Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   44237   clinical trials with a EudraCT protocol, of which   7338   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A multicentre, open label, randomized Phase II trial of the MEK inhibitor pimasertib or dacarbazine in previously untreated subjects with N-Ras mutated locally advanced or metastatic malignant cutaneous melanoma

    Summary
    EudraCT number
    		 2012-002669-37
    Trial protocol
    		 NL   GB   DE   BE   ES   SE   IT  
    Global end of trial date
    24 Oct 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    08 Nov 2017
    First version publication date
    08 Nov 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    EMR 200066-007
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01693068
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck KGaA
    Sponsor organisation address
    Frankfurter Strasse 250, Darmstadt, Germany, 64293
    Public contact
    Communication Center Merck KGaA, Merck KGaA, + 49 6151 72 5200, service@merckgroup.com
    Scientific contact
    Communication Center Merck KGaA, Merck KGaA, + 49 6151 72 5200, service@merckgroup.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
    04 Jul 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    04 Jul 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Oct 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the progression free survival (PFS) of previously untreated subjects with N-Ras mutated locally advanced or metastatic cutaneous melanoma randomized to either pimasertib or dacarbazine treatment.
    Protection of trial subjects
    Subject protection was ensured by following high medical and ethical standards in accordance with the principles laid down in the Declaration of Helsinki, and that are consistent with Good Clinical Practice and applicable regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Dec 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 46 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 12
    Country: Number of subjects enrolled
    Sweden: 1
    Country: Number of subjects enrolled
    United Kingdom: 7
    Country: Number of subjects enrolled
    United States: 15
    Country: Number of subjects enrolled
    Australia: 13
    Country: Number of subjects enrolled
    Belgium: 11
    Country: Number of subjects enrolled
    France: 72
    Country: Number of subjects enrolled
    Germany: 22
    Country: Number of subjects enrolled
    Israel: 2
    Country: Number of subjects enrolled
    Italy: 19
    Country: Number of subjects enrolled
    Netherlands: 13
    Country: Number of subjects enrolled
    New Zealand: 7
    Worldwide total number of subjects
    194
    EEA total number of subjects
    157
    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)
    101
    From 65 to 84 years
    93
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 First/last subject (informed consent): 05 December 2012/. Cut-off date: 04 July 2015. Last subject last visit: 24 October 2016.

    Pre-assignment
    Screening details
    		 A total of 194 subjects were randomized in trial. 64 subjects were randomized to the dacarbazine group and 130 subjects were randomized to pimasertib group. 41 of the 64 subjects randomized to dacarbazine crossed over to pimasertib treatment during the trial on progression of their disease. Data presented based on the cut-off date of 04 July 2015.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Dacarbazine
    Arm description
    		 Subjects received dacarbazine intravenously at dose of 1000 milligram per square meter (mg/m^2) of body surface area every 3 weeks on Day 1 of each 21-days cycle until progression of the disease, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurred first. Eligible subjects with documented tumor progression on dacarbazine were offered to switch to pimasertib treatment. 41 of the 64 subjects randomized to dacarbazine group crossed over to pimasertib treatment during the trial on progression of their disease.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received dacarbazine intravenously at dose of 1000 mg/m^2 of body surface area every 3 weeks on Day 1 of each 21-days cycle.

    Arm title
    		 Pimasertib
    Arm description
    		 Subjects received pimasertib orally as monotherapy at a dose of 60 milligram (mg) twice daily continuously. Treatment consisted of repeated 21-day cycles which was continued until progression of the disease, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurred first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pimasertib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Pimasertib was administered as oral capsule at a dose of 60 milligram (mg) twice daily continuously.

    Number of subjects in period 1
    		Dacarbazine Pimasertib
    Started
    64
    130
    Treated
    61
    130
    Completed
    61
    125
    Not completed
    3
    5
         On-study
    3
    5

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Dacarbazine
    Reporting group description
    		 Subjects received dacarbazine intravenously at dose of 1000 milligram per square meter (mg/m^2) of body surface area every 3 weeks on Day 1 of each 21-days cycle until progression of the disease, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurred first. Eligible subjects with documented tumor progression on dacarbazine were offered to switch to pimasertib treatment. 41 of the 64 subjects randomized to dacarbazine group crossed over to pimasertib treatment during the trial on progression of their disease.

    Reporting group title
    Pimasertib
    Reporting group description
    		 Subjects received pimasertib orally as monotherapy at a dose of 60 milligram (mg) twice daily continuously. Treatment consisted of repeated 21-day cycles which was continued until progression of the disease, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurred first.

    Reporting group values
    		 Dacarbazine Pimasertib Total
    Number of subjects
    		 64 130 194
    Age categorical
    Units: Subjects
        <=18 years
    		 0 0 0
        Between 18 and 65 years
    		 36 65 101
        >=65 years
    		 28 65 93
    Gender categorical
    Units: Subjects
        Female
    		 28 62 90
        Male
    		 36 68 104

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Dacarbazine
    Reporting group description
    		 Subjects received dacarbazine intravenously at dose of 1000 milligram per square meter (mg/m^2) of body surface area every 3 weeks on Day 1 of each 21-days cycle until progression of the disease, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurred first. Eligible subjects with documented tumor progression on dacarbazine were offered to switch to pimasertib treatment. 41 of the 64 subjects randomized to dacarbazine group crossed over to pimasertib treatment during the trial on progression of their disease.

    Reporting group title
    Pimasertib
    Reporting group description
    		 Subjects received pimasertib orally as monotherapy at a dose of 60 milligram (mg) twice daily continuously. Treatment consisted of repeated 21-day cycles which was continued until progression of the disease, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurred first.

    Subject analysis set title
    Pimaserib (Crossover)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects who were randomized and received dacarbazine and were allowed to crossover to pimasertib treatment on progression of their disease.

    Primary: Progression Free Survival (PFS)

    		 Close Top of page
    End point title
    		 Progression Free Survival (PFS)
    End point description
    PFS was defined as the duration (in weeks) from randomization until the first progressive disease (PD) observation as assessed by the Investigator according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1, or death due to any cause when death occurred within 12 weeks after the last tumor assessment (otherwise censored), whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters of the target lesions, taking as reference the smallest sum since the treatment started (including baseline), or appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions. ITT analysis set included all subjects who were randomized to trial treatment.
    End point type
    Primary
    End point timeframe
    From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut-off date (04-Jul-2015)
    End point values
    		 Dacarbazine Pimasertib
    Number of subjects analysed
    64
    130
    Units: Weeks
        median (confidence interval 95%)
    6.86 (6 to 12.14)
    13 (12.29 to 17.71)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The Hazard Ratio is obtained from the Cox Proportional Hazards model based on dacarbazine and pimasertib only stratified by baseline ECOG Performance Status.
    Comparison groups
    Pimasertib v Dacarbazine
    Number of subjects included in analysis
    194
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 = 0.0022
    Method
    		 [Stratified Log Rank Test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 0.83
    Notes
    [1] - A log-rank test stratified by baseline ECOG PS (using the IVRS value) will tested the null hypothesis of no difference between the Pimasertib (first line) and the Dacarbazine treatment groups at the 5% level.

