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    Clinical Trial Results:
    Sunitinib treatment of renal adjuvant cancer (S TRAC): A randomized double blind phase 3 study of adjuvant sunitinib vs. placebo in subjects at high risk of recurrent renal cell carcinoma (RCC)

    Summary
    EudraCT number
    		 2006-004024-37
    Trial protocol
    		 FR   GB   CZ   DE   GR   AT   IT   IE   SE   PL   SK   DK   ES  
    Global end of trial date

    Results information
    Results version number
    		 v1
    This version publication date
    23 Mar 2017
    First version publication date
    23 Mar 2017
    Other versions
    		 v2 , v3

    Trial information

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    Trial identification
    Sponsor protocol code
    A6181109
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00375674
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 East 42nd Street, New York, United States, 10017
    Public contact
    Pfizer, Inc., Pfizer ClinicalTrials.gov Call Center, 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer, Inc., Pfizer ClinicalTrials.gov Call Center, 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Interim
    Date of interim/final analysis
    07 Apr 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    07 Apr 2016
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate an improvement in disease-free survival (DFS) in patients with RCC at high risk of disease recurrence after nephrectomy (per modified UISS criteria) randomly assigned to adjuvant sunitinib 50 mg once daily (QD) on Schedule 4/2 (4 weeks on, 2 weeks off treatment) for 1 year (9 cycles) versus placebo.
    Protection of trial subjects
    This study was conducted in compliance with the ethical principles originating in or derived from the declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of trial participants.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Sep 2007
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 4 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 7
    Country: Number of subjects enrolled
    China: 20
    Country: Number of subjects enrolled
    Colombia: 1
    Country: Number of subjects enrolled
    Czech Republic: 21
    Country: Number of subjects enrolled
    Denmark: 17
    Country: Number of subjects enrolled
    France: 99
    Country: Number of subjects enrolled
    Germany: 80
    Country: Number of subjects enrolled
    Greece: 9
    Country: Number of subjects enrolled
    Ireland: 15
    Country: Number of subjects enrolled
    Israel: 13
    Country: Number of subjects enrolled
    Italy: 45
    Country: Number of subjects enrolled
    Korea, Republic of: 25
    Country: Number of subjects enrolled
    Malaysia: 1
    Country: Number of subjects enrolled
    Poland: 46
    Country: Number of subjects enrolled
    Slovakia: 33
    Country: Number of subjects enrolled
    Spain: 41
    Country: Number of subjects enrolled
    Sweden: 14
    Country: Number of subjects enrolled
    Switzerland: 10
    Country: Number of subjects enrolled
    Taiwan: 27
    Country: Number of subjects enrolled
    United Kingdom: 43
    Country: Number of subjects enrolled
    United States: 48
    Worldwide total number of subjects
    615
    EEA total number of subjects
    463
    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)
    457
    From 65 to 84 years
    158
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study was conducted at 97 centers in Australia, China, Colombia, Czech Republic, Denmark, France, Germany, Greece, Ireland, Israel, Italy, Malaysia, Poland, Korea, Slovakia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, and United States. All the enrolled participants were included in the trial.

    Pre-assignment
    Screening details
    		 The study consisted of 2 cohorts, a Global cohort and a China cohort. The data from the China cohort is intended to be analyzed separately. Follow-up is currently ongoing in the China cohort. The focus of this summary is the Global cohort. Data cut off date: Global cohort: 07Apr16 China cohort (projected): Sep17

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Sunitinib
    Arm description
    		 Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sunitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Sunitinib was self administered orally at the same time each day (eg, morning or evening), without regard to meals, beginning on Cycle 1 Day 1 of study treatment. Patients experiencing toxicity were managed by treatment interruption or dose reduction to 37.5 mg QD, and/or permanent discontinuation from study treatment.

    Arm title
    		 Placebo
    Arm description
    		 Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo was self administered orally at the same time each day (eg, morning or evening), without regard to meals, beginning on Cycle 1 Day 1 of study treatment. Patients experiencing toxicity were managed by treatment interruption or dose reduction to 37.5 mg QD, and/or permanent discontinuation from study treatment.

    Number of subjects in period 1
    		Sunitinib Placebo
    Started
    309
    306
    Completed
    186
    191
    Not completed
    123
    115
         Death
    61
    64
         Other
    24
    16
         Subject refused further follow-up
    24
    23
         Lost to follow-up
    14
    12

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Sunitinib
    Reporting group description
    		 Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.

    Reporting group values
    		 Sunitinib Placebo Total
    Number of subjects
    		 309 306 615
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 233 224 457
        From 65-84 years
    		 76 82 158
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 56.8 ( 10.6 ) 57.9 ( 10.6 ) -
    Gender categorical
    Units: Subjects
        Female
    		 87 77 164
        Male
    		 222 229 451

    End points

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    End points reporting groups
    Reporting group title
    Sunitinib
    Reporting group description
    		 Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.

    Primary: Disease-free survival (DFS)- Assessed by Blinded Independent Central Review

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    End point title
    		 Disease-free survival (DFS)- Assessed by Blinded Independent Central Review
    End point description
    DFS was defined as the time interval (in years) from the date of randomization to the first date of recurrence or occurrence of a secondary malignancy or death. Recurrence refers to relapse of the primary tumor in-situ or at metastatic sites. Date of recurrence or occurrence: The date of the recurrence or occurrence of a secondary malignancy for the first time, either by blinded independent central review (BICR) or investigator assessment for the respective analyses. Participants were followed with tumor imaging for recurrence or occurrence of a secondary malignancy for the remainder of the follow-up period unless the patient had withdrawn consent. According to the statistical analysis plan there are two cohorts: 1.Global Cohort: primary analysis of DFS was performed approximately 5 years after last subject in the Global Cohort is randomized; 2. China Cohort: primary analysis of DFS was performed approximately 3 years after the last subject in China Cohort was randomized.
    End point type
    Primary
    End point timeframe
    Every 12 weeks during the first 3 years and every 6 months after that unless the patient had withdrawn consent
    End point values
    		 Sunitinib Placebo
    Number of subjects analysed
    309
    306
    Units: Years
    number (confidence interval 95%)
        DFS- Assessed by BICR
    6.8 (5.8 to 9999)
    5.6 (3.8 to 6.6)
    Statistical analysis title
    		 DFS- Assessed by BICR
    Comparison groups
    Sunitinib v Placebo
    Number of subjects included in analysis
    615
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.03
    Method
    		 Cox Proportional hazards model
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.761
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.594
         upper limit
    		 0.975

    Secondary: DFS- Assessed by the Investigator (Stratified by UISS High Risk Group-Intent to Treat Population)

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    End point title
    		 DFS- Assessed by the Investigator (Stratified by UISS High Risk Group-Intent to Treat Population)
    End point description
    DFS was defined as the time interval (in years) from the date of randomization to the first date of recurrence or occurrence of a secondary malignancy or death. Recurrence refers to relapse of the primary tumor in-situ or at metastatic sites. Date of recurrence or occurrence: The date of the recurrence or occurrence of a secondary malignancy for the first time, either by BICR or investigator assessment for the respective analyses. Participants were followed with tumor imaging for recurrence or occurrence of a secondary malignancy for the remainder of the follow-up period unless the patient had withdrawn consent. According to the statistical analysis plan there are two cohorts: 1.Global Cohort: primary analysis of DFS was performed approximately 5 years after last subject in the Global Cohort is randomized; 2. China Cohort: primary analysis of DFS was performed approximately 3 years after the last subject in China Cohort was randomized.
    End point type
    Secondary
    End point timeframe
    Every 12 weeks during the first 3 years and every 6 months after that unless the patient had withdrawn consent
    End point values
    		 Sunitinib Placebo
    Number of subjects analysed
    309
    306
    Units: Years
    number (confidence interval 95%)
        DFS- Assessed by the Investigator
    6.5 (4.7 to 7)
    4.5 (3.8 to 5.9)
    Statistical analysis title
    		 DFS- Assessed by the Investigator
    Comparison groups
    Sunitinib v Placebo
    Number of subjects included in analysis
    615
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.077
    Method
    		 Cox Proportional hazards model
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.811
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.643
         upper limit
    		 1.023

    Secondary: Overall survival (OS)- (Stratified by UISS High Risk Group-Intent to Treat Population)

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    End point title
    		 Overall survival (OS)- (Stratified by UISS High Risk Group-Intent to Treat Population)
    End point description
    OS was defined as the time from the date of randomization to the date of death due to any cause. OS data were not mature at the time of data cutoff and the median OS was not reached for either arm.
    End point type
    Secondary
    End point timeframe
    Every 12 weeks until 5 years from Last Subject First Visit (LSFV)
    End point values
    		 Sunitinib Placebo
    Number of subjects analysed
    309
    306
    Units: Years
    median (confidence interval 95%)
        Overall survival
    0 (0 to 0)
    0 (0 to 0)
    Statistical analysis title
    		 OS- Stratified by UISS High Risk Group
    Comparison groups
    Sunitinib v Placebo
    Number of subjects included in analysis
    615
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.938
    Method
    		 Cox Proportional hazards model
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.014
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.716
         upper limit
    		 1.435

