Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   44393   clinical trials with a EudraCT protocol, of which   7405   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase III, Double-blind, Randomised Study to Assess the Efficacy and Safety of AZD9291 versus a Standard of Care Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor as First-line Treatment in Patients with Epidermal Growth Factor Receptor Mutation-positive, Locally-advanced or Metastatic Non-small-cell Lung Cancer (FLAURA)

    Summary
    EudraCT number
    		 2014-002694-11
    Trial protocol
    		 HU   GB   IT   DE   ES   BE   SE   CZ   FR   PL   BG   PT  
    Global end of trial date
    20 Nov 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Apr 2026
    First version publication date
    01 Apr 2026
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    D5160C00007
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02296125
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca AB
    Sponsor organisation address
    Not applicable, Södertälje, Sweden, SE-151 85
    Public contact
    Global Clinical Lead, AstraZeneca AB, 1 +46 766 346712, ClinicalTrialTransparency@astrazeneca.com
    Scientific contact
    Global Clinical Leader, AstraZeneca AB, 1 +46 766 346712, ClinicalTrialTransparency@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    25 Jun 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Nov 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the efficacy of single agent osimertinib compared with SoC EGFR-TKI therapy as measured by progression free survival (PFS).
    Protection of trial subjects
    This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Conference on Harmonisation (ICH)/Good Clinical Practice (GCP), applicable regulatory requirements, and the AstraZeneca policy on Bioethics. The study was approved by the institutional review board (IRB)/independent ethics committee (IEC) associated with each study centre. All CSP amendments were approved by each IRB/IEC and, if applicable, the national regulatory authority before implementation. Local requirements were followed for the revised CSPs. If a CSP amendment required a change to a study centre’s informed consent form (ICF), AstraZeneca and the study centre’s IRB/IEC approved the revised ICF before the revised ICF was used. Informed consent was obtained from all patients prior to enrolment into the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    03 Dec 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 25
    Country: Number of subjects enrolled
    Belgium: 12
    Country: Number of subjects enrolled
    Brazil: 1
    Country: Number of subjects enrolled
    Canada: 18
    Country: Number of subjects enrolled
    China: 136
    Country: Number of subjects enrolled
    Czechia: 2
    Country: Number of subjects enrolled
    France: 13
    Country: Number of subjects enrolled
    Germany: 16
    Country: Number of subjects enrolled
    Hungary: 5
    Country: Number of subjects enrolled
    Israel: 8
    Country: Number of subjects enrolled
    Italy: 21
    Country: Number of subjects enrolled
    Japan: 121
    Country: Number of subjects enrolled
    Malaysia: 22
    Country: Number of subjects enrolled
    Philippines: 9
    Country: Number of subjects enrolled
    Poland: 8
    Country: Number of subjects enrolled
    Portugal: 7
    Country: Number of subjects enrolled
    Romania: 2
    Country: Number of subjects enrolled
    Russian Federation: 18
    Country: Number of subjects enrolled
    Korea, Republic of: 47
    Country: Number of subjects enrolled
    Spain: 27
    Country: Number of subjects enrolled
    Sweden: 2
    Country: Number of subjects enrolled
    Switzerland: 6
    Country: Number of subjects enrolled
    Taiwan: 24
    Country: Number of subjects enrolled
    Thailand: 74
    Country: Number of subjects enrolled
    Turkey: 1
    Country: Number of subjects enrolled
    Ukraine: 8
    Country: Number of subjects enrolled
    United Kingdom: 11
    Country: Number of subjects enrolled
    United States: 23
    Country: Number of subjects enrolled
    Viet Nam: 6
    Worldwide total number of subjects
    673
    EEA total number of subjects
    115
    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)
    372
    From 65 to 84 years
    295
    85 years and over
    6

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 556 subjects in Global cohort were randomized to treatment in 29 countries. Further 117 subjects enrolled into China cohort. There were 19 Chinese subjects who were included in both global and China cohorts giving total of 692. To avoid tool error 19 subjects have been double counted for Country China under-Population of Trial Subjects.

