629 )
        C6 D1 (n= 108, 41)
    30.731 ( 3.973 )
    31.439 ( 4.249 )
        C7 D1 (n= 100, 38)
    30.920 ( 4.373 )
    30.632 ( 4.365 )
        C8 D1 (n= 89, 37)
    30.966 ( 4.144 )
    30.703 ( 5.195 )
        C9 D1 (n= 82, 33)
    31.012 ( 3.783 )
    30.667 ( 4.884 )
        C10 D1 (n= 74, 27)
    30.986 ( 4.133 )
    30.926 ( 4.215 )
        C11 D1 (n= 66, 22)
    31.212 ( 4.033 )
    32.045 ( 3.579 )
        C12 D1 (n= 59, 22)
    31.356 ( 3.443 )
    32.000 ( 3.338 )
        C13 D1 (n= 55, 20)
    31.418 ( 3.775 )
    32.100 ( 2.989 )
        C14 D1 (n= 50, 15)
    32.100 ( 3.321 )
    32.800 ( 2.274 )
        C15 D1 (n= 44, 13)
    32.000 ( 2.861 )
    32.769 ( 2.279 )
        C16 D1 (n= 38, 12)
    31.921 ( 3.372 )
    33.167 ( 2.167 )
        C17 D1 (n= 33, 10)
    32.061 ( 3.344 )
    32.800 ( 2.898 )
        C18 D1 (n= 29, 8)
    31.931 ( 3.116 )
    32.625 ( 2.615 )
        C19 D1 (n= 22, 7)
    32.364 ( 2.341 )
    32.429 ( 4.429 )
        C20 D1 (n= 21, 6)
    31.905 ( 2.998 )
    33.500 ( 2.168 )
        C21 D1 (n= 16, 6)
    33.125 ( 2.473 )
    33.500 ( 2.345 )
        End of treatment (n= 37, 27)
    28.216 ( 5.662 )
    29.519 ( 4.661 )
        Follow-up (n= 13, 12)
    24.692 ( 4.366 )
    27.500 ( 6.762 )
    No statistical analyses for this end point

    Other pre-specified: Euro Quality of Life Questionnaire- 5 Dimensions (EQ-5D) Index Score: First-Line Subjects

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    End point title
    		 Euro Quality of Life Questionnaire- 5 Dimensions (EQ-5D) Index Score: First-Line Subjects
    End point description
    EQ-5D: Subject rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. FAS treatment-naive population. Here ‘Number of subjects analysed’ signifies those subjects who were evaluable for this endpoint and ‘n’ signifies those subjects evaluated for this endpoint at specific time points for each group respectively.
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C23, end of treatment (up to Week 107), follow-up (28 days after last dose)
    End point values
    		 Axitinib (First-line Subjects): PCD Sorafenib (First-line Subjects): PCD
    Number of subjects analysed
    183
    94
    Units: units on a scale
    arithmetic mean (standard deviation)
        C1 D1 (n= 183, 94)
    0.710 ( 0.254 )
    0.712 ( 0.272 )
        C2 D1 (n= 175, 90)
    0.709 ( 0.214 )
    0.693 ( 0.237 )
        C3 D1 (n= 163, 84)
    0.694 ( 0.251 )
    0.687 ( 0.261 )
        C4 D1 (n= 156, 81)
    0.696 ( 0.235 )
    0.668 ( 0.265 )
        C5 D1 (n= 153, 77)
    0.708 ( 0.221 )
    0.673 ( 0.269 )
        C6 D1 (n= 140, 72)
    0.683 ( 0.263 )
    0.641 ( 0.281 )
        C7 D1 (n= 139, 65)
    0.685 ( 0.225 )
    0.676 ( 0.676 )
        C8 D1 (n= 131, 60)
    0.678 ( 0.274 )
    0.717 ( 0.244 )
        C9 D1 (n= 126, 59)
    0.704 ( 0.239 )
    0.729 ( 0.202 )
        C10 D1 (n= 122, 55)
    0.682 ( 0.277 )
    0.723 ( 0.238 )
        C11 D1 (n= 114, 48)
    0.698 ( 0.260 )
    0.748 ( 0.199 )
        C12 D1 (n= 105, 44)
    0.708 ( 0.227 )
    0.742 ( 0.218 )
        C13 D1 (n= 99, 44)
    0.708 ( 0.253 )
    0.761 ( 0.220 )
        C14 D1 (n= 95, 37)
    0.703 ( 0.260 )
    0.731 ( 0.254 )
        C15 D1 (n= 85, 37)
    0.689 ( 0.269 )
    0.755 ( 0.225 )
        C16 D1 (n= 82, 33)
    0.702 ( 0.244 )
    0.775 ( 0.186 )
        C17 D1 (n= 78, 30)
    0.706 ( 0.250 )
    0.738 ( 0.250 )
        C18 D1 (n= 71, 28)
    0.699 ( 0.259 )
    0.777 ( 0.191 )
        C19 D1 (n= 56, 24)
    0.713 ( 0.256 )
    0.762 ( 0.261 )
        C20 D1 (n= 45, 21)
    0.699 ( 0.261 )
    0.710 ( 0.300 )
        C21 D1 (n= 36, 18)
    0.712 ( 0.232 )
    0.702 ( 0.307 )
        C22 D1 (n= 23, 12)
    0.737 ( 0.255 )
    0.774 ( 0.177 )
        C23 D1 (n= 14, 7)
    0.736 ( 0.275 )
    0.789 ( 0.187 )
        End of treatment (n= 70, 42)
    0.635 ( 0.268 )
    0.588 ( 0.291 )
        Follow-up (n= 41, 26)
    0.545 ( 0.434 )
    0.618 ( 0.254 )
    No statistical analyses for this end point

    Other pre-specified: Euro Quality of Life Questionnaire- 5 Dimensions (EQ-5D) Index Score: Second-Line Subjects

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    End point title