    Secondary: Objective Response Rate (ORR)

    		 Close Top of page
    End point title
    		 Objective Response Rate (ORR)
    End point description
    ORR was defined as the percentage of subjects with complete response (CR) or partial response (PR) according to RECIST version 1.1 criteria. CR: defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR: defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters along with absence of new lesions and disease progression in non-target lesions. ITT analysis set included all subjects who were randomised to trial treatment.
    End point type
    Secondary
    End point timeframe
    From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut-off date (04-Jul-2015)
    End point values
    		 Dacarbazine Pimasertib
    Number of subjects analysed
    64
    130
    Units: percentage of subjects
        number (confidence interval 95%)
    14.1 (6.6 to 25)
    26.9 (19.5 to 35.4)
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR)

    		 Close Top of page
    End point title
    		 Disease Control Rate (DCR)
    End point description
    DCR was defined as the percentage of subjects with CR, PR, or stable disease (SD) for greater than (>) 3 months assessed by investigator according to RECIST version 1.1. CR: defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than <10 mm. PR: defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters along with absence of new lesions and disease progression in non-target lesions. SD: defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. ITT analysis set included all subjects who were randomized to trial treatment.
    End point type
    Secondary
    End point timeframe
    From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut-off date (04-Jul-2015)
    End point values
    		 Dacarbazine Pimasertib
    Number of subjects analysed
    64
    130
    Units: percentage of subjects
        number (confidence interval 95%)
    15.6 (7.8 to 26.9)
    33.1 (25.1 to 41.9)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Progression-free Survival (PFS) at 6 Months

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Progression-free Survival (PFS) at 6 Months
    End point description
    PFS was defined as the duration (in weeks) from randomization until the first progressive disease (PD) observation as assessed by the Investigator according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1, or death due to any cause when death occurred within 12 weeks after the last tumor assessment, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters of the target lesions, taking as reference the smallest sum since the treatment started (including baseline), or appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions. Percentage of Subjects with PFS at 6 Months were reported. ITT analysis set included all subjects who were randomized to trial treatment.
    End point type
    Secondary
    End point timeframe
    6 months
    End point values
    		 Dacarbazine Pimasertib
    Number of subjects analysed
    64
    130
    Units: percentage of subjects
        number (confidence interval 95%)
    9.4 (3.6 to 18.6)
    17.3 (10.2 to 26)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Overall Survival (OS)
    End point description
    OS was defined as the time (in months) from randomization to death due to any cause. Subjects without a death date were to be censored at the minimum of last known date alive, defined as the latest date available on the electronic case report form, and cut-off date. ITT analysis set included all subjects who were randomized to trial treatment.
    End point type
    Secondary
    End point timeframe
    From date of randomization until date of death from any cause, assessed up to cut-off date (04-Jul-2015)
    End point values
    		 Dacarbazine Pimasertib
    Number of subjects analysed
    64
    130
    Units: months
        median (confidence interval 95%)
    10.61 (7.26 to 16.49)
    8.87 (7.46 to 15.51)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Overall Survival (OS) at 12 Months

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Overall Survival (OS) at 12 Months
    End point description
    OS was defined as the time (in months) from randomization to death due to any cause. Subjects without a death date were to be censored at the minimum of last known date alive, defined as the latest date available on the electronic case report form, and cut-off date. Percentage of Subjects with OS at 12 months were reported. ITT analysis set included all subjects who were randomized to trial treatment.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Dacarbazine Pimasertib
    Number of subjects analysed
    64
    130
    Units: percentage of subjects
        number (confidence interval 95%)
    44.5 (31.6 to 56.6)
    43.3 (34.5 to 51.8)
    No statistical analyses for this end point

    Secondary: Change From Baseline in Subject-reported Quality of Life Assessed by Functional Assessment Cancer Therapy - Melanoma Total Score (FACT-M TS) at Day 1 of Pre-Specified Cycles and End of Treatment (EOT)

    		 Close Top of page
    End point title
    		 Change From Baseline in Subject-reported Quality of Life Assessed by Functional Assessment Cancer Therapy - Melanoma Total Score (FACT-M TS) at Day 1 of Pre-Specified Cycles and End of Treatment (EOT)
    End point description
    QoL assessed using FACT-M assessment tool. This includes 27-item FACT-G questionnaire which consists of 24 questions; 7 relating to PWB, 7 relating to SWB,6 relating to EWB and 7 relating to FWB. Also, it includes melanoma-specific subscale consists of 16 questions for MS and 8 questions for MSS. Each of these questions could have a response of Not at all, a little bit, somewhat, quite a bit and very much. The responses were given a value between 0 and 4 with 4 being best response. The FACT-M TS ranges from 0 to 172 and is derived as follows: FACT-M TS= PWB Score + SWB Score + EWB Score + FWB Score + MS Score. Higher scores represent a better quality of life. Here "99999" signifies data was not available for categories with n=1 because standard deviation could not be estimated if there was only 1 subject analysed and "99999"signifies data was not available for categories with n=0 because there were no subject analysed at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31, 32, 33, 35, 36, 37 and EOT (up to cut-off date [04-Jul-2015])
    End point values
    		 Dacarbazine Pimasertib
    Number of subjects analysed
    58 [2]
    126 [3]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n=58, 126)
    126.2 ( 23.828 )
    132.24 ( 22.179 )
        Change at Day 1 Cycle 2 (n=45, 99)
    -3.05 ( 14.815 )
    -3.06 ( 18.492 )
        Change at Day 1 Cycle 3 (n=24, 73)
    0.6 ( 19.965 )
    -6.77 ( 21.716 )
        Change at Day 1 Cycle 4 (n=23, 63)
    4.11 ( 14.746 )
    -6.54 ( 19.919 )
        Change at Day 1 Cycle 5 (n=10, 45)
    0.62 ( 11.81 )
    -2.81 ( 17.202 )
        Change at Day 1 Cycle 6 (n=9, 33)
    -3.71 ( 15.674 )
    -8.45 ( 20.939 )
        Change at Day 1 Cycle 7 (n=9, 29)
    -1.1 ( 13.318 )
    -8.84 ( 19.128 )
        Change at Day 1 Cycle 8 (n=8, 18)
    1.28 ( 12.928 )
    -14.67 ( 18.508 )
        Change at Day 1 Cycle 9 (n=6, 12)
    2.21 ( 16.224 )
    -13.67 ( 21.388 )
        Change at Day 1 Cycle 10 (n=6, 10)
    4.4 ( 14.818 )
    -13.26 ( 20.716 )
        Change at Day 1 Cycle 11 (n=4, 11)
    1.02 ( 19.161 )
    -14.1 ( 21.157 )
        Change at Day 1 Cycle 12 (n=4, 11)
    1.56 ( 19.932 )
    -10.52 ( 18.895 )
        Change at Day 1 Cycle 13 (n=4, 6)
    5.51 ( 20.191 )
    -13.38 ( 23.69 )
        Change at Day 1 Cycle 14 (n=2,8)
    11.5 ( 21.92 )
    -18.24 ( 22.998 )
        Change at Day 1 Cycle 15 (n=3, 7)
    9.6 ( 15.345 )
    -11.33 ( 19.787 )
        Change at Day 1 Cycle 16 (n=3, 7)
    10.56 ( 14.935 )
    -11.18 ( 23.68 )
        Change at Day 1 Cycle 17 (n=2, 6)
    3 ( 5.657 )
    -9.18 ( 24.166 )
        Change at Day 1 Cycle 18 (n=1, 5)
    27 ( 99999 )
    -3.92 ( 9.64 )
        Change at Day 1 Cycle 19 (n=2, 4)
    16.5 ( 14.849 )
    -1.15 ( 8.147 )
        Change at Day 1 Cycle 20 (n=2, 3)
    16 ( 15.556 )
    1.17 ( 5.947 )
        Change at Day 1 Cycle 21 (n=2, 3)
    17 ( 14.142 )
    4.17 ( 8.918 )
        Change at Day 1 Cycle 22 (n=2, 3)
    18 ( 12.728 )
    1.32 ( 11.163 )
        Change at Day 1 Cycle 23 (n=1, 2)
    27 ( 99999 )
    -13.69 ( 15.354 )
        Change at Day 1 Cycle 24 (n=2, 1)
    13.5 ( 19.092 )
    -3.83 ( 99999 )
        Change at Day 1 Cycle 25 (n=2, 1)
    14.5 ( 17.678 )
    -3.83 ( 99999 )
        Change at Day 1 Cycle 26 (n=1, 1)
    27 ( 99999 )
    -2.83 ( 99999 )
        Change at Day 1 Cycle 27 (n=1, 0)
    27 ( 99999 )
    99999 ( 99999 )
        Change at Day 1 Cycle 28 (n=1, 1)
    27 ( 99999 )
    -0.83 ( 99999 )
        Change at Day 1 Cycle 30 (n=0, 1)
    99999 ( 99999 )
    -1.83 ( 99999 )
        Change at Day 1 Cycle 31 (n=0, 1)
    99999 ( 99999 )
    -7.83 ( 99999 )
        Change at Day 1 Cycle 32 (n=0, 1)
    99999 ( 99999 )
    -7.83 ( 99999 )
        Change at Day 1 Cycle 33 (n=0, 1)
    99999 ( 99999 )
    -8.83 ( 99999 )
        Change at Day 1 Cycle 35 (n=0, 1)
    99999 ( 99999 )
    -1.83 ( 99999 )
        Change at Day 1 Cycle 36 (n=0, 1)
    99999 ( 99999 )
    -3.83 ( 99999 )
        Change at Day 1 Cycle 37 (n=0, 1)
    99999 ( 99999 )
    -4.83 ( 99999 )
        Change at EOT (n=28, 75)
    -7.91 ( 23.119 )
    -9.98 ( 20.56 )
    Notes
    [2] - Number of subjects = those evaluable for this outcome. n=subjects evaluable at each time point.
    [3] - Number of subjects = those evaluable for this outcome. n=subjects evaluable at each time point.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Subject-reported Quality of Life Assessed by Functional Assessment Cancer Therapy - Melanoma Trial Outcome Index (FACT-M TOI) at Day 1 of Pre-Specified Cycles and EOT

