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    Clinical Trial Results:
    Study VEG108844, A study of Pazopanib versus Sunitinib in the Treatment of Subjects with Locally Advanced and/or Metastatic Renal Cell Carcinoma

    Summary
    EudraCT number
    		 2008-002102-19
    Trial protocol
    		 IE   GB   ES   SE   NL   IT   DE  
    Global end of trial date
    24 Mar 2021

    Results information
    Results version number
    		 v2(current)
    This version publication date
    16 Apr 2025
    First version publication date
    06 Apr 2022
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    108844
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00720941
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Novartis: CPZP034A2301, GlaxoSmithKline: VEG108844
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    Novartis Campus, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.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
    24 Mar 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Mar 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective was to compare progression-free survival of subjects treated with pazopanib to those treated with sunitinib.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Aug 2008
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 51
    Country: Number of subjects enrolled
    Canada: 46
    Country: Number of subjects enrolled
    China: 209
    Country: Number of subjects enrolled
    Germany: 55
    Country: Number of subjects enrolled
    Ireland: 17
    Country: Number of subjects enrolled
    Italy: 36
    Country: Number of subjects enrolled
    Japan: 61
    Country: Number of subjects enrolled
    Korea, Republic of: 68
    Country: Number of subjects enrolled
    Netherlands: 19
    Country: Number of subjects enrolled
    Spain: 41
    Country: Number of subjects enrolled
    Sweden: 16
    Country: Number of subjects enrolled
    Taiwan: 29
    Country: Number of subjects enrolled
    United Kingdom: 126
    Country: Number of subjects enrolled
    United States: 336
    Worldwide total number of subjects
    1110
    EEA total number of subjects
    184
    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)
    676
    From 65 to 84 years
    428
    85 years and over
    6

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants were stratified based on Karnofsky Performance Scale scores (70 or 80; 90 or 100), Baseline levels of lactate dehydrogenase (>1.5 versus <=1.5 times the upper limit of normal [ULN]), and previous nephrectomy (yes versus no) and were randomized in a 1:1 ratio to receive either pazopanib or sunitinib.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Pazopanib 800 mg
    Arm description
    		 Participants were administered pazopanib 800 milligrams (mg) (2 x 400 mg tablets) orally once daily (OD) continuously. Pazopanib was to be taken at least one hour before or at least two hours after a meal. Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pazopanib
    Investigational medicinal product code
    Other name
    GW786034
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    800 mg (2 x 400 mg tablets or 4 x 200 mg tablets) administered orally once daily (continuously) at least 1 hour before or at least 2 hours after a meal.

    Arm title
    		 Sunitinib 50 mg
    Arm description
    		 Participants were administered sunitinib 50 mg orally once daily in 6-week cycles (4 weeks of treatment, followed by 2 weeks without treatment). Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Sunitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg administered in 6-week cycles orally once daily with or without food, for 4 weeks of treatment followed by 2 weeks without treatment.

    Number of subjects in period 1
    		Pazopanib 800 mg Sunitinib 50 mg
    Started
    557
    553
    Safety Population
    554
    548
    Completed
    485
    481
    Not completed
    72
    72
         Physician decision
    14
    12
         Consent withdrawn by subject
    29
    36
         Lost to follow-up
    20
    15
         Protocol deviation
    1
    2
         Transitioned to another mechanism of cont. therapy
    8
    7

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Pazopanib 800 mg
    Reporting group description
    		 Participants were administered pazopanib 800 milligrams (mg) (2 x 400 mg tablets) orally once daily (OD) continuously. Pazopanib was to be taken at least one hour before or at least two hours after a meal. Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.

    Reporting group title
    Sunitinib 50 mg
    Reporting group description
    		 Participants were administered sunitinib 50 mg orally once daily in 6-week cycles (4 weeks of treatment, followed by 2 weeks without treatment). Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.

    Reporting group values
    		 Pazopanib 800 mg Sunitinib 50 mg Total
    Number of subjects
    		 557 553 1110
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 344 332 676
        From 65-84 years
    		 208 220 428
        85 years and over
    		 5 1 6
    Gender categorical
    Units: Subjects
        Female
    		 159 138 297
        Male
    		 398 415 813
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 349 358 707
        Asian
    		 194 188 382
        African American/African Heritage
    		 10 5 15
        American Indian or Alaska Native
    		 3 0 3
        American Indian or Alaska Native & White
    		 0 1 1
        Unknown
    		 1 1 2
    GenderNIH
    Units: Subjects
        Female
    		 159 138 297
        Male
    		 398 415 813
    AgeContinuous
    Units: Years
        arithmetic mean (standard deviation)
    		 60.9 ( 10.89 ) 61.2 ( 10.98 ) -

    End points

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    End points reporting groups
    Reporting group title
    Pazopanib 800 mg
    Reporting group description
    		 Participants were administered pazopanib 800 milligrams (mg) (2 x 400 mg tablets) orally once daily (OD) continuously. Pazopanib was to be taken at least one hour before or at least two hours after a meal. Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.

    Reporting group title
    Sunitinib 50 mg
    Reporting group description
    		 Participants were administered sunitinib 50 mg orally once daily in 6-week cycles (4 weeks of treatment, followed by 2 weeks without treatment). Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.

    Primary: Progression-free Survival (PFS)

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    End point title
    		 Progression-free Survival (PFS)
    End point description
    PFS was defined as the interval between the date of randomization and the earliest date of progressive disease (PD), as defined by the Independent Review Committee (IRC), or death due to any cause. The IRC defined PD per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1. Per RECIST, PD is defined as a >=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of >=1 new lesion.
    End point type
    Primary
    End point timeframe
    From randomization until the earliest date of disease progression or date of death from any cause, assessed up to approximately 39 months
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    557
    553
    Units: Months
        median (confidence interval 95%)
    8.4 (8.3 to 10.9)
    9.5 (8.3 to 11.1)
    Statistical analysis title
    		 Progression-free Survival (PFS)
    Comparison groups
    Pazopanib 800 mg v Sunitinib 50 mg
    Number of subjects included in analysis
    1110
    Analysis specification
    Pre-specified
    Analysis type
    		 [1]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.0466
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8982
         upper limit
    		 1.2195
    Notes
    [1] - Non-inferiority is defined as excluding a difference of greater than 25% in the hazards. The upper limit of the 95% confidence interval must be <1.25.