    		 Euro Quality of Life Questionnaire- 5 Dimensions (EQ-5D) Index Score: Second-Line Subjects
    End point description
    EQ-5D: Subject rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. FAS previously-treated Asian population. Here ‘Number of subjects analysed’ signifies those subjects who were evaluable for this endpoint and ‘n’ signifies those subjects evaluated for this endpoint at specific time points for each group respectively.
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C21, end of treatment (up to Week 103), follow-up (28 days after last dose)
    End point values
    		 Axitinib (Second-line Subjects): PCD Sorafenib (Second-line Subjects): PCD
    Number of subjects analysed
    134
    69
    Units: units on a scale
    arithmetic mean (standard deviation)
        C1 D1 (n= 134, 69)
    0.812 ( 0.225 )
    0.831 ( 0.186 )
        C2 D1 (n= 127, 65)
    0.769 ( 0.218 )
    0.754 ( 0.251 )
        C3 D1 (n= 124, 58)
    0.772 ( 0.206 )
    0.755 ( 0.278 )
        C4 D1 (n= 116, 53)
    0.737 ( 0.272 )
    0.759 ( 0.211 )
        C5 D1 (n= 111, 48)
    0.780 ( 0.203 )
    0.768 ( 0.275 )
        C6 D1 (n= 108, 41)
    0.767 ( 0.251 )
    0.753 ( 0.245 )
        C7 D1 (n= 100, 38)
    0.762 ( 0.252 )
    0.768 ( 0.239 )
        C8 D1 (n= 89, 37)
    0.758 ( 0.241 )
    0.733 ( 0.339 )
        C9 D1 (n= 82, 33)
    0.796 ( 0.203 )
    0.794 ( 0.262 )
        C10 D1 (n= 74, 27)
    0.768 ( 0.243 )
    0.820 ( 0.169 )
        C11 D1 (n= 66, 22)
    0.792 ( 0.210 )
    0.848 ( 0.158 )
        C12 D1 (n= 59, 22)
    0.797 ( 0.201 )
    0.837 ( 0.157 )
        C13 D1 (n= 55, 20)
    0.786 ( 0.217 )
    0.814 ( 0.156 )
        C14 D1 (n= 50, 15)
    0.833 ( 0.162 )
    0.871 ( 0.131 )
        C15 D1 (n= 44, 13)
    0.819 ( 0.151 )
    0.829 ( 0.152 )
        C16 D1 (n= 38, 12)
    0.811 ( 0.186 )
    0.828 ( 0.142 )
        C17 D1 (n= 33, 10)
    0.834 ( 0.158 )
    0.865 ( 0.122 )
        C18 D1 (n= 29, 8)
    0.830 ( 0.164 )
    0.829 ( 0.160 )
        C19 D1 (n= 22, 7)
    0.830 ( 0.148 )
    0.861 ( 0.139 )
        C20 D1 (n= 21, 6)
    0.832 ( 0.163 )
    0.923 ( 0.129 )
        C21 D1 (n= 16, 6)
    0.859 ( 0.155 )
    0.852 ( 0.176 )
        End of treatment (n= 37, 27)
    0.582 ( 0.406 )
    0.623 ( 0.296 )
        Follow-up (n= 13, 12)
    0.429 ( 0.358 )
    0.418 ( 0.565 )
    No statistical analyses for this end point

    Other pre-specified: Euro Quality of Life Questionnaire- 5 Dimensions (EQ-5D) Visual Analog Scale (VAS): First-Line Subjects

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    End point title
    		 Euro Quality of Life Questionnaire- 5 Dimensions (EQ-5D) Visual Analog Scale (VAS): First-Line Subjects
    End point description
    EQ-5D: Subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0: worst imaginable health state to 100: best imaginable health state; higher scores indicate a better health state. FAS treatment-naive population. Here ‘Number of subjects analysed’ signifies those subjects who were evaluable for this endpoint and ‘n’ signifies those subjects evaluated for this endpoint at specific time points for each group respectively.
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C23, end of treatment (up to Week 107), follow-up (28 days after last dose)
    End point values
    		 Axitinib (First-line Subjects): PCD Sorafenib (First-line Subjects): PCD
    Number of subjects analysed
    182
    94
    Units: units on a scale
    arithmetic mean (standard deviation)
        C1 D1 (n= 182, 94)
    71.181 ( 19.641 )
    72.362 ( 16.466 )
        C2 D1 (n= 175, 90)
    71.714 ( 16.583 )
    72.422 ( 14.576 )
        C3 D1 (n= 165, 83)
    72.006 ( 16.971 )
    71.241 ( 16.252 )
        C4 D1 (n= 156, 81)
    72.179 ( 16.980 )
    72.086 ( 14.904 )
        C5 D1 (n= 153, 78)
    72.451 ( 18.237 )
    73.615 ( 14.665 )
        C6 D1 (n= 141, 72)
    71.574 ( 18.929 )
    69.944 ( 17.535 )
        C7 D1 (n= 139, 65)
    71.050 ( 18.967 )
    73.923 ( 13.998 )
        C8 D1 (n= 131, 60)
    71.031 ( 19.081 )
    73.183 ( 16.674 )
        C9 D1 (n= 126, 59)
    72.690 ( 18.789 )
    73.780 ( 16.180 )
