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    Clinical Trial Results:
    A Multicenter Phase 3 randomized, open-label study of bosutinib versus imatinib in adult subjects with newly diagnosed chronic phase chronic myelogenous leukemia (BFORE)

    Summary
    EudraCT number
    		 2013-005101-31
    Trial protocol
    		 BE   GB   IT   SE   CZ   HU   SK   FI   NO   ES   DK   NL   PL   FR  
    Global end of trial date

    Results information
    Results version number
    		 v1
    This version publication date
    28 Jul 2018
    First version publication date
    28 Jul 2018
    Other versions
    		 v2

    Trial information

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    Trial identification
    Sponsor protocol code
    B1871053
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02130557
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 1-800-718-1021, ClinicalTrials.gov_inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Interim
    Date of interim/final analysis
    20 Apr 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    11 Aug 2016
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To compare the proportion of patients demonstrating Major Molecular Response (MMR) at 12 months (48 weeks) in the bosutinib arm with that of the imatinib arm in newly diagnosed Philadelphia chromosome positive (Ph+) chronic phase (CP) chronic myelogenous leukemia (CML) patients harboring b2a2 and/or b3a2 transcripts.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and The study was in compliance in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Jul 2014
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 7
    Country: Number of subjects enrolled
    Belgium: 8
    Country: Number of subjects enrolled
    Canada: 18
    Country: Number of subjects enrolled
    Czech Republic: 11
    Country: Number of subjects enrolled
    Denmark: 6
    Country: Number of subjects enrolled
    Finland: 5
    Country: Number of subjects enrolled
    France: 18
    Country: Number of subjects enrolled
    Germany: 21
    Country: Number of subjects enrolled
    Hungary: 22
    Country: Number of subjects enrolled
    Israel: 2
    Country: Number of subjects enrolled
    Italy: 36
    Country: Number of subjects enrolled
    Korea, Republic of: 26
    Country: Number of subjects enrolled
    Mexico: 14
    Country: Number of subjects enrolled
    Netherlands: 6
    Country: Number of subjects enrolled
    Norway: 6
    Country: Number of subjects enrolled
    Poland: 25
    Country: Number of subjects enrolled
    Singapore: 17
    Country: Number of subjects enrolled
    Slovakia: 1
    Country: Number of subjects enrolled
    South Africa: 10
    Country: Number of subjects enrolled
    Spain: 35
    Country: Number of subjects enrolled
    Sweden: 15
    Country: Number of subjects enrolled
    Taiwan: 7
    Country: Number of subjects enrolled
    Thailand: 9
    Country: Number of subjects enrolled
    Ukraine: 81
    Country: Number of subjects enrolled
    United Kingdom: 42
    Country: Number of subjects enrolled
    United States: 88
    Worldwide total number of subjects
    536
    EEA total number of subjects
    257
    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)
    435
    From 65 to 84 years
    101
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Data reported was based on primary analysis date (11 August 2016).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Bosutinib
    Arm description
    		 Subjects with Philadelphia chromosome-positive chronic myeloid leukemia (CML) received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Subjects who completed the core treatment period, entered into extension period and received same treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bosutinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received bosutinib at a dose of 400 mg, orally once daily.

    Arm title
    		 Imatinib
    Arm description
    		 Subjects with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Subjects who completed the core treatment period, entered into extension period and received same treatment.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Imatinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received imatinib at a dose of 400 mg, orally once daily.

    Number of subjects in period 1
    		Bosutinib Imatinib
    Started
    268
    268
    Treated
    268
    265
    mITT population
    246
    241
    Completed
    0
    0
    Not completed
    268
    268
         Deceased
    1
    6
         Consent withdrawn by subject
    5
    2
         Ongoing
    260
    255
         Lost to follow-up
    2
    2
         Randomized, not treated
    -
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Bosutinib
    Reporting group description
    		 Subjects with Philadelphia chromosome-positive chronic myeloid leukemia (CML) received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Subjects who completed the core treatment period, entered into extension period and received same treatment.

    Reporting group title
    Imatinib
    Reporting group description
    		 Subjects with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Subjects who completed the core treatment period, entered into extension period and received same treatment.

    Reporting group values
    		 Bosutinib Imatinib Total
    Number of subjects
    		 268 268 536
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 215 220 435
        From 65-84 years
    		 53 48 101
        85 years and over
    		 0 0 0
    Age Continuous
    Units: years
        median (full range (min-max))
    		 53.0 (18 to 84) 53.0 (19 to 84) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 112 113 225
        Male
    		 156 155 311

    End points

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    End points reporting groups
    Reporting group title
    Bosutinib
    Reporting group description
    		 Subjects with Philadelphia chromosome-positive chronic myeloid leukemia (CML) received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Subjects who completed the core treatment period, entered into extension period and received same treatment.

    Reporting group title
    Imatinib
    Reporting group description
    		 Subjects with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Subjects who completed the core treatment period, entered into extension period and received same treatment.

    Primary: Percentage of Subjects With Major Molecular Response (MMR) at Month 12

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    End point title
    		 Percentage of Subjects With Major Molecular Response (MMR) at Month 12
    End point description
    MMR was defined as a ratio of breakpoint cluster region to abelson (Bcr-Abl/Abl) less than or equal to (<=) 0.1 percent (%) on the international scale (IS) (greater than or equal to [>=] 3 log reduction from standardized baseline in ratio of Bcr-Abl to Abl transcripts [>=3000 Abl required]) by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). Modified intent-to-treat (mITT) population included all randomized subjects with Philadephia chromosome positive CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies greater than (>) 0 with study drug assignment designated according to initial randomization.
    End point type
    Primary
    End point timeframe
    Month 12
    End point values
    		 Bosutinib Imatinib
    Number of subjects analysed
    246
    241
    Units: percentage of subjects
        number (confidence interval 95%)
    47.2 (40.9 to 53.4)
    36.9 (30.8 to 43.0)
    Statistical analysis title
    		 Bosutinib vs Imatinib
    Statistical analysis description
    95% CI for the odds ratio adjusted for sokal risk group and region are based on asymptotic wald confidence limits.
    Comparison groups
    Bosutinib v Imatinib
    Number of subjects included in analysis
    487
    Analysis specification
    Pre-specified
    Analysis type
    		 [1]
    P-value
    		 = 0.01 [2]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.547
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.072
         upper limit
    		 2.233
    Notes
    [1] - A total sample size of 500 Ph+ subjects is required for the study to provide >= 90% power to detect at least 15% difference (assuming 25% in the imatinib vs 40% in the bosutinib arm) in the MMR rates at 12 months (48 weeks) with a 1-sided alpha of 2.5%, and 2 interim futility analyses at 33% and 66% of patients with adequate follow-up with early stopping for futility only (non-binding, O’Brien-Fleming analog beta spending function).
    [2] - 1-sided p-value was based on a CMH test for general association between treatment and response with stratification by sokal risk group (low, intermediate, high) and region (1-3) as determined at time of randomization.

    Secondary: Duration of Major Molecular Response (MMR)

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    End point title
    		 Duration of Major Molecular Response (MMR)
    End point description
    Time from the first date of MMR until the date of the confirmed loss of MMR or censoring. Confirmed Loss of MMR was Bcr-Abl/Abl IS ratio >0.1% in association with a >=5-fold increase in Bcr-Abl/Abl IS ratio from the lowest value achieved up to that time-point confirmed by a second assessment at least 28 days later. Treatment discontinuation due to progressive disease(PD) or death due to PD within 28 days of last dose were considered confirmed loss of MMR. PD was defined as disease progression to accelerated phase(AP) or blast phase(BP) CML. Kaplan-meier analysis was used for determation of duration of MMR.Duration of response will be analyzed for responders only therefore duration of response will be excluded from the long-term family of secondary endpoints.mITT analysis set.N(overall number of subjects analyzed)=number of subjects evaluable for this endpoint.99999 represents median and 95% C.I. could not be reached due to immaturity of events at the data cutoff date.
    End point type
    Secondary
    End point timeframe
    From the date of first MMR until the date of confirmed loss of MMR or censoring (up to 752 days)
    End point values
    		 Bosutinib Imatinib
    Number of subjects analysed
    142
    122
    Units: weeks
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Complete Cytogenetic Response (CCyR) by Month 12