    Secondary: Overall Response Rate (ORR) as assessed by independent review

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    End point title
    		 Overall Response Rate (ORR) as assessed by independent review
    End point description
    The number of participants with evidence of Complete Response (CR) (the disappearance of all target and non-target lesions), Partial Response (PR) (at least a 30% decrease in the sum of the longest diameters [LD] of target lesions, taking as a reference the Baseline sum LD), Stable Disease (small changes that do not meet previously given criteria, taking as reference the smallest sum LD since the treatment started), or Progressive Disease (a >=20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since the treatment started) was evaluated by an independent review per RECIST, Version 1.
    End point type
    Secondary
    End point timeframe
    From randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 39 months
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    557
    553
    Units: Participants
        Complete Response
    1
    3
        Partial Response
    170
    134
        Stable Disease
    216
    242
        Progressive Disease
    97
    105
        Unknown
    73
    69
    No statistical analyses for this end point

    Secondary: Overall Survival

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    End point title
    		 Overall Survival
    End point description
    Overall survival was defined as the time from randomization until death due to any cause.
    End point type
    Secondary
    End point timeframe
    From randomization until date of death from any cause, assessed up to approximately 62 months
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    557
    553
    Units: Months
        median (confidence interval 95%)
    28.3 (26.0 to 35.5)
    29.1 (25.4 to 33.1)
    No statistical analyses for this end point

    Secondary: Time to Response

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    End point title
    		 Time to Response
    End point description
    Time to response was defined as the time from the start of treatment until the first documented evidence of CR (the disappearance of all target and non-target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD), whichever comes first. CR and PR were evaluated by an independent review per RECIST, Version 1.
    End point type
    Secondary
    End point timeframe
    From randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 39 months
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    171
    137
    Units: Weeks
        median (confidence interval 95%)
    11.9 (11.3 to 12.1)
    17.4 (12.7 to 18.0)
    No statistical analyses for this end point

    Secondary: Change from Baseline in Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) scale scores at Day 28 of Cycles 1-4

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    End point title
    		 Change from Baseline in Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) scale scores at Day 28 of Cycles 1-4
    End point description
    FACIT Fatigue Subscale is a short, 13-item, easy to administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The total score range is from 0-52. The higher the score, the lower the fatigue level.
    End point type
    Secondary
    End point timeframe
    Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    353
    375
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Week 4 (n=353,375)
    -5.3 ( 11.00 )
    -6.7 ( 10.93 )
        Week 10 (n=293,330)
    -4.0 ( 10.28 )
    -6.3 ( 10.65 )
        Week 16 (n=273,280)
    -3.8 ( 10.13 )
    -6.9 ( 11.16 )
        Week 22 (n=227,240)
    -2.9 ( 9.77 )
    -6.5 ( 10.51 )
    No statistical analyses for this end point

    Secondary: Number of participants with Adverse Events

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    End point title
    		 Number of participants with Adverse Events
    End point description
    The distribution of adverse events was done via the analysis of frequencies for Adverse Event (AEs) and Serious Adverse Event (SAEs), through the monitoring of relevant clinical and laboratory safety parameters.
    End point type
    Secondary
    End point timeframe
    From study treatment start date till 28 days safety follow-up, assessed up to approximately 152 months
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    554
    548
    Units: Participants
        Adverse Events (AEs)
    551
    535
        Serious Adverse Events (SAEs)
    242
    227
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

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    End point title
    		 Duration of Response (DOR)
    End point description
    DOR was defined as the time from the first documented evidence of response (CR or PR) until the first documented sign of disease progression (a >=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of >=1 new lesion) or death, if sooner. CR=the disappearance of all target and non-target lesions. PR=at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD.
    End point type
    Secondary
    End point timeframe
    From the date of the first documented response (CR or PR) to the date of first documented progression or death due to any cause, assessed up to approximately 39 months
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    171
    137
    Units: Months
        median (confidence interval 95%)
    13.8 (12.2 to 16.4)
    18.0 (14.3 to 22.1)
    No statistical analyses for this end point

    Secondary: Change from Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) scale disease-related symptoms-physical (DRS-P) domain score at Day 28 of Cycles 1-4

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    End point title
    		 Change from Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) scale disease-related symptoms-physical (DRS-P) domain score at Day 28 of Cycles 1-4
    End point description
    Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains (Disease-Related Symptoms – Physical (FKSI-DRS-P), Disease-Related Symptoms – Emotional (FKSI-DRS-E), Treatment Side-Effects (FKSI-TSE), Function/Well-Being (FKSI-FWB)) experienced in the past 7 days. Participants are asked to respond to a total of 19 questions regarding symptoms, side effects, and well being by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total score of 0 to 76). A negative mean indicates a worsening of condition.
    End point type
    Secondary
    End point timeframe
    Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    358
    378
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Week 4 (n=358,378)
    -2.9 ( 6.39 )
    -3.9 ( 6.87 )
        Week 10 (n=296,336)
    -2.3 ( 6.69 )
    -3.2 ( 6.76 )
        Week 16 (n=269,283)
    -2.6 ( 6.70 )
    -3.2 ( 6.61 )
        Week 22 (n=224,238)
    -1.3 ( 6.29 )
    -2.7 ( 6.42 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) scale disease related symptoms-emotional (DRS-E) domain score at Day 28 of Cycles 1-4

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    End point title
    		 Change from Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) scale disease related symptoms-emotional (DRS-E) domain score at Day 28 of Cycles 1-4
    End point description
    Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains (Disease-Related Symptoms – Physical (FKSI-DRS-P), Disease-Related Symptoms – Emotional (FKSI-DRS-E), Treatment Side-Effects (FKSI-TSE), Function/Well-Being (FKSI-FWB)) experienced in the past 7 days. Participants are asked to respond to a total of 19 questions regarding symptoms, side effects, and well being by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total score of 0 to 76). A negative mean indicates a worsening of condition.
    End point type
    Secondary
    End point timeframe
    Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    344
    367
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Week 4 (n=344,367)
    0.3 ( 1.31 )
    0.4 ( 1.22 )
        Week 10 (n=287,329)
    0.4 ( 1.33 )
    0.5 ( 1.32 )
        Week 16 (n=260,277)
    0.5 ( 1.39 )
    0.6 ( 1.30 )
        Week 22 (n=220,233)
    0.6 ( 1.27 )
    0.6 ( 1.20 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) scale treatment side effects (TSE) domain score at Day 28 of Cycles 1-4

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    End point title
    		 Change from Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) scale treatment side effects (TSE) domain score at Day 28 of Cycles 1-4
    End point description
    Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains (Disease-Related Symptoms – Physical (FKSI-DRS-P), Disease-Related Symptoms – Emotional (FKSI-DRS-E), Treatment Side-Effects (FKSI-TSE), Function/Well-Being (FKSI-FWB)) experienced in the past 7 days. Participants are asked to respond to a total of 19 questions regarding symptoms, side effects, and well being by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total score of 0 to 76). A negative mean indicates a worsening of condition.
    End point type
    Secondary
    End point timeframe
    Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    326
    350
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Week 4 (n=326,350)
    -1.5 ( 2.45 )
    -2.0 ( 2.35 )
        Week 10 (n=267,305)
    -1.9 ( 2.66 )
    -2.4 ( 2.62 )
        Week 16 (n=244,254)
    -2.1 ( 2.79 )
    -2.8 ( 2.46 )
        Week 22 (n=201,218)
    -2.4 ( 2.75 )
    -2.4 ( 2.33 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) scale functional well being (FWB) domain score at Day 28 of Cycles 1-4

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    End point title
    		 Change from Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) scale functional well being (FWB) domain score at Day 28 of Cycles 1-4
    End point description
    Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains (Disease-Related Symptoms – Physical (FKSI-DRS-P), Disease-Related Symptoms – Emotional (FKSI-DRS-E), Treatment Side-Effects (FKSI-TSE), Function/Well-Being (FKSI-FWB)) experienced in the past 7 days. Participants are asked to respond to a total of 19 questions regarding symptoms, side effects, and well being by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total score of 0 to 76). A negative mean indicates a worsening of condition.
    End point type
    Secondary
    End point timeframe
    Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    357
    378
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Week 4 (n=357,378)
    -1.0 ( 4.01 )
    -1.3 ( 3.63 )
        Week 10 (n=298,331)
    -0.6 ( 4.00 )
    -1.1 ( 3.94 )
        Week 16 (n=267,278)
    -0.8 ( 4.08 )
    -1.0 ( 3.96 )
        Week 22 (n=228,234)
    -0.7 ( 3.93 )
    -1.0 ( 3.82 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) scale total score at Day 28 of Cycles 1-4