        C10 D1 (n= 122, 55)
    72.910 ( 19.354 )
    72.400 ( 18.814 )
        C11 D1 (n= 114, 48)
    72.763 ( 18.174 )
    72.271 ( 18.512 )
        C12 D1 (n= 105, 44)
    73.610 ( 18.275 )
    75.295 ( 17.052 )
        C13 D1 (n= 99, 44)
    73.030 ( 18.348 )
    75.432 ( 17.907 )
        C14 D1 (n= 95, 37)
    73.147 ( 17.546 )
    75.108 ( 18.371 )
        C15 D1 (n= 85, 37)
    74.494 ( 17.938 )
    74.405 ( 17.650 )
        C16 D1 (n= 82, 33)
    73.878 ( 18.289 )
    75.818 ( 17.716 )
        C17 D1 (n= 78, 30)
    73.090 ( 17.717 )
    74.333 ( 18.654 )
        C18 D1 (n= 71, 28)
    73.817 ( 17.288 )
    75.571 ( 18.550 )
        C19 D1 (n= 56, 24)
    72.089 ( 18.169 )
    75.125 ( 20.919 )
        C20 D1 (n= 45, 21)
    74.244 ( 17.044 )
    74.190 ( 20.425 )
        C21 D1 (n= 36, 18)
    75.694 ( 11.918 )
    70.500 ( 21.637 )
        C22 D1 (n= 23, 12)
    78.000 ( 12.544 )
    73.917 ( 15.900 )
        C23 D1 (n= 14, 7)
    77.143 ( 12.697 )
    72.571 ( 14.820 )
        End of treatment (n= 71, 42)
    67.254 ( 19.495 )
    67.048 ( 22.570 )
        Follow-up (n= 41, 26)
    69.195 ( 20.366 )
    64.885 ( 19.916 )
    No statistical analyses for this end point

    Other pre-specified: Euro Quality of Life Questionnaire- 5 Dimensions (EQ-5D) Visual Analog Scale (VAS): Second-Line Subjects

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    End point title
    		 Euro Quality of Life Questionnaire- 5 Dimensions (EQ-5D) Visual Analog Scale (VAS): Second-Line Subjects
    End point description
    EQ-5D: Subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0: worst imaginable health state to 100: best imaginable health state; higher scores indicate a better health state. FAS previously-treated Asian population. Here ‘Number of subjects analysed’ signifies those subjects who were evaluable for this endpoint and ‘n’ signifies those endpoint evaluated for this measure at specific time points for each group respectively.
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C21, end of treatment (up to Week 103), follow-up (28 days after last dose)
    End point values
    		 Axitinib (Second-line Subjects): PCD Sorafenib (Second-line Subjects): PCD
    Number of subjects analysed
    134
    69
    Units: units on a scale
    arithmetic mean (standard deviation)
        C1 D1 (n= 134, 69)
    82.799 ( 13.351 )
    82.058 ( 14.021 )
        C2 D1 (n= 127, 65)
    81.102 ( 13.895 )
    78.231 ( 15.823 )
        C3 D1 (n= 124, 58)
    80.895 ( 13.387 )
    80.534 ( 16.453 )
        C4 D1 (n= 116, 53)
    81.138 ( 13.508 )
    81.245 ( 14.590 )
        C5 D1 (n= 111, 48)
    83.018 ( 12.829 )
    80.250 ( 15.495 )
        C6 D1 (n= 108, 41)
    82.222 ( 13.793 )
    80.829 ( 15.091 )
        C7 D1 (n= 100, 38)
    82.900 ( 13.287 )
    80.868 ( 16.140 )
        C8 D1 (n= 89, 37)
    83.382 ( 12.636 )
    81.000 ( 14.606 )
        C9 D1 (n= 82, 33)
    84.171 ( 11.260 )
    83.788 ( 10.349 )
        C10 D1 (n= 74, 27)
    83.041 ( 13.042 )
    82.778 ( 11.440 )
        C11 D1 (n= 66, 22)
    84.136 ( 14.231 )
    83.000 ( 11.832 )
        C12 D1 (n= 59, 22)
    84.305 ( 13.211 )
    83.500 ( 12.188 )
        C13 D1 (n= 55, 20)
    82.927 ( 17.317 )
    83.300 ( 11.263 )
        C14 D1 (n= 50, 15)
    86.520 ( 10.831 )
    86.667 ( 8.715 )
        C15 D1 (n= 44, 13)
    85.841 ( 11.783 )
    86.462 ( 8.678 )
        C16 D1 (n= 38, 12)
    87.579 ( 10.391 )
    86.083 ( 8.816 )
        C17 D1 (n= 33, 10)
    88.424 ( 10.866 )
    84.300 ( 10.328 )
        C18 D1 (n= 29, 8)
    86.586 ( 13.605 )
    83.125 ( 8.839 )
        C19 D1 (n= 22, 7)
    89.500 ( 8.684 )
    82.143 ( 11.495 )
        C20 D1 (n= 21, 6)
    90.333 ( 8.679 )
    86.000 ( 9.695 )
        C21 D1 (n= 16, 6)
    90.313 ( 9.741 )
    84.167 ( 9.704 )
        End of treatment (n= 37, 27)
    75.568 ( 17.934 )
    74.741 ( 17.623 )
        Follow-up (n= 13, 12)
    58.154 ( 20.760 )
    64.333 ( 25.564 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to at least 3 years after the randomization of the last subject
    Adverse event reporting additional description