    Pre-assignment
    Screening details
    		 Subjects were enrolled based on presence in their tumour of at least 1 of 2 most frequent Epidermal growth factor receptor (EGFR) mutations. At time of enrolment, all subjects were required to provide biopsy tissue for central testing of Exon 19 deletion (Ex19del) and L858R mutations. Subjects were treatment-naïve for their advanced EGFRm NSCLC.

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

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Osimertinib 80 mg (Global Cohort)
    Arm description
    		 Randomized subjects received Osimertinib 80 mg orally once daily (QD)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Osimertinib
    Investigational medicinal product code
    AZD9291
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received once-daily oral administration of Osimertinib (80 mg and 40 mg tablets)

    Arm title
    		 SoC EGFR-TKI (Global Cohort)
    Arm description
    		 Randomized subjects received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD
    Arm type
    		 Experimental

    Investigational medicinal product name
    Erlotinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received erlotinib 150 mg orally once daily

    Investigational medicinal product name
    Gefitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received gefitinib 250 mg orally once daily

    Arm title
    		 Osimertinib 80 mg (China Cohort)
    Arm description
    		 Randomized subjects received Osimertinib 80 mg orally once daily (QD)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Osimertinib
    Investigational medicinal product code
    AZD9291
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received once-daily oral administration of Osimertinib (80 mg and 40 mg tablets)

    Arm title
    		 SoC EGFR-TKI (China Cohort)
    Arm description
    		 Randomized subjects received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD
    Arm type
    		 Experimental

    Investigational medicinal product name
    Gefitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received gefitinib 250 mg orally once daily

    Number of subjects in period 1
    		Osimertinib 80 mg (Global Cohort) SoC EGFR-TKI (Global Cohort) Osimertinib 80 mg (China Cohort) SoC EGFR-TKI (China Cohort)
    Started
    279
    277
    71
    65
    Completed
    61
    13
    15
    3
    Not completed
    218
    264
    56
    62
         Severe non-compliance to protocol
    -
    1
    -
    -
         Consent withdrawn by subject
    18
    8
    6
    2
         Adverse event, non-fatal
    41
    52
    9
    4
         Any reason not specifically recorded
    6
    4
    2
    -
         Condition under investigation worsened
    153
    199
    39
    56

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Osimertinib 80 mg (Global Cohort)
    Reporting group description
    		 Randomized subjects received Osimertinib 80 mg orally once daily (QD)

    Reporting group title
    SoC EGFR-TKI (Global Cohort)
    Reporting group description
    		 Randomized subjects received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD

    Reporting group title
    Osimertinib 80 mg (China Cohort)
    Reporting group description
    		 Randomized subjects received Osimertinib 80 mg orally once daily (QD)

    Reporting group title
    SoC EGFR-TKI (China Cohort)
    Reporting group description
    		 Randomized subjects received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD

    Reporting group values
    		 Osimertinib 80 mg (Global Cohort) SoC EGFR-TKI (Global Cohort) Osimertinib 80 mg (China Cohort) SoC EGFR-TKI (China Cohort) Total
    Number of subjects
    		 279 277 71 65 692
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 153 145 49 42 389
        From 65-84 years
    		 125 127 22 23 297
        85 years and over
    		 1 5 0 0 6
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 62.7 ( 10.70 ) 63.3 ( 10.90 ) 59.1 ( 9.66 ) 59.0 ( 10.94 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 178 172 43 46 439
        Male
    		 101 105 28 19 253
    Smoking status
    Units: Subjects
        Never smoked
    		 182 175 53 50 460
        Current smokers
    		 8 9 3 4 24
        Former smokers
    		 89 93 15 11 208

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Osimertinib 80 mg (Global Cohort)
    Reporting group description
    		 Randomized subjects received Osimertinib 80 mg orally once daily (QD)