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    End point title
    		 Change from Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) scale total score at Day 28 of Cycles 1-4
    End point description
    Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains (Disease-Related Symptoms – Physical (FKSI-DRS-P), Disease-Related Symptoms – Emotional (FKSI-DRS-E), Treatment Side-Effects (FKSI-TSE), Function/Well-Being (FKSI-FWB)) experienced in the past 7 days. Participants are asked to respond to a total of 19 questions regarding symptoms, side effects, and well being by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total score of 0 to 76). A negative mean indicates a worsening of condition.
    End point type
    Secondary
    End point timeframe
    Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    358
    379
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Week 4 (n=358,379)
    -5.0 ( 10.82 )
    -6.6 ( 10.55 )
        Week 10 (n=296,337)
    -4.2 ( 10.95 )
    -6.3 ( 11.21 )
        Week 16 (n=267,284)
    -4.8 ( 11.13 )
    -6.3 ( 10.67 )
        Week 22 (n=225,238)
    -3.7 ( 10.49 )
    -5.5 ( 10.13 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Supplementary Quality of Life Questions (SQLQ) scale worst soreness scores at Day 28 of Cycles 1-4

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    End point title
    		 Change from Baseline in the Supplementary Quality of Life Questions (SQLQ) scale worst soreness scores at Day 28 of Cycles 1-4
    End point description
    The SQLQ scale consists of 5 items that assess the worst mouth and throat, hand, and foot soreness, as well as limitations due to mouth/throat and foot soreness. Participants were asked to assess their worst mouth/throat, hand, and foot soreness by answering the question of " In the past 4 weeks, what was your worst mouth/throat, hand, and foot soreness?" by using the following 4-point scale: 0, I never had any soreness; 1, I had a little bit of soreness; 2, I had quite a lot of soreness; 3, I had severe soreness. A positive mean change from Baseline represents a worsening of condition.
    End point type
    Secondary
    End point timeframe
    Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    202
    184
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Mouth and Throat Soreness, Week 4 (n=202,180)
    0.4 ( 0.87 )
    1.0 ( 0.99 )
        Mouth and Throat Soreness, Week 10 (n=164,155)
    0.4 ( 0.88 )
    0.9 ( 0.99 )
        Mouth and Throat Soreness, Week 16 (n=137,138)
    0.3 ( 0.73 )
    0.8 ( 0.89 )
        Mouth and Throat Soreness, Week 22 (n=120,117)
    0.2 ( 0.75 )
    0.8 ( 0.81 )
        Hand Soreness, Week 4 (n=200,184)
    0.2 ( 0.71 )
    0.3 ( 0.72 )
        Hand Soreness, Week 10 (n=164,153)
    0.3 ( 0.84 )
    0.7 ( 0.85 )
        Hand Soreness, Week 16 (n=139,136)
    0.4 ( 0.76 )
    0.6 ( 0.80 )
        Hand Soreness, Week 22 (n=123,115)
    0.3 ( 0.69 )
    0.6 ( 0.82 )
        Foot Soreness, Week 4 (n=199,182)
    0.2 ( 0.86 )
    0.4 ( 0.80 )
        Foot Soreness, Week 10 (n=163,153)
    0.3 ( 1.00 )
    0.6 ( 0.99 )
        Foot Soreness, Week 16 (n=140,136)
    0.3 ( 1.07 )
    0.8 ( 0.99 )
        Foot Soreness, Week 22 (n=123,116)
    0.3 ( 1.04 )
    0.9 ( 0.96 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Supplementary Quality of Life Questions (SQLQ) limitations due to mouth and throat soreness score at Day 28 of Cycles 1-4

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    End point title
    		 Change from Baseline in the Supplementary Quality of Life Questions (SQLQ) limitations due to mouth and throat soreness score at Day 28 of Cycles 1-4
    End point description
    The SQLQ consists of 5 items assessing the worst mouth/throat, hand, and foot soreness, and limitations due to mouth/throat and foot soreness. Participants assessed the limitations caused by their mouth/throat soreness by answering the question of "In the past 4 weeks, how much did your worst mouth/throat soreness limit you in the following activities: swallowing/eating/drinking/talking/sleeping" by using the following 4-point scale: 0, not limited; 1, limited a little; 2, limited a lot; 3, unable to do. The overall limitation score (15=best; 0=worst), based on the individual scores for the 5 activities, is derived as follows: the actual scores were rescored by subtracting the actual score from "3" for each of the 5 categories. A high score indicates less limitation. Change from Baseline was calculated as the assessment week value minus the Baseline value. A negative mean change from Baseline represents a worsening of condition.
    End point type
    Secondary
    End point timeframe
    Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    177
    170
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Week 4 (n=177,170)
    -0.9 ( 2.09 )
    -1.8 ( 2.91 )
        Week 10 (n=144,137)
    -0.9 ( 1.91 )
    -1.8 ( 3.06 )
        Week 16 (n=125,122)
    -0.6 ( 1.56 )
    -1.3 ( 2.30 )
        Week 22 (n=111,107)
    -0.4 ( 1.67 )
    -1.4 ( 1.85 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in the Supplementary Quality of Life Questions (SQLQ) Limitations Due to Foot Soreness Scores at Day 28 of Cycles 1-4

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    End point title
    		 Change From Baseline in the Supplementary Quality of Life Questions (SQLQ) Limitations Due to Foot Soreness Scores at Day 28 of Cycles 1-4
    End point description
    The SQLQ consists of 5 items assessing the worst mouth/throat, hand, and foot soreness, and limitations due to mouth/throat and foot soreness. Participants assessed the limitations caused by their foot soreness by answering the question of "In the past 4 weeks, how much did your worst foot soreness limit you in each of the following activities: standing/walking/climbing stairs/sleeping/ability to do usual activities" by using the following 4-point scale: 0, not limited; 1, limited a little; 2, limited a lot; 3, unable to do. The overall limitation score (15=best; 0=worst), based on the individual scores for the 5 activities, is derived as follows: the actual scores were rescored by subtracting the actual score from "3" for each of the 5 categories. A high score indicates less limitation. Change from Baseline was calculated as the assessment week value minus the Baseline value. A negative mean change from Baseline represents a worsening of condition.
    End point type
    Secondary
    End point timeframe
    Baseline (predose), Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    170
    163
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Week 4 (n=170,163)
    -0.6 ( 2.94 )
    -1.0 ( 2.94 )
        Week 10 (n=133,136)
    -1.1 ( 3.02 )
    -1.5 ( 3.76 )
        Week 16 (n=114,126)
    -1.2 ( 3.42 )
    -2.2 ( 3.50 )
        Week 22 (n=105,108)
    -1.3 ( 3.25 )
    -2.1 ( 3.52 )
    No statistical analyses for this end point

    Secondary: Summary of Analysis for the Cancer Treatment Satisfaction Questionnaire (CTSQ) Score at Day 28 of Cycles 1-4