    Secondary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity

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    End point title
    		 Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity
    End point description
    TEAEs are all AEs (serious and non-serious) occurred, for the first time, on or after the first day of study treatment. AEs started before the first dose of study treatment but increased in severity (CTC grade) over the baseline will also be considered TEAEs. Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be “chronic” or “stable,” whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent.
    End point type
    Secondary
    End point timeframe
    From Cycle 1/Day 1 until at least 28 days post treatment
    End point values
    		 Sunitinib Placebo
    Number of subjects analysed
    306
    304
    Units: Number of participants
        Patients With AEs
    305
    269
        Patients With Serious Adverse Events (SAEs)
    67
    52
        Patients With Grade 3 or Grade 4 AEs
    189
    61
        Patients With Grade 5 AEs
    5
    5
        Patients Discontinued Due to AEs
    86
    17
        Patients With Dose Reduced Due to AEs
    105
    6
        Patients With Temporary Discontinuation Due to AEs
    142
    40
    No statistical analyses for this end point

    Secondary: Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles)

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    End point title
    		 Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles)
    End point description
    TEAEs are all AEs (serious and non-serious) occurred, for the first time, on or after the first day of study treatment. AEs started before the first dose of study treatment but increased in severity (CTC grade) over the baseline will also be considered TEAEs. Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be “chronic” or “stable,” whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent.
    End point type
    Secondary
    End point timeframe
    From Cycle 1/Day 1 until at least 28 days post treatment
    End point values
    		 Sunitinib Placebo
    Number of subjects analysed
    306
    304
    Units: Mean
    arithmetic mean (standard deviation)
        Benign Neoplasm of Thyroid Gland, (n=0,1)
    0 ( 0 )
    35.1 ( 0 )
        Goitre, (n=0,2)
    0 ( 0 )
    305.6 ( 97.08 )
        Hyperthyroidism, (n=12,2)
    23.2 ( 25.95 )
    110.8 ( 146.57 )
        Hypothyroidism, (n=56,4)
    46.9 ( 75.3 )
    58 ( 62.06 )
        Papillary Thyroid Cancer, (n=0,1)
    0 ( 0 )
    22.1 ( 0 )
        Thyroid Disorder, (n=1,0)
    19 ( 0 )
    0 ( 0 )
        Thyroid Mass, (n=0,1)
    0 ( 0 )
    20.4 ( 0 )
    No statistical analyses for this end point

    Secondary: Patient-reported outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores

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    End point title
    		 Patient-reported outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores
    End point description
    PROs was defined as health-related quality of life using the self administered EORTC Quality of Life Questionnaire -C30 (EORTC QLQ-C30) and health status using the EuroQoL Group EQ-5D questionnaire. The EORTC QLQ-C30 measures 5 functional domains of physical, role, cognitive, emotional and social and symptom scales of fatigue, pain, nausea and vomiting, and general health status. Participants completed the questionnaire at the clinic prior to administration of study medications or other clinical activities. End of treatment was defined as collection of the final data point in the study.
    End point type
    Secondary
    End point timeframe
    From Cycle 1/Day 1 or approximately every 6 weeks up to End of treatment
    End point values
    		 Sunitinib Placebo
    Number of subjects analysed
    309
    306
    Units: Scores on scale
    arithmetic mean (standard error)
        Cycle 1 (Baseline), (n=292,288)
    74.83 ( 1.044 )
    75.61 ( 1.044 )
        Cycle 2, (n=260,274)
    69.71 ( 1.289 )
    75.49 ( 1.097 )
        Cycle 3, (n=241,265)
    69.67 ( 1.278 )
    74.09 ( 1.142 )
        Cycle 4, (n=227,249)
    66.52 ( 1.307 )
    74.93 ( 1.109 )
        Cycle 5, (n=219,234)
    68.34 ( 1.34 )
    74.61 ( 1.179 )
        Cycle 6, (n=210,231)
    66.27 ( 1.396 )
    75.69 ( 1.172 )
        Cycle 7, (n=200,220)
    67.42 ( 1.447 )
    73.98 ( 1.222 )
        Cycle 8, (n=185,212)
    68.33 ( 1.376 )
    74.49 ( 1.26 )
        Cycle 9, (n=177,203)
    68.31 ( 1.556 )
    74.06 ( 1.338 )
        End of treatment (EOT), (n=250,250)
    64.43 ( 1.367 )
    73.37 ( 1.264 )
    No statistical analyses for this end point

    Secondary: PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison

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    End point title
    		 PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison
    End point description
    PROs was defined as health-related quality of life using the self administered EORTC Quality of Life Questionnaire -C30 (EORTC QLQ-C30) and health status using the EuroQoL Group EQ-5D questionnaire. The EORTC QLQ-C30 measures 5 functional domains of physical, role, cognitive, emotional and social and symptom scales of fatigue, pain, nausea and vomiting, and general health status. Participants completed the questionnaire at the clinic prior to administration of study medications or other clinical activities. End of treatment was defined as collection of the final data point in the study.
    End point type
    Secondary
    End point timeframe
    From Cycle 1/ Day 1 or approximately every 6 weeks up to End of treatment
    End point values
    		 Sunitinib Placebo
    Number of subjects analysed
    309
    306
    Units: Scores on scale
    arithmetic mean (confidence interval 95%)
        Physical
    83.54 (82.4 to 84.68)
    87.53 (86.42 to 88.64)
        Role
    78.94 (77.14 to 80.74)
    85.46 (83.7 to 87.23)
        Emotional
    80.92 (79.58 to 82.27)
    82.97 (81.66 to 84.29)
        Cognitive
    85.5 (84.17 to 86.83)
    87.43 (86.13 to 88.73)
        Social
    80.62 (79.04 to 82.21)
    87.99 (86.44 to 89.53)
    No statistical analyses for this end point

    Secondary: PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison

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    End point title
    		 PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison
    End point description
    PROs was defined as health-related quality of life using the self administered EORTC Quality of Life Questionnaire -C30 (EORTC QLQ-C30) and health status using the EuroQoL Group EQ-5D questionnaire. The EORTC QLQ-C30 measures 5 functional domains of physical, role, cognitive, emotional and social and symptom scales of fatigue, pain, nausea and vomiting, and general health status. Participants completed the questionnaire at the clinic prior to administration of study medications or other clinical activities. End of treatment was defined as collection of the final data point in the study.
    End point type
    Secondary
    End point timeframe
    From Cycle 1/ Day 1 or approximately every 6 weeks up to End of treatment
    End point values
    		 Sunitinib Placebo
    Number of subjects analysed
    309
    306
    Units: Scores on scale
    arithmetic mean (confidence interval 95%)
        Fatigue
    29.94 (28.33 to 31.56)
    21.74 (20.16 to 23.31)
        Nausea and Vomiting
    7.35 (6.38 to 8.33)
    3.46 (2.51 to 4.41)
        Pain
    21.81 (20.1 to 23.52)
    16.63 (14.96 to 18.3)
        Dyspnoea
    14.97 (13.38 to 16.57)
    11.89 (10.33 to 13.45)
        Insomnia
    22.22 (20.26 to 24.19)
    20.73 (18.81 to 22.65)
        Appetite Loss
    14.66 (13.12 to 16.21)
    4.62 (3.11 to 6.13)
        Constipation
    11.24 (9.66 to 12.82)
    9.83 (8.29 to 11.37)
        Diarrhoea
    19.25 (17.54 to 20.95)
    7.25 (5.59 to 8.91)
        Financial Difficulties
    15.12 (13.42 to 16.82)
    13.92 (12.26 to 15.59)
    No statistical analyses for this end point

    Secondary: PROs- EuroQoL EQ-5D Observed Means

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    End point title
    		 PROs- EuroQoL EQ-5D Observed Means
    End point description
    PROs was defined as health-related quality of life using the self administered EORTC Quality of Life Questionnaire -C30 (EORTC QLQ-C30) and health status using the EuroQoL Group EQ-5D questionnaire. The EQ-5D comprises of 5 dimensions of health (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression). A unique EQ-5D health state was defined by combining one level from each of the 5 dimensions and was converted to a single summary index or health utility value. The EQ- 5D questionnaire was completed during each clinic visit prior to any other interventions. End of treatment was defined as collection of the final data point in the study.
    End point type
    Secondary
    End point timeframe
    From Cycle 1/ Day 1 or approximately every 6 weeks up to End of treatment
    End point values
    		 Sunitinib Placebo
    Number of subjects analysed
    309
    306
    Units: Mean
    arithmetic mean (standard error)
        Cycle 1 (Baseline), (n=293,287)
    0.84 ( 0.011 )
    0.83 ( 0.011 )
        Cycle 2, (n=255,271)
    0.83 ( 0.011 )
    0.84 ( 0.011 )
        Cycle 3, (n=235,267)
    0.8 ( 0.013 )
    0.82 ( 0.012 )
        Cycle 4, (n=231,245)
    0.77 ( 0.014 )
    0.84 ( 0.011 )
        Cycle 5, (n=218,230)
    0.77 ( 0.016 )
    0.084 ( 0.13 )
        Cycle 6, (n=211,234)
    0.78 ( 0.016 )
    0.85 ( 0.012 )
        Cycle 7, (n=199,216)
    0.77 ( 0.016 )
    0.83 ( 0.014 )
        Cycle 8, (n=185,207)
    0.8 ( 0.015 )
    0.84 ( 0.013 )
        Cycle 9, (n=174,202)
    0.081 ( 0.015 )
    0.85 ( 0.013 )
        EOT, (n=250,245)
    0.75 ( 0.017 )
    0.83 ( 0.015 )
    No statistical analyses for this end point