    Reporting group title
    SoC EGFR-TKI (Global Cohort)
    Reporting group description
    		 Randomized subjects received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD

    Reporting group title
    Osimertinib 80 mg (China Cohort)
    Reporting group description
    		 Randomized subjects received Osimertinib 80 mg orally once daily (QD)

    Reporting group title
    SoC EGFR-TKI (China Cohort)
    Reporting group description
    		 Randomized subjects received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD

    Primary: Median progression free survival (PFS) (months)

    		 Close Top of page
    End point title
    		 Median progression free survival (PFS) (months)
    End point description
    Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent osimertinib compared with SoC EGFR-TKI therapy as measured by PFS. The primary endpoint of PFS was based on based on Investigator assessment according to Response Evaluation Criteria in Solid Tumors version (RECIST v1.1).
    End point type
    Primary
    End point timeframe
    At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression
    End point values
    		 Osimertinib 80 mg (Global Cohort) SoC EGFR-TKI (Global Cohort) Osimertinib 80 mg (China Cohort) SoC EGFR-TKI (China Cohort)
    Number of subjects analysed
    279
    277
    71
    65
    Units: Months
        median (confidence interval 95%)
    18.9 (15.2 to 21.4)
    10.2 (9.6 to 11.1)
    17.8 (13.6 to 20.7)
    9.8 (8.3 to 13.8)
    Statistical analysis title
    		 Osimertinib 80 mg vs SoC EGFR-TKI (Global Cohort)
    Comparison groups
    Osimertinib 80 mg (Global Cohort) v SoC EGFR-TKI (Global Cohort)
    Number of subjects included in analysis
    556
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.37
         upper limit
    		 0.57
    Statistical analysis title
    		 Osimertinib 80 mg vs SoC EGFR-TKI (China Cohort)
    Comparison groups
    Osimertinib 80 mg (China Cohort) v SoC EGFR-TKI (China Cohort)
    Number of subjects included in analysis
    136
    Analysis specification
    Pre-specified
    Analysis type
    		 [1]
    P-value
    		 = 0.0065
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.37
         upper limit
    		 0.85
    Notes
    [1] - The china cohort was not powered for superiority

    Primary: Percentage of subjects in progression free survival at 6, 12, and 18 months

    		 Close Top of page
    End point title
    		 Percentage of subjects in progression free survival at 6, 12, and 18 months [2]
    End point description
    Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the subject withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent osimertinib compared with SoC EGFR-TKI therapy as measured by PFS.
    End point type
    Primary
    End point timeframe
    At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses have been performed
    End point values
    		 Osimertinib 80 mg (Global Cohort) SoC EGFR-TKI (Global Cohort) Osimertinib 80 mg (China Cohort) SoC EGFR-TKI (China Cohort)
    Number of subjects analysed
    279
    277
    71
    65
    Units: Percentage of Subjects
    number (not applicable)
        Progression free at 6 months (%)
    88.4
    75.2
    78.8
    72.3
        Progression free at 12 months (%)
    68.2
    42.3
    67.3
    44.6
        Progression free at 18 months (%)
    50.9
    24.4
    46.9
    25.8
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR)