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    End point title
    		 Summary of Analysis for the Cancer Treatment Satisfaction Questionnaire (CTSQ) Score at Day 28 of Cycles 1-4
    End point description
    The CTSQ assesses 3 domains related to the participant’s satisfaction with cancer therapy: Expectations of Therapy (ET), Feelings about Side Effects (FSE), and Satisfaction with Therapy (SWT). Participants shared their thoughts on their cancer therapy (9 questions), their satisfaction with their most recently administered cancer therapy (6 questions), and if they would take the same cancer therapy if given the choice to do so again. All questions were assessed on a 5-point scale; 1, never; 5, always. Scores were averaged and transformed to a 0-100 scale; higher scores represent better treatment satisfaction.
    End point type
    Secondary
    End point timeframe
    Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    383
    386
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        ET, Week 4 (n=383,386)
    71.7 ( 22.13 )
    71.3 ( 22.38 )
        ET, Week 10 (n=321,346)
    73.4 ( 21.62 )
    73.4 ( 19.37 )
        ET, Week 16 (n=296,293)
    73.9 ( 21.56 )
    72.9 ( 21.43 )
        ET, Week 22 (n=250,250)
    73.0 ( 21.40 )
    73.4 ( 20.43 )
        FSE, Week 4 (n=340,360)
    66.3 ( 24.00 )
    58.5 ( 23.59 )
        FSE, Week 10 (n=298,323)
    66.0 ( 23.09 )
    56.0 ( 22.23 )
        FSE, Week 16 (n=274,277)
    65.0 ( 23.01 )
    56.6 ( 22.02 )
        FSE, Week 22 (n=235, 232)
    67.1 ( 22.62 )
    57.8 ( 21.28 )
        SWT, Week 4 (n=355,374)
    80.9 ( 15.49 )
    79.0 ( 15.23 )
        SWT, Week 10 (n=309,336)
    84.5 ( 13.74 )
    80.4 ( 15.15 )
        SWT, Week 16 (n=287,284)
    85.3 ( 14.77 )
    80.5 ( 15.08 )
        SWT, Week 22 (n=241,240)
    85.4 ( 13.48 )
    81.4 ( 15.04 )
    No statistical analyses for this end point

    Secondary: Mean Number of Non-study Medical Visits, Telephone Consultations, Hospital Days, and Emergency Room (ER) Visits Per 30 Days Through Week 24

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    End point title
    		 Mean Number of Non-study Medical Visits, Telephone Consultations, Hospital Days, and Emergency Room (ER) Visits Per 30 Days Through Week 24
    End point description
    Non-study medical visits were defined as the sum of primary care physician visits, nurse practitioner/physician’s assistant/nurse visits, and medical or surgical specialist visits. Days hospitalized were defined as the sum of days in the general ward and days in intensive care. The number of telephone consultations and ER visits was assessed via individual questions on the electronic Case Report Form. The endpoint was totaled through Week 24, divided by the number of days on treatment for each participant, then multiplied by 30 days to get the number of visits per 30 days.
    End point type
    Secondary
    End point timeframe
    From Day 1 up to Week 24
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    429
    432
    Units: events per 30 days
    arithmetic mean (standard deviation)
        Non-Study Medical Visits
    0.726 ( 1.472 )
    0.779 ( 1.690 )
        Telephone Consultations
    0.279 ( 0.718 )
    0.312 ( 0.656 )
        Hospital Days
    0.402 ( 2.273 )
    0.562 ( 2.187 )
        ER Visits
    0.037 ( 0.156 )
    0.067 ( 0.195 )
    No statistical analyses for this end point

    Secondary: Mean Number of Laboratory Visits, Radiology Visits, Home Healthcare Visits, and Medical Procedures at Day 28 of Cycles 1-4

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    End point title
    		 Mean Number of Laboratory Visits, Radiology Visits, Home Healthcare Visits, and Medical Procedures at Day 28 of Cycles 1-4
    End point description
    The number of non-study laboratory visits (NSLVs), non-study radiology visits (NSRVs), and home healthcare visits (HHVs) were each collected as a single question on the eCRF. The number of non-study medical or surgical procedures (MSPs) was defined as the sum of procedures performed at outpatient or physician clinics, as well as those performed during any inpatient hospitalization.
    End point type
    Secondary
    End point timeframe
    Day 28 of Cycles 1-4 (average of Weeks 4, 10, 16, and 22, respectively)
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    429
    432
    Units: visits
    arithmetic mean (standard deviation)
        NSLV, Cycle 1 (n=417,414)
    0.3 ( 1.25 )
    0.3 ( 1.14 )
        NSLV, Cycle 2 (n=345,363)
    0.3 ( 0.97 )
    0.4 ( 1.35 )
        NSLV, Cycle 3 (n=299,304)
    0.2 ( 0.67 )
    0.2 ( 0.58 )
        NSLV, Cycle 4 (n=265,254)
    0.1 ( 0.49 )
    0.1 ( 0.47 )
        NSRV, Cycle 1 (n=419,414)
    0.1 ( 0.44 )
    0.1 ( 0.56 )
        NSRV, Cycle 2 (n=348,364)
    0.1 ( 0.36 )
    0.1 ( 0.88 )
        NSRV, Cycle 3 (n=299,305)
    0.0 ( 0.28 )
    0.1 ( 0.33 )
        NSRV, Cycle 4 (n=266,255)
    0.0 ( 0.24 )
    0.1 ( 0.46 )
        HHV, Cycle 1 (n=418,411)
    0.0 ( 0.44 )
    0.1 ( 0.77 )
        HHV, Cycle 2 (n=343,363)
    0.1 ( 0.52 )
    0.1 ( 0.64 )
        HHV, Cycle 3 (n=298,304)
    0.1 ( 0.72 )
    0.0 ( 0.37 )
        HHV, Cycle 4 (n=265,254)
    0.0 ( 0.49 )
    0.1 ( 1.77 )
        NSP, Cycle 1 (n=417,413)
    0.2 ( 0.69 )
    0.3 ( 2.52 )
        NSP, Cycle 2 (n=344,363)
    0.2 ( 0.68 )
    0.2 ( 1.17 )
        NSP, Cycle 3 (n=298,304)
    0.2 ( 0.60 )
    0.3 ( 1.98 )
        NSP, Cycle 4 (n=266,254)
    0.2 ( 0.85 )
    0.3 ( 1.73 )
    No statistical analyses for this end point

    Other pre-specified: All collected deaths

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    End point title
    		 All collected deaths
    End point description
    Pre-treatment deaths were collected from day of participant’s informed consent to the day before first dose of study medication. On-treatment deaths were collected from first dose of study medication to 28 days after last dose of study medication (on-treatment), up to approximately 129 months. ​ Deaths were collected in the post treatment survival follow up from 29 days after last dose of study medication until the end of the study, up to approximately 152 months.
    End point type
    Other pre-specified
    End point timeframe
    Pre-treatment deaths: Up to 21 days prior to treatment. On-treatment deaths: Up to 129 months. Post-treatment deaths: up to 152 months.
    End point values
    		 Pazopanib 800 mg Sunitinib 50 mg
    Number of subjects analysed
    557
    553
    Units: Participants
        Pre-treatment deaths
    0
    0
        On-treatment deaths
    25
    22
        Post-treatment deaths
    310
    312
        All deaths
    335
    334
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events (AEs) were collected from first dose of study medication until the last dose plus 28 days post-treat follow-up, assessed up to approximately 129 months.
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Pazopanib
    Reporting group description
    		 Pazopanib