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    End point title
    		 Percentage of Subjects With Complete Cytogenetic Response (CCyR) by Month 12
    End point description
    Complete Cytogenetic Response (CCyR) was based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow (BM) aspirate. CCyR was achieved when there was 0 % Ph+ metaphases among cells in a BM sample when at least 20 metaphases from a BM sample were analyzed, or MMR if no BM was available. mITT population included all randomized subjects with Philadephia chromosome positive CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies >0 with study drug assignment designated according to initial randomization.
    End point type
    Secondary
    End point timeframe
    up to Month 12
    End point values
    		 Bosutinib Imatinib
    Number of subjects analysed
    246
    241
    Units: percentage of subjects
        number (confidence interval 95%)
    77.2 (72.0 to 82.5)
    66.4 (60.4 to 72.4)
    Statistical analysis title
    		 Bosutinib vs Imatinib
    Statistical analysis description
    95% CI for the odds ratio adjusted for sokal risk group and region are based on asymptotic wald confidence limits.
    Comparison groups
    Bosutinib v Imatinib
    Number of subjects included in analysis
    487
    Analysis specification
    Pre-specified
    Analysis type
    		 [3]
    P-value
    		 = 0.0037 [4]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.16
         upper limit
    		 2.61
    Notes
    [3] - If the primary analysis was significant, each endpoint of the short-term family (CCyR by Month 12) was tested via the Bonferroni’s procedure at the 1-sided 0.0125 significance level.
    [4] - 1-sided p-value was based on a CMH test for general association between treatment and response with stratification by sokal risk group (low, intermediate, high) and region (1-3) as determined at time of randomization.

    Secondary: Duration of Complete Cytogenetic Response (CCyR)

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    End point title
    		 Duration of Complete Cytogenetic Response (CCyR)
    End point description
    It was defined as the time from the first date of CCyR until the date of the confirmed loss of CCyR or censoring. Confirmed Loss of CCyR was the presence of at least one Ph+ metaphase confirmed by a second assessment at least 28 days later. Treatment discontinuation due to PD or death due to PD within 28 days of last dose were considered confirmed loss of CCyR. PD was defined as disease progression to accelerated phase or blast phase CML. Kaplan meier analysis was used for the determination of duration of CCyR. Duration of response will be analyzed for responders only therefore duration of response will be excluded from the long-term family of secondary endpoints. mITT analysis set. N=number of subjects evaluable for this endpoint. 99999 states that median and 95% C.I. was not estimable due to less number of subjects who had event.
    End point type
    Secondary
    End point timeframe
    From the date of first CCyR until the date of confirmed loss of CCyR or censoring (up to 752 days)
    End point values
    		 Bosutinib Imatinib
    Number of subjects analysed
    197
    175
    Units: weeks
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Cumulative Incidence of Event Free Survival (EFS) Events at Month 12

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    End point title
    		 Cumulative Incidence of Event Free Survival (EFS) Events at Month 12
    End point description
    EFS was defined as the time from randomization to death due to any cause, transformation to AP or BP at any time, confirmed loss of complete hematologic response (CHR), confirmed loss of CCyR or censoring. Loss of CHR was defined as a hematologic assessment of non-CHR [chronic phase, AP, or BP] confirmed by 2 assessments at least 4 weeks apart). Loss of CCyR was defined as at least 1 Ph+ metaphase from analysis of <100 metaphases confirmed by a follow up cytogenetic analysis after 1 month. Cumulative incidence of EFS event at month 12 was adjusted for competing risk of treatment discontinuation without the event. The comparative analysis between two arms for this member of long term secondary family will be done at the end of the study. mITT population included all randomized subjects with Philadephia chromosome positive CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies >0 with study drug assignment designated according to initial randomization.
    End point type
    Secondary
    End point timeframe
    Month 12
    End point values
    		 Bosutinib Imatinib
    Number of subjects analysed
    246
    241
    Units: percentage of subjects
        number (confidence interval 95%)
    3.7 (1.8 to 6.7)
    6.4 (3.7 to 10.0)
    No statistical analyses for this end point

    Secondary: Overall survival (OS) at Month 12

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    End point title
    		 Overall survival (OS) at Month 12
    End point description
    OS was defined as the time (in months) from randomization to the occurrence of death due to any cause or censoring. Kaplan-meier analysis was used for determination of OS. The comparative analysis between the two arms for this member of the long-term secondary family will be done at the end of the study. mITT population included all randomized subjects with Philadephia chromosome positive CML harboring the b2a2 and/or b3a2 transcript and baseline BCR-ABL copies >0 with study drug assignment designated according to initial randomization.
    End point type
    Secondary
    End point timeframe
    Month 12
    End point values
    		 Bosutinib Imatinib
    Number of subjects analysed
    246
    241
    Units: Months
        number (confidence interval 95%)
    99.6 (97.0 to 99.9)
    97.9 (95.0 to 99.1)
    No statistical analyses for this end point

    Other pre-specified: Summary of Trough Plasma Concentration by Complete Cytogenetic Response (CCyR)

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    End point title
    		 Summary of Trough Plasma Concentration by Complete Cytogenetic Response (CCyR) [5]
    End point description
    CCyR is based on the prevalence of Ph+ metaphases among cells in metaphase on a BM aspirate. CCyR was achieved when there was 0 % Ph+ metaphases among cells in a BM sample when at least 20 metaphases from a BM sample were analyzed, or MMR if no BM was available. Trough plasma concentration of participants who had CCyR are presented in this endpoint. Pharmacokinetic (PK) population included all enrolled subjects who received at least 1 dose of bosutinib and had sufficient plasma results available. Here,"N" signifies number of subjects evaluable for this endpoint and "n" signifies subjects evaluable at specified time points only.
    End point type
    Other pre-specified
    End point timeframe
    Day 28, 56, 84
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Descriptive analysis was planned to be reported for Bosutinib arm only.
    End point values
    		 Bosutinib
    Number of subjects analysed
    191
    Units: nanogram per milliliter (ng/mL)
    arithmetic mean (standard deviation)
        Day 28 (n =181)
    71.282 ± 46.0545
        Day 56 (n =184)
    73.069 ± 45.1349
        Day 84 (n =184)
    83.973 ± 64.3206
    No statistical analyses for this end point

    Other pre-specified: Summary of Trough Plasma Concentration by Major Molecular Response (MMR)

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    End point title
    		 Summary of Trough Plasma Concentration by Major Molecular Response (MMR) [6]
    End point description
    MMR was defined as a ratio of Bcr-Abl/Abl <=0.1% on the international scale (>=3 log reduction from standardized baseline in ratio of Bcr-Abl to Abl transcripts) by quantitative RT-qPCR. Trough plasma concentration of subjects who had MMR are presented in this endpoint. PK population included all enrolled subjects who received at least 1 dose of bosutinib and had sufficient plasma results available. Here,"N" signifies number of subjects evaluable for this endpoint and "n" signifies subjects evaluable at specified time points only.
    End point type
    Other pre-specified
    End point timeframe
    Day 28, 56, 84
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Descriptive analysis was planned to be reported for Bosutinib arm only.
    End point values
    		 Bosutinib
    Number of subjects analysed
    141
    Units: ng/mL
    arithmetic mean (standard deviation)
        Day 28 (n =140)
    75.050 ± 51.9551
        Day 56 (n =140)
    78.437 ± 43.6019
        Day 84 (n =141)
    91.081 ± 72.1500
    No statistical analyses for this end point

    Other pre-specified: Summary of Trough Plasma Concentration by Presence of Grade 1 or Higher Adverse Events (AEs)

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    End point title
    		 Summary of Trough Plasma Concentration by Presence of Grade 1 or Higher Adverse Events (AEs) [7]
    End point description
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to maximum severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Grade 1 =mild; Grade 2 =moderate; within normal limits, Grade 3 =severe or medically significant but not immediately life-threatening; Grade 4 =life-threatening or disabling; urgent intervention indicated; Grade 5 =death. Trough plasma concentration of subjects who had grade 1 or higher AE are presented in this endpoint. Data of plasma concentration is reported separately for each preferred term of AE. PK population included all enrolled subjects who received at least 1 dose of bosutinib and had sufficient plasma results available. Here,"N" signifies number of subjects evaluable for this endpoint and "n" signifies subjects evaluable at specified time points only.
    End point type
    Other pre-specified
    End point timeframe
    Day 28, 56, 84
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Descriptive analysis was planned to be reported for Bosutinib arm only.
    End point values
    		 Bosutinib
    Number of subjects analysed
    177
    Units: ng/mL
    arithmetic mean (standard deviation)
        Day 28: Diarrhea (n =177)
    69.402 ± 55.5005
        Day 28: Thrombocytopenia (n =60)
    63.529 ± 40.9949
        Day 28: Rash (n =84)
    74.779 ± 60.6257
        Day 28: Nausea (n =86)
    66.011 ± 42.6437
        Day 28: Vomiting (n =44)
    71.684 ± 60.7208
        Day 56: Diarrhea (n =172)
    68.834 ± 42.6621
        Day 56: Thrombocytopenia (n =61)
    65.327 ± 43.2859
        Day 56: Rash (n =84)
    70.016 ± 38.7506
        Day 56: Nausea (n =85)
    61.626 ± 44.4007
        Day 56: Vomiting (n =40)
    65.980 ± 45.9064
        Day 84: Diarrhea (n =165)
    81.269 ± 64.6462
        Day 84: Thrombocytopenia (n =63)
    71.585 ± 33.6674
        Day 84: Rash (n =85)
    89.080 ± 69.5237
        Day 84: Nausea (n =80)
    77.702 ± 61.6179
        Day 84: Vomiting (n =41)
    86.949 ± 55.3041
    No statistical analyses for this end point