    		 Close Top of page
    End point title
    		 Objective Response Rate (ORR)
    End point description
    ORR was defined as the number (%) of subjects with measurable disease with at least 1 visit response of Complete response (CR) or Partial response (PR) and it was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy. ORR was based on Investigator assessment according to RECIST v1.1.
    End point type
    Secondary
    End point timeframe
    At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression
    End point values
    		 Osimertinib 80 mg (Global Cohort) SoC EGFR-TKI (Global Cohort) Osimertinib 80 mg (China Cohort) SoC EGFR-TKI (China Cohort)
    Number of subjects analysed
    279
    277
    71
    65
    Units: Percentage of subjects
        number (confidence interval 95%)
    76.7 (71.29 to 81.53)
    69.0 (63.14 to 74.35)
    76.1 (64.5 to 85.4)
    70.8 (58.2 to 81.4)
    Statistical analysis title
    		 Osimertinib 80 mg vs SoC EGFR-TKI (Global Cohort)
    Comparison groups
    Osimertinib 80 mg (Global Cohort) v SoC EGFR-TKI (Global Cohort)
    Number of subjects included in analysis
    556
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.036
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.03
         upper limit
    		 2.22
    Statistical analysis title
    		 Osimertinib 80 mg vs SoC EGFR-TKI (China Cohort)
    Comparison groups
    Osimertinib 80 mg (China Cohort) v SoC EGFR-TKI (China Cohort)
    Number of subjects included in analysis
    136
    Analysis specification
    Pre-specified
    Analysis type
    		 [3]
    P-value
    		 = 0.485
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 2.84
    Notes
    [3] - The china cohort was not powered for superiority

    Secondary: Duration of response (DoR)

    		 Close Top of page
    End point title
    		 Duration of response (DoR)
    End point description
    Duration of response was defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy. Here arbitrary number 999.999 reflects that upper limit is not calculable at this data cut-off.
    End point type
    Secondary
    End point timeframe
    At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression
    End point values
    		 Osimertinib 80 mg (Global Cohort) SoC EGFR-TKI (Global Cohort) Osimertinib 80 mg (China Cohort) SoC EGFR-TKI (China Cohort)
    Number of subjects analysed
    279
    277
    71
    65
    Units: Months
        median (confidence interval 95%)
    17.2 (13.8 to 22.0)
    8.5 (7.3 to 9.8)
    16.4 (12.3 to 999.999)
    10.9 (8.3 to 13.8)
    Statistical analysis title
    		 Osimertinib 80 mg vs SoC EGFR-TKI (China Cohort)
    Comparison groups
    Osimertinib 80 mg (China Cohort) v SoC EGFR-TKI (China Cohort)
    Number of subjects included in analysis
    136
    Analysis specification
    Pre-specified
    Analysis type
    		 [4]
    P-value
    		 = 0.0133
    Method
    		 Log Normal Distribution
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.21
         upper limit
    		 5.09
    Notes
    [4] - The china cohort was not powered for superiority
    Statistical analysis title
    		 Osimertinib 80 mg vs SoC EGFR-TKI (Global Cohort)
    Comparison groups
    Osimertinib 80 mg (Global Cohort) v SoC EGFR-TKI (Global Cohort)
    Number of subjects included in analysis
    556
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Log Normal Distribution
    Parameter type
    		 Mean difference (final values)
    Point estimate
    2.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.68
         upper limit
    		 3.08

    Secondary: Disease control rate (DCR)

    		 Close Top of page
    End point title
    		 Disease control rate (DCR)
    End point description
    The DCR was defined as the percentage of subjects who had a best overall response (BOR) of Complete response (CR), Partial response (PR) or Stable disease (SD) ≥6 weeks prior to any Progressive disease (PD) event and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy. DCR was based on Investigator assessment according to RECIST v1.1.
    End point type
    Secondary
    End point timeframe
    At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression
    End point values
    		 Osimertinib 80 mg (Global Cohort) SoC EGFR-TKI (Global Cohort) Osimertinib 80 mg (China Cohort) SoC EGFR-TKI (China Cohort)
    Number of subjects analysed
    279
    277
    71
    65
    Units: Percentage of Subjects
        number (confidence interval 95%)
    97.1 (94.4 to 98.8)
    92.4 (88.6 to 95.2)
    97.2 (90.2 to 99.7)
    95.4 (87.1 to 99.0)
    Statistical analysis title
    		 Osimertinib 80 mg vs SoC EGFR-TKI (Global Cohort)
    Comparison groups
    Osimertinib 80 mg (Global Cohort) v SoC EGFR-TKI (Global Cohort)
    Number of subjects included in analysis
    556
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.011
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.25
         upper limit
    		 6.78
    Statistical analysis title
    		 Osimertinib 80 mg vs SoC EGFR-TKI (China Cohort)
    Comparison groups
    Osimertinib 80 mg (China Cohort) v SoC EGFR-TKI (China Cohort)
    Number of subjects included in analysis
    136
    Analysis specification
    Pre-specified
    Analysis type
    		 [5]
    P-value
    		 = 0.5772
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.27
         upper limit
    		 12.98
    Notes
    [5] - The china cohort was not powered for superiority