    		 Close Top of page
    End point title
    		 Change From Baseline in Subject-reported Quality of Life Assessed by Functional Assessment Cancer Therapy - Melanoma Trial Outcome Index (FACT-M TOI) at Day 1 of Pre-Specified Cycles and EOT
    End point description
    QoL assessed using FACT-M assessment tool. This includes 27-item FACT-G questionnaire which consists of 24 questions; 7 relating to PWB, 7 relating to SWB, 6 relating to EWB and 7 relating to FWB. Also, it includes melanoma-specific subscale consists of 16 questions for MS and 8 questions for the MSS. Each of these questions could have a response of Not at all, a little bit, somewhat, quite a bit and very much. The responses were given a value between 0 and 4 with 4 being best response. The FACT-M Trial Outcome Index (FACT-M TOI) ranges from 0 to a high of 120 and is derived as: FACT-M TOI = PWB Score + FWB Score +MS Score. Higher scores represent a better quality of life. Here "99999" signifies data was not available for categories with n=1 because standard deviation could not be estimated if there was only 1 subject analysed and "99999"signifies data was not available for categories with n=0 because there were no subjects analyzed at specified time point for those categories.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31, 32, 33, 35, 36, 37 and EOT (up to cut-off date [04-Jul-2015])
    End point values
    		 Dacarbazine Pimasertib
    Number of subjects analysed
    58 [4]
    126 [5]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n=58, 126)
    90.35 ( 19.348 )
    94.07 ( 17.534 )
        Change at Day 1 Cycle 2 (n=45, 99)
    -3.33 ( 12.015 )
    -4.4 ( 14.286 )
        Change at Day 1 Cycle 3 (n=24, 73)
    -0.69 ( 15.974 )
    -7.99 ( 17.089 )
        Change at Day 1 Cycle 4 (n=23, 63)
    1.54 ( 10.304 )
    -7.97 ( 16.741 )
        Change at Day 1 Cycle 5 (n=10, 45)
    -0.86 ( 5.405 )
    -4.37 ( 14.084 )
        Change at Day 1 Cycle 6 (n=9, 33)
    -3.29 ( 7.752 )
    -9.15 ( 18.813 )
        Change at Day 1 Cycle 7 (n=9, 29)
    -2.07 ( 6.859 )
    -8.99 ( 14.783 )
        Change at Day 1 Cycle 8 (n=8, 18)
    0.83 ( 5.161 )
    -15.09 ( 14.458 )
        Change at Day 1 Cycle 9 (n=6, 12)
    -1.93 ( 6.3 )
    -13.79 ( 17.198 )
        Change at Day 1 Cycle 10 (n=6, 10)
    -1.1 ( 5.654 )
    -12.37 ( 17.058 )
        Change at Day 1 Cycle 11 (n=4, 11)
    -2.9 ( 7.722 )
    -13.95 ( 17.006 )
        Change at Day 1 Cycle 12 (n=4, 11)
    -2.4 ( 7.408 )
    -11.95 ( 17.311 )
        Change at Day 1 Cycle 13 (n=4, 6)
    0.8 ( 7.697 )
    -13.57 ( 21.699 )
        Change at Day 1 Cycle 14 (n=2, 8)
    0 ( 4.243 )
    -18.55 ( 19.88 )
        Change at Day 1 Cycle 15 (n=3, 7)
    1.6 ( 4.084 )
    -13.59 ( 15.747 )
        Change at Day 1 Cycle 16 (n=3, 7)
    0.61 ( 3.994 )
    -13.15 ( 19.13 )
        Change at Day 1 Cycle 17 (n=2, 6)
    2.5 ( 0.707 )
    -10.66 ( 20.007 )
        Change at Day 1 Cycle 18 (n=1, 5)
    3 ( 99999 )
    -5.72 ( 4.614 )
        Change at Day 1 Cycle 19 (n=2, 4)
    2.5 ( 0.707 )
    -4.94 ( 5.238 )
        Change at Day 1 Cycle 20 (n=2, 3)
    4 ( 1.414 )
    -2.33 ( 1.155 )
        Change at Day 1 Cycle 21 (n=2, 3)
    3.5 ( 0.707 )
    0 ( 2 )
        Change at Day 1 Cycle 22 (n=2, 3)
    4 ( 1.414 )
    -1.4 ( 3.831 )
        Change at Day 1 Cycle 23 (n=1, 2)
    3 ( 99999 )
    -13.36 ( 16.061 )
        Change at Day 1 Cycle 24 (n=2, 1)
    2.5 ( 0.707 )
    -2 ( 99999 )
        Change at Day 1 Cycle 25 (n=2, 1)
    3.5 ( 0.707 )
    -1 ( 99999 )
        Change at Day 1 Cycle 26 (n=1, 1)
    3 ( 99999 )
    0 ( 99999 )
        Change at Day 1 Cycle 27 (n=1, 0)
    3 ( 99999 )
    99999 ( 99999 )
        Change at Day 1 Cycle 28 (n=1, 1)
    3 ( 99999 )
    1 ( 99999 )
        Change at Day 1 Cycle 30 (n=0, 1)
    99999 ( 99999 )
    1 ( 99999 )
        Change at Day 1 Cycle 31 (n=0, 1)
    99999 ( 99999 )
    -3 ( 99999 )
        Change at Day 1 Cycle 32 (n=0, 1)
    99999 ( 99999 )
    -4 ( 99999 )
        Change at Day 1 Cycle 33 (n=0, 1)
    99999 ( 99999 )
    -3 ( 99999 )
        Change at Day 1 Cycle 35 (n=0, 1)
    99999 ( 99999 )
    0 ( 99999 )
        Change at Day 1 Cycle 36 (n=0, 1)
    99999 ( 99999 )
    0 ( 99999 )
        Change at Day 1 Cycle 37 (n=0, 1)
    99999 ( 99999 )
    -3 ( 99999 )
        Change at EOT (n=28, 75)
    -8.18 ( 16.41 )
    -10.42 ( 16.256 )
    Notes
    [4] - Number of subjects = those evaluable for this outcome. n=subjects evaluable at each time point.
    [5] - Number of subjects = those evaluable for this outcome. n=subjects evaluable at each time point.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death