    Other pre-specified: Summary of Trough Plasma Concentration by Presence of Grade 3 or Higher Adverse Events (AEs)

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    End point title
    		 Summary of Trough Plasma Concentration by Presence of Grade 3 or Higher Adverse Events (AEs) [8]
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. AE was assessed according to maximum severity grading based on NCI CTCAE Version 4.0. Grade 1 =mild; Grade 2 =moderate; within normal limits, Grade 3 =severe or medically significant but not immediately life-threatening; Grade 4 =life-threatening or disabling; urgent intervention indicated; Grade 5 =death. Trough plasma concentration of participants who had grade 3 or higher AE are presented in this endpoint. Data of plasma concentration is reported separately for each preferred term of AE. PK population included all enrolled subjects who received at least 1 dose of bosutinib and had sufficient plasma results available. "N"=number of subjects evaluable for this endpoint and "n"=subjects evaluable at specified time points only. 99999 states that as only 1 subject was analyzed, standard deviation could not be calculated.
    End point type
    Other pre-specified
    End point timeframe
    Day 28, 56, 84
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Descriptive analysis was planned to be reported for Bosutinib arm only.
    End point values
    		 Bosutinib
    Number of subjects analysed
    24
    Units: ng/mL
    arithmetic mean (standard deviation)
        Day 28: Diarrhea (n =19)
    87.769 ± 102.6181
        Day 28: Thrombocytopenia (n =23)
    49.220 ± 36.3461
        Day 28: Rash (n =4)
    71.150 ± 43.3246
        Day 28: Vomiting (n =3)
    14.663 ± 21.5799
        Day 56: Diarrhea (n =16)
    68.513 ± 45.2672
        Day 56: Thrombocytopenia (n =24)
    56.853 ± 34.3892
        Day 56: Rash (n =4)
    58.925 ± 18.8656
        Day 56: Vomiting (n =1)
    38.200 ± 99999
        Day 84: Diarrhea (n =17)
    76.782 ± 46.3006
        Day 84: Thrombocytopenia (n =23)
    67.623 ± 35.3084
        Day 84: Rash (n =3)
    83.967 ± 19.2542
        Day 84: Vomiting (n =1)
    12.400 ± 99999
    No statistical analyses for this end point

    Other pre-specified: Number of Subjects With Vital Signs Abnormalities

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    End point title
    		 Number of Subjects With Vital Signs Abnormalities
    End point description
    Criteria for vital signs abnormalities: systolic blood pressure (SBP) less than (<) 80 millimeter of mercury (mmHg), >210 mmHg; diastolic blood pressure (DBP) <40 mmHg, >130 mmHg; heart rate <40 beats per minute (bpm), >150 bpm; temperature <32 degree celsius, >40 degree celsius. Safety population included all subjects who received at least 1 dose of study medication with treatment assignments designated to actual study treatment received.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to 752 days
    End point values
    		 Bosutinib Imatinib
    Number of subjects analysed
    268
    265
    Units: subjects
    0
    0
    No statistical analyses for this end point

    Other pre-specified: Number of Subjects With Laboratory Test Abnormalities Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) Version 4.03

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    End point title
    		 Number of Subjects With Laboratory Test Abnormalities Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) Version 4.03
    End point description
    Laboratory parameters included hematological (haemoglobin, lymphocytes (absolute), neutrophils (absolute), platelets and leukocytes) and biochemistry (albumin, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, amylase, bilirubin, creatinine kinase, calcium, creatinine, glucose, potassium, lipase, magnesium, phosphate, sodium, urate) parameters. Abnormalities in laboratory tests were graded by NCI CTCAE version 4.03 as Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Safety population included all subjects who received at least 1 dose of study medication with treatment assignments designated to actual study treatment received.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to 752 days
    End point values
    		 Bosutinib Imatinib
    Number of subjects analysed
    268
    265
    Units: subjects
        Grade 1|
    15
    17
        Grade 2|
    84
    87
        Grade 3|
    114
    116
        Grade 4|
    54
    45
    No statistical analyses for this end point

    Other pre-specified: Number of Subjects With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern

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    End point title
    		 Number of Subjects With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern
    End point description
    Criteria for ECG abnormalities : heart rate: increase of >15 bpm from baseline value and >=120 bpm, decrease of >15 bpm from baseline value and <=45 bpm; PR interval: change of >=20 msec from baseline value and >=220 milliseconds (msec); QRS interval >=120 msec; QTcB interval >500 msec, increase of >60 msec from baseline; QT interval using Fridericia’s correction (QTcF) >500 msec, increase of >60 msec from baseline, <=450 msec (Men) or <=470 msec (Women), >450 msec (Men) or >470 msec (Women). Safety population included all subjects who received at least 1 dose of study medication with treatment assignments designated to actual study treatment received.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to 752 days
    End point values
    		 Bosutinib Imatinib
    Number of subjects analysed
    268
    265
    Units: subjects
    6
    6
    No statistical analyses for this end point

    Other pre-specified: Number of Subjects With Adverse Events (AEs) Leading to Study Drug Discontinuation

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    End point title
    		 Number of Subjects With Adverse Events (AEs) Leading to Study Drug Discontinuation
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Safety population included all subjects who received at least 1 dose of study medication with treatment assignments designated to actual study treatment received.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to 752 days
    End point values
    		 Bosutinib Imatinib
    Number of subjects analysed
    268
    265
    Units: subjects
    38
    28
    No statistical analyses for this end point

    Other pre-specified: Number of Subjects With Treatment-Emergent Adverse Events By National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03)

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    End point title
    		 Number of Subjects With Treatment-Emergent Adverse Events By National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03)
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. AE was assessed according to severity grading based on NCI CTCAE version 4.03. Grade 1 =mild; Grade 2 =moderate; Grade 3 =severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4 =life-threatening or disabling, urgent intervention indicated; Grade 5 =death. Treatment-emergent events were events between first dose of study drug and up to 752 days that were absent before treatment that worsened relative to pretreatment state. If the same subject in a given treatment had more than 1 adverse event, only the maximum CTCAE was reported. Safety population included all subjects who received at least 1 dose of study medication with treatment assignments designated to actual study treatment received.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to 752 days
    End point values
    		 Bosutinib Imatinib
    Number of subjects analysed
    268
    265
    Units: subjects
        Grade 1|
    20
    44
        Grade 2|
    92
    100
        Grade 3|
    120
    90
        Grade 4|
    30
    19
        Grade 5|
    1
    4
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to 752 days
    Adverse event reporting additional description
    Same event may appear as both an AE and serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another, or a subject may have experienced both a serious and non-serious event.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Bosutinib
    Reporting group description
    		 Subjects with Philadelphia chromosome-positive CML received bosutinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Subjects who completed the core treatment period, entered into extension period and received same treatment.

    Reporting group title
    Imatinib
    Reporting group description
    		 Subjects with Philadelphia chromosome-positive CML received imatinib at a dose of 400 mg, orally once daily in the core treatment period of 12 months. Subjects who completed the core treatment period, entered into extension period and received same treatment.