    Secondary: Depth of response

    		 Close Top of page
    End point title
    		 Depth of response
    End point description
    The Depth of response was defined as the relative change in the sum of the longest diameters of Response Evaluation Criteria in Solid Tumors (RECIST) Target lesions (TLs) at the nadir, in the absence of new lesions (NLs) or progression of Non-target lesions (NTLs), compared to baseline and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy
    End point type
    Secondary
    End point timeframe
    At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression
    End point values
    		 Osimertinib 80 mg (Global Cohort) SoC EGFR-TKI (Global Cohort) Osimertinib 80 mg (China Cohort) SoC EGFR-TKI (China Cohort)
    Number of subjects analysed
    279
    277
    71
    65
    Units: Percentage of Change
        arithmetic mean (standard deviation)
    -52.36 ( 25.065 )
    -45.66 ( 28.270 )
    -49.17 ( 24.303 )
    -42.92 ( 26.814 )
    Statistical analysis title
    		 Osimertinib 80 mg vs SoC EGFR-TKI (China Cohort)
    Comparison groups
    Osimertinib 80 mg (China Cohort) v SoC EGFR-TKI (China Cohort)
    Number of subjects included in analysis
    136
    Analysis specification
    Pre-specified
    Analysis type
    		 [6]
    P-value
    		 = 0.1348
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -6.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.246
         upper limit
    		 2.072
    Notes
    [6] - The china cohort was not powered for superiority
    Statistical analysis title
    		 Osimertinib 80 mg vs SoC EGFR-TKI (Global Cohort)
    Comparison groups
    Osimertinib 80 mg (Global Cohort) v SoC EGFR-TKI (Global Cohort)
    Number of subjects included in analysis
    556
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0025
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -6.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.205
         upper limit
    		 -2.403

    Secondary: Overall Survival (OS)- Number of Subjects with an Event

    		 Close Top of page
    End point title
    		 Overall Survival (OS)- Number of Subjects with an Event
    End point description
    Overall survival was defined as the time from the date of randomisation until death from any cause and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy
    End point type
    Secondary
    End point timeframe
    From first dose to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks (approximately 29 months)
    End point values
    		 Osimertinib 80 mg (Global Cohort) SoC EGFR-TKI (Global Cohort) Osimertinib 80 mg (China Cohort) SoC EGFR-TKI (China Cohort)
    Number of subjects analysed
    279
    277
    71
    65
    Units: Subjects
        Death
    155
    166
    45
    44
        Still in survival follow-up
    104
    86
    25
    17
        Terminated prior to death
    20
    25
    1
    4
    Statistical analysis title
    		 Osimertinib 80 mg vs SoC EGFR-TKI (China Cohort)
    Comparison groups
    Osimertinib 80 mg (China Cohort) v SoC EGFR-TKI (China Cohort)
    Number of subjects included in analysis
    136
    Analysis specification
    Pre-specified
    Analysis type
    		 [7]
    P-value
    		 = 0.4416
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.848
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5568
         upper limit
    		 1.291
    Notes
    [7] - The china cohort was not powered for superiority
    Statistical analysis title
    		 Osimertinib 80 mg vs SoC EGFR-TKI (Global Cohort)
    Comparison groups
    Osimertinib 80 mg (Global Cohort) v SoC EGFR-TKI (Global Cohort)
    Number of subjects included in analysis
    556
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0462
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.799
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6409
         upper limit
    		 0.9963