    Same event may appear as both adverse event(AE) and serious AE(SAE). What is presented are distinct events. An event may be categorised as serious in 1 subject and as non-serious in another, or a subject may have experienced both serious and non-serious event. Safety analysis set. Safety reported for all subjects excluding subjects from China.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Axitinib (Second-line Subjects)
    Reporting group description
    		 Asian subjects with prior systemic first-line therapy containing sunitinib or cytokine received axitinib (AG-013736) tablet at a starting dose of 5 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.

    Reporting group title
    Sorafenib (Second-line Subjects)
    Reporting group description
    		 Asian subjects with prior systemic first-line therapy containing sunitinib or cytokine received sorafenib tablet at a starting dose of 400 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.

    Reporting group title
    Axitinib (First-line Subjects)
    Reporting group description
    		 Subjects with no prior systemic first-line therapy received axitinib (AG-013736) tablet at a starting dose of 5 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.

    Reporting group title
    Sorafenib (First-line Subjects)
    Reporting group description
    		 Subjects with no prior systemic first-line therapy received sorafenib tablet at a starting dose of 400 mg orally twice daily, dose adjustment was done based on the tolerability, as per investigator’s discretion. Study medication was administered in cycles of 4 weeks.

    Serious adverse events
    		 Axitinib (Second-line Subjects) Sorafenib (Second-line Subjects) Axitinib (First-line Subjects) Sorafenib (First-line Subjects)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 11 (54.55%)
    3 / 5 (60.00%)
    77 / 173 (44.51%)
    26 / 88 (29.55%)
         number of deaths (all causes)
    9
    3
    117
    63
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cardiac neoplasm unspecified
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    2 / 173 (1.16%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Renal cancer metastatic
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    2 / 173 (1.16%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Tumour haemorrhage
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    3 / 173 (1.73%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Angiopathy
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    20 / 173 (11.56%)
    6 / 88 (6.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 20
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 20
    0 / 6
    Asthenia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    2 / 173 (1.16%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    2 / 173 (1.16%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Impaired healing
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    2 / 173 (1.16%)
    3 / 88 (3.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    2 / 173 (1.16%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Haemoglobin decreased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    2 / 173 (1.16%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    3 / 173 (1.73%)
    2 / 88 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Myocardial ischaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    2 / 88 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    3 / 173 (1.73%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 3
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    2 / 173 (1.16%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Axonal and demyelinating polyneuropathy
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraparesis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 11 (27.27%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 5 (20.00%)
    1 / 173 (0.58%)
    3 / 88 (3.41%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    8 / 173 (4.62%)
    2 / 88 (2.27%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    6 / 8
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal distension
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peptic ulcer