    Serious adverse events
    		 Bosutinib Imatinib
    Total subjects affected by serious adverse events
         subjects affected / exposed
    54 / 268 (20.15%)
    45 / 265 (16.98%)
         number of deaths (all causes)
    0
    4
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Chronic myeloid leukaemia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatic adenoma
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertensive crisis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    4 / 268 (1.49%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperthermia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Implant site haematoma
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Prostatic dysplasia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine haemorrhage
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary toxicity
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 268 (1.12%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood sodium decreased
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Headache
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 268 (0.37%)
    3 / 265 (1.13%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Retinal vein occlusion
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    3 / 268 (1.12%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal necrosis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Food poisoning
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermatitis allergic
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lichen planus
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Swelling face
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Calculus bladder
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteochondrosis
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    4 / 268 (1.49%)
    3 / 265 (1.13%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastroenteritis
         subjects affected / exposed
    5 / 268 (1.87%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    4 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Subcutaneous abscess
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Candida pneumonia
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective pericardial effusion
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrotising fasciitis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periorbital cellulitis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenic infection
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic infection
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour lysis syndrome
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Bosutinib Imatinib
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    263 / 268 (98.13%)
    257 / 265 (96.98%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    3 / 268 (1.12%)
    0 / 265 (0.00%)
         occurrences all number
    3
    0
    Acanthoma
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Adrenal adenoma
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Prostatic adenoma
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Seborrhoeic keratosis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Skin cancer
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Anogenital warts
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Leukaemic retinopathy
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Skin papilloma
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Lipoma
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Melanocytic naevus
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    13 / 268 (4.85%)
    16 / 265 (6.04%)
         occurrences all number
    13
    16
    Haematoma
         subjects affected / exposed
    5 / 268 (1.87%)
    3 / 265 (1.13%)
         occurrences all number
    5
    3
    Hypotension
         subjects affected / exposed
    5 / 268 (1.87%)
    5 / 265 (1.89%)
         occurrences all number
    5
    5
    Angiopathy
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Capillary fragility
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Flushing
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Hot flush
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Jugular vein distension
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Pallor
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Periphlebitis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Phlebitis
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Venous thrombosis limb
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Iliac artery occlusion
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Peripheral coldness
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Surgical and medical procedures
    Cholecystectomy
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Debridement
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Hernia hiatus repair
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Hip arthroplasty
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Inguinal hernia repair
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Medical induction of coma
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Tooth extraction
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Transfusion
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Cyst drainage
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Endodontic procedure
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Vitrectomy
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Muscle pain/ Joint pain
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Fatigue
         subjects affected / exposed
    54 / 268 (20.15%)
    47 / 265 (17.74%)
         occurrences all number
    54
    47
    Pyrexia
         subjects affected / exposed
    33 / 268 (12.31%)
    21 / 265 (7.92%)
         occurrences all number
    33
    21
    Asthenia
         subjects affected / exposed
    32 / 268 (11.94%)
    18 / 265 (6.79%)
         occurrences all number
    32
    18
    Oedema peripheral
         subjects affected / exposed
    12 / 268 (4.48%)
    36 / 265 (13.58%)
         occurrences all number
    12
    36
    Influenza like illness
         subjects affected / exposed
    10 / 268 (3.73%)
    3 / 265 (1.13%)
         occurrences all number
    10
    3
    Non-cardiac chest pain
         subjects affected / exposed
    9 / 268 (3.36%)
    6 / 265 (2.26%)
         occurrences all number
    9
    6
    Chills
         subjects affected / exposed
    7 / 268 (2.61%)
    6 / 265 (2.26%)
         occurrences all number
    7
    6
    Chest pain
         subjects affected / exposed
    5 / 268 (1.87%)
    6 / 265 (2.26%)
         occurrences all number
    5
    6
    Face oedema
         subjects affected / exposed
    5 / 268 (1.87%)
    15 / 265 (5.66%)
         occurrences all number
    5
    15
    Pain
         subjects affected / exposed
    4 / 268 (1.49%)
    8 / 265 (3.02%)
         occurrences all number
    4
    8
    Feeling hot
         subjects affected / exposed
    3 / 268 (1.12%)
    0 / 265 (0.00%)
         occurrences all number
    3
    0
    Malaise
         subjects affected / exposed
    3 / 268 (1.12%)
    4 / 265 (1.51%)
         occurrences all number
    3
    4
    Peripheral swelling
         subjects affected / exposed
    3 / 268 (1.12%)
    4 / 265 (1.51%)
         occurrences all number
    3
    4
    Chest discomfort
         subjects affected / exposed
    2 / 268 (0.75%)
    3 / 265 (1.13%)
         occurrences all number
    2
    3
    Mucosal inflammation
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    Cyst
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Discomfort
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Early satiety
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Granuloma
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Mucosal dryness
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Thirst
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Xerosis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Axillary pain
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Feeling abnormal
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Feeling cold
         subjects affected / exposed
    0 / 268 (0.00%)
    6 / 265 (2.26%)
         occurrences all number
    0
    6
    Impaired healing
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Local swelling
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Nodule
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Polyp
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Swelling
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Ulcer
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    2 / 268 (0.75%)
    2 / 265 (0.75%)
         occurrences all number
    2
    2
    Food allergy
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Rubber sensitivity
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Seasonal allergy
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Drug hypersensitivity
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Reproductive system and breast disorders
    Amenorrhoea
         subjects affected / exposed
    2 / 268 (0.75%)
    2 / 265 (0.75%)
         occurrences all number
    2
    2
    Benign prostatic hyperplasia
         subjects affected / exposed
    2 / 268 (0.75%)
    2 / 265 (0.75%)
         occurrences all number
    2
    2
    Dysmenorrhoea
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Menstruation irregular
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Adnexa uteri cyst
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Breast haematoma
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Endometriosis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Menopausal symptoms
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Menorrhagia
         subjects affected / exposed
    1 / 268 (0.37%)
    3 / 265 (1.13%)
         occurrences all number
    1
    3
    Prostatitis
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Prostatomegaly
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Testicular mass
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Erectile dysfunction
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Genital haemorrhage
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Menstruation delayed
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Pelvic pain
         subjects affected / exposed
    0 / 268 (0.00%)
    4 / 265 (1.51%)
         occurrences all number
    0
    4
    Prostatic dysplasia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Sexual dysfunction
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 268 (0.00%)
    3 / 265 (1.13%)
         occurrences all number
    0
    3
    Vulvovaginal pruritus
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    22 / 268 (8.21%)
    10 / 265 (3.77%)
         occurrences all number
    22
    10
    Cough
         subjects affected / exposed
    21 / 268 (7.84%)
    18 / 265 (6.79%)
         occurrences all number
    21
    18
    Oropharyngeal pain
         subjects affected / exposed
    13 / 268 (4.85%)
    9 / 265 (3.40%)
         occurrences all number
    13
    9
    Epistaxis
         subjects affected / exposed
    10 / 268 (3.73%)
    7 / 265 (2.64%)
         occurrences all number
    10
    7
    Pleural effusion
         subjects affected / exposed
    4 / 268 (1.49%)
    3 / 265 (1.13%)
         occurrences all number
    4
    3
    Productive cough
         subjects affected / exposed
    4 / 268 (1.49%)
    3 / 265 (1.13%)
         occurrences all number
    4
    3
    Rhinorrhoea
         subjects affected / exposed
    3 / 268 (1.12%)
    2 / 265 (0.75%)
         occurrences all number
    3
    2
    Asthma
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    Catarrh
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Dysphonia
         subjects affected / exposed
    1 / 268 (0.37%)
    4 / 265 (1.51%)
         occurrences all number
    1
    4
    Emphysema
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Haemoptysis
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Lung infiltration
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Nasal congestion
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Pleuritic pain
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Respiratory tract congestion
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Rhinitis allergic
         subjects affected / exposed
    1 / 268 (0.37%)
    3 / 265 (1.13%)
         occurrences all number
    1
    3
    Sinus congestion