    Secondary: Plasma concentrations of AZD9291

    		 Close Top of page
    End point title
    		 Plasma concentrations of AZD9291 [8]
    End point description
    To characterise the pharmacokinetics (PK) of osimertinib. Here arbitrary number "9999.9999" reflects that the values were non-quantifiable and not calculable.
    End point type
    Secondary
    End point timeframe
    Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)
    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: No statistical analyses have been performed
    End point values
    		 Osimertinib 80 mg (Global Cohort) Osimertinib 80 mg (China Cohort)
    Number of subjects analysed
    279
    71
    Units: Nano moles
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1-Predose
    9999.9999 ( 9999.9999 )
    9999.9999 ( 9999.9999 )
        Cycle 1 Day 1-0.5 - 2 hours
    4.9487 ( 1173.3679 )
    5.0249 ( 816.7305 )
        Cycle 1 Day 1-3 - 5 hours
    129.3340 ( 171.2983 )
    131.5669 ( 120.5979 )
        Cycle 3 Day 1- Predose
    394.3489 ( 43.9296 )
    441.5606 ( 55.0039 )
        Cycle 3 Day 1, 0.5 - 2 hours
    397.7406 ( 45.8548 )
    441.7343 ( 60.0626 )
        Cycle 3 Day 1, 3 - 5 hours
    512.4012 ( 44.0653 )
    553.8090 ( 60.9883 )
        Cycle 5 Day 1, Predose
    358.5487 ( 53.8212 )
    419.5893 ( 63.2507 )
        Cycle 5 Day 1, 0.5 - 2 hours
    369.0696 ( 51.3284 )
    426.8197 ( 60.3841 )
        Cycle 5 Day 1, 3-5 hours
    485.8142 ( 47.2759 )
    570.7729 ( 61.4401 )
        Cycle 7 Day 1-Predose
    347.6176 ( 47.7442 )
    397.5857 ( 54.9006 )
        Cycle 7 Day 1-0.5 - 2 hours
    357.8529 ( 45.0713 )
    411.6170 ( 49.4107 )
        Cycle 7 Day 1-3-5 hours
    475.6587 ( 41.5778 )
    530.7212 ( 56.5184 )
        Cycle 9 Day 1-Predose
    359.5284 ( 47.0592 )
    383.2238 ( 67.7153 )
        Cycle 9 Day 1-0.5-2 hours
    363.0106 ( 48.3837 )
    395.2179 ( 71.5532 )
        Cycle 9 Day 1-3-5 hours
    485.6006 ( 46.6459 )
    490.5964 ( 70.3383 )
        Cycle 11 Day 1-Predose
    354.5330 ( 44.4308 )
    410.4023 ( 66.2329 )
        Cycle 11 Day 1-0.5 -2 hours
    367.7450 ( 45.2003 )
    415.2427 ( 64.6174 )
        Cycle 11 Day 1-3-5 hours
    476.4472 ( 44.4457 )
    528.8081 ( 68.4645 )
        Cycle 13 Day 1-Predose
    369.9834 ( 40.1071 )
    404.2678 ( 62.0291 )
        Cycle 13 Day 1-0.5 -2 hours
    371.4157 ( 42.9794 )
    393.1688 ( 62.1053 )
        Cycle 13 Day 1-3-5 hours
    496.6866 ( 40.8757 )
    499.0220 ( 62.5485 )
    No statistical analyses for this end point