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    3 / 173 (1.73%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortoenteric fistula
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Erythema multiforme
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    2 / 88 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Ureteric obstruction
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis infective
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 5 (20.00%)
    4 / 173 (2.31%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    2 / 173 (1.16%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Skin bacterial infection
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    2 / 173 (1.16%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    1 / 173 (0.58%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    2 / 88 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Axitinib (Second-line Subjects) Sorafenib (Second-line Subjects) Axitinib (First-line Subjects) Sorafenib (First-line Subjects)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 11 (100.00%)
    5 / 5 (100.00%)
    161 / 173 (93.06%)
    83 / 88 (94.32%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Anal neoplasm
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    4 / 11 (36.36%)
    1 / 5 (20.00%)
    83 / 173 (47.98%)
    28 / 88 (31.82%)
         occurrences all number
    11
    3
    242
    43
    Hypotension
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    13 / 173 (7.51%)
    3 / 88 (3.41%)
         occurrences all number
    0
    0
    18
    4
    Surgical and medical procedures
    Haemostasis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 5 (20.00%)
    9 / 173 (5.20%)
    7 / 88 (7.95%)
         occurrences all number
    1
    1
    15
    7
    Fatigue
         subjects affected / exposed
    4 / 11 (36.36%)
    2 / 5 (40.00%)
    55 / 173 (31.79%)
    25 / 88 (28.41%)
         occurrences all number
    7
    2
    121
    33
    Pyrexia
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 5 (0.00%)
    9 / 173 (5.20%)
    4 / 88 (4.55%)
         occurrences all number
    2
    0
    10
    4
    Asthenia
         subjects affected / exposed
    5 / 11 (45.45%)
    0 / 5 (0.00%)
    41 / 173 (23.70%)
    15 / 88 (17.05%)
         occurrences all number
    6
    0
    67
    20
    Mucosal inflammation
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    21 / 173 (12.14%)
    9 / 88 (10.23%)
         occurrences all number
    1
    0
    42
    11
    Oedema peripheral
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    10 / 173 (5.78%)
    4 / 88 (4.55%)
         occurrences all number
    1
    0
    15
    5
    Reproductive system and breast disorders
    Breast mass
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 5 (20.00%)
    33 / 173 (19.08%)
    14 / 88 (15.91%)
         occurrences all number
    2
    2
    44
    22
    Dysphonia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    37 / 173 (21.39%)
    10 / 88 (11.36%)
         occurrences all number
    0
    0
    49
    10
    Dyspnoea
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    24 / 173 (13.87%)
    11 / 88 (12.50%)
         occurrences all number
    0
    0
    32
    14
    Pleural effusion
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    3 / 173 (1.73%)
    5 / 88 (5.68%)
         occurrences all number
    0
    0
    3
    5
    Epistaxis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    7 / 173 (4.05%)
    5 / 88 (5.68%)
         occurrences all number
    0
    0
    8
    5
    Oropharyngeal pain
         subjects affected / exposed
    4 / 11 (36.36%)
    0 / 5 (0.00%)
    12 / 173 (6.94%)
    5 / 88 (5.68%)
         occurrences all number
    5
    0
    20
    5
    Dry throat
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    10 / 173 (5.78%)
    0 / 88 (0.00%)
         occurrences all number
    0
    0
    14
    0
    Insomnia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    10 / 173 (5.78%)
    5 / 88 (5.68%)
         occurrences all number
    1
    0
    13
    5
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    19 / 173 (10.98%)