    Secondary: PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means

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    End point title
    		 PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means
    End point description
    PROs was defined as health-related quality of life using the self administered EORTC Quality of Life Questionnaire -C30 (EORTC QLQ-C30) and health status using the EuroQoL Group EQ-5D questionnaire. The EuroQoL EQ-5D consists of 2 parts, the EQ-5D index (or simply EQ-5D) and EQ-VAS. The EQ-VAS is a visual analog scale where the patient indicated how good or bad his health on that day by marking an appropriate point on a line between 0 (worst imaginable health states) to 100 (best imaginable health states). End of treatment was defined as collection of the final data point in the study.
    End point type
    Secondary
    End point timeframe
    From Cycle 1/ Day 1 or approximately every 6 weeks upto End of treatment
    End point values
    		 Sunitinib Placebo
    Number of subjects analysed
    309
    306
    Units: Mean
    arithmetic mean (standard error)
        Cycle 1 (Baseline), (N= 293,287)
    77.31 ( 0.999 )
    75.67 ( 1.08 )
        Cycle 2, (N= 261,268)
    74.39 ( 1.188 )
    76.99 ( 1.08 )
        Cycle 3, (N= 234,261)
    74.2 ( 1.093 )
    76.85 ( 1.122 )
        Cycle 4, (N= 231,246)
    74.14 ( 1.118 )
    77.34 ( 1.115 )
        Cycle 5, (N= 218,233)
    73.3 ( 1.22 )
    77.56 ( 1.212 )
        Cycle 6, (N= 211,232)
    73.51 ( 1.25 )
    78.61 ( 1.13 )
        Cycle 7, (N= 199,218)
    72.27 ( 1.267 )
    77.49 ( 1.18 )
        Cycle 8, (N= 186,209)
    73.96 ( 1.226 )
    77.65 ( 1.213 )
        Cycle 9, (N= 174,203)
    72.93 ( 1.424 )
    79.02 ( 1.168 )
        EOT, (N= 251,246)
    71.79 ( 1.139 )
    76.93 ( 1.283 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Tolerability Symptoms

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    End point title
    		 Number of Participants With Tolerability Symptoms
    End point description
    Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be “chronic” or “stable,” whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent. This table provides the summary of discontinuations de to adverse events.
    End point type
    Secondary
    End point timeframe
    From Cycle 1/Day 1 until 28 days post treatment
    End point values
    		 Sunitinib Placebo
    Number of subjects analysed
    309
    306
    Units: Number of Events]
    number (not applicable)
        Palmar-plantar erythrodysaesthesia syndrome
    13
    0
        Hypertension
    6
    0
        Asthenia
    4
    0
        Fatigue
    3
    1
        Pulmonary embolism
    3
    1
        Gastrooesophageal reflux disease
    3
    0
        Ejection fraction decreased
    2
    1
        Left ventricular dysfunction
    2
    1
        Acute myocardial infarction
    2
    0
        Blood creatinine increased
    2
    0
        Dehydration
    2
    0
        Dyspepsia
    2
    0
        Proteinuria
    2
    0
        Thrombocytopenia
    2
    0
        Upper gastrointestinal haemorrhage
    2
    0
        Vomiting
    2
    0
        Electrocardiogram QT prolonged
    1
    1
        Lethargy
    1
    1
        Transient ischaemic attack
    1
    1
        Depression
    0
    2
        Abdominal pain
    1
    0
        Abdominal pain upper
    1
    0
        Acute kidney injury
    1
    0
        Ageusia
    1
    0
        Alanine aminotransferase increased
    1
    0
        Anal inflammation
    1
    0
        Anal pruritus
    1
    0
        Aspartate aminotransferase increased
    1
    0
        Atrial fibrillation
    1
    0
        Atrial flutter
    1
    0
        Diarrhoea
    1
    0
        Disease progression
    1
    0
        Dysgeusia
    1
    0
        Electrocardiogram ST segment abnormal
    1
    0
        Embolism venous
    1
    0
        Eyelid oedema
    1
    0
        Gastritis haemorrhagic
    1
    0
        Glossodynia
    1
    0
        Hepatic function abnormal
    1
    0
        Hepatitis acute
    1
    0
        Hypercreatininaemia
    1
    0
        Hypertransaminasaemia
    1
    0
        Hypothyroidism
    1
    0
        Influenza like illness
    1
    0
        Mental status changes
    1
    0
        Mucosal inflammation
    1
    0
        Myalgia
    1
    0
        Myocardial infarction
    1
    0
        Myocarditis
    1
    0
        Necrosis
    1
    0
        Nephrotic syndrome
    1
    0
        Neutropenia
    1
    0
        Oedema peripheral
    1
    0
        Pancytopenia
    1
    0
        Post procedural infection
    1
    0
        Presyncope
    1
    0
        Pyrexia
    1
    0
        Stomatitis
    1
    0
        Therapeutic response unexpected
    1
    0
        Tremor
    1
    0
        Vena cava thrombosis
    1
    0
        Vertigo
    1
    0
        Agitated depression
    0
    1
        Angina unstable
    0
    1
        Brain cancer metastatic
    0
    1
        Hepatitis
    0
    1
        Hypersensitivity
    0
    1
        Metastases to lung
    0
    1
        Mood altered
    0
    1
        Renal impairment
    0
    1
        Tinnitus
    0
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Day 1 of start of study treatment until Day 28 post treatment.
    Adverse event reporting additional description
    Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be “chronic” or “stable,” whichever was later.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off.

    Reporting group title
    Sunitinib
    Reporting group description
    		 Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off.