    		 Close Top of page
    End point title
    		 Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death
    End point description
    AE was defined as any untoward medical occurrence which does not necessarily have causal relationship with this study drug. An AE was defined as any unfavourable and unintended sign(including an abnormal laboratory finding, vital signs electrocardiogram changes), symptom, or disease temporally associated with use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening;persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 33 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. TEAEs include both Serious TEAEs and non-serious TEAEs. TEAEs were to be reported separately for dacarbazine, pimasertib and pimasertib (crossover) reporting arms.
    End point type
    Secondary
    End point timeframe
    Baseline up to cut-off date (04-Jul-2015)
    End point values
    		 Dacarbazine Pimasertib Pimaserib (Crossover)
    Number of subjects analysed
    61
    130
    41
    Units: subjects
    number (not applicable)
        Retinal vein occlusion
    0
    5
    2
        Serious retinal detatchment
    0
    76
    21
        CPK/Isoenzyme TEAE of Special Interest (>=Grade 2)
    0
    74
    24
        Acute renal failure (Grade >= 2 )
    1
    9
    2
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinically Significant Change From Baseline in Laboratory Parameter, Vital Signs, Electrocardiogram (ECG) and Ophthalmologic Findings

    		 Close Top of page
    End point title
    		 Number of Subjects With Clinically Significant Change From Baseline in Laboratory Parameter, Vital Signs, Electrocardiogram (ECG) and Ophthalmologic Findings
    End point description
    Subjects were presented under 3 reporting groups: Dacarbazine group: for subjects who received at least 1 dose of dacarbazine; Pimasertib group: for subjects who received at least 1 dose of pimasertib; Pimasertib (Crossover) group: for subjects who were initially randomized and received dacarbazine, but crossed over to pimasertib treatment on progression of their disease.
    End point type
    Secondary
    End point timeframe
    Baseline up to cut-off date (04-Jul-2015)
    End point values
    		 Dacarbazine Pimasertib Pimaserib (Crossover)
    Number of subjects analysed
    61
    130
    41
    Units: number of subjects
        Laboratory Parameter
    0
    0
    0
        Vital Signs
    0
    0
    0
        ECG
    0
    0
    0
        Ophthalmologic Findings
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Adverse Events (AEs) of Special interest

    		 Close Top of page
    End point title
    		 Number of Subjects With Adverse Events (AEs) of Special interest
    End point description
    Adverse events of special interest included ocular TEAEs, creatinine phosphokinase (CPK) Elevation and Isoenzymes TEAEs and CPK Elevation and Isoenzymes TEAEs with Grade 2 or higher. Subjects were presented under 3 reporting groups: Dacarbazine group: for subjects who received at least 1 dose of dacarbazine; Pimasertib group: for subjects who received at least 1 dose of pimasertib; Pimasertib (Crossover) group: for subjects who were initially randomized and received dacarbazine, but crossed over to pimasertib treatment on progression of their disease.
    End point type
    Secondary
    End point timeframe
    Baseline up to cut-off date (04-Jul-2015)
    End point values
    		 Dacarbazine Pimasertib Pimaserib (Crossover)
    Number of subjects analysed
    61
    130
    41
    Units: number of subjects
        Ocular TEAE of Special Interest
    0
    76
    21
        CPK Elevation/Isoenzymes TEAE of Special Interest
    3
    89
    29
        CPK/Isoenzyme TEAE of Special Interest (>=Grade 2)
    0
    74
    24
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to cut-off date (04-Jul-2015)
    Adverse event reporting additional description
    Subjects presented under 3 reporting groups: Dacarbazine: for subjects who received at least 1 dose of dacarbazine; Pimasertib: for subjects who received at least 1 dose of pimasertib; Pimasertib (Crossover): for subjects who were initially randomized and received dacarbazine, but crossed over to pimasertib treatment on disease progression.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Dacarbazine
    Reporting group description
    		 Subjects received dacarbazine intravenously at dose of 1000 mg/m^2 of body surface area every 3 weeks on Day 1 of each 21-days cycle until progression of the disease, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurred first. Eligible subjects with documented tumor progression on dacarbazine were offered to switch to pimasertib treatment.

    Reporting group title
    Pimasertib
    Reporting group description
    		 Subjects received pimasertib orally as monotherapy at a dose of 60 mg twice daily continuously. Treatment consisted of repeated 21-day cycles which was continued until progression of the disease, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurred first.

    Reporting group title
    Pimasertib (Crossover)
    Reporting group description
    		 Subjects who were randomized and received dacarbazine and were allowed to crossover to pimasertib treatment on progression of their disease.