    8 / 88 (9.09%)
         occurrences all number
    0
    0
    36
    14
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    17 / 173 (9.83%)
    8 / 88 (9.09%)
         occurrences all number
    0
    0
    27
    12
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    7 / 173 (4.05%)
    6 / 88 (6.82%)
         occurrences all number
    0
    0
    14
    7
    Blood creatinine increased
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 5 (20.00%)
    14 / 173 (8.09%)
    6 / 88 (6.82%)
         occurrences all number
    9
    2
    29
    7
    Blood phosphorus decreased
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    17 / 173 (9.83%)
    2 / 88 (2.27%)
         occurrences all number
    1
    0
    20
    2
    Lipase increased
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 5 (20.00%)
    7 / 173 (4.05%)
    5 / 88 (5.68%)
         occurrences all number
    5
    1
    25
    9
    Weight decreased
         subjects affected / exposed
    4 / 11 (36.36%)
    1 / 5 (20.00%)
    70 / 173 (40.46%)
    24 / 88 (27.27%)
         occurrences all number
    13
    1
    198
    63
    Amylase increased
         subjects affected / exposed
    3 / 11 (27.27%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    4
    2
    0
    0
    Blood bicarbonate decreased
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    3
    1
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Blood calcium increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood chloride increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood cholesterol increased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Blood urea increased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Glomerular filtration rate decreased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Creatinine renal clearance decreased
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Eosinophil count increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Haematocrit increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Haemoglobin decreased
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Haemoglobin increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Liver function test increased
         subjects affected / exposed
    1 / 11 (9.09%)
    2 / 5 (40.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    2
    0
    0
    International normalised ratio increased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Lymphocyte percentage decreased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Protein total decreased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Tri-iodothyronine free decreased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Blood pressure increased
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    10 / 173 (5.78%)
    0 / 88 (0.00%)
         occurrences all number
    2
    0
    12
    0
    Mucosal excoriation
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin abrasion
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Spinal compression fracture
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    14 / 173 (8.09%)
    2 / 88 (2.27%)
         occurrences all number
    2
    0
    22
    3
    Headache
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    23 / 173 (13.29%)
    6 / 88 (6.82%)
         occurrences all number
    1
    0
    42
    7
    Dizziness exertional
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dysaesthesia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Neuralgia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 11 (18.18%)
    2 / 5 (40.00%)
    15 / 173 (8.67%)
    9 / 88 (10.23%)
         occurrences all number
    8
    6
    30
    19
    Anisocytosis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Macrocytosis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Polychromasia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Thrombocytosis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    0
    6
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 11 (27.27%)
    0 / 5 (0.00%)
    17 / 173 (9.83%)
    8 / 88 (9.09%)
         occurrences all number