    Serious adverse events
    		 Placebo Sunitinib
    Total subjects affected by serious adverse events
         subjects affected / exposed
    52 / 304 (17.11%)
    67 / 306 (21.90%)
         number of deaths (all causes)
    64
    63
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute promyelocytic leukaemia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign neoplasm of bladder
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carcinoid tumour of the gastrointestinal tract
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial adenocarcinoma
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to lung
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Axonal neuropathy
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haematoma
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    2 / 304 (0.66%)
    8 / 306 (2.61%)
         occurrences causally related to treatment / all
    0 / 3
    7 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vena cava thrombosis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Venous thrombosis limb
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Gastrectomy
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenectomy
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Malaise
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 304 (0.00%)
    5 / 306 (1.63%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Menorrhagia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 304 (0.33%)
    5 / 306 (1.63%)
         occurrences causally related to treatment / all
    1 / 1
    4 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory acidosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Agitated depression
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Meniscus injury
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Myocardial infarction
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphopenia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    6 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 304 (0.33%)
    7 / 306 (2.29%)
         occurrences causally related to treatment / all
    0 / 1
    7 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Tympanic membrane perforation
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diplopia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vitreous haemorrhage
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocutaneous fistula
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis haemorrhagic
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Acute hepatic failure
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis acute
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Albuminuria
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis viral
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paronychia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia legionella
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 304 (0.99%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo Sunitinib
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    269 / 304 (88.49%)
    303 / 306 (99.02%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign neoplasm of bladder
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Benign neoplasm of thyroid gland
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Brain cancer metastatic
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Cancer pain
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Lipoma
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Malignant melanoma
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Seborrhoeic keratosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Tumour haemorrhage
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Tumour pain
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Arteriosclerosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Capillary disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Embolism venous
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Endothelial dysfunction
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Flushing
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    1
    4
    Surgical and medical procedures
    Abdominal hernia repair
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Cancer surgery
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Dental implantation
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Hysterectomy
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Injection
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Palatal operation
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Spleen operation
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Therapeutic procedure
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Tooth extraction
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences all number
    1
    2
    Wisdom teeth removal
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    36 / 304 (11.84%)
    69 / 306 (22.55%)
         occurrences all number
    70
    198
    Chest discomfort
         subjects affected / exposed
    2 / 304 (0.66%)
    3 / 306 (0.98%)
         occurrences all number
    4
    3
    Chest pain
         subjects affected / exposed
    13 / 304 (4.28%)
    11 / 306 (3.59%)
         occurrences all number
    14
    15
    Chills
         subjects affected / exposed
    4 / 304 (1.32%)
    10 / 306 (3.27%)
         occurrences all number
    4
    12
    Cyst
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Death
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Face oedema
         subjects affected / exposed
    1 / 304 (0.33%)
    28 / 306 (9.15%)
         occurrences all number
    1
    38
    Facial pain
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Fatigue
         subjects affected / exposed
    74 / 304 (24.34%)
    112 / 306 (36.60%)
         occurrences all number
    114
    259
    Feeling abnormal
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Feeling cold
         subjects affected / exposed
    2 / 304 (0.66%)
    4 / 306 (1.31%)
         occurrences all number
    2
    6
    Feeling hot
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    4
    0
    Feeling of body temperature change
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    General physical health deterioration
         subjects affected / exposed
    2 / 304 (0.66%)
    3 / 306 (0.98%)
         occurrences all number
    2
    3
    Generalised oedema
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Hernia
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Hypothermia
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Impaired healing
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Influenza like illness
         subjects affected / exposed
    5 / 304 (1.64%)
    11 / 306 (3.59%)
         occurrences all number
    6
    16
    Infusion site extravasation
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Injection site haematoma
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Injection site inflammation
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Localised oedema
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Malaise
         subjects affected / exposed
    1 / 304 (0.33%)
    6 / 306 (1.96%)
         occurrences all number
    2
    12
    Mucosal dryness
         subjects affected / exposed
    1 / 304 (0.33%)
    4 / 306 (1.31%)
         occurrences all number
    1
    6
    Mucosal induration
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Mucosal inflammation
         subjects affected / exposed
    25 / 304 (8.22%)
    102 / 306 (33.33%)
         occurrences all number
    26
    246
    Necrosis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Oedema
         subjects affected / exposed
    2 / 304 (0.66%)
    10 / 306 (3.27%)
         occurrences all number
    3
    17
    Oedema mucosal
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    0
    0
    Oedema peripheral
         subjects affected / exposed
    16 / 304 (5.26%)
    24 / 306 (7.84%)
         occurrences all number
    17
    36
    Pain
         subjects affected / exposed
    9 / 304 (2.96%)
    9 / 306 (2.94%)
         occurrences all number
    10
    11
    Peripheral swelling
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences all number
    0
    4
    Pyrexia
         subjects affected / exposed
    17 / 304 (5.59%)
    32 / 306 (10.46%)
         occurrences all number
    21
    45
    Secretion discharge
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Swelling
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Temperature intolerance
         subjects affected / exposed
    0 / 304 (0.00%)
    4 / 306 (1.31%)
         occurrences all number
    0
    4
    Therapeutic response unexpected
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Xerosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Immune system disorders
    Contrast media allergy
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Drug hypersensitivity
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Hypersensitivity
         subjects affected / exposed
    5 / 304 (1.64%)
    3 / 306 (0.98%)
         occurrences all number
    6
    3
    Seasonal allergy
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Social circumstances
    Disability
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Walking disability
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Amenorrhoea
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Balanoposthitis
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    5
    Breast pain
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Breast tenderness
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Erectile dysfunction
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Genital rash
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Gynaecomastia
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 306 (0.00%)
         occurrences all number
    3
    0
    Haematospermia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Menometrorrhagia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Menorrhagia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Ovarian cyst
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Ovarian disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Pelvic pain
         subjects affected / exposed
    2 / 304 (0.66%)
    2 / 306 (0.65%)
         occurrences all number
    2
    2
    Penile pain
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Prostatitis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Prostatomegaly
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Scrotal erythema
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Scrotal pain
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Testicular pain
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 306 (0.00%)
         occurrences all number
    3
    0
    Testicular swelling
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Testis discomfort
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Vulvovaginal dryness
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Asphyxia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Bronchial hyperreactivity
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Bronchial obstruction
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Cough
         subjects affected / exposed
    20 / 304 (6.58%)
    22 / 306 (7.19%)
         occurrences all number
    24
    24
    Dry throat
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Dysphonia
         subjects affected / exposed
    5 / 304 (1.64%)
    10 / 306 (3.27%)
         occurrences all number
    5
    12
    Dyspnoea
         subjects affected / exposed
    19 / 304 (6.25%)
    18 / 306 (5.88%)
         occurrences all number
    23
    21
    Dyspnoea exertional
         subjects affected / exposed
    4 / 304 (1.32%)
    5 / 306 (1.63%)
         occurrences all number
    5
    6
    Epistaxis
         subjects affected / exposed
    9 / 304 (2.96%)
    55 / 306 (17.97%)
         occurrences all number
    9
    92
    Haemoptysis
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences all number
    1
    2
    Hiccups
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    3
    Hydrothorax
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Laryngeal pain
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Lung disorder
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Lung infiltration
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Nasal congestion
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences all number
    0
    4
    Nasal discomfort
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Nasal disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    3
    Nasal dryness
         subjects affected / exposed
    1 / 304 (0.33%)
    5 / 306 (1.63%)
         occurrences all number
    1
    5
    Nasal inflammation
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Oropharyngeal discomfort
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    10 / 304 (3.29%)
    17 / 306 (5.56%)
         occurrences all number
    11
    29
    Pharyngeal erythema
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Pharyngeal ulceration
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Pleural effusion
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Pneumonitis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Productive cough
         subjects affected / exposed
    5 / 304 (1.64%)
    0 / 306 (0.00%)
         occurrences all number
    5
    0
    Pulmonary embolism
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Respiratory disorder
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Respiratory tract haemorrhage
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Rhinalgia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Rhinitis allergic
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    5 / 304 (1.64%)
    4 / 306 (1.31%)
         occurrences all number
    5
    6
    Sneezing
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Sputum discoloured
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Tachypnoea
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Throat irritation
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Tonsillar hypertrophy
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Wheezing
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Psychiatric disorders
    Affective disorder
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Agitated depression
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Agitation
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Anger
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Anxiety
         subjects affected / exposed
    14 / 304 (4.61%)
    10 / 306 (3.27%)
         occurrences all number
    15
    10
    Apathy
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Confusional state
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Depressed mood
         subjects affected / exposed
    4 / 304 (1.32%)
    3 / 306 (0.98%)
         occurrences all number
    4
    3
    Depression
         subjects affected / exposed
    9 / 304 (2.96%)
    3 / 306 (0.98%)
         occurrences all number
    9
    5
    Insomnia
         subjects affected / exposed
    19 / 304 (6.25%)
    30 / 306 (9.80%)
         occurrences all number
    21
    39
    Irritability
         subjects affected / exposed
    4 / 304 (1.32%)
    5 / 306 (1.63%)
         occurrences all number
    5
    6
    Listless
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Mental disorder
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Mood altered
         subjects affected / exposed
    3 / 304 (0.99%)
    5 / 306 (1.63%)
         occurrences all number
    4
    5
    Nervousness
         subjects affected / exposed
    2 / 304 (0.66%)
    4 / 306 (1.31%)
         occurrences all number
    2
    5
    Persecutory delusion
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    1
    3
    Sleep disorder
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    1
    3
    Stress
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Tension
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Cholecystitis acute
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Cholelithiasis
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    3
    Hepatic steatosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Hepatitis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Hepatitis acute
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Hepatotoxicity
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Hyperbilirubinaemia
         subjects affected / exposed
    2 / 304 (0.66%)
    5 / 306 (1.63%)
         occurrences all number
    3
    10
    Hypertransaminasaemia
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences all number
    1
    3
    Jaundice
         subjects affected / exposed
    0 / 304 (0.00%)
    20 / 306 (6.54%)
         occurrences all number
    0
    22
    Liver disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Portal vein thrombosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Alanine aminotransferase
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 304 (0.66%)
    15 / 306 (4.90%)
         occurrences all number