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Throat irritation
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Throat tightness
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Tonsillar hypertrophy
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Wheezing
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Dry throat
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Dyspnoea exertional
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Hypoxia
         subjects affected / exposed
    0 / 268 (0.00%)
    3 / 265 (1.13%)
         occurrences all number
    0
    3
    Laryngeal inflammation
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Nasal ulcer
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Rales
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Respiratory failure
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Sneezing
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    15 / 268 (5.60%)
    16 / 265 (6.04%)
         occurrences all number
    15
    16
    Anxiety
         subjects affected / exposed
    10 / 268 (3.73%)
    10 / 265 (3.77%)
         occurrences all number
    10
    10
    Depression
         subjects affected / exposed
    8 / 268 (2.99%)
    10 / 265 (3.77%)
         occurrences all number
    8
    10
    Libido decreased
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Confusional state
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Delirium
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Depressive symptom
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Mood altered
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Sleep disorder
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Irritability
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Mood swings
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Nightmare
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    81 / 268 (30.22%)
    15 / 265 (5.66%)
         occurrences all number
    81
    15
    Aspartate aminotransferase increased
         subjects affected / exposed
    60 / 268 (22.39%)
    17 / 265 (6.42%)
         occurrences all number
    60
    17
    Lipase increased
         subjects affected / exposed
    36 / 268 (13.43%)
    22 / 265 (8.30%)
         occurrences all number
    36
    22
    Platelet count decreased
         subjects affected / exposed
    33 / 268 (12.31%)
    20 / 265 (7.55%)
         occurrences all number
    33
    20
    Blood alkaline phosphatase increased
         subjects affected / exposed
    15 / 268 (5.60%)
    9 / 265 (3.40%)
         occurrences all number
    15
    9
    Blood creatinine increased
         subjects affected / exposed
    15 / 268 (5.60%)
    17 / 265 (6.42%)
         occurrences all number
    15
    17
    Amylase increased
         subjects affected / exposed
    14 / 268 (5.22%)
    7 / 265 (2.64%)
         occurrences all number
    14
    7
    Blood bilirubin increased
         subjects affected / exposed
    13 / 268 (4.85%)
    6 / 265 (2.26%)
         occurrences all number
    13
    6
    Blood creatine phosphokinase increased
         subjects affected / exposed
    9 / 268 (3.36%)
    19 / 265 (7.17%)
         occurrences all number
    9
    19
    Weight decreased
         subjects affected / exposed
    8 / 268 (2.99%)
    5 / 265 (1.89%)
         occurrences all number
    8
    5
    Weight increased
         subjects affected / exposed
    8 / 268 (2.99%)
    13 / 265 (4.91%)
         occurrences all number
    8
    13
    Blood uric acid increased
         subjects affected / exposed
    7 / 268 (2.61%)
    2 / 265 (0.75%)
         occurrences all number
    7
    2
    Transaminases increased
         subjects affected / exposed
    7 / 268 (2.61%)
    2 / 265 (0.75%)
         occurrences all number
    7
    2
    Blood cholesterol increased
         subjects affected / exposed
    6 / 268 (2.24%)
    1 / 265 (0.38%)
         occurrences all number
    6
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    6 / 268 (2.24%)
    4 / 265 (1.51%)
         occurrences all number
    6
    4
    White blood cell count decreased
         subjects affected / exposed
    6 / 268 (2.24%)
    14 / 265 (5.28%)
         occurrences all number
    6
    14
    Electrocardiogram QT prolonged
         subjects affected / exposed
    4 / 268 (1.49%)
    8 / 265 (3.02%)
         occurrences all number
    4
    8
    Hepatic enzyme increased
         subjects affected / exposed
    4 / 268 (1.49%)
    0 / 265 (0.00%)
         occurrences all number
    4
    0
    Neutrophil count decreased
         subjects affected / exposed
    4 / 268 (1.49%)
    11 / 265 (4.15%)
         occurrences all number
    4
    11
    Blood urea increased
         subjects affected / exposed
    3 / 268 (1.12%)
    2 / 265 (0.75%)
         occurrences all number
    3
    2
    Haemoglobin decreased
         subjects affected / exposed
    3 / 268 (1.12%)
    4 / 265 (1.51%)
         occurrences all number
    3
    4
    Lymphocyte count decreased
         subjects affected / exposed
    3 / 268 (1.12%)
    4 / 265 (1.51%)
         occurrences all number
    3
    4
    Blood glucose increased
         subjects affected / exposed
    2 / 268 (0.75%)
    3 / 265 (1.13%)
         occurrences all number
    2
    3
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    Liver function test increased
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    White blood cell count increased
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Aspartate aminotransferase
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Blood bicarbonate decreased
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Blood chloride increased
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Blood iron decreased
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Blood phosphorus decreased
         subjects affected / exposed
    1 / 268 (0.37%)
    3 / 265 (1.13%)
         occurrences all number
    1
    3
    Blood urine present
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    C-reactive protein increased
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Cardiac murmur
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Electrocardiogram QT interval
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Electrocardiogram ST-T segment abnormal
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Electrocardiogram T wave amplitude decreased
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Eosinophil count decreased
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Occult blood positive
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Platelet count increased
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Protein urine
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Serum ferritin decreased
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Basophil count increased
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Blood creatine phosphokinase MB increased
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Blood folate decreased
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Blood magnesium decreased
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Blood potassium decreased
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Blood pressure systolic increased
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Blood triglycerides increased
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Body temperature increased
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Eosinophil count increased
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Globulins decreased
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Heart rate increased
         subjects affected / exposed
    0 / 268 (0.00%)
    4 / 265 (1.51%)
         occurrences all number
    0
    4
    Heart rate irregular
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    International normalised ratio increased
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Lipids abnormal
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Lymph node palpable
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Lymphocyte count increased
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Neutrophil count increased
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Nicotinamide decreased
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Prostatic specific antigen increased
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Protein total decreased
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Prothrombin time prolonged
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Pulmonary arterial pressure increased
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Urinary sediment present
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Bilirubin conjugated increased
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    7 / 268 (2.61%)
    3 / 265 (1.13%)
         occurrences all number
    7
    3
    Fall
         subjects affected / exposed
    4 / 268 (1.49%)
    0 / 265 (0.00%)
         occurrences all number
    4
    0
    Arthropod bite
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Hand fracture
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Heavy exposure to ultraviolet light
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Laceration
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Ligament sprain
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Limb injury
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Lip injury
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Nerve injury
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Post procedural haematoma
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Procedural pain
         subjects affected / exposed
    1 / 268 (0.37%)
    3 / 265 (1.13%)
         occurrences all number
    1
    3
    Radius fracture
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Rib fracture
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Spinal fracture
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Sunburn
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Tooth fracture
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Wound dehiscence
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Animal bite
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Eye injury
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Gun shot wound
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Keratorhexis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Muscle rupture
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Muscle strain
         subjects affected / exposed
    0 / 268 (0.00%)
    3 / 265 (1.13%)
         occurrences all number
    0
    3
    Poisoning
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Skin abrasion
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Wound
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Ankle fracture
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Foot fracture
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Congenital, familial and genetic disorders
    Trisomy 8
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Cytogenetic abnormality
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    5 / 268 (1.87%)
    8 / 265 (3.02%)
         occurrences all number
    5
    8
    Sinus bradycardia
         subjects affected / exposed
    4 / 268 (1.49%)
    0 / 265 (0.00%)
         occurrences all number
    4
    0
    Atrial fibrillation
         subjects affected / exposed
    3 / 268 (1.12%)
    1 / 265 (0.38%)
         occurrences all number
    3
    1
    Angina pectoris
         subjects affected / exposed
    3 / 268 (1.12%)
    1 / 265 (0.38%)
         occurrences all number
    3
    1
    Bradycardia
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Myocardial ischaemia
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Diastolic dysfunction
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Extrasystoles
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Pericardial effusion
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Supraventricular extrasystoles
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Tachycardia
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Bundle branch block right
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Left ventricular hypertrophy
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Sinus tachycardia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Tricuspid valve incompetence
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    49 / 268 (18.28%)
    35 / 265 (13.21%)