    Reporting group title
    Total
    Reporting group description
    		 Total

    Reporting group title
    Sunitinib
    Reporting group description
    		 Sunitinib

    Serious adverse events
    		 Pazopanib Total Sunitinib
    Total subjects affected by serious adverse events
         subjects affected / exposed
    242 / 554 (43.68%)
    469 / 1102 (42.56%)
    227 / 548 (41.42%)
         number of deaths (all causes)
    335
    669
    334
         number of deaths resulting from adverse events
    3
    11
    8
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lipoma
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemangioblastoma
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endometrial cancer metastatic
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholesteatoma
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cancer pain
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    1 / 554 (0.18%)
    3 / 1102 (0.27%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Metastases to liver
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Metastases to lung
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastasis
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Paraneoplastic syndrome
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parathyroid tumour benign
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal cancer metastatic
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Signet-ring cell carcinoma
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour associated fever
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Tumour rupture
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic thrombosis
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arterial rupture
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dry gangrene
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Giant cell arteritis
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    7 / 554 (1.26%)
    13 / 1102 (1.18%)
    6 / 548 (1.09%)
         occurrences causally related to treatment / all
    5 / 7
    9 / 13
    4 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    2 / 554 (0.36%)
    3 / 1102 (0.27%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vena cava thrombosis
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    5 / 554 (0.90%)
    18 / 1102 (1.63%)
    13 / 548 (2.37%)
         occurrences causally related to treatment / all
    3 / 5
    10 / 18
    7 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumatosis
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 554 (0.18%)
    4 / 1102 (0.36%)
    3 / 548 (0.55%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    3 / 554 (0.54%)
    15 / 1102 (1.36%)
    12 / 548 (2.19%)
         occurrences causally related to treatment / all
    3 / 3
    14 / 16
    11 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Death
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Chest pain
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    2 / 554 (0.36%)
    6 / 1102 (0.54%)
    4 / 548 (0.73%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 6
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Penile oedema
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bartholin's cyst
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Hypoxia
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hiccups
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    3 / 554 (0.54%)
    5 / 1102 (0.45%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    1 / 3
    3 / 5
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 554 (0.00%)
    6 / 1102 (0.54%)
    6 / 548 (1.09%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 6
    4 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    5 / 554 (0.90%)
    13 / 1102 (1.18%)
    8 / 548 (1.46%)
         occurrences causally related to treatment / all
    1 / 5
    4 / 14
    3 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Laryngeal haemorrhage
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 554 (0.00%)
    2 / 1102 (0.18%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 2
    1 / 2
    Acute respiratory failure
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung infiltration
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 554 (0.18%)
    12 / 1102 (1.09%)
    11 / 548 (2.01%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 14
    2 / 13
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    Pleurisy
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 554 (0.18%)
    3 / 1102 (0.27%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary artery thrombosis
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    8 / 554 (1.44%)
    15 / 1102 (1.36%)
    7 / 548 (1.28%)
         occurrences causally related to treatment / all
    5 / 8
    9 / 15
    4 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary pain
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    2 / 554 (0.36%)
    4 / 1102 (0.36%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 2
    1 / 4
    1 / 2
    Pneumothorax
         subjects affected / exposed
    2 / 554 (0.36%)
    4 / 1102 (0.36%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sleep disorder
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Emotional distress
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 554 (0.18%)
    3 / 1102 (0.27%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    35 / 554 (6.32%)
    43 / 1102 (3.90%)
    8 / 548 (1.46%)
         occurrences causally related to treatment / all
    36 / 37
    42 / 45
    6 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Amylase increased
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    17 / 554 (3.07%)
    19 / 1102 (1.72%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    16 / 17
    18 / 19
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    2 / 554 (0.36%)
    4 / 1102 (0.36%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood calcium increased
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatine increased
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood glucose decreased
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood magnesium decreased
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood potassium increased
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 554 (0.00%)
    9 / 1102 (0.82%)
    9 / 548 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    8 / 9
    8 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Liver function test increased
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lipase increased
         subjects affected / exposed
    7 / 554 (1.26%)
    11 / 1102 (1.00%)
    4 / 548 (0.73%)
         occurrences causally related to treatment / all
    6 / 7
    10 / 11
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    6 / 554 (1.08%)
    7 / 1102 (0.64%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    6 / 6
    7 / 7
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    3 / 554 (0.54%)
    3 / 1102 (0.27%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    1 / 554 (0.18%)
    3 / 1102 (0.27%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 554 (0.00%)
    2 / 1102 (0.18%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Craniocerebral injury
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ilium fracture
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain herniation
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acetabulum fracture
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chemical poisoning
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Coronary artery stenosis
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 554 (0.18%)
    5 / 1102 (0.45%)
    4 / 548 (0.73%)
         occurrences causally related to treatment / all
    1 / 1
    5 / 5
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial thrombosis
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    Acute myocardial infarction
         subjects affected / exposed
    3 / 554 (0.54%)
    5 / 1102 (0.45%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    2 / 3
    3 / 5
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    3 / 554 (0.54%)
    7 / 1102 (0.64%)
    4 / 548 (0.73%)
         occurrences causally related to treatment / all
    2 / 3
    6 / 7
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Torsade de pointes
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Central nervous system haemorrhage
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    2 / 554 (0.36%)
    3 / 1102 (0.27%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic cerebral infarction
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    2 / 554 (0.36%)
    3 / 1102 (0.27%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular insufficiency
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral small vessel ischaemic disease
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 554 (0.00%)
    2 / 1102 (0.18%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Cerebral haemorrhage
         subjects affected / exposed
    5 / 554 (0.90%)
    6 / 1102 (0.54%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    3 / 5
    4 / 6
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Cerebellar haemorrhage
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hemianaesthesia
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 554 (0.18%)
    5 / 1102 (0.45%)
    4 / 548 (0.73%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 5
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    4 / 554 (0.72%)
    7 / 1102 (0.64%)
    3 / 548 (0.55%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    2 / 554 (0.36%)
    5 / 1102 (0.45%)
    3 / 548 (0.55%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Paraplegia
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Motor dysfunction
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lethargy
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    3 / 554 (0.54%)
    4 / 1102 (0.36%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    2 / 3
    3 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Immune thrombocytopenia
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Microangiopathic haemolytic anaemia
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    Lymphopenia
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    9 / 554 (1.62%)
    18 / 1102 (1.63%)
    9 / 548 (1.64%)
         occurrences causally related to treatment / all
    6 / 9
    13 / 18
    7 / 9
         deaths causally related to treatment / all
    1 / 1
    2 / 2
    1 / 1
    Febrile neutropenia
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    4 / 554 (0.72%)
    28 / 1102 (2.54%)
    24 / 548 (4.38%)
         occurrences causally related to treatment / all
    4 / 4
    29 / 29
    25 / 25
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Polycythaemia
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    2 / 554 (0.36%)
    9 / 1102 (0.82%)
    7 / 548 (1.28%)
         occurrences causally related to treatment / all
    2 / 2
    8 / 9
    6 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Sudden hearing loss