    2
    21
    Amylase increased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Aspartate aminotransferase
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 304 (0.66%)
    16 / 306 (5.23%)
         occurrences all number
    6
    20
    Basophil count increased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Blood albumin decreased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    3
    4
    Blood bicarbonate increased
         subjects affected / exposed
    2 / 304 (0.66%)
    3 / 306 (0.98%)
         occurrences all number
    2
    3
    Blood bilirubin increased
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    4
    3
    Blood calcium decreased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Blood chloride decreased
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Blood chloride increased
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Blood cholesterol increased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Blood creatine abnormal
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Blood creatine increased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Blood creatine phosphokinase MB increased
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Blood creatine phosphokinase increased
         subjects affected / exposed
    18 / 304 (5.92%)
    16 / 306 (5.23%)
         occurrences all number
    22
    25
    Blood creatinine increased
         subjects affected / exposed
    24 / 304 (7.89%)
    21 / 306 (6.86%)
         occurrences all number
    28
    28
    Blood glucose increased
         subjects affected / exposed
    2 / 304 (0.66%)
    4 / 306 (1.31%)
         occurrences all number
    4
    5
    Blood lactate dehydrogenase decreased
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    3 / 304 (0.99%)
    15 / 306 (4.90%)
         occurrences all number
    3
    16
    Blood magnesium decreased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Blood potassium decreased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Blood potassium increased
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 306 (0.00%)
         occurrences all number
    3
    0
    Blood pressure diastolic increased
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Blood pressure increased
         subjects affected / exposed
    2 / 304 (0.66%)
    6 / 306 (1.96%)
         occurrences all number
    2
    10
    Blood pressure orthostatic
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Blood pressure systolic increased
         subjects affected / exposed
    3 / 304 (0.99%)
    1 / 306 (0.33%)
         occurrences all number
    3
    1
    Blood sodium decreased
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Blood thyroid stimulating hormone decreased
         subjects affected / exposed
    1 / 304 (0.33%)
    6 / 306 (1.96%)
         occurrences all number
    1
    6
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    7 / 304 (2.30%)
    23 / 306 (7.52%)
         occurrences all number
    9
    28
    Blood triglycerides increased
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    3
    0
    Blood urea increased
         subjects affected / exposed
    7 / 304 (2.30%)
    4 / 306 (1.31%)
         occurrences all number
    9
    5
    Blood uric acid increased
         subjects affected / exposed
    2 / 304 (0.66%)
    3 / 306 (0.98%)
         occurrences all number
    2
    5
    Body temperature increased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Cardiac murmur
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Cardiac stress test abnormal
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Chest X-ray abnormal
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Ejection fraction decreased
         subjects affected / exposed
    6 / 304 (1.97%)
    3 / 306 (0.98%)
         occurrences all number
    6
    3
    Electrocardiogram QT interval abnormal
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 304 (0.33%)
    4 / 306 (1.31%)
         occurrences all number
    7
    6
    Electrocardiogram ST segment abnormal
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Electrocardiogram ST segment depression
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Electrocardiogram ST segment elevation
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Electrocardiogram ST-T change
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Electrocardiogram T wave inversion
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Electrocardiogram T wave peaked
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Eosinophil count increased
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences all number
    1
    5
    Haemoglobin decreased
         subjects affected / exposed
    2 / 304 (0.66%)
    7 / 306 (2.29%)
         occurrences all number
    4
    8
    Hepatic enzyme increased
         subjects affected / exposed
    2 / 304 (0.66%)
    2 / 306 (0.65%)
         occurrences all number
    3
    2
    International normalised ratio increased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Liver function test increased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Low density lipoprotein increased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Monocyte count increased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Neutrophil count
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    7
    Neutrophil count decreased
         subjects affected / exposed
    3 / 304 (0.99%)
    12 / 306 (3.92%)
         occurrences all number
    3
    27
    Platelet count
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Platelet count decreased
         subjects affected / exposed
    1 / 304 (0.33%)
    8 / 306 (2.61%)
         occurrences all number
    2
    11
    Platelet count increased
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Prostatic specific antigen increased
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Protein total decreased
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences all number
    0
    3
    Protein total increased
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Protein urine present
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    QRS axis abnormal
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Red blood cell count increased
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Staphylococcus test positive
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Thyroid function test abnormal
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Thyroxine decreased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Thyroxine free decreased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Transaminases increased
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Visual acuity tests
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Troponin T increased
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Weight decreased
         subjects affected / exposed
    2 / 304 (0.66%)
    14 / 306 (4.58%)
         occurrences all number
    2
    16
    Weight increased
         subjects affected / exposed
    18 / 304 (5.92%)
    8 / 306 (2.61%)
         occurrences all number
    24
    10
    White blood cell count
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    White blood cell count decreased
         subjects affected / exposed
    2 / 304 (0.66%)
    14 / 306 (4.58%)
         occurrences all number
    3
    18
    Xanthochromia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Burn oesophageal
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Burn oral cavity
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Chest injury
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Contusion
         subjects affected / exposed
    2 / 304 (0.66%)
    7 / 306 (2.29%)
         occurrences all number
    2
    9
    Fall
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Femur fracture
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Incisional hernia
         subjects affected / exposed
    7 / 304 (2.30%)
    0 / 306 (0.00%)
         occurrences all number
    8
    0
    Laceration
         subjects affected / exposed
    3 / 304 (0.99%)
    1 / 306 (0.33%)
         occurrences all number
    3
    1
    Ligament injury
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Limb injury
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Patella fracture
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Post procedural complication
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Procedural pain
         subjects affected / exposed
    5 / 304 (1.64%)
    2 / 306 (0.65%)
         occurrences all number
    5
    2
    Rib fracture
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Skin abrasion
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Skin injury
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Soft tissue injury
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Tibia fracture
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Wound complication
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Wound dehiscence
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Congenital, familial and genetic disorders
    Dermoid cyst
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 304 (0.33%)
    5 / 306 (1.63%)
         occurrences all number
    1
    6
    Aortic valve stenosis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Arrhythmia
         subjects affected / exposed
    5 / 304 (1.64%)
    2 / 306 (0.65%)
         occurrences all number
    5
    2
    Arrhythmia supraventricular
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Atrial fibrillation
         subjects affected / exposed
    5 / 304 (1.64%)
    1 / 306 (0.33%)
         occurrences all number
    5
    1
    Bradycardia
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    2
    Bundle branch block left
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Cardiac failure
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Cardiovascular disorder
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Conduction disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Diastolic dysfunction
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Extrasystoles
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Left ventricular dysfunction
         subjects affected / exposed
    3 / 304 (0.99%)
    7 / 306 (2.29%)
         occurrences all number
    3
    10
    Left ventricular hypertrophy
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Mitral valve prolapse
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Myocardial ischaemia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Myocarditis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Palpitations
         subjects affected / exposed
    3 / 304 (0.99%)
    1 / 306 (0.33%)
         occurrences all number
    3
    1
    Pericardial effusion
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Pericarditis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Sinus bradycardia
         subjects affected / exposed
    2 / 304 (0.66%)
    2 / 306 (0.65%)
         occurrences all number
    3
    2
    Supraventricular extrasystoles
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Tachycardia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Tricuspid valve incompetence
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Ventricular hypokinesia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Carotid arteriosclerosis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Carotid artery stenosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Ageusia
         subjects affected / exposed
    0 / 304 (0.00%)
    21 / 306 (6.86%)
         occurrences all number
    0
    32
    Aphonia
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Balance disorder
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Burning sensation
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Cerebral infarction
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Cognitive disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Dementia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Disturbance in attention
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences all number
    1
    2
    Dizziness
         subjects affected / exposed
    18 / 304 (5.92%)
    23 / 306 (7.52%)
         occurrences all number
    22
    29
    Dizziness postural
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Dysaesthesia
         subjects affected / exposed
    1 / 304 (0.33%)
    4 / 306 (1.31%)
         occurrences all number
    1
    5
    Dysgeusia
         subjects affected / exposed
    18 / 304 (5.92%)
    103 / 306 (33.66%)
         occurrences all number
    20
    163
    Facial nerve disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Facial paralysis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Formication
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    3
    0
    Head discomfort
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Headache
         subjects affected / exposed
    36 / 304 (11.84%)
    56 / 306 (18.30%)
         occurrences all number
    39
    84
    Hyperaesthesia
         subjects affected / exposed
    3 / 304 (0.99%)
    5 / 306 (1.63%)
         occurrences all number
    3
    6
    Hypoaesthesia
         subjects affected / exposed
    1 / 304 (0.33%)
    4 / 306 (1.31%)
         occurrences all number
    2
    4
    Hypogeusia
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Hypotonia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Lethargy
         subjects affected / exposed
    9 / 304 (2.96%)
    9 / 306 (2.94%)
         occurrences all number
    12
    18
    Loss of consciousness
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Memory impairment
         subjects affected / exposed
    3 / 304 (0.99%)
    4 / 306 (1.31%)
         occurrences all number
    4
    5
    Migraine
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Muscle contractions involuntary
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Neuralgia
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Neuropathy peripheral
         subjects affected / exposed
    4 / 304 (1.32%)
    7 / 306 (2.29%)
         occurrences all number
    5
    9
    Paraesthesia
         subjects affected / exposed
    11 / 304 (3.62%)
    12 / 306 (3.92%)
         occurrences all number
    15
    15
    Parkinson’s disease
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Peripheral motor neuropathy
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    7 / 304 (2.30%)
    2 / 306 (0.65%)
         occurrences all number
    12
    2
    Polyneuropathy
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Presyncope
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Restless legs syndrome
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Sciatica
         subjects affected / exposed
    0 / 304 (0.00%)
    6 / 306 (1.96%)
         occurrences all number
    0
    6
    Seizure
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Sensory disturbance
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Sensory loss
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Sleep phase rhythm disturbance
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Somnolence
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Syncope
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    4
    Tongue paralysis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Tremor
         subjects affected / exposed
    3 / 304 (0.99%)
    3 / 306 (0.98%)
         occurrences all number
    3
    3
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    7 / 304 (2.30%)
    33 / 306 (10.78%)
         occurrences all number
    8
    65
    Eosinopenia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Erythropenia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Hyperglobulinaemia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Increased tendency to bruise
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Leukocytosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Leukopenia
         subjects affected / exposed
    2 / 304 (0.66%)
    45 / 306 (14.71%)
         occurrences all number
    3
    92
    Lymphadenopathy
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Lymphopenia
         subjects affected / exposed
    1 / 304 (0.33%)
    8 / 306 (2.61%)
         occurrences all number
    1
    14
    Monocytopenia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Neutropenia
         subjects affected / exposed
    2 / 304 (0.66%)
    71 / 306 (23.20%)
         occurrences all number
    3
    193
    Thrombocytopenia
         subjects affected / exposed
    4 / 304 (1.32%)
    61 / 306 (19.93%)
         occurrences all number
    8
    87
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Deafness unilateral
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Ear discomfort
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Ear pain
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    1
    3
    External ear pain
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Hypoacusis
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences all number
    0
    4
    Meniere’s disease
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Tinnitus
         subjects affected / exposed