    Serious adverse events
    		 Dacarbazine Pimasertib Pimasertib (Crossover)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 61 (19.67%)
    74 / 130 (56.92%)
    26 / 41 (63.41%)
         number of deaths (all causes)
    4
    6
    6
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour associated fever
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cyst rupture
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Disease progression
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    1 / 1
    Fatigue
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 130 (1.54%)
    4 / 41 (9.76%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    Impaired healing
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Necrosis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 61 (1.64%)
    4 / 130 (3.08%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    Reproductive system and breast disorders
    Breast haematoma
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 61 (0.00%)
    5 / 130 (3.85%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 61 (1.64%)
    3 / 130 (2.31%)
    2 / 41 (4.88%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 61 (0.00%)
    26 / 130 (20.00%)
    8 / 41 (19.51%)
         occurrences causally related to treatment / all
    0 / 0
    25 / 26
    8 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    0 / 61 (0.00%)
    5 / 130 (3.85%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    5 / 5
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lipase increased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Subdural haematoma
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Cor pulmonale acute
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuralgia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    2 / 41 (4.88%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphopenia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    3 / 61 (4.92%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Eye disorders
    Chorioretinopathy
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystoid macular oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Macular detachment
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Macular oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retinal vein occlusion
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ulcerative keratitis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 61 (1.64%)
    6 / 130 (4.62%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    1 / 1
    4 / 6
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal obstruction
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mouth ulceration
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 61 (1.64%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    2 / 41 (4.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 61 (1.64%)
    3 / 130 (2.31%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis acneiform
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug eruption
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash macular
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash maculo−papular
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin toxicity
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal mass
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Candida infection
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Catheter site infection
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 61 (0.00%)
    7 / 130 (5.38%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 7
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Skin infection
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Streptococcal sepsis
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypoglycaemia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour lysis syndrome
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Dacarbazine Pimasertib Pimasertib (Crossover)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    59 / 61 (96.72%)
    130 / 130 (100.00%)
    41 / 41 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Blepharal papilloma
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Breast neoplasm
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Cancer pain
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Malignant melanoma
         subjects affected / exposed
    2 / 61 (3.28%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    2
    0
    1
    Metastatic pain
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Monoclonal gammopathy
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Pyogenic granuloma
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Skin cancer
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Skin papilloma
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Tumour haemorrhage
         subjects affected / exposed
    2 / 61 (3.28%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    0
    Tumour pain
         subjects affected / exposed
    2 / 61 (3.28%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    0
    Vascular disorders
    Capillary leak syndrome
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Diastolic hypertension
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Flushing
         subjects affected / exposed
    2 / 61 (3.28%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    2
    1
    1
    Haematoma
         subjects affected / exposed
    2 / 61 (3.28%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    2
    1
    0
    Hot flush
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Hypertension
         subjects affected / exposed
    2 / 61 (3.28%)
    21 / 130 (16.15%)
    6 / 41 (14.63%)
         occurrences all number
    2
    21
    6
    Hypotension
         subjects affected / exposed
    3 / 61 (4.92%)
    4 / 130 (3.08%)
    2 / 41 (4.88%)
         occurrences all number
    3
    4
    2
    Lymphoedema
         subjects affected / exposed
    2 / 61 (3.28%)
    11 / 130 (8.46%)
    3 / 41 (7.32%)
         occurrences all number
    2
    11
    3
    Pelvic venous thrombosis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Peripheral coldness
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Peripheral venous disease
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Phlebitis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Thrombophlebitis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Vascular compression
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Vena cava thrombosis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    13 / 61 (21.31%)
    39 / 130 (30.00%)
    10 / 41 (24.39%)
         occurrences all number
    13
    39
    10
    Axillary pain
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    1
    1
    1
    Catheter site pain
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Chest discomfort
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Chest pain
         subjects affected / exposed
    3 / 61 (4.92%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences all number
    3
    2
    1
    Chills
         subjects affected / exposed
    3 / 61 (4.92%)
    11 / 130 (8.46%)
    3 / 41 (7.32%)
         occurrences all number
    3
    11
    3
    Crying
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Disease progression
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Drug intolerance
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Enanthema
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Face oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    12 / 130 (9.23%)
    9 / 41 (21.95%)
         occurrences all number
    5
    12
    9
    Facial pain
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Fatigue
         subjects affected / exposed
    23 / 61 (37.70%)
    39 / 130 (30.00%)
    11 / 41 (26.83%)
         occurrences all number
    23
    39
    11
    Feeling cold
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    0
    3
    0
    Gait disturbance
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    General physical health deterioration
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Generalised oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Hyperpyrexia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Hyperthermia
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Hypothermia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Inflammation
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Influenza like illness
         subjects affected / exposed
    1 / 61 (1.64%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    1
    3
    0
    Injection site haematoma
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Localised oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Malaise
         subjects affected / exposed
    2 / 61 (3.28%)
    5 / 130 (3.85%)
    2 / 41 (4.88%)
         occurrences all number
    2
    5
    2
    Mucosal dryness
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Non−cardiac chest pain
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    1
    0
    1
    Oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences all number
    0
    2
    1
    Oedema peripheral
         subjects affected / exposed
    6 / 61 (9.84%)
    59 / 130 (45.38%)
    18 / 41 (43.90%)
         occurrences all number
    6
    59
    18
    Pain
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Papillitis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Peripheral swelling
         subjects affected / exposed
    0 / 61 (0.00%)
    5 / 130 (3.85%)
    2 / 41 (4.88%)
         occurrences all number
    0
    5
    2
    Pyrexia
         subjects affected / exposed
    5 / 61 (8.20%)
    27 / 130 (20.77%)
    10 / 41 (24.39%)
         occurrences all number
    5
    27
    10
    Secretion discharge
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Sensation of foreign body
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Temperature intolerance
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Vessel puncture site haematoma
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Vessel puncture site inflammation
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Vessel puncture site pain
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Xerosis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    2 / 41 (4.88%)
         occurrences all number
    0
    1
    2
    Immune system disorders
    Sarcoidosis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Reproductive system and breast disorders
    Amenorrhoea
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Breast pain
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Genital discomfort
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Genital erythema
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    1
    0
    1
    Haematospermia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Pelvic pain
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Scrotal haematocoele
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Scrotal oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Asthma
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Atelectasis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Bronchospasm
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Cough
         subjects affected / exposed
    5 / 61 (8.20%)
    9 / 130 (6.92%)
    3 / 41 (7.32%)
         occurrences all number
    5
    9
    3
    Dry throat
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Dysphonia
         subjects affected / exposed
    1 / 61 (1.64%)
    5 / 130 (3.85%)
    1 / 41 (2.44%)
         occurrences all number
    1
    5
    1
    Dyspnoea
         subjects affected / exposed
    4 / 61 (6.56%)
    26 / 130 (20.00%)
    6 / 41 (14.63%)
         occurrences all number
    4
    26
    6
    Dyspnoea exertional