    Secondary: Plasma concentrations of metabolites AZ5104

    		 Close Top of page
    End point title
    		 Plasma concentrations of metabolites AZ5104 [9]
    End point description
    To characterise the pharmacokinetics (PK) of osimertinib metabolite AZ5104. Here arbitrary number "9999.9999" reflects that the values were non-quantifiable and not calculable.
    End point type
    Secondary
    End point timeframe
    Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)
    Notes
    [9] - 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: No statistical analyses have been performed
    End point values
    		 Osimertinib 80 mg (Global Cohort) Osimertinib 80 mg (China Cohort)
    Number of subjects analysed
    279
    71
    Units: Nano moles
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1 Predose
    9999.9999 ( 9999.9999 )
    9999.9999 ( 9999.9999 )
        Cycle 1 Day 1-0.5 - 2 hours
    0.1542 ( 230.5161 )
    9999.9999 ( 9999.9999 )
        Cycle 1 Day 1-3 - 5 hours
    3.9399 ( 153.7651 )
    6.3053 ( 123.9308 )
        Cycle 3 Day 1-Predose
    42.9123 ( 50.2410 )
    56.8319 ( 51.0378 )
        Cycle 3 Day 1, 0.5 - 2 hours
    42.7434 ( 52.8557 )
    55.9947 ( 59.1318 )
        Cycle 3 Day 1, 3 - 5 hours
    48.3547 ( 50.4286 )
    64.0621 ( 54.2058 )
        Cycle 5 Day 1, Predose
    39.3718 ( 56.6226 )
    56.0330 ( 57.5022 )
        Cycle 5 Day 1, 0.5 - 2 hours
    39.4145 ( 55.3468 )
    55.3767 ( 55.9096 )
        Cycle 5 Day 1, 3-5 hours
    45.6842 ( 54.3876 )
    63.9216 ( 56.4249 )
        Cycle 7 Day 1- Predose
    38.3847 ( 50.0861 )
    52.5786 ( 51.0588 )
        Cycle 7 Day 1, 0.5-2 hours
    38.5301 ( 49.6296 )
    52.7638 ( 47.4797 )
        Cycle 7 Day 1, 3-5 hours
    44.4670 ( 48.4730 )
    60.6201 ( 50.6931 )
        Cycle 9 Day 1, Predose
    40.1230 ( 47.0682 )
    54.4349 ( 51.3447 )
        Cycle 9 Day 1, 0.5-2 hours
    40.4987 ( 47.6483 )
    54.7158 ( 54.6783 )
        Cycle 9 Day 1, 3-5 hours
    46.0310 ( 44.6875 )
    60.4649 ( 52.6147 )
        Cycle 11 Day 1, Predose
    38.3859 ( 48.5351 )
    56.4782 ( 59.1303 )
        Cycle 11 Day 1, 0.5-2 hours
    38.7620 ( 48.1414 )
    57.4095 ( 57.0891 )
        Cycle 11 Day 1, 3-5 hours
    43.9135 ( 50.6779 )
    65.1943 ( 58.5043 )
        Cycle 13 Day 1, Predose
    40.4356 ( 47.2671 )
    55.1162 ( 54.3493 )
        Cycle 13 Day 1, 0.5- 2 hours
    40.1116 ( 46.3929 )
    54.3858 ( 49.9148 )
        Cycle 13 Day 1, 3-5 hours
    45.9083 ( 44.8309 )
    61.7426 ( 51.2924 )
    No statistical analyses for this end point