    5 / 304 (1.64%)
    5 / 306 (1.63%)
         occurrences all number
    6
    8
    Tympanic membrane perforation
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Vertigo
         subjects affected / exposed
    10 / 304 (3.29%)
    7 / 306 (2.29%)
         occurrences all number
    13
    15
    Eye disorders
    Blindness unilateral
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Cataract
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    1
    3
    Cataract subcapsular
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Diplopia
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Dry eye
         subjects affected / exposed
    1 / 304 (0.33%)
    4 / 306 (1.31%)
         occurrences all number
    1
    6
    Eye discharge
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Eye haemorrhage
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Eye inflammation
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Eye irritation
         subjects affected / exposed
    0 / 304 (0.00%)
    5 / 306 (1.63%)
         occurrences all number
    0
    6
    Eye oedema
         subjects affected / exposed
    0 / 304 (0.00%)
    7 / 306 (2.29%)
         occurrences all number
    0
    10
    Eye pain
         subjects affected / exposed
    2 / 304 (0.66%)
    3 / 306 (0.98%)
         occurrences all number
    2
    3
    Eye pruritus
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Eye swelling
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    6
    Eyelash discolouration
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Eyelid bleeding
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Eyelid oedema
         subjects affected / exposed
    1 / 304 (0.33%)
    21 / 306 (6.86%)
         occurrences all number
    1
    33
    Eyelid pain
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Glaucoma
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Lacrimal disorder
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Lacrimal gland enlargement
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Lacrimation increased
         subjects affected / exposed
    1 / 304 (0.33%)
    12 / 306 (3.92%)
         occurrences all number
    1
    16
    Ocular hyperaemia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Ocular surface disease
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Oscillopsia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Periorbital oedema
         subjects affected / exposed
    0 / 304 (0.00%)
    7 / 306 (2.29%)
         occurrences all number
    0
    15
    Photophobia
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Photopsia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Retinopathy hypertensive
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Vision blurred
         subjects affected / exposed
    3 / 304 (0.99%)
    2 / 306 (0.65%)
         occurrences all number
    3
    2
    Visual acuity reduced
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences all number
    1
    2
    Visual impairment
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    1
    3
    Gastrointestinal disorders
    Abdominal adhesions
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Abdominal discomfort
         subjects affected / exposed
    8 / 304 (2.63%)
    8 / 306 (2.61%)
         occurrences all number
    8
    11
    Abdominal distension
         subjects affected / exposed
    4 / 304 (1.32%)
    10 / 306 (3.27%)
         occurrences all number
    4
    13
    Abdominal hernia
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Abdominal pain
         subjects affected / exposed
    15 / 304 (4.93%)
    42 / 306 (13.73%)
         occurrences all number
    17
    70
    Abdominal pain lower
         subjects affected / exposed
    1 / 304 (0.33%)
    7 / 306 (2.29%)
         occurrences all number
    1
    7
    Abdominal pain upper
         subjects affected / exposed
    13 / 304 (4.28%)
    39 / 306 (12.75%)
         occurrences all number
    15
    75
    Abdominal rigidity
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Abdominal tenderness
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Abnormal faeces
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Anal fissure
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Anal haemorrhage
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    3
    Anal inflammation
         subjects affected / exposed
    0 / 304 (0.00%)
    6 / 306 (1.96%)
         occurrences all number
    0
    7
    Anal pruritus
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences all number
    0
    5
    Anal skin tags
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Anorectal discomfort
         subjects affected / exposed
    1 / 304 (0.33%)
    4 / 306 (1.31%)
         occurrences all number
    1
    6
    Anorectal disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Aphthous ulcer
         subjects affected / exposed
    2 / 304 (0.66%)
    12 / 306 (3.92%)
         occurrences all number
    2
    20
    Bowel movement irregularity
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Breath odour
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    3
    0
    Change of bowel habit
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Chapped lips
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences all number
    1
    2
    Colitis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Colitis ulcerative
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Constipation
         subjects affected / exposed
    32 / 304 (10.53%)
    36 / 306 (11.76%)
         occurrences all number
    42
    61
    Dental caries
         subjects affected / exposed
    0 / 304 (0.00%)
    4 / 306 (1.31%)
         occurrences all number
    0
    4
    Diarrhoea
         subjects affected / exposed
    65 / 304 (21.38%)
    174 / 306 (56.86%)
         occurrences all number
    85
    458
    Diverticulum intestinal
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Dry mouth
         subjects affected / exposed
    8 / 304 (2.63%)
    14 / 306 (4.58%)
         occurrences all number
    9
    18
    Duodenal ulcer
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Duodenitis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Duodenogastric reflux
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences all number
    0
    6
    Dyspepsia
         subjects affected / exposed
    19 / 304 (6.25%)
    82 / 306 (26.80%)
         occurrences all number
    23
    149
    Dysphagia
         subjects affected / exposed
    1 / 304 (0.33%)
    15 / 306 (4.90%)
         occurrences all number
    1
    24
    Eructation
         subjects affected / exposed
    1 / 304 (0.33%)
    4 / 306 (1.31%)
         occurrences all number
    1
    4
    Flatulence
         subjects affected / exposed
    14 / 304 (4.61%)
    26 / 306 (8.50%)
         occurrences all number
    16
    32
    Frequent bowel movements
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Functional gastrointestinal disorder
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    2
    Gastric mucosa erythema
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Gastritis
         subjects affected / exposed
    4 / 304 (1.32%)
    5 / 306 (1.63%)
         occurrences all number
    5
    5
    Gastrointestinal disorder
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Gastrointestinal dysplasia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Gastrointestinal hypermotility
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    4
    Gastrointestinal motility disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Gastrointestinal obstruction
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal pain
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    9 / 304 (2.96%)
    27 / 306 (8.82%)
         occurrences all number
    9
    40
    Gingival bleeding
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Gingival oedema
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    1
    4
    Gingival pain
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    1
    4
    Gingival recession
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Gingival swelling
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Gingival ulceration
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Glossitis
         subjects affected / exposed
    1 / 304 (0.33%)
    4 / 306 (1.31%)
         occurrences all number
    1
    5
    Glossodynia
         subjects affected / exposed
    0 / 304 (0.00%)
    7 / 306 (2.29%)
         occurrences all number
    0
    9
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Haemorrhoids
         subjects affected / exposed
    3 / 304 (0.99%)
    12 / 306 (3.92%)
         occurrences all number
    5
    18
    Hiatus hernia
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Hyperchlorhydria
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences all number
    0
    6
    Hypoaesthesia oral
         subjects affected / exposed
    0 / 304 (0.00%)
    4 / 306 (1.31%)
         occurrences all number
    0
    5
    Impaired gastric emptying
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Inguinal hernia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Large intestine polyp
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Lip disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Lip dry
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Lip ulceration
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Loose tooth
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Mouth cyst
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Mouth ulceration
         subjects affected / exposed
    3 / 304 (0.99%)
    9 / 306 (2.94%)
         occurrences all number
    3
    16
    Nausea
         subjects affected / exposed
    42 / 304 (13.82%)
    103 / 306 (33.66%)
         occurrences all number
    62
    213
    Odynophagia
         subjects affected / exposed
    0 / 304 (0.00%)
    5 / 306 (1.63%)
         occurrences all number
    0
    9
    Oesophageal pain
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences all number
    0
    4
    Oesophagitis
         subjects affected / exposed
    1 / 304 (0.33%)
    14 / 306 (4.58%)
         occurrences all number
    3
    25
    Oral discomfort
         subjects affected / exposed
    0 / 304 (0.00%)
    4 / 306 (1.31%)
         occurrences all number
    0
    6
    Oral disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences all number
    0
    4
    Oral mucosal blistering
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Oral mucosal erythema
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Oral pain
         subjects affected / exposed
    2 / 304 (0.66%)
    7 / 306 (2.29%)
         occurrences all number
    2
    7
    Oral toxicity
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Palatal oedema
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Palatal swelling
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Pancreatic steatosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Perianal erythema
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Proctalgia
         subjects affected / exposed
    1 / 304 (0.33%)
    7 / 306 (2.29%)
         occurrences all number
    1
    12
    Proctitis
         subjects affected / exposed
    1 / 304 (0.33%)
    9 / 306 (2.94%)
         occurrences all number
    1
    14
    Rectal haemorrhage
         subjects affected / exposed
    1 / 304 (0.33%)
    6 / 306 (1.96%)
         occurrences all number
    1
    8
    Regurgitation
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Salivary hypersecretion
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Sensitivity of teeth
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences all number
    1
    2
    Stomatitis
         subjects affected / exposed
    13 / 304 (4.28%)
    81 / 306 (26.47%)
         occurrences all number
    17
    154
    Swollen tongue
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Tongue disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Tongue oedema
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Tongue ulceration
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    1
    3
    Tooth loss
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Toothache
         subjects affected / exposed
    3 / 304 (0.99%)
    5 / 306 (1.63%)
         occurrences all number
    3
    5
    Vomiting
         subjects affected / exposed
    20 / 304 (6.58%)
    55 / 306 (17.97%)
         occurrences all number
    24
    98
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 304 (0.33%)
    6 / 306 (1.96%)
         occurrences all number
    2
    14
    Alopecia
         subjects affected / exposed
    2 / 304 (0.66%)
    26 / 306 (8.50%)
         occurrences all number
    2
    27
    Blister
         subjects affected / exposed
    1 / 304 (0.33%)
    6 / 306 (1.96%)
         occurrences all number
    1
    9
    Cold sweat
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Dermal cyst
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Dermatitis
         subjects affected / exposed
    3 / 304 (0.99%)
    5 / 306 (1.63%)
         occurrences all number
    3
    6
    Dry skin
         subjects affected / exposed
    17 / 304 (5.59%)
    43 / 306 (14.05%)
         occurrences all number
    19
    59
    Dyshidrotic eczema
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Eczema
         subjects affected / exposed
    3 / 304 (0.99%)
    5 / 306 (1.63%)
         occurrences all number
    4
    8
    Erythema
         subjects affected / exposed
    9 / 304 (2.96%)
    13 / 306 (4.25%)
         occurrences all number
    12
    19
    Erythema multiforme
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Erythrosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Exfoliative rash
         subjects affected / exposed
    0 / 304 (0.00%)
    5 / 306 (1.63%)
         occurrences all number
    0
    7
    Granuloma annulare
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Hair colour changes
         subjects affected / exposed
    7 / 304 (2.30%)
    68 / 306 (22.22%)
         occurrences all number
    8
    78
    Hair growth abnormal
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Hair texture abnormal
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Hyperhidrosis
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    2
    Hyperkeratosis
         subjects affected / exposed
    2 / 304 (0.66%)
    10 / 306 (3.27%)
         occurrences all number
    2
    13
    Ingrowing nail
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Keloid scar
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Macule
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Nail bed bleeding
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Nail discolouration
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Nail disorder
         subjects affected / exposed
    2 / 304 (0.66%)
    6 / 306 (1.96%)
         occurrences all number
    2
    7
    Nail growth abnormal
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Nail toxicity
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences all number
    0
    4
    Night sweats
         subjects affected / exposed
    2 / 304 (0.66%)
    2 / 306 (0.65%)
         occurrences all number
    2
    5
    Palmar erythema
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    3
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    31 / 304 (10.20%)
    154 / 306 (50.33%)
         occurrences all number
    42
    505
    Panniculitis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Papule
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Petechiae
         subjects affected / exposed
    0 / 304 (0.00%)
    5 / 306 (1.63%)
         occurrences all number
    0
    5
    Photosensitivity reaction
         subjects affected / exposed
    2 / 304 (0.66%)
    3 / 306 (0.98%)
         occurrences all number
    2
    3
    Pigmentation disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Plantar erythema
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Pruritus
         subjects affected / exposed
    21 / 304 (6.91%)
    21 / 306 (6.86%)
         occurrences all number
    30
    31
    Pruritus generalised
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    4
    Psoriasis
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences all number
    1
    2
    Rash
         subjects affected / exposed
    29 / 304 (9.54%)
    59 / 306 (19.28%)
         occurrences all number
    42
    78
    Rash erythematous
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Rash follicular
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Rash generalised
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Rash macular
         subjects affected / exposed
    1 / 304 (0.33%)
    4 / 306 (1.31%)
         occurrences all number
    1
    9
    Rash papular
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Rash vesicular
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Scar pain
         subjects affected / exposed
    7 / 304 (2.30%)
    1 / 306 (0.33%)
         occurrences all number
    8
    1
    Seborrhoeic dermatitis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Skin burning sensation