         occurrences all number
    49
    35
    Dizziness
         subjects affected / exposed
    19 / 268 (7.09%)
    19 / 265 (7.17%)
         occurrences all number
    19
    19
    Paraesthesia
         subjects affected / exposed
    6 / 268 (2.24%)
    2 / 265 (0.75%)
         occurrences all number
    6
    2
    Lethargy
         subjects affected / exposed
    5 / 268 (1.87%)
    6 / 265 (2.26%)
         occurrences all number
    5
    6
    Memory impairment
         subjects affected / exposed
    5 / 268 (1.87%)
    2 / 265 (0.75%)
         occurrences all number
    5
    2
    Disturbance in attention
         subjects affected / exposed
    4 / 268 (1.49%)
    1 / 265 (0.38%)
         occurrences all number
    4
    1
    Dysgeusia
         subjects affected / exposed
    4 / 268 (1.49%)
    9 / 265 (3.40%)
         occurrences all number
    4
    9
    Hypoaesthesia
         subjects affected / exposed
    4 / 268 (1.49%)
    2 / 265 (0.75%)
         occurrences all number
    4
    2
    Peripheral sensory neuropathy
         subjects affected / exposed
    4 / 268 (1.49%)
    1 / 265 (0.38%)
         occurrences all number
    4
    1
    Dysaesthesia
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Amnesia
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Ataxia
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Burning sensation
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Dizziness postural
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Migraine
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Muscle contractions involuntary
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Nerve compression
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Neuralgia
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Neuropathy peripheral
         subjects affected / exposed
    1 / 268 (0.37%)
    3 / 265 (1.13%)
         occurrences all number
    1
    3
    Peripheral motor neuropathy
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Presyncope
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Sciatica
         subjects affected / exposed
    1 / 268 (0.37%)
    4 / 265 (1.51%)
         occurrences all number
    1
    4
    Somnolence
         subjects affected / exposed
    1 / 268 (0.37%)
    6 / 265 (2.26%)
         occurrences all number
    1
    6
    Syncope
         subjects affected / exposed
    1 / 268 (0.37%)
    4 / 265 (1.51%)
         occurrences all number
    1
    4
    Tremor
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Ageusia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Balance disorder
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Intercostal neuralgia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Migraine with aura
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Restless legs syndrome
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    63 / 268 (23.51%)
    32 / 265 (12.08%)
         occurrences all number
    63
    32
    Anaemia
         subjects affected / exposed
    47 / 268 (17.54%)
    52 / 265 (19.62%)
         occurrences all number
    47
    52
    Neutropenia
         subjects affected / exposed
    26 / 268 (9.70%)
    44 / 265 (16.60%)
         occurrences all number
    26
    44
    Leukopenia
         subjects affected / exposed
    9 / 268 (3.36%)
    15 / 265 (5.66%)
         occurrences all number
    9
    15
    Lymphopenia
         subjects affected / exposed
    8 / 268 (2.99%)
    3 / 265 (1.13%)
         occurrences all number
    8
    3
    Leukocytosis
         subjects affected / exposed
    7 / 268 (2.61%)
    4 / 265 (1.51%)
         occurrences all number
    7
    4
    Increased tendency to bruise
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Thrombocytosis
         subjects affected / exposed
    2 / 268 (0.75%)
    5 / 265 (1.89%)
         occurrences all number
    2
    5
    Haemorrhagic anaemia
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Lymphadenopathy
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Lymphocytosis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Mastocytosis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Microcytosis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Normochromic normocytic anaemia
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Pancytopenia
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Eosinophilia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Granulocytopenia
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Monocytopenia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Spontaneous haematoma
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    5 / 268 (1.87%)
    2 / 265 (0.75%)
         occurrences all number
    5
    2
    Tinnitus
         subjects affected / exposed
    5 / 268 (1.87%)
    1 / 265 (0.38%)
         occurrences all number
    5
    1
    Vertigo
         subjects affected / exposed
    3 / 268 (1.12%)
    5 / 265 (1.89%)
         occurrences all number
    3
    5
    Cerumen impaction
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Deafness
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Inner ear inflammation
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Vertigo positional
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Hypoacusis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Eye disorders
    Eye swelling
         subjects affected / exposed
    4 / 268 (1.49%)
    10 / 265 (3.77%)
         occurrences all number
    4
    10
    Periorbital oedema
         subjects affected / exposed
    4 / 268 (1.49%)
    37 / 265 (13.96%)
         occurrences all number
    4
    37
    Vision blurred
         subjects affected / exposed
    4 / 268 (1.49%)
    12 / 265 (4.53%)
         occurrences all number
    4
    12
    Eye pain
         subjects affected / exposed
    3 / 268 (1.12%)
    7 / 265 (2.64%)
         occurrences all number
    3
    7
    Conjunctival haemorrhage
         subjects affected / exposed
    2 / 268 (0.75%)
    8 / 265 (3.02%)
         occurrences all number
    2
    8
    Eye haemorrhage
         subjects affected / exposed
    2 / 268 (0.75%)
    2 / 265 (0.75%)
         occurrences all number
    2
    2
    Eye pruritus
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Ocular hyperaemia
         subjects affected / exposed
    2 / 268 (0.75%)
    3 / 265 (1.13%)
         occurrences all number
    2
    3
    Photophobia
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    Retinal haemorrhage
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Vitreous floaters
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Cataract
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Conjunctivitis allergic
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Eye irritation
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Eyelid oedema
         subjects affected / exposed
    1 / 268 (0.37%)
    25 / 265 (9.43%)
         occurrences all number
    1
    25
    Eyelid ptosis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Lacrimal disorder
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Ocular discomfort
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Retinal disorder
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Uveitis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Visual acuity reduced
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Visual impairment
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Vitreous detachment
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Conjunctival hyperaemia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Diabetic retinopathy
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Diplopia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Dry eye
         subjects affected / exposed
    0 / 268 (0.00%)
    11 / 265 (4.15%)
         occurrences all number
    0
    11
    Eye discharge
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Eye oedema
         subjects affected / exposed
    0 / 268 (0.00%)
    4 / 265 (1.51%)
         occurrences all number
    0
    4
    Eyelid pain
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Glaucoma
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Hypermetropia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Lacrimation increased
         subjects affected / exposed
    0 / 268 (0.00%)
    16 / 265 (6.04%)
         occurrences all number
    0
    16
    Ocular toxicity
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Orbital oedema
         subjects affected / exposed
    0 / 268 (0.00%)
    6 / 265 (2.26%)
         occurrences all number
    0
    6
    Retinal detachment
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Retinopathy haemorrhagic
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Scleral haemorrhage
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    189 / 268 (70.52%)
    88 / 265 (33.21%)
         occurrences all number
    189
    88
    Nausea
         subjects affected / exposed
    94 / 268 (35.07%)
    102 / 265 (38.49%)
         occurrences all number
    94
    102
    Vomiting
         subjects affected / exposed
    48 / 268 (17.91%)
    43 / 265 (16.23%)
         occurrences all number
    48
    43
    Abdominal pain
         subjects affected / exposed
    47 / 268 (17.54%)
    19 / 265 (7.17%)
         occurrences all number
    47
    19
    Constipation
         subjects affected / exposed
    26 / 268 (9.70%)
    14 / 265 (5.28%)
         occurrences all number
    26
    14
    Abdominal pain upper
         subjects affected / exposed
    20 / 268 (7.46%)
    19 / 265 (7.17%)
         occurrences all number
    20
    19
    Dyspepsia
         subjects affected / exposed
    18 / 268 (6.72%)
    19 / 265 (7.17%)
         occurrences all number
    18
    19
    Haemorrhoids
         subjects affected / exposed
    10 / 268 (3.73%)
    4 / 265 (1.51%)
         occurrences all number
    10
    4
    Abdominal distension
         subjects affected / exposed
    8 / 268 (2.99%)
    3 / 265 (1.13%)
         occurrences all number
    8
    3
    Toothache
         subjects affected / exposed
    6 / 268 (2.24%)
    3 / 265 (1.13%)
         occurrences all number
    6
    3
    Flatulence
         subjects affected / exposed
    5 / 268 (1.87%)
    4 / 265 (1.51%)
         occurrences all number
    5
    4
    Gastrooesophageal reflux disease
         subjects affected / exposed
    5 / 268 (1.87%)
    8 / 265 (3.02%)
         occurrences all number
    5
    8
    Abdominal discomfort
         subjects affected / exposed
    4 / 268 (1.49%)
    6 / 265 (2.26%)
         occurrences all number
    4
    6
    Dry mouth
         subjects affected / exposed
    4 / 268 (1.49%)
    7 / 265 (2.64%)
         occurrences all number
    4
    7
    Mouth ulceration
         subjects affected / exposed
    4 / 268 (1.49%)
    3 / 265 (1.13%)
         occurrences all number
    4
    3
    Haematochezia
         subjects affected / exposed
    3 / 268 (1.12%)
    0 / 265 (0.00%)
         occurrences all number
    3
    0
    Epigastric discomfort
         subjects affected / exposed
    2 / 268 (0.75%)
    2 / 265 (0.75%)
         occurrences all number
    2
    2
    Gastritis
         subjects affected / exposed
    2 / 268 (0.75%)
    2 / 265 (0.75%)
         occurrences all number
    2
    2
    Paraesthesia oral
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Proctalgia
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Rectal haemorrhage
         subjects affected / exposed
    2 / 268 (0.75%)
    3 / 265 (1.13%)
         occurrences all number
    2
    3
    Abdominal hernia
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Anal fissure
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Anal incontinence
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Aphthous ulcer
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Colitis
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Colitis ulcerative
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Dental caries
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Dental discomfort
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Dysphagia
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Faeces discoloured
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Food poisoning
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Gastric disorder
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Gastric ulcer
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Gastrointestinal necrosis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal pain