         subjects affected / exposed
    1 / 61 (1.64%)
    4 / 130 (3.08%)
    1 / 41 (2.44%)
         occurrences all number
    1
    4
    1
    Epistaxis
         subjects affected / exposed
    2 / 61 (3.28%)
    8 / 130 (6.15%)
    2 / 41 (4.88%)
         occurrences all number
    2
    8
    2
    Hiccups
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Hypoventilation
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Hypoxia
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Lung disorder
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Nasal oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Nocturnal dyspnoea
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 61 (1.64%)
    4 / 130 (3.08%)
    3 / 41 (7.32%)
         occurrences all number
    1
    4
    3
    Nasal disorder
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Orthopnoea
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Pharyngeal inflammation
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Pharyngeal ulceration
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Pleural effusion
         subjects affected / exposed
    1 / 61 (1.64%)
    4 / 130 (3.08%)
    0 / 41 (0.00%)
         occurrences all number
    1
    4
    0
    Pneumonitis
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences all number
    0
    2
    1
    Productive cough
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Pulmonary embolism
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 130 (1.54%)
    2 / 41 (4.88%)
         occurrences all number
    1
    2
    2
    Rales
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    1
    1
    0
    Respiratory disorder
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Respiratory failure
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    0
    3
    0
    Rhinalgia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    2 / 61 (3.28%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    0
    Throat irritation
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    1
    1
    0
    Wheezing
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Anxiety
         subjects affected / exposed
    6 / 61 (9.84%)
    3 / 130 (2.31%)
    2 / 41 (4.88%)
         occurrences all number
    6
    3
    2
    Confusional state
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    0
    3
    0
    Depressed mood
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Depression
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    1
    1
    0
    Dyssomnia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Euphoric mood
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Hallucination
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Hallucination, visual
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Insomnia
         subjects affected / exposed
    4 / 61 (6.56%)
    7 / 130 (5.38%)
    1 / 41 (2.44%)
         occurrences all number
    4
    7
    1
    Irritability
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Mood altered
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Nervousness
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Nightmare
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Persecutory delusion
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Psychomotor retardation
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    2 / 41 (4.88%)
         occurrences all number
    0
    0
    2
    Investigations
    Body temperature increased
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 61 (6.56%)
    6 / 130 (4.62%)
    1 / 41 (2.44%)
         occurrences all number
    4
    6
    1
    Amylase increased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 61 (4.92%)
    17 / 130 (13.08%)
    4 / 41 (9.76%)
         occurrences all number
    3
    17
    4
    Blood albumin decreased
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    0
    3
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 61 (3.28%)
    5 / 130 (3.85%)
    3 / 41 (7.32%)
         occurrences all number
    2
    5
    3
    Blood bicarbonate decreased
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Blood bilirubin increased
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    1
    1
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    3 / 61 (4.92%)
    86 / 130 (66.15%)
    28 / 41 (68.29%)
         occurrences all number
    3
    86
    28
    Blood creatinine increased
         subjects affected / exposed
    2 / 61 (3.28%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences all number
    2
    2
    1
    Blood fibrinogen decreased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    1 / 61 (1.64%)
    3 / 130 (2.31%)
    1 / 41 (2.44%)
         occurrences all number
    1
    3
    1
    Blood phosphorus increased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Blood potassium increased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Blood pressure increased
         subjects affected / exposed
    2 / 61 (3.28%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    0
    Blood urea increased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Breath sounds abnormal
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Creatinine renal clearance decreased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    C−reactive protein increased
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Ejection fraction decreased
         subjects affected / exposed
    0 / 61 (0.00%)
    13 / 130 (10.00%)
    3 / 41 (7.32%)
         occurrences all number
    0
    13
    3
    Electrocardiogram PR prolongation
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Electrocardiogram QRS complex prolonged
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    1 / 41 (2.44%)
         occurrences all number
    0
    4
    1
    Electrocardiogram repolarisation abnormality
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 61 (3.28%)
    4 / 130 (3.08%)
    3 / 41 (7.32%)
         occurrences all number
    2
    4
    3
    Glomerular filtration rate decreased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Haemoglobin decreased
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    1
    1
    0
    International normalised ratio increased
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Intraocular pressure increased
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    1 / 41 (2.44%)
         occurrences all number
    0
    3
    1
    Lipase increased
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 130 (1.54%)
    2 / 41 (4.88%)
         occurrences all number
    1
    2
    2
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 61 (0.00%)
    5 / 130 (3.85%)
    0 / 41 (0.00%)
         occurrences all number
    0
    5
    0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 61 (1.64%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    1
    3
    0
    Oxygen saturation decreased
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Platelet count decreased
         subjects affected / exposed
    1 / 61 (1.64%)
    6 / 130 (4.62%)
    1 / 41 (2.44%)
         occurrences all number
    1
    6
    1
    Protein total decreased
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Protein total increased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Pupillary light reflex tests abnormal
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Troponin increased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Weight decreased
         subjects affected / exposed
    2 / 61 (3.28%)
    8 / 130 (6.15%)
    3 / 41 (7.32%)
         occurrences all number
    2
    8
    3
    Weight increased
         subjects affected / exposed
    0 / 61 (0.00%)
    9 / 130 (6.92%)
    2 / 41 (4.88%)
         occurrences all number
    0
    9
    2
    White blood cell count decreased
         subjects affected / exposed
    2 / 61 (3.28%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    2
    2
    0
    White blood cell count increased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Injury, poisoning and procedural complications
    Chest injury
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Clavicle fracture
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Concussion
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Excoriation
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Fall
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    0
    3
    0
    Lip injury
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Muscle strain
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Optic nerve injury
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Procedural pain
         subjects affected / exposed
    2 / 61 (3.28%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    0
    Rib fracture
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    1
    1
    0
    Scratch
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Spinal compression fracture
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Sunburn
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Tendon rupture
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Traumatic shock
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Wound
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    0
    3
    0
    Wound complication
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Congenital, familial and genetic disorders
    Optic nerve hypoplasia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Ventricular septal defec
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    1
    2
    0
    Aortic valve disease
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Aortic valve incompetence
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    2 / 41 (4.88%)
         occurrences all number
    0
    3
    2
    Aortic valve stenosis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Atrial fibrillation
         subjects affected / exposed
    2 / 61 (3.28%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    2
    2
    0
    Atrioventricular block
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    0
    3
    0
    Atrioventricular block first degree
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    1
    0
    1
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Bradycardia
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences all number
    0
    2
    1
    Bundle branch block
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Bundle branch block right
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Diastolic dysfunction
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Left ventricular dysfunction
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    0 / 41 (0.00%)
         occurrences all number
    0
    4
    0
    Left ventricular hypertrophy
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    2 / 41 (4.88%)
         occurrences all number
    0
    4
    2
    Mitral valve sclerosis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Palpitations
         subjects affected / exposed
    2 / 61 (3.28%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    0
    Pericardial effusion
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Pulmonary valve incompetence
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Sinus bradycardia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    0
    3
    0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    2 / 41 (4.88%)
         occurrences all number
    0
    0
    2
    Tachycardia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Tricuspid valve incompetence
         subjects affected / exposed
    0 / 61 (0.00%)
    5 / 130 (3.85%)
    4 / 41 (9.76%)
         occurrences all number
    0
    5
    4
    Ventricular hypokinesia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Nervous system disorders