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    2
    Skin depigmentation
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Skin discolouration
         subjects affected / exposed
    1 / 304 (0.33%)
    24 / 306 (7.84%)
         occurrences all number
    1
    27
    Skin disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Skin exfoliation
         subjects affected / exposed
    0 / 304 (0.00%)
    11 / 306 (3.59%)
         occurrences all number
    0
    18
    Skin fissures
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences all number
    0
    5
    Skin hyperpigmentation
         subjects affected / exposed
    2 / 304 (0.66%)
    12 / 306 (3.92%)
         occurrences all number
    2
    13
    Skin hypertrophy
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Skin hypopigmentation
         subjects affected / exposed
    1 / 304 (0.33%)
    9 / 306 (2.94%)
         occurrences all number
    1
    10
    Skin irritation
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Skin lesion
         subjects affected / exposed
    2 / 304 (0.66%)
    9 / 306 (2.94%)
         occurrences all number
    2
    14
    Skin mass
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Skin odour abnormal
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Skin reaction
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Skin toxicity
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Splinter haemorrhages
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Swelling face
         subjects affected / exposed
    0 / 304 (0.00%)
    5 / 306 (1.63%)
         occurrences all number
    0
    13
    Urticaria
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences all number
    1
    4
    Urticaria thermal
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Yellow skin
         subjects affected / exposed
    2 / 304 (0.66%)
    32 / 306 (10.46%)
         occurrences all number
    3
    45
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Albuminuria
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Bladder disorder
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Bladder pain
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Bladder spasm
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Chromaturia
         subjects affected / exposed
    0 / 304 (0.00%)
    9 / 306 (2.94%)
         occurrences all number
    0
    18
    Dysuria
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Haematuria
         subjects affected / exposed
    5 / 304 (1.64%)
    7 / 306 (2.29%)
         occurrences all number
    6
    11
    Nocturia
         subjects affected / exposed
    6 / 304 (1.97%)
    1 / 306 (0.33%)
         occurrences all number
    6
    2
    Pollakiuria
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 306 (0.00%)
         occurrences all number
    3
    0
    Proteinuria
         subjects affected / exposed
    9 / 304 (2.96%)
    18 / 306 (5.88%)
         occurrences all number
    10
    27
    Pyelocaliectasis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Renal cyst
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Renal failure
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Renal impairment
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Renal pain
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Urinary incontinence
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Urinary retention
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Urinary tract obstruction
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Benign prostatic hyperplasia
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 306 (0.00%)
         occurrences all number
    3
    0
    Breast engorgement
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Endocrine disorders
    Goitre
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Hyperparathyroidism
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Hyperthyroidism
         subjects affected / exposed
    2 / 304 (0.66%)
    12 / 306 (3.92%)
         occurrences all number
    2
    13
    Hypothyroidism
         subjects affected / exposed
    4 / 304 (1.32%)
    56 / 306 (18.30%)
         occurrences all number
    4
    72
    Oestrogen deficiency
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Thyroid disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Thyroid mass
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    29 / 304 (9.54%)
    35 / 306 (11.44%)
         occurrences all number
    34
    52
    Arthritis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Back pain
         subjects affected / exposed
    26 / 304 (8.55%)
    28 / 306 (9.15%)
         occurrences all number
    29
    33
    Bone pain
         subjects affected / exposed
    8 / 304 (2.63%)
    4 / 306 (1.31%)
         occurrences all number
    8
    5
    Bursitis
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Fibromyalgia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Flank pain
         subjects affected / exposed
    4 / 304 (1.32%)
    3 / 306 (0.98%)
         occurrences all number
    6
    3
    Groin pain
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    1
    4
    Haemarthrosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Interspinous osteoarthritis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Joint stiffness
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Joint swelling
         subjects affected / exposed
    2 / 304 (0.66%)
    4 / 306 (1.31%)
         occurrences all number
    2
    4
    Limb discomfort
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Muscle fatigue
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Muscle mass
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Muscle spasms
         subjects affected / exposed
    13 / 304 (4.28%)
    25 / 306 (8.17%)
         occurrences all number
    13
    30
    Muscular weakness
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    1
    3
    Musculoskeletal chest pain
         subjects affected / exposed
    4 / 304 (1.32%)
    6 / 306 (1.96%)
         occurrences all number
    4
    6
    Musculoskeletal discomfort
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Musculoskeletal disorder
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    14 / 304 (4.61%)
    13 / 306 (4.25%)
         occurrences all number
    17
    16
    Musculoskeletal stiffness
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences all number
    1
    2
    Myalgia
         subjects affected / exposed
    15 / 304 (4.93%)
    25 / 306 (8.17%)
         occurrences all number
    15
    32
    Myalgia intercostal
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Myositis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Neck pain
         subjects affected / exposed
    5 / 304 (1.64%)
    5 / 306 (1.63%)
         occurrences all number
    5
    10
    Nodal osteoarthritis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Osteoarthritis
         subjects affected / exposed
    3 / 304 (0.99%)
    4 / 306 (1.31%)
         occurrences all number
    3
    4
    Osteochondrosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Osteoporosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Osteoporosis postmenopausal
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Pain in extremity
         subjects affected / exposed
    20 / 304 (6.58%)
    45 / 306 (14.71%)
         occurrences all number
    23
    63
    Periarthritis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Soft tissue disorder
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Spinal column stenosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Spinal osteoarthritis
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Spinal pain
         subjects affected / exposed
    2 / 304 (0.66%)
    8 / 306 (2.61%)
         occurrences all number
    2
    9
    Synovial cyst
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Tendonitis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Tenosynovitis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Dysplastic naevus
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Haemangioma
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Infections and infestations
    Angular cheilitis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Bronchitis
         subjects affected / exposed
    6 / 304 (1.97%)
    6 / 306 (1.96%)
         occurrences all number
    6
    7
    Bronchitis viral
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Candida infection
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Cellulitis
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences all number
    0
    3
    Conjunctivitis
         subjects affected / exposed
    4 / 304 (1.32%)
    8 / 306 (2.61%)
         occurrences all number
    6
    12
    Cystitis
         subjects affected / exposed
    2 / 304 (0.66%)
    3 / 306 (0.98%)
         occurrences all number
    3
    3
    Diverticulitis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Ear infection
         subjects affected / exposed
    4 / 304 (1.32%)
    2 / 306 (0.65%)
         occurrences all number
    4
    3
    Enteritis infectious
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Erysipelas
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Folliculitis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Fungal infection
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences all number
    0
    3
    Fungal skin infection
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Gastroenteritis
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences all number
    1
    2
    Gastroenteritis viral
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Genital candidiasis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Genital herpes
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Gingivitis
         subjects affected / exposed
    0 / 304 (0.00%)
    8 / 306 (2.61%)
         occurrences all number
    0
    8
    Helicobacter gastritis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Herpes simplex
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Herpes virus infection
         subjects affected / exposed
    1 / 304 (0.33%)
    5 / 306 (1.63%)
         occurrences all number
    1
    5
    Herpes zoster
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Hordeolum
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Influenza
         subjects affected / exposed
    3 / 304 (0.99%)
    6 / 306 (1.96%)
         occurrences all number
    3
    7
    Laryngitis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Liver abscess
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Localised infection
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences all number
    0
    3
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Lung infection
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Nasopharyngitis
         subjects affected / exposed
    20 / 304 (6.58%)
    15 / 306 (4.90%)
         occurrences all number
    25
    16
    Oral herpes
         subjects affected / exposed
    3 / 304 (0.99%)
    7 / 306 (2.29%)
         occurrences all number
    4
    8
    Oral infection
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Osteomyelitis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Otitis externa
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Paronychia
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Periodontitis
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Peritonsillitis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    2
    Pharyngitis
         subjects affected / exposed
    5 / 304 (1.64%)
    6 / 306 (1.96%)
         occurrences all number
    5
    6
    Pharyngitis streptococcal
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Pilonidal cyst
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Pneumonia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Post procedural infection
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Postoperative wound infection
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Pulpitis dental
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Retinitis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Rhinitis
         subjects affected / exposed
    3 / 304 (0.99%)
    7 / 306 (2.29%)
         occurrences all number
    3
    7
    Rhinolaryngitis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Sinobronchitis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Sinusitis
         subjects affected / exposed
    2 / 304 (0.66%)
    4 / 306 (1.31%)
         occurrences all number
    2
    10
    Skin infection
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Staphylococcal scalded skin syndrome
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Tinea pedis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Tooth abscess
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    2
    Tooth infection
         subjects affected / exposed
    2 / 304 (0.66%)
    3 / 306 (0.98%)
         occurrences all number
    2
    4
    Tracheitis
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 306 (0.00%)
         occurrences all number
    2
    0
    Upper respiratory tract infection
         subjects affected / exposed
    5 / 304 (1.64%)
    6 / 306 (1.96%)
         occurrences all number
    5
    6
    Urinary tract infection
         subjects affected / exposed
    7 / 304 (2.30%)
    7 / 306 (2.29%)
         occurrences all number
    11
    16
    Urogenital infection fungal
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Vaginal infection
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences all number
    1
    2
    Viral hepatitis carrier
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Viral infection
         subjects affected / exposed
    0 / 304 (0.00%)
    4 / 306 (1.31%)
         occurrences all number
    0
    4
    Viral labyrinthitis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Vulvitis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Vulvovaginal mycotic infection
         subjects affected / exposed
    1 / 304 (0.33%)
    1 / 306 (0.33%)
         occurrences all number
    1
    1
    Wound infection
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Alkalosis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Decreased appetite
         subjects affected / exposed
    16 / 304 (5.26%)
    59 / 306 (19.28%)
         occurrences all number
    20
    99
    Diabetes mellitus
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    3
    1
    Dyslipidaemia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Fluid retention
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Gout
         subjects affected / exposed
    1 / 304 (0.33%)
    4 / 306 (1.31%)
         occurrences all number
    1
    4
    Hypercalcaemia
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Hypercholesterolaemia
         subjects affected / exposed
    7 / 304 (2.30%)
    3 / 306 (0.98%)
         occurrences all number
    10
    3
    Hypercreatininaemia
         subjects affected / exposed
    0 / 304 (0.00%)
    2 / 306 (0.65%)
         occurrences all number
    0
    3
    Hyperglycaemia
         subjects affected / exposed
    11 / 304 (3.62%)
    9 / 306 (2.94%)
         occurrences all number
    18
    10
    Hyperkalaemia
         subjects affected / exposed
    3 / 304 (0.99%)
    1 / 306 (0.33%)
         occurrences all number
    3
    1
    Hyperlipidaemia
         subjects affected / exposed
    1 / 304 (0.33%)
    2 / 306 (0.65%)
         occurrences all number
    1
    2
    Hypertriglyceridaemia
         subjects affected / exposed
    2 / 304 (0.66%)
    3 / 306 (0.98%)
         occurrences all number
    2
    9
    Hyperuricaemia
         subjects affected / exposed
    5 / 304 (1.64%)
    4 / 306 (1.31%)
         occurrences all number
    6
    7
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    1
    3
    Hypocalcaemia
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    1
    3
    Hypoglycaemia
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 306 (0.00%)
         occurrences all number
    4
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 304 (0.00%)
    3 / 306 (0.98%)
         occurrences all number
    0
    5
    Hypomagnesaemia
         subjects affected / exposed
    2 / 304 (0.66%)
    1 / 306 (0.33%)
         occurrences all number
    2
    1
    Hyponatraemia
         subjects affected / exposed
    1 / 304 (0.33%)
    3 / 306 (0.98%)
         occurrences all number
    1
    6
    Hypophagia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Hypophosphataemia
         subjects affected / exposed
    3 / 304 (0.99%)
    7 / 306 (2.29%)
         occurrences all number
    4
    14
    Hypoproteinaemia
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Hypovitaminosis
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Increased appetite
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Iron deficiency
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Malnutrition
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 306 (0.00%)
         occurrences all number
    1
    0
    Vitamin D deficiency
         subjects affected / exposed
    0 / 304 (0.00%)
    1 / 306 (0.33%)
         occurrences all number
    0
    1