    7
    0
    72
    11
    Abdominal pain upper
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 5 (0.00%)
    32 / 173 (18.50%)
    7 / 88 (7.95%)
         occurrences all number
    2
    0
    51
    9
    Constipation
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 5 (20.00%)
    17 / 173 (9.83%)
    10 / 88 (11.36%)
         occurrences all number
    2
    1
    25
    12
    Diarrhoea
         subjects affected / exposed
    6 / 11 (54.55%)
    2 / 5 (40.00%)
    88 / 173 (50.87%)
    34 / 88 (38.64%)
         occurrences all number
    16
    3
    495
    170
    Mouth ulceration
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nausea
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    38 / 173 (21.97%)
    15 / 88 (17.05%)
         occurrences all number
    2
    0
    138
    22
    Stomatitis
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 5 (20.00%)
    20 / 173 (11.56%)
    4 / 88 (4.55%)
         occurrences all number
    3
    2
    60
    6
    Vomiting
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    38 / 173 (21.97%)
    11 / 88 (12.50%)
         occurrences all number
    0
    0
    176
    29
    Abdominal distension
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    9 / 173 (5.20%)
    1 / 88 (1.14%)
         occurrences all number
    1
    0
    11
    1
    Dry mouth
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    10 / 173 (5.78%)
    1 / 88 (1.14%)
         occurrences all number
    0
    0
    13
    1
    Dyspepsia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    13 / 173 (7.51%)
    3 / 88 (3.41%)
         occurrences all number
    1
    0
    15
    3
    Flatulence
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    10 / 173 (5.78%)
    3 / 88 (3.41%)
         occurrences all number
    0
    0
    11
    4
    Abdominal discomfort
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Anal fissure
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Cheilitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Duodenitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastric ulcer
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gingival bleeding
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Glossodynia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Haematemesis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hiatus hernia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hyperchlorhydria
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Melaena
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Oesophagitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oral disorder
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Toothache
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 5 (20.00%)
    6 / 173 (3.47%)
    17 / 88 (19.32%)
         occurrences all number
    1
    4
    8
    20
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    4 / 11 (36.36%)
    4 / 5 (80.00%)
    41 / 173 (23.70%)
    31 / 88 (35.23%)
         occurrences all number
    17
    8
    206
    79
    Rash
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    15 / 173 (8.67%)
    18 / 88 (20.45%)
         occurrences all number
    2
    0
    19
    27
    Erythema
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    5 / 173 (2.89%)
    21 / 88 (23.86%)
         occurrences all number
    0
    0
    6
    27
    Pruritus
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 5 (20.00%)
    7 / 173 (4.05%)
    9 / 88 (10.23%)
         occurrences all number
    1
    3
    7
    13
    Skin exfoliation
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    3 / 173 (1.73%)
    6 / 88 (6.82%)
         occurrences all number
    1
    0
    3
    7
    Blister
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dry skin
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pain of skin
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Eczema
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pigmentation disorder
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin fissures
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rash erythematous