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal distension
         subjects affected / exposed
    0 / 554 (0.00%)
    2 / 1102 (0.18%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    3 / 554 (0.54%)
    8 / 1102 (0.73%)
    5 / 548 (0.91%)
         occurrences causally related to treatment / all
    1 / 3
    4 / 8
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal ulcer haemorrhage
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric fistula
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 554 (0.00%)
    2 / 1102 (0.18%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    3 / 554 (0.54%)
    4 / 1102 (0.36%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    3 / 3
    3 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    5 / 554 (0.90%)
    15 / 1102 (1.36%)
    10 / 548 (1.82%)
         occurrences causally related to treatment / all
    5 / 5
    14 / 16
    9 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    2 / 554 (0.36%)
    4 / 1102 (0.36%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erosive oesophagitis
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 554 (0.18%)
    3 / 1102 (0.27%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    2 / 554 (0.36%)
    4 / 1102 (0.36%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 2
    1 / 2
    Inguinal hernia
         subjects affected / exposed
    2 / 554 (0.36%)
    3 / 1102 (0.27%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    3 / 554 (0.54%)
    3 / 1102 (0.27%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 554 (0.00%)
    2 / 1102 (0.18%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Glossodynia
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 554 (0.36%)
    4 / 1102 (0.36%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 4
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 554 (0.18%)
    3 / 1102 (0.27%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal haemorrhage
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    2 / 554 (0.36%)
    3 / 1102 (0.27%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Swollen tongue
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    5 / 554 (0.90%)
    7 / 1102 (0.64%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    5 / 6
    7 / 8
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis ulcerative
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    6 / 554 (1.08%)
    13 / 1102 (1.18%)
    7 / 548 (1.28%)
         occurrences causally related to treatment / all
    5 / 6
    11 / 13
    6 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peptic ulcer
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 554 (0.36%)
    3 / 1102 (0.27%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    7 / 554 (1.26%)
    15 / 1102 (1.36%)
    8 / 548 (1.46%)
         occurrences causally related to treatment / all
    3 / 7
    10 / 16
    7 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Jaundice cholestatic
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 554 (0.00%)
    2 / 1102 (0.18%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    8 / 554 (1.44%)
    8 / 1102 (0.73%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    8 / 8
    8 / 8
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    7 / 554 (1.26%)
    11 / 1102 (1.00%)
    4 / 548 (0.73%)
         occurrences causally related to treatment / all
    7 / 7
    11 / 11
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    1 / 554 (0.18%)
    3 / 1102 (0.27%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    Cholelithiasis
         subjects affected / exposed
    2 / 554 (0.36%)
    3 / 1102 (0.27%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 554 (0.18%)
    3 / 1102 (0.27%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    2 / 554 (0.36%)
    3 / 1102 (0.27%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gallbladder rupture
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Actinic keratosis
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Decubitus ulcer
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Ureteric obstruction
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal haemorrhage
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 554 (0.18%)
    5 / 1102 (0.45%)
    4 / 548 (0.73%)
         occurrences causally related to treatment / all
    0 / 1
    4 / 5
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    Proteinuria
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    2 / 554 (0.36%)
    5 / 1102 (0.45%)
    3 / 548 (0.55%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 6
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    4 / 554 (0.72%)
    13 / 1102 (1.18%)
    9 / 548 (1.64%)
         occurrences causally related to treatment / all
    2 / 4
    7 / 13
    5 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 554 (0.00%)
    2 / 1102 (0.18%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 554 (0.18%)
    3 / 1102 (0.27%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc compression
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemarthrosis
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Groin pain
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    2 / 554 (0.36%)
    3 / 1102 (0.27%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fistula
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    3 / 554 (0.54%)
    8 / 1102 (0.73%)
    5 / 548 (0.91%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 8
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteolysis
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 554 (0.18%)
    2 / 1102 (0.18%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Complicated appendicitis
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 554 (0.18%)
    3 / 1102 (0.27%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    H1N1 influenza
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 554 (0.00%)
    2 / 1102 (0.18%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Perinephric abscess
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 554 (0.54%)
    4 / 1102 (0.36%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    Septic shock
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 554 (0.54%)
    4 / 1102 (0.36%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    2 / 3
    2 / 4
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    1 / 2
    0 / 1
    Salmonella sepsis
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal abscess
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal abscess
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    7 / 554 (1.26%)
    13 / 1102 (1.18%)
    6 / 548 (1.09%)
         occurrences causally related to treatment / all
    1 / 7
    2 / 14
    1 / 7
         deaths causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 554 (0.36%)
    4 / 1102 (0.36%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    2 / 554 (0.36%)
    2 / 1102 (0.18%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperuricaemia
         subjects affected / exposed
    1 / 554 (0.18%)
    3 / 1102 (0.27%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 6
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperlipasaemia
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    5 / 554 (0.90%)
    6 / 1102 (0.54%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 9
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperamylasaemia
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    1 / 554 (0.18%)
    1 / 1102 (0.09%)
    0 / 548 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    8 / 554 (1.44%)
    19 / 1102 (1.72%)
    11 / 548 (2.01%)
         occurrences causally related to treatment / all
    4 / 8
    15 / 21
    11 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    2 / 554 (0.36%)
    4 / 1102 (0.36%)
    2 / 548 (0.36%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    4 / 554 (0.72%)
    11 / 1102 (1.00%)
    7 / 548 (1.28%)
         occurrences causally related to treatment / all
    1 / 4
    6 / 11
    5 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypophosphataemia
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 1102 (0.09%)
    1 / 548 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Pazopanib Total Sunitinib
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    541 / 554 (97.65%)
    1076 / 1102 (97.64%)
    535 / 548 (97.63%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    256 / 554 (46.21%)
    476 / 1102 (43.19%)
    220 / 548 (40.15%)
         occurrences all number
    314
    605
    291
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    47 / 554 (8.48%)
    124 / 1102 (11.25%)
    77 / 548 (14.05%)
         occurrences all number
    58
    165
    107
    Oedema peripheral
         subjects affected / exposed
    58 / 554 (10.47%)
    144 / 1102 (13.07%)
    86 / 548 (15.69%)
         occurrences all number
    71
    194
    123
    Oedema
         subjects affected / exposed
    15 / 554 (2.71%)
    52 / 1102 (4.72%)
    37 / 548 (6.75%)
         occurrences all number
    16
    61
    45
    Mucosal inflammation
         subjects affected / exposed
    62 / 554 (11.19%)
    203 / 1102 (18.42%)
    141 / 548 (25.73%)
         occurrences all number
    73
    322
    249
    Fatigue
         subjects affected / exposed
    305 / 554 (55.05%)
    647 / 1102 (58.71%)
    342 / 548 (62.41%)
         occurrences all number
    392
    1041
    649
    Face oedema
         subjects affected / exposed
    12 / 554 (2.17%)
    52 / 1102 (4.72%)
    40 / 548 (7.30%)
         occurrences all number
    12
    79
    67
    Chills
         subjects affected / exposed
    15 / 554 (2.71%)
    58 / 1102 (5.26%)
    43 / 548 (7.85%)
         occurrences all number
    15
    66
    51
    Asthenia
         subjects affected / exposed
    47 / 554 (8.48%)
    105 / 1102 (9.53%)
    58 / 548 (10.58%)
         occurrences all number
    91
    195
    104
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    86 / 554 (15.52%)
    191 / 1102 (17.33%)
    105 / 548 (19.16%)
         occurrences all number
    113
    241
    128
    Oropharyngeal pain
         subjects affected / exposed
    39 / 554 (7.04%)
    93 / 1102 (8.44%)
    54 / 548 (9.85%)
         occurrences all number
    41
    108
    67
    Epistaxis
         subjects affected / exposed
    49 / 554 (8.84%)
    145 / 1102 (13.16%)
    96 / 548 (17.52%)
         occurrences all number
    65
    220
    155
    Dyspnoea
         subjects affected / exposed
    79 / 554 (14.26%)
    171 / 1102 (15.52%)
    92 / 548 (16.79%)
         occurrences all number
    95
    202
    107
    Dysphonia
         subjects affected / exposed
    42 / 554 (7.58%)
    54 / 1102 (4.90%)
    12 / 548 (2.19%)
         occurrences all number
    47
    59
    12
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    58 / 554 (10.47%)
    119 / 1102 (10.80%)
    61 / 548 (11.13%)
         occurrences all number
    59
    122
    63
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    143 / 554 (25.81%)
    236 / 1102 (21.42%)