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Duodenitis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Glossodynia
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Gingival erythema
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Ileus
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Lip pain
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Oral pain
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Mouth haemorrhage
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Pancreatitis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Peristalsis visible
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Proctitis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Rectal tenesmus
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Retching
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Salivary gland enlargement
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Stomatitis
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Tongue discolouration
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Tongue disorder
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Abdominal pain lower
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Anal haemorrhage
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Ascites
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Chronic gastritis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Eructation
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Faeces soft
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Frequent bowel movements
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Gingival bleeding
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Gingival pain
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Haematemesis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Inguinal hernia
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Large intestine polyp
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Lip dry
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Lip swelling
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Oesophagitis
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Salivary hypersecretion
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Tongue dry
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Tooth disorder
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Umbilical hernia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Hepatobiliary disorders
    Hepatotoxicity
         subjects affected / exposed
    4 / 268 (1.49%)
    0 / 265 (0.00%)
         occurrences all number
    4
    0
    Hyperbilirubinaemia
         subjects affected / exposed
    4 / 268 (1.49%)
    1 / 265 (0.38%)
         occurrences all number
    4
    1
    Drug-induced liver injury
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Hepatitis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Hepatitis toxic
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Hepatocellular injury
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Jaundice
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Cholestasis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Hepatic steatosis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Liver disorder
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    53 / 268 (19.78%)
    36 / 265 (13.58%)
         occurrences all number
    53
    36
    Pruritus
         subjects affected / exposed
    25 / 268 (9.33%)
    7 / 265 (2.64%)
         occurrences all number
    25
    7
    Rash maculo-papular
         subjects affected / exposed
    14 / 268 (5.22%)
    14 / 265 (5.28%)
         occurrences all number
    14
    14
    Alopecia
         subjects affected / exposed
    12 / 268 (4.48%)
    12 / 265 (4.53%)
         occurrences all number
    12
    12
    Dry skin
         subjects affected / exposed
    12 / 268 (4.48%)
    10 / 265 (3.77%)
         occurrences all number
    12
    10
    Erythema
         subjects affected / exposed
    9 / 268 (3.36%)
    4 / 265 (1.51%)
         occurrences all number
    9
    4
    Rash pruritic
         subjects affected / exposed
    7 / 268 (2.61%)
    0 / 265 (0.00%)
         occurrences all number
    7
    0
    Acne
         subjects affected / exposed
    6 / 268 (2.24%)
    1 / 265 (0.38%)
         occurrences all number
    6
    1
    Dermatitis acneiform
         subjects affected / exposed
    5 / 268 (1.87%)
    1 / 265 (0.38%)
         occurrences all number
    5
    1
    Urticaria
         subjects affected / exposed
    5 / 268 (1.87%)
    3 / 265 (1.13%)
         occurrences all number
    5
    3
    Eczema
         subjects affected / exposed
    4 / 268 (1.49%)
    6 / 265 (2.26%)
         occurrences all number
    4
    6
    Hyperhidrosis
         subjects affected / exposed
    4 / 268 (1.49%)
    6 / 265 (2.26%)
         occurrences all number
    4
    6
    Rash papular
         subjects affected / exposed
    4 / 268 (1.49%)
    0 / 265 (0.00%)
         occurrences all number
    4
    0
    Dermatitis
         subjects affected / exposed
    3 / 268 (1.12%)
    1 / 265 (0.38%)
         occurrences all number
    3
    1
    Nail discolouration
         subjects affected / exposed
    3 / 268 (1.12%)
    1 / 265 (0.38%)
         occurrences all number
    3
    1
    Rash erythematous
         subjects affected / exposed
    3 / 268 (1.12%)
    2 / 265 (0.75%)
         occurrences all number
    3
    2
    Skin lesion
         subjects affected / exposed
    3 / 268 (1.12%)
    1 / 265 (0.38%)
         occurrences all number
    3
    1
    Actinic keratosis
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    Dermatitis allergic
         subjects affected / exposed
    2 / 268 (0.75%)
    4 / 265 (1.51%)
         occurrences all number
    2
    4
    Dyshidrotic eczema
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Miliaria
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    Pruritus generalised
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    Skin discolouration
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    Skin exfoliation
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    Angioedema
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Blister
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Dermal cyst
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Dermatitis exfoliative
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Drug reaction with eosinophilia and systemic symptoms
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Ecchymosis
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Generalised erythema
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Hyperkeratosis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Hypertrichosis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Ingrowing nail
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Mucocutaneous ulceration
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Nail disorder
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Nail dystrophy
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Perivascular dermatitis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Photosensitivity reaction
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Purpura
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Rash generalised
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Sebaceous glands overactivity
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Skin fragility
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Skin mass
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Skin ulcer
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Swelling face
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Vitiligo
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Dandruff
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Diffuse alopecia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Eczema asteatotic
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Erythema multiforme
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Erythema nodosum
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Petechiae
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Psoriasis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Rash macular
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Skin hypopigmentation
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Stasis dermatitis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Toxic skin eruption
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Papule
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Night sweats
         subjects affected / exposed
    5 / 268 (1.87%)
    9 / 265 (3.40%)
         occurrences all number
    5
    9
    Renal and urinary disorders
    Nocturia
         subjects affected / exposed
    3 / 268 (1.12%)
    1 / 265 (0.38%)
         occurrences all number
    3
    1
    Acute kidney injury
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    Dysuria
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Haematuria
         subjects affected / exposed
    2 / 268 (0.75%)
    6 / 265 (2.26%)
         occurrences all number
    2
    6
    Pollakiuria
         subjects affected / exposed
    2 / 268 (0.75%)
    3 / 265 (1.13%)
         occurrences all number
    2
    3
    Renal impairment
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Urethritis noninfective
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Bladder diverticulum
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Calculus urinary
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Chromaturia
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Nephritis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Nephrocalcinosis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Nephroptosis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Oliguria
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Polyuria
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Proteinuria
         subjects affected / exposed
    1 / 268 (0.37%)
    3 / 265 (1.13%)
         occurrences all number
    1
    3
    Renal cyst
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Urinary tract pain
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Urine abnormality
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Acute prerenal failure
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Calculus urethral
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Nephropathy
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Nephrotic syndrome
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Renal injury
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Urinary retention
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Urinary tract inflammation
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Hyperparathyroidism
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Thyroid disorder
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Thyroid mass
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    32 / 268 (11.94%)
    35 / 265 (13.21%)
         occurrences all number
    32
    35
    Back pain
         subjects affected / exposed
    22 / 268 (8.21%)
    19 / 265 (7.17%)
         occurrences all number
    22
    19
    Pain in extremity
         subjects affected / exposed
    12 / 268 (4.48%)
    34 / 265 (12.83%)
         occurrences all number
    12
    34
    Myalgia
         subjects affected / exposed
    8 / 268 (2.99%)
    41 / 265 (15.47%)
         occurrences all number
    8
    41
    Bone pain
         subjects affected / exposed
    7 / 268 (2.61%)
    18 / 265 (6.79%)
         occurrences all number
    7
    18
    Musculoskeletal pain
         subjects affected / exposed
    7 / 268 (2.61%)
    8 / 265 (3.02%)
         occurrences all number
    7
    8
    Muscle spasms
         subjects affected / exposed
    6 / 268 (2.24%)
    70 / 265 (26.42%)
         occurrences all number
    6
    70
    Neck pain
         subjects affected / exposed
    6 / 268 (2.24%)
    4 / 265 (1.51%)
         occurrences all number
    6
    4
    Musculoskeletal chest pain
         subjects affected / exposed
    4 / 268 (1.49%)
    0 / 265 (0.00%)
         occurrences all number
    4
    0
    Flank pain
         subjects affected / exposed
    3 / 268 (1.12%)
    2 / 265 (0.75%)
         occurrences all number
    3
    2
    Muscular weakness
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    Osteoarthritis
         subjects affected / exposed
    2 / 268 (0.75%)
    3 / 265 (1.13%)
         occurrences all number
    2
    3