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Jan 2007
    Changed treatment administration from 37.5 mg continuous dosing to 50 mg Schedule 4/2, and duration of treatment from 2 years to 1 year. • Sample size was re estimated and the number of DFS changed from 127 to 101 events. • Included that the primary DFS analysis will be based on independent blinded third party review and DFS based on investigator assessments as a secondary analysis. • Removed Relapse Free Survival as a secondary endpoint. • Added an additional interim analysis after the first 75 events (75% of the events) had occurred. • Added UISS Prognostic Model. • Added the collection of blood and tumor tissue samples for subsequent de identified.
    18 Apr 2007
    Clarified how suspected unexpected serious adverse event reactions would be reported. • Statement that adequate contraception was to be used by fertile patients was added. The definition of adequate contraception was outlined in the protocol.
    24 Jul 2007
    Amendment was not released.
    01 Jan 2008
    Deleted visits Cycle 1 Day 15 and Cycle 2 Day 15, and added visit Cycle 1 Day 28. • Added laboratory tests: (TSH, creatine phosphokinase, and magnesium). • Added 12 lead ECG at Cycle 1 Day 28 and at 3, 6, and 12 months or for cause. • Added 2 D ECHO or MUGA at 3, 6 and 12 months or for cause. • Prolonged time period between surgery and randomization/start treatment to 12 weeks. • Deleted pre nephrectomy ECOG PS (ECOG PS needs to be determined prior to randomization and dosing). • Revised collection of survival status information to every 12 weeks instead of every 3 months by telephone. • Extended the maximum allowable time of treatment for toxicity issues to 6 weeks rather than 4 weeks.
    01 Jan 2008
    (Country specific: United Kingdom) • The changes made in Amendment 4 were included in this amendment. • Inclusion Criterion 12 and Life Style Guidelines section were updated to provide clarification of language regarding acceptable barrier contraception methods.
    19 Jun 2008
    Urinalysis was included for assessment of proteinuria. • Group a. was extended to T3 N0 or NX, M0, any Fuhrman’s grade, and any ECOG PS. • Added statement that pre nephrectomy ECOG evaluation was the preferred baseline measure. • Instructions were provided regarding the addition of ECGs to be completed for intrapatient sunitinib dose modification. • The timing of the additional MUGA or ECHO assessments was clarified to better correlate the request for testing at 3, 6, and 12 months. • Exclusion criterion 17 and the Life Style Guidelines were modified to reiterate that patients had to agree to continue using adequate contraception for 3 months after the last dose of study treatment. • Additional CYP3A4 inhibitors were added to the concomitant medication section. • Instructions on when additional ECGs were to be performed in the safety assessment section of the protocol were added. • Clarified that this clinical study used the Investigator’s Brochure as the reference document for determining expectedness of AEs for regulatory purposes. • Several regulatory agencies required reporting of study results at the end of each clinical study. The definition of “End of Trial” was clarified in this study. The End of Trial was defined as the date of the final data point to be included in the final CSR. • Appendix 1 was updated to included magnesium and urinalysis based on above rationale for revised ECG monitoring and proteinuria monitoring. • Sections 11, 12, and 13 of the protocol were updated based on revised protocol template language for all clinical studies at Pfizer. • Minor administrative changes were made to correct typographical errors, emphasize subtle points or improve internal consistency and clarity of the protocol.
    28 Apr 2009
    Sample size was re calculated based on population changes in Amendment 6 and updated survival analysis in the mRCC population. • The assumptions of 2 year DFS rates for the placebo treatment group and sunitinib treatment group for the 3 risk groups were revised. • The minimal number DFS events required to detect the statistical difference in DFS between the 2 treatment groups was increased from 101 to 320 DFS events. • The estimated number of patients to enroll increased from 236 to 500 patients. • Coagulation tests (prothrombin time and international normalized ratio) at screening were removed.
    17 Feb 2010
    Amendment not implemented due to differences between the amendment and the Molecular Profiling supplement: • Pharmacogenomics blood samples were increased. • End of study/withdrawal procedures section was updated. • 21 new sites and 1 country (China) were added. • Statistical analysis was updated and some clarifications added.
    20 Jun 2010
    The changes made in Amendment 8 (not released) were included in this amendment. • Tumor images including CT or MRI of chest, abdomen, and pelvis were to be performed every 12 weeks at Day 1 of Cycles 3, 5, 7, and 9 (odd numbered cycles). • Included blood collection pre dose for patients who signed Part II of the ICD on Cycle 1 Day 1 and Day 28 for DNA, RNA, and biomarker analyses and at end of treatment/withdrawal for RNA and biomarker analyses at time of recurrence. • Criteria for futility will be provided in SAP. • For the second interim analysis, re estimate the sample size by the method outlined by Cui will be employed, which will preserve the type I error at the target rate. • Number of years that some patients will be followed for survival increased from 7 to 8 years.
    20 Apr 2011
    120 Chinese patients to estimate an improvement of DFS in Chinese patients at the high risk of recurrent RCC were added. Analyses of this Chinese subpopulation will be provided in a separate report.
    04 Oct 2011
    The timing of the first interim analysis was adjusted. • Number of patients was increased from 500 to 600. • Collection time point of Prep D1 (whole blood collection optimized for DNA analysis) and blood volume of Molecular Profiling samples was corrected.
    09 Oct 2011
    Guidance for potential cases of drug induced liver injury was added. • The sponsor’s IOBU SDMC information was included. • AE reporting period was clarified. • Publications were updated.
    14 Jun 2012
    Summary Rationale and Introduction safety and efficacy sections were updated according to the most updated information. • Medication errors language was updated to align with CT 3 guidance on the collection, verification and presentation of adverse reaction reports arising from clinical studies on medicinal products for human use. • AE reporting section updated due to alignment with CT 3 guidance (effective 11 June 2011) and US FDA Final Rule (effective 28 September 2011).
    17 Jul 2014
    Time for final analysis was changed to 5 years after LSFV or when approximately 258 DFS events had occurred. • Data analysis/statistical methods and study design sections were updated to be in line with new time for final analysis. • AE reporting period section was updated. • Medication errors section was moved to Section 8 and minor administrative changes were made to align with the last version of the protocol template. • China specific study design information was added. • Exclusion criterion regarding contraception was revised. • Appendices 10, 11 and 12 were removed and summary of changes for Amendments 7, 8, and 9 were included.

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

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