    93 / 548 (16.97%)
         occurrences all number
    176
    310
    134
    Amylase increased
         subjects affected / exposed
    39 / 554 (7.04%)
    63 / 1102 (5.72%)
    24 / 548 (4.38%)
         occurrences all number
    54
    102
    48
    Aspartate aminotransferase increased
         subjects affected / exposed
    128 / 554 (23.10%)
    224 / 1102 (20.33%)
    96 / 548 (17.52%)
         occurrences all number
    164
    338
    174
    Blood alkaline phosphatase increased
         subjects affected / exposed
    40 / 554 (7.22%)
    70 / 1102 (6.35%)
    30 / 548 (5.47%)
         occurrences all number
    41
    87
    46
    Blood bilirubin increased
         subjects affected / exposed
    51 / 554 (9.21%)
    86 / 1102 (7.80%)
    35 / 548 (6.39%)
         occurrences all number
    82
    153
    71
    Blood creatinine increased
         subjects affected / exposed
    52 / 554 (9.39%)
    137 / 1102 (12.43%)
    85 / 548 (15.51%)
         occurrences all number
    98
    300
    202
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    40 / 554 (7.22%)
    100 / 1102 (9.07%)
    60 / 548 (10.95%)
         occurrences all number
    64
    243
    179
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    33 / 554 (5.96%)
    97 / 1102 (8.80%)
    64 / 548 (11.68%)
         occurrences all number
    45
    162
    117
    Blood triglycerides increased
         subjects affected / exposed
    21 / 554 (3.79%)
    56 / 1102 (5.08%)
    35 / 548 (6.39%)
         occurrences all number
    42
    103
    61
    Haemoglobin decreased
         subjects affected / exposed
    34 / 554 (6.14%)
    109 / 1102 (9.89%)
    75 / 548 (13.69%)
         occurrences all number
    47
    237
    190
    Lipase increased
         subjects affected / exposed
    43 / 554 (7.76%)
    75 / 1102 (6.81%)
    32 / 548 (5.84%)
         occurrences all number
    66
    119
    53
    Neutrophil count decreased
         subjects affected / exposed
    23 / 554 (4.15%)
    83 / 1102 (7.53%)
    60 / 548 (10.95%)
         occurrences all number
    48
    192
    144
    Platelet count decreased
         subjects affected / exposed
    36 / 554 (6.50%)
    133 / 1102 (12.07%)
    97 / 548 (17.70%)
         occurrences all number
    68
    330
    262
    Weight decreased
         subjects affected / exposed
    86 / 554 (15.52%)
    119 / 1102 (10.80%)
    33 / 548 (6.02%)
         occurrences all number
    99
    134
    35
    White blood cell count decreased
         subjects affected / exposed
    31 / 554 (5.60%)
    105 / 1102 (9.53%)
    74 / 548 (13.50%)
         occurrences all number
    55
    223
    168
    Nervous system disorders
    Taste disorder
         subjects affected / exposed
    99 / 554 (17.87%)
    244 / 1102 (22.14%)
    145 / 548 (26.46%)
         occurrences all number
    106
    368
    262
    Headache
         subjects affected / exposed
    124 / 554 (22.38%)
    246 / 1102 (22.32%)
    122 / 548 (22.26%)
         occurrences all number
    159
    338
    179
    Dysgeusia
         subjects affected / exposed
    49 / 554 (8.84%)
    107 / 1102 (9.71%)
    58 / 548 (10.58%)
         occurrences all number
    58
    136
    78
    Dizziness
         subjects affected / exposed
    71 / 554 (12.82%)
    153 / 1102 (13.88%)
    82 / 548 (14.96%)
         occurrences all number
    87
    192
    105
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    51 / 554 (9.21%)
    151 / 1102 (13.70%)
    100 / 548 (18.25%)
         occurrences all number
    114
    364
    250
    Neutropenia
         subjects affected / exposed
    60 / 554 (10.83%)
    207 / 1102 (18.78%)
    147 / 548 (26.82%)
         occurrences all number
    121
    504
    383
    Thrombocytopenia
         subjects affected / exposed
    56 / 554 (10.11%)
    236 / 1102 (21.42%)
    180 / 548 (32.85%)
         occurrences all number
    118
    614
    496
    Anaemia
         subjects affected / exposed
    36 / 554 (6.50%)
    135 / 1102 (12.25%)
    99 / 548 (18.07%)
         occurrences all number
    49
    209
    160
    Eye disorders
    Eyelid oedema
         subjects affected / exposed
    18 / 554 (3.25%)
    57 / 1102 (5.17%)
    39 / 548 (7.12%)
         occurrences all number
    32
    124
    92
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    24 / 554 (4.33%)
    57 / 1102 (5.17%)
    33 / 548 (6.02%)
         occurrences all number
    32
    70
    38
    Abdominal distension
         subjects affected / exposed
    34 / 554 (6.14%)
    61 / 1102 (5.54%)
    27 / 548 (4.93%)
         occurrences all number
    35
    67
    32
    Abdominal pain
         subjects affected / exposed
    72 / 554 (13.00%)
    146 / 1102 (13.25%)
    74 / 548 (13.50%)
         occurrences all number
    86
    194
    108
    Abdominal pain upper
         subjects affected / exposed
    69 / 554 (12.45%)
    118 / 1102 (10.71%)
    49 / 548 (8.94%)
         occurrences all number
    89
    152
    63
    Constipation
         subjects affected / exposed
    97 / 554 (17.51%)
    230 / 1102 (20.87%)
    133 / 548 (24.27%)
         occurrences all number
    112
    301
    189
    Diarrhoea
         subjects affected / exposed
    349 / 554 (63.00%)
    661 / 1102 (59.98%)
    312 / 548 (56.93%)
         occurrences all number
    752
    1616
    864
    Dyspepsia
         subjects affected / exposed
    78 / 554 (14.08%)
    213 / 1102 (19.33%)
    135 / 548 (24.64%)
         occurrences all number
    93
    302
    209
    Dry mouth
         subjects affected / exposed
    26 / 554 (4.69%)
    55 / 1102 (4.99%)
    29 / 548 (5.29%)
         occurrences all number
    29
    61
    32
    Vomiting
         subjects affected / exposed
    158 / 554 (28.52%)
    306 / 1102 (27.77%)
    148 / 548 (27.01%)
         occurrences all number
    303
    629
    326
    Stomatitis
         subjects affected / exposed
    78 / 554 (14.08%)
    232 / 1102 (21.05%)
    154 / 548 (28.10%)
         occurrences all number
    99
    402
    303
    Oral pain
         subjects affected / exposed
    12 / 554 (2.17%)
    40 / 1102 (3.63%)
    28 / 548 (5.11%)
         occurrences all number
    14
    58
    44
    Nausea
         subjects affected / exposed
    248 / 554 (44.77%)
    501 / 1102 (45.46%)
    253 / 548 (46.17%)
         occurrences all number
    399
    879
    480
    Mouth ulceration
         subjects affected / exposed
    22 / 554 (3.97%)
    57 / 1102 (5.17%)
    35 / 548 (6.39%)
         occurrences all number
    28
    80
    52
    Gastrooesophageal reflux disease
         subjects affected / exposed
    19 / 554 (3.43%)
    74 / 1102 (6.72%)
    55 / 548 (10.04%)
         occurrences all number
    19
    88
    69
    Flatulence
         subjects affected / exposed
    32 / 554 (5.78%)
    47 / 1102 (4.26%)
    15 / 548 (2.74%)
         occurrences all number
    37
    57
    20
    Skin and subcutaneous tissue disorders
    Yellow skin
         subjects affected / exposed
    4 / 554 (0.72%)
    97 / 1102 (8.80%)
    93 / 548 (16.97%)
         occurrences all number
    5
    156
    151
    Pruritus
         subjects affected / exposed
    23 / 554 (4.15%)
    68 / 1102 (6.17%)
    45 / 548 (8.21%)
         occurrences all number
    29
    86
    57
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    163 / 554 (29.42%)
    438 / 1102 (39.75%)
    275 / 548 (50.18%)
         occurrences all number
    248
    863
    615
    Hair colour changes
         subjects affected / exposed
    168 / 554 (30.32%)
    222 / 1102 (20.15%)
    54 / 548 (9.85%)
         occurrences all number
    178
    237
    59
    Dry skin
         subjects affected / exposed
    44 / 554 (7.94%)
    91 / 1102 (8.26%)
    47 / 548 (8.58%)
         occurrences all number
    53
    106
    53
    Alopecia
         subjects affected / exposed
    77 / 554 (13.90%)
    122 / 1102 (11.07%)
    45 / 548 (8.21%)
         occurrences all number
    83
    129
    46
    Rash
         subjects affected / exposed
    95 / 554 (17.15%)
    221 / 1102 (20.05%)
    126 / 548 (22.99%)
         occurrences all number
    143
    344
    201
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    99 / 554 (17.87%)
    175 / 1102 (15.88%)
    76 / 548 (13.87%)
         occurrences all number
    148
    301
    153
    Haematuria
         subjects affected / exposed
    24 / 554 (4.33%)
    52 / 1102 (4.72%)
    28 / 548 (5.11%)
         occurrences all number
    29
    70
    41
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    7 / 554 (1.26%)
    36 / 1102 (3.27%)
    29 / 548 (5.29%)
         occurrences all number
    7
    38
    31
    Hypothyroidism
         subjects affected / exposed
    71 / 554 (12.82%)
    209 / 1102 (18.97%)
    138 / 548 (25.18%)
         occurrences all number
    74
    247
    173
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    70 / 554 (12.64%)
    163 / 1102 (14.79%)
    93 / 548 (16.97%)
         occurrences all number
    82
    217
    135
    Myalgia
         subjects affected / exposed
    34 / 554 (6.14%)
    71 / 1102 (6.44%)
    37 / 548 (6.75%)
         occurrences all number
    39
    83
    44
    Muscle spasms
         subjects affected / exposed
    38 / 554 (6.86%)
    61 / 1102 (5.54%)
    23 / 548 (4.20%)
         occurrences all number
    50
    81
    31
    Arthralgia
         subjects affected / exposed
    98 / 554 (17.69%)
    180 / 1102 (16.33%)
    82 / 548 (14.96%)
         occurrences all number
    133
    249
    116
    Back pain
         subjects affected / exposed
    91 / 554 (16.43%)
    180 / 1102 (16.33%)
    89 / 548 (16.24%)
         occurrences all number
    110
    246
    136
    Flank pain
         subjects affected / exposed
    14 / 554 (2.53%)
    44 / 1102 (3.99%)
    30 / 548 (5.47%)
         occurrences all number
    18
    58
    40
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    46 / 554 (8.30%)
    88 / 1102 (7.99%)
    42 / 548 (7.66%)
         occurrences all number
    77
    142
    65
    Upper respiratory tract infection
         subjects affected / exposed
    30 / 554 (5.42%)
    64 / 1102 (5.81%)
    34 / 548 (6.20%)
         occurrences all number
    40
    87
    47
    Urinary tract infection
         subjects affected / exposed
    23 / 554 (4.15%)
    52 / 1102 (4.72%)
    29 / 548 (5.29%)
         occurrences all number
    32
    72
    40
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    207 / 554 (37.36%)
    410 / 1102 (37.21%)
    203 / 548 (37.04%)
         occurrences all number
    305
    633
    328
    Hyperglycaemia
         subjects affected / exposed
    16 / 554 (2.89%)
    46 / 1102 (4.17%)
    30 / 548 (5.47%)
         occurrences all number
    24
    64
    40
    Hyponatraemia
         subjects affected / exposed
    22 / 554 (3.97%)
    58 / 1102 (5.26%)
    36 / 548 (6.57%)
         occurrences all number
    34
    86
    52
    Hypophosphataemia
         subjects affected / exposed
    21 / 554 (3.79%)
    53 / 1102 (4.81%)
    32 / 548 (5.84%)
         occurrences all number
    35
    92
    57