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin hyperpigmentation
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin mass
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Skin lesion
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Skin toxicity
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin ulcer
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    6 / 11 (54.55%)
    0 / 5 (0.00%)
    19 / 173 (10.98%)
    9 / 88 (10.23%)
         occurrences all number
    34
    0
    63
    11
    Chronic kidney disease
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Dysuria
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Haematuria
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pollakiuria
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    3 / 11 (27.27%)
    0 / 5 (0.00%)
    36 / 173 (20.81%)
    5 / 88 (5.68%)
         occurrences all number
    7
    0
    46
    5
    Hyperthyroidism
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    5 / 11 (45.45%)
    1 / 5 (20.00%)
    28 / 173 (16.18%)
    10 / 88 (11.36%)
         occurrences all number
    7
    1
    66
    18
    Musculoskeletal pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Back pain
         subjects affected / exposed
    6 / 11 (54.55%)
    0 / 5 (0.00%)
    29 / 173 (16.76%)
    14 / 88 (15.91%)
         occurrences all number
    11
    0
    52
    17
    Pain in extremity
         subjects affected / exposed
    4 / 11 (36.36%)
    0 / 5 (0.00%)
    23 / 173 (13.29%)
    6 / 88 (6.82%)
         occurrences all number
    5
    0
    36
    8
    Muscle spasms
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    3 / 173 (1.73%)
    6 / 88 (6.82%)
         occurrences all number
    0
    0
    7
    8
    Arthritis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    7 / 173 (4.05%)
    5 / 88 (5.68%)
         occurrences all number
    0
    0
    8
    6
    Flank pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gouty arthritis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    6
    0
    0
    0
    Myalgia
         subjects affected / exposed
    4 / 11 (36.36%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Osteoarthritis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Joint swelling
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Periarthritis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 5 (0.00%)
    10 / 173 (5.78%)
    3 / 88 (3.41%)
         occurrences all number
    2
    0
    10
    5
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 5 (20.00%)
    14 / 173 (8.09%)
    1 / 88 (1.14%)
         occurrences all number
    0
    1
    18
    1
    Urinary tract infection
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 5 (0.00%)
    10 / 173 (5.78%)
    4 / 88 (4.55%)
         occurrences all number
    2
    0
    15
    5
    Haemorrhoid infection
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pharyngotonsillitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Sinusitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rhinitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tooth infection
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tonsillitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    5 / 11 (45.45%)
    0 / 5 (0.00%)
    48 / 173 (27.75%)
    16 / 88 (18.18%)
         occurrences all number
    5
    0
    85
    21
    Hyperkalaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hyperlipidaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 5 (0.00%)
    6 / 173 (3.47%)
    5 / 88 (5.68%)
         occurrences all number
    0
    0
    12
    9
    Hyperuricaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 5 (0.00%)
    0 / 173 (0.00%)
    0 / 88 (0.00%)
         occurrences all number
    2
    0
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Objective of statistical analysis for secondary endpoints:summarize data using descriptive statistics without performing hypothesis testing. All subjects from sites in China are excluded from updated safety reporting due to lack of HGRAC filings.
    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.

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