    Ageusia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Altered state of consciousness
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Amnesia
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Aphasia
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    1
    1
    0
    Ataxia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Autonomic nervous system imbalance
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Balance disorder
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Cervicobrachial syndrome
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Cognitive disorder
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Dizziness
         subjects affected / exposed
    3 / 61 (4.92%)
    17 / 130 (13.08%)
    5 / 41 (12.20%)
         occurrences all number
    3
    17
    5
    Dizziness postural
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Dysaesthesia
         subjects affected / exposed
    4 / 61 (6.56%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    4
    1
    0
    Dysarthria
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    1
    2
    0
    Dysgeusia
         subjects affected / exposed
    6 / 61 (9.84%)
    11 / 130 (8.46%)
    4 / 41 (9.76%)
         occurrences all number
    6
    11
    4
    Headache
         subjects affected / exposed
    8 / 61 (13.11%)
    16 / 130 (12.31%)
    0 / 41 (0.00%)
         occurrences all number
    8
    16
    0
    Hyperaesthesia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Hypoaesthesia
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 130 (0.77%)
    2 / 41 (4.88%)
         occurrences all number
    1
    1
    2
    Lethargy
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Loss of consciousness
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Memory impairment
         subjects affected / exposed
    0 / 61 (0.00%)
    5 / 130 (3.85%)
    1 / 41 (2.44%)
         occurrences all number
    0
    5
    1
    Migraine
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Motor dysfunction
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    1
    0
    1
    Muscle contractions involuntary
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Myasthenic syndrome
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Neurotoxicity
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Paraesthesia
         subjects affected / exposed
    9 / 61 (14.75%)
    4 / 130 (3.08%)
    2 / 41 (4.88%)
         occurrences all number
    9
    4
    2
    Peripheral motor neuropathy
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Presyncope
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    2 / 41 (4.88%)
         occurrences all number
    0
    3
    2
    Sciatica
         subjects affected / exposed
    3 / 61 (4.92%)
    5 / 130 (3.85%)
    3 / 41 (7.32%)
         occurrences all number
    3
    5
    3
    Sensorimotor disorder
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Sensory disturbance
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences all number
    0
    2
    1
    Somnolence
         subjects affected / exposed
    0 / 61 (0.00%)
    6 / 130 (4.62%)
    1 / 41 (2.44%)
         occurrences all number
    0
    6
    1
    Syncope
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    1 / 41 (2.44%)
         occurrences all number
    0
    4
    1
    Tremor
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    1
    2
    0
    Visual field defect
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Blood and lymphatic system disorders
    Eosinophilia
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    1
    0
    1
    Hypochromic anaemia
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Increased tendency to bruise
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Leukocytosis
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences all number
    0
    2
    1
    Leukopenia
         subjects affected / exposed
    6 / 61 (9.84%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    6
    1
    0
    Lymph node pain
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Lymphadenitis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Lymphadenopathy
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    1
    2
    0
    Lymphocytosis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Lymphopenia
         subjects affected / exposed
    1 / 61 (1.64%)
    9 / 130 (6.92%)
    2 / 41 (4.88%)
         occurrences all number
    1
    9
    2
    Neutropenia
         subjects affected / exposed
    13 / 61 (21.31%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    13
    1
    0
    Normochromic normocytic anaemia
         subjects affected / exposed
    2 / 61 (3.28%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences all number
    2
    2
    1
    Thrombocytopenia
         subjects affected / exposed
    12 / 61 (19.67%)
    8 / 130 (6.15%)
    3 / 41 (7.32%)
         occurrences all number
    12
    8
    3
    Thrombocytosis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Anaemia
         subjects affected / exposed
    8 / 61 (13.11%)
    13 / 130 (10.00%)
    3 / 41 (7.32%)
         occurrences all number
    8
    13
    3
    Anaemia of chronic disease
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Ear and labyrinth disorders
    Cerumen impaction
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Ear congestion
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Ear pain
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    0
    3
    0
    Hypoacusis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Middle ear inflammation
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Tinnitus
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences all number
    0
    2
    1
    Vertigo
         subjects affected / exposed
    2 / 61 (3.28%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    2
    3
    0
    Eye disorders
    Blepharitis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Blindness
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Cataract
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Chalazion
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Chorioretinopathy
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    0
    3
    0
    Chromatopsia
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Colour blindness acquired
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Conjunctival oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Cystoid macular oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Deposit eye
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Detachment of retinal pigment epithelium
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    2 / 41 (4.88%)
         occurrences all number
    0
    3
    2
    Diplopia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Dry eye
         subjects affected / exposed
    1 / 61 (1.64%)
    5 / 130 (3.85%)
    0 / 41 (0.00%)
         occurrences all number
    1
    5
    0
    Erythema of eyelid
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Eye discharge
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Eye disorder
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Eye haemorrhage
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Eye inflammation
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Eye oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Eye pain
         subjects affected / exposed
    1 / 61 (1.64%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    1
    3
    0
    Eye pruritus
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Eye swelling
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Eyelid haematoma
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Eyelid oedema
         subjects affected / exposed
    1 / 61 (1.64%)
    18 / 130 (13.85%)
    2 / 41 (4.88%)
         occurrences all number
    1
    18
    2
    Eyelid ptosis
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    0
    3
    0
    Glaucoma
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Lacrimation increased
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    0
    3
    0
    Macular cyst
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Macular degeneration
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Macular detachment
         subjects affected / exposed
    0 / 61 (0.00%)
    10 / 130 (7.69%)
    2 / 41 (4.88%)
         occurrences all number
    0
    10
    2
    Macular fibrosis
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    0 / 41 (0.00%)
         occurrences all number
    0
    4
    0
    Macular oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    6 / 130 (4.62%)
    1 / 41 (2.44%)
         occurrences all number
    0
    6
    1
    Myopia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Ocular hyperaemia
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    1
    1
    0
    Ocular hypertension
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    2 / 41 (4.88%)
         occurrences all number
    0
    3
    2
    Optic disc haemorrhage
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Periorbital oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    12 / 130 (9.23%)
    1 / 41 (2.44%)
         occurrences all number
    0
    12
    1
    Photophobia
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Photopsia
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Presbyopia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Retinal deposits
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Retinal detachment
         subjects affected / exposed
    0 / 61 (0.00%)
    56 / 130 (43.08%)
    15 / 41 (36.59%)
         occurrences all number
    0
    56
    15
    Retinal disorder
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    2 / 41 (4.88%)
         occurrences all number
    0
    0
    2
    Retinal haemorrhage
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Retinal oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Retinal pigment epitheliopathy
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Retinal vein occlusion
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Retinopathy
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Subretinal fluid
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Vision blurred
         subjects affected / exposed
    0 / 61 (0.00%)
    29 / 130 (22.31%)
    9 / 41 (21.95%)
         occurrences all number
    0
    29
    9
    Visual acuity reduced
         subjects affected / exposed
    0 / 61 (0.00%)
    5 / 130 (3.85%)
    0 / 41 (0.00%)
         occurrences all number
    0
    5
    0
    Visual impairment
         subjects affected / exposed
    0 / 61 (0.00%)
    12 / 130 (9.23%)
    2 / 41 (4.88%)
         occurrences all number
    0
    12
    2
    Vitreous detachment
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Vitreous floaters
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Xerophthalmia
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    1 / 61 (1.64%)
    4 / 130 (3.08%)
    2 / 41 (4.88%)
         occurrences all number
    1
    4
    2
    Abdominal pain
         subjects affected / exposed
    10 / 61 (16.39%)
    31 / 130 (23.85%)
    7 / 41 (17.07%)
         occurrences all number
    10
    31
    7
    Abdominal pain upper
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    2 / 41 (4.88%)
         occurrences all number
    0
    3
    2
    Abdominal pain lower
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Anal polyp
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Aphthous stomatitis
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    2 / 41 (4.88%)
         occurrences all number
    0
    4
    2
    Aptyalism
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Ascites
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Cheilitis
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    1 / 41 (2.44%)