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Oct 2008
    Amendment 1: Country Specific Amendment for Japan to add pharmacokinetic sampling for subjects randomized to pazopanib
    01 Apr 2009
    Amendment 2: Updates to Inclusion/Exclusion criteria, dose modification guidelines for liver toxicity, concomitant medication, addition of pharmacogenetic sampling and Supplementary Quality of Life Questions.
    15 Jun 2009
    Amendment 3: Country Specific Amendment for China to permit using 12.5 mg capsules of sunitinib for 50 mg, 37.5 mg, and 25 mg dose levels.
    25 Mar 2011
    Amendment 4: Change to safety visit schedule to decrease number of visits after Cycle 9 from Day 28 and Day 42 per cycle, to Day 42 per cycle. Changes in Data Analysis section to sample size assumptions and inclusion of subjects from Study A2201 for the analysis of safety and efficacy.
    17 May 2013
    Amendment 5: Changes to allow subjects continued access to pazopanib or sunitinib therapy following the Treatment Phase (in the absence of unacceptable toxicity, disease progression, or subject withdrawal). Subject treatment and disease management was conducted as indicated by local standard of medical care. Subjects who had already discontinued study treatment and were in progressive disease follow-up or survival follow-up were considered as having completed the study. Frequency of clinic visits reduced. Collection of safety information reduced to SAEs, pregnancies, AEs leading to study treatment discontinuation or other AEs the investigator deems important to report, and all other reasons leading to study treatment discontinuation.
    05 Dec 2017
    Amendment 6: Country specific amendment for China to permit use of pazopanib 200mg tablets (commercial supply) instead of 400mg tablets (clinical supply) in China.

    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.
    The full investigators lists and other Clinical Study Report appendices were not transferred over during the change in sponsorship from GlaxoSmithKline (GSK) to Novartis, the team could not confirm or quality control the investigator sites list.
    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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