    Spinal pain
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    Synovial cyst
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    Intervertebral disc disorder
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Joint effusion
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Joint instability
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Limb discomfort
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Muscle fatigue
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal discomfort
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Myopathy
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Osteoporosis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Spinal column stenosis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Spinal osteoarthritis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Arthritis
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Dupuytren's contracture
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Foot deformity
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Growing pains
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Joint laxity
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Joint stiffness
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Muscle contracture
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Muscle twitching
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Osteochondrosis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Pain in jaw
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Rhabdomyolysis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Temporomandibular joint syndrome
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Tenosynovitis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Torticollis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Trismus
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Tendonitis
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    26 / 268 (9.70%)
    24 / 265 (9.06%)
         occurrences all number
    26
    24
    Upper respiratory tract infection
         subjects affected / exposed
    23 / 268 (8.58%)
    27 / 265 (10.19%)
         occurrences all number
    23
    27
    Urinary tract infection
         subjects affected / exposed
    17 / 268 (6.34%)
    9 / 265 (3.40%)
         occurrences all number
    17
    9
    Bronchitis
         subjects affected / exposed
    8 / 268 (2.99%)
    4 / 265 (1.51%)
         occurrences all number
    8
    4
    Influenza
         subjects affected / exposed
    7 / 268 (2.61%)
    8 / 265 (3.02%)
         occurrences all number
    7
    8
    Sinusitis
         subjects affected / exposed
    7 / 268 (2.61%)
    5 / 265 (1.89%)
         occurrences all number
    7
    5
    Gastroenteritis
         subjects affected / exposed
    6 / 268 (2.24%)
    5 / 265 (1.89%)
         occurrences all number
    6
    5
    Folliculitis
         subjects affected / exposed
    5 / 268 (1.87%)
    2 / 265 (0.75%)
         occurrences all number
    5
    2
    Pharyngitis
         subjects affected / exposed
    5 / 268 (1.87%)
    6 / 265 (2.26%)
         occurrences all number
    5
    6
    Lower respiratory tract infection
         subjects affected / exposed
    4 / 268 (1.49%)
    1 / 265 (0.38%)
         occurrences all number
    4
    1
    Respiratory tract infection
         subjects affected / exposed
    4 / 268 (1.49%)
    2 / 265 (0.75%)
         occurrences all number
    4
    2
    Cellulitis
         subjects affected / exposed
    3 / 268 (1.12%)
    0 / 265 (0.00%)
         occurrences all number
    3
    0
    Conjunctivitis
         subjects affected / exposed
    3 / 268 (1.12%)
    6 / 265 (2.26%)
         occurrences all number
    3
    6
    Otitis media
         subjects affected / exposed
    3 / 268 (1.12%)
    2 / 265 (0.75%)
         occurrences all number
    3
    2
    Pneumonia
         subjects affected / exposed
    3 / 268 (1.12%)
    1 / 265 (0.38%)
         occurrences all number
    3
    1
    Rhinitis
         subjects affected / exposed
    3 / 268 (1.12%)
    5 / 265 (1.89%)
         occurrences all number
    3
    5
    Viral infection
         subjects affected / exposed
    3 / 268 (1.12%)
    7 / 265 (2.64%)
         occurrences all number
    3
    7
    Cystitis
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    Ear infection
         subjects affected / exposed
    2 / 268 (0.75%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    Eye infection
         subjects affected / exposed
    2 / 268 (0.75%)
    2 / 265 (0.75%)
         occurrences all number
    2
    2
    Gastroenteritis viral
         subjects affected / exposed
    2 / 268 (0.75%)
    2 / 265 (0.75%)
         occurrences all number
    2
    2
    Oral herpes
         subjects affected / exposed
    2 / 268 (0.75%)
    2 / 265 (0.75%)
         occurrences all number
    2
    2
    Candida infection
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Chlamydial infection
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Ear lobe infection
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Erysipelas
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal infection
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Hepatitis B
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Herpes zoster
         subjects affected / exposed
    1 / 268 (0.37%)
    3 / 265 (1.13%)
         occurrences all number
    1
    3
    Infection
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Lice infestation
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Lip infection
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Lymphadenitis bacterial
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Paronychia
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Pulpitis dental
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Skin infection
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Staphylococcal infection
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Tooth abscess
         subjects affected / exposed
    1 / 268 (0.37%)
    2 / 265 (0.75%)
         occurrences all number
    1
    2
    Tooth infection
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Adenovirus infection
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Carbuncle
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Diarrhoea infectious
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Enterocolitis infectious
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Fungal skin infection
         subjects affected / exposed
    0 / 268 (0.00%)
    3 / 265 (1.13%)
         occurrences all number
    0
    3
    Genital abscess
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Gingivitis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Helicobacter infection
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Herpes simplex
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Hordeolum
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Labyrinthitis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Localised infection
         subjects affected / exposed
    0 / 268 (0.00%)
    4 / 265 (1.51%)
         occurrences all number
    0
    4
    Lung infection
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Meningococcal infection
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Nail infection
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Onychomycosis
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Parainfluenzae virus infection
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 268 (0.00%)
    2 / 265 (0.75%)
         occurrences all number
    0
    2
    Pneumonia bacterial
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Pyelonephritis chronic
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Tonsillitis bacterial
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Vaginal infection
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    26 / 268 (9.70%)
    16 / 265 (6.04%)
         occurrences all number
    26
    16
    Hyperuricaemia
         subjects affected / exposed
    5 / 268 (1.87%)
    4 / 265 (1.51%)
         occurrences all number
    5
    4
    Hypophosphataemia
         subjects affected / exposed
    5 / 268 (1.87%)
    14 / 265 (5.28%)
         occurrences all number
    5
    14
    Gout
         subjects affected / exposed
    4 / 268 (1.49%)
    2 / 265 (0.75%)
         occurrences all number
    4
    2
    Hyperglycaemia
         subjects affected / exposed
    4 / 268 (1.49%)
    8 / 265 (3.02%)
         occurrences all number
    4
    8
    Hyperkalaemia
         subjects affected / exposed
    4 / 268 (1.49%)
    4 / 265 (1.51%)
         occurrences all number
    4
    4
    Hypertriglyceridaemia
         subjects affected / exposed
    4 / 268 (1.49%)
    2 / 265 (0.75%)
         occurrences all number
    4
    2
    Hypokalaemia
         subjects affected / exposed
    4 / 268 (1.49%)
    18 / 265 (6.79%)
         occurrences all number
    4
    18
    Hypercholesterolaemia
         subjects affected / exposed
    3 / 268 (1.12%)
    0 / 265 (0.00%)
         occurrences all number
    3
    0
    Hypocalcaemia
         subjects affected / exposed
    3 / 268 (1.12%)
    8 / 265 (3.02%)
         occurrences all number
    3
    8
    Hypomagnesaemia
         subjects affected / exposed
    3 / 268 (1.12%)
    2 / 265 (0.75%)
         occurrences all number
    3
    2
    Vitamin D deficiency
         subjects affected / exposed
    3 / 268 (1.12%)
    0 / 265 (0.00%)
         occurrences all number
    3
    0
    Dehydration
         subjects affected / exposed
    2 / 268 (0.75%)
    2 / 265 (0.75%)
         occurrences all number
    2
    2
    Hyperchloraemia
         subjects affected / exposed
    2 / 268 (0.75%)
    0 / 265 (0.00%)
         occurrences all number
    2
    0
    Hyponatraemia
         subjects affected / exposed
    2 / 268 (0.75%)
    2 / 265 (0.75%)
         occurrences all number
    2
    2
    Diabetes mellitus
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Folate deficiency
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 268 (0.37%)
    4 / 265 (1.51%)
         occurrences all number
    1
    4
    Hypoglycaemia
         subjects affected / exposed
    1 / 268 (0.37%)
    5 / 265 (1.89%)
         occurrences all number
    1
    5
    Iron deficiency
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Obesity
         subjects affected / exposed
    1 / 268 (0.37%)
    0 / 265 (0.00%)
         occurrences all number
    1
    0
    Vitamin B12 deficiency
         subjects affected / exposed
    1 / 268 (0.37%)
    1 / 265 (0.38%)
         occurrences all number
    1
    1
    Electrolyte imbalance
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Fluid retention
         subjects affected / exposed
    0 / 268 (0.00%)
    8 / 265 (3.02%)
         occurrences all number
    0
    8
    Hypermagnesaemia
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Increased appetite
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1
    Metabolic syndrome
         subjects affected / exposed
    0 / 268 (0.00%)
    1 / 265 (0.38%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Mar 2014
    Updated information for assessments of vital signs, inclusion/exclusion criteria, laboratory assessments, timing of efficacy endpoints, exploratory efficacy endpoints, study durations, timing of assessments, terms and definitions, study populations, adverse event assessments, and administrative information.
    14 Jan 2015
    Updated information for contact details, study duration, subject populations, inclusion/exclusion criteria definitions, bosutinib formulation details, assessment timings (eg, schedule of events, pre-randomization Sokal score assessment), timing of assessments, timing for collection of adverse events/reporting, study drug dosing requirements, compliance recording, statitstical analysis (primary and secondary efficacy analysis), pharmacokinetic analysis, and administrative information.
    09 Sep 2016
    Updated information for sample size, study populations, efficacy analysis, interim analyses, time to response description, and administrative information.
    07 Dec 2016
    Updated information for change of Sponsor details, sample size, study populations, methodology for statistical analyses, efficacy analysis, interim analyses, time to response description, extension phase visit window, sample drug diary cards, and administrative information.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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