         occurrences all number
    0
    4
    1
    Colitis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Constipation
         subjects affected / exposed
    21 / 61 (34.43%)
    24 / 130 (18.46%)
    7 / 41 (17.07%)
         occurrences all number
    21
    24
    7
    Diarrhoea
         subjects affected / exposed
    10 / 61 (16.39%)
    106 / 130 (81.54%)
    31 / 41 (75.61%)
         occurrences all number
    10
    106
    31
    Dry mouth
         subjects affected / exposed
    2 / 61 (3.28%)
    20 / 130 (15.38%)
    8 / 41 (19.51%)
         occurrences all number
    2
    20
    8
    Duodenal ulcer
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Dyspepsia
         subjects affected / exposed
    0 / 61 (0.00%)
    11 / 130 (8.46%)
    3 / 41 (7.32%)
         occurrences all number
    0
    11
    3
    Dysphagia
         subjects affected / exposed
    1 / 61 (1.64%)
    5 / 130 (3.85%)
    2 / 41 (4.88%)
         occurrences all number
    1
    5
    2
    Epigastric discomfort
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    1
    0
    1
    Faeces discoloured
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Flatulence
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences all number
    0
    2
    1
    Gastric ulcer
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    1
    1
    0
    Gastritis
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Gastritis erosive
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 61 (3.28%)
    5 / 130 (3.85%)
    2 / 41 (4.88%)
         occurrences all number
    2
    5
    2
    Glossitis
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences all number
    0
    2
    1
    Glossodynia
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Haematemesis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Haematochezia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 61 (1.64%)
    4 / 130 (3.08%)
    1 / 41 (2.44%)
         occurrences all number
    1
    4
    1
    Hyperchlorhydria
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Intestinal obstruction
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Lip dry
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Lip oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Lip pain
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Melaena
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Mesenteric vein thrombosis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Mouth swelling
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Mouth ulceration
         subjects affected / exposed
    0 / 61 (0.00%)
    7 / 130 (5.38%)
    1 / 41 (2.44%)
         occurrences all number
    0
    7
    1
    Nausea
         subjects affected / exposed
    25 / 61 (40.98%)
    47 / 130 (36.15%)
    17 / 41 (41.46%)
         occurrences all number
    25
    47
    17
    Odynophagia
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    0 / 41 (0.00%)
         occurrences all number
    0
    4
    0
    Oesophagitis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Oral discomfort
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Oral dysaesthesia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Oral mucosal eruption
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Oral mucosal erythema
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Oral pain
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Oral pruritus
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Oral toxicity
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Paraesthesia oral
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 61 (0.00%)
    8 / 130 (6.15%)
    1 / 41 (2.44%)
         occurrences all number
    0
    8
    1
    Regurgitation
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Salivary hypersecretion
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Stomatitis
         subjects affected / exposed
    3 / 61 (4.92%)
    21 / 130 (16.15%)
    4 / 41 (9.76%)
         occurrences all number
    3
    21
    4
    Subileus
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Tongue disorder
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Tongue oedema
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Tongue ulceration
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Toothache
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Umbilical hernia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Vomiting
         subjects affected / exposed
    14 / 61 (22.95%)
    30 / 130 (23.08%)
    16 / 41 (39.02%)
         occurrences all number
    14
    30
    16
    Hepatobiliary disorders
    Cholestasis
         subjects affected / exposed
    1 / 61 (1.64%)
    4 / 130 (3.08%)
    0 / 41 (0.00%)
         occurrences all number
    1
    4
    0
    Hepatic pain
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Hepatocellular injury
         subjects affected / exposed
    0 / 61 (0.00%)
    7 / 130 (5.38%)
    0 / 41 (0.00%)
         occurrences all number
    0
    7
    0
    Hepatomegaly
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    3 / 41 (7.32%)
         occurrences all number
    0
    4
    3
    Alopecia
         subjects affected / exposed
    2 / 61 (3.28%)
    13 / 130 (10.00%)
    4 / 41 (9.76%)
         occurrences all number
    2
    13
    4
    Decubitus ulcer
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Dermatitis
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    1 / 41 (2.44%)
         occurrences all number
    0
    3
    1
    Dermatitis acneiform
         subjects affected / exposed
    0 / 61 (0.00%)
    47 / 130 (36.15%)
    9 / 41 (21.95%)
         occurrences all number
    0
    47
    9
    Dermatitis exfoliative
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    2 / 41 (4.88%)
         occurrences all number
    0
    2
    2
    Diffuse alopecia
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Drug eruption
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Dry skin
         subjects affected / exposed
    1 / 61 (1.64%)
    11 / 130 (8.46%)
    3 / 41 (7.32%)
         occurrences all number
    1
    11
    3
    Eczema
         subjects affected / exposed
    0 / 61 (0.00%)
    8 / 130 (6.15%)
    1 / 41 (2.44%)
         occurrences all number
    0
    8
    1
    Erythema
         subjects affected / exposed
    2 / 61 (3.28%)
    14 / 130 (10.77%)
    4 / 41 (9.76%)
         occurrences all number
    2
    14
    4
    Erythrosis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Haemorrhage subcutaneous
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Hair growth abnormal
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Hirsutism
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Hyperhidrosis
         subjects affected / exposed
    2 / 61 (3.28%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    2
    2
    0
    Hyperkeratosis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Ingrowing nail
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences all number
    0
    2
    1
    Intertrigo
         subjects affected / exposed
    1 / 61 (1.64%)
    4 / 130 (3.08%)
    0 / 41 (0.00%)
         occurrences all number
    1
    4
    0
    Nail bed inflammation
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Nail discolouration
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Nail disorder
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Night sweats
         subjects affected / exposed
    2 / 61 (3.28%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    0
    Onycholysis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Pain of skin
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    0 / 41 (0.00%)
         occurrences all number
    0
    4
    0
    Palmar−plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 61 (0.00%)
    6 / 130 (4.62%)
    0 / 41 (0.00%)
         occurrences all number
    0
    6
    0
    Papule
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    0
    3
    0
    Petechiae
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Photosensitivity reaction
         subjects affected / exposed
    2 / 61 (3.28%)
    3 / 130 (2.31%)
    0 / 41 (0.00%)
         occurrences all number
    2
    3
    0
    Pigmentation disorder
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    1 / 41 (2.44%)
         occurrences all number
    0
    1
    1
    Prurigo
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 61 (1.64%)
    17 / 130 (13.08%)
    7 / 41 (17.07%)
         occurrences all number
    1
    17
    7
    Pruritus generalised
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Psoriasis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Rash
         subjects affected / exposed
    5 / 61 (8.20%)
    46 / 130 (35.38%)
    18 / 41 (43.90%)
         occurrences all number
    5
    46
    18
    Rash erythematous
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    2 / 41 (4.88%)
         occurrences all number
    0
    4
    2
    Rash generalised
         subjects affected / exposed
    0 / 61 (0.00%)
    5 / 130 (3.85%)
    1 / 41 (2.44%)
         occurrences all number
    0
    5
    1
    Rash macular
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences all number
    0
    2
    1
    Rash maculo-papular
         subjects affected / exposed
    0 / 61 (0.00%)
    12 / 130 (9.23%)
    6 / 41 (14.63%)
         occurrences all number
    0
    12
    6
    Rash morbilliform
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Rash papular
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    0 / 41 (0.00%)
         occurrences all number
    0
    4
    0
    Rash pruritic
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Rosacea
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 130 (1.54%)
    1 / 41 (2.44%)
         occurrences all number
    1
    2
    1
    Scab
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    1
    2
    0
    Seborrhoeic dermatitis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Skin burning sensation
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Skin erosion
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Skin exfoliation
         subjects affected / exposed
    1 / 61 (1.64%)
    4 / 130 (3.08%)
    1 / 41 (2.44%)
         occurrences all number
    1
    4
    1
    Skin fissures
         subjects affected / exposed
    0 / 61 (0.00%)
    17 / 130 (13.08%)
    2 / 41 (4.88%)
         occurrences all number
    0
    17
    2
    Skin irritation
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Skin lesion
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Skin mass
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 130 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    0
    Skin reaction
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Skin ulcer
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Solar dermatitis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Stasis dermatitis
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Swelling face
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    0 / 41 (0.00%)
         occurrences all number
    0
    4
    0
    Toxic skin eruption
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 130 (0.77%)
    0 / 41 (0.00%)
         occurrences all number
    0
    1
    0
    Urticaria
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 130 (1.54%)
    0 / 41 (0.00%)
         occurrences all number
    0
    2
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 61 (0.00%)
    4 / 130 (3.08%)
    1 / 41 (2.44%)
         occurrences all number
    0
    4
    1
    Cystitis noninfective
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 130 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    0
    0
    1
    Dysuria
         subjects affected / exposed
    0 / 61 (0.00%)
    8 / 130 (6.15%)