    Secondary: Plasma concentrations of metabolite AZ7550

    		 Close Top of page
    End point title
    		 Plasma concentrations of metabolite AZ7550 [10]
    End point description
    To characterise the pharmacokinetics (PK) of osimertinib metabolite AZ7550. Here arbitrary number "9999.9999" reflects that the values were non-quantifiable and not calculable.
    End point type
    Secondary
    End point timeframe
    Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)
    Notes
    [10] - 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: No statistical analyses have been performed
    End point values
    		 Osimertinib 80 mg (Global Cohort) Osimertinib 80 mg (China Cohort)
    Number of subjects analysed
    279
    71
    Units: Nano moles
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1, Predose
    9999.9999 ( 9999.9999 )
    9999.9999 ( 9999.9999 )
        Cycle 1 Day 1, 0.5 - 2 hours
    0.1437 ( 168.2087 )
    9999.9999 ( 9999.9999 )
        Cycle 1 Day 1, 3 - 5 hours
    1.8610 ( 147.4624 )
    2.1876 ( 123.6012 )
        Cycle 3 Day 1, Predose
    46.1286 ( 45.1082 )
    55.9958 ( 50.5705 )
        Cycle 3 Day 1, 0.5 - 2 hours
    46.0045 ( 45.9584 )
    55.6754 ( 53.0925 )
        Cycle 3 Day 1, 3 - 5 hours
    51.7182 ( 45.3240 )
    62.3493 ( 53.5513 )
        Cycle 5 Day 1, Predose
    44.4537 ( 54.9882 )
    53.0434 ( 52.2936 )
        Cycle 5 Day 1, 0.5 - 2 hours
    45.2186 ( 51.6418 )
    53.1901 ( 51.5506 )
        Cycle 5 Day 1, 3-5 hours
    51.4018 ( 51.3627 )
    62.5218 ( 51.0627 )
        Cycle 7 Day 1, Predose
    46.2912 ( 49.8713 )
    53.4167 ( 50.8399 )
        Cycle 7 Day 1, 0.5-2 hours
    46.3540 ( 49.0845 )
    54.3942 ( 46.1253 )
        Cycle 7 Day 1,3-5 hours
    52.3533 ( 47.6489 )
    61.9004 ( 51.6117 )
        Cycle 9 Day 1, Predose
    49.6058 ( 45.5050 )
    54.8207 ( 50.2534 )
        Cycle 9 Day 1, 0.5-2 hours
    49.9381 ( 46.4568 )
    55.2437 ( 52.5736 )
        Cycle 9 Day 1, 3-5 hours
    56.5354 ( 45.6736 )
    60.8933 ( 50.3474 )
        Cycle 11 Day 1, Predose
    50.9710 ( 46.8840 )
    56.4643 ( 51.2351 )
        Cycle 11 Day 1, 0.5- 2 hours
    51.9773 ( 45.3186 )
    57.4778 ( 47.3639 )
        Cycle 11 Day 1, 3- 5 hours
    57.6986 ( 48.2382 )
    65.3053 ( 49.6916 )
        Cycle 13 Day 1, Predose
    54.5238 ( 43.8481 )
    56.0666 ( 51.2464 )
        Cycle 13 Day 1, 0.5-2 hours
    54.1224 ( 43.7869 )
    56.8750 ( 47.4338 )
        Cycle 13 Day 1, 3-5 hours
    61.6053 ( 42.2947 )
    63.3365 ( 46.3082 )
    No statistical analyses for this end point

    Secondary: Subjects Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 items (CTSQ-16 Questionnaire)

    		 Close Top of page
    End point title
    		 Subjects Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 items (CTSQ-16 Questionnaire)
    End point description
    The CTSQ-16 was a 16-item questionnaire measuring 3 domains related to subject's satisfaction with cancer therapy: Expectations of therapy, Feelings about side effects, and Satisfaction with therapy. Scores ranged from 0 to 100 for each domain, with a higher score associated with the best outcome on each domain. The results of the analyses were presented in terms of mean together with standard deviation.
    End point type
    Secondary
    End point timeframe
    Questionnaire completed in cycle 2 and 3, prior to Week 6 scan (approximately 2 months)
    End point values
    		 Osimertinib 80 mg (Global Cohort) SoC EGFR-TKI (Global Cohort) Osimertinib 80 mg (China Cohort) SoC EGFR-TKI (China Cohort)
    Number of subjects analysed
    279
    277
    71
    65
    Units: Unit on scale
    arithmetic mean (standard deviation)
        Expectations with Therapy, Week 3
    74.1 ( 22.42 )
    70.3 ( 21.85 )
    77.1 ( 20.60 )
    79.2 ( 18.58 )
        Expectations with Therapy, Week 6
    76.3 ( 20.58 )
    74.0 ( 19.46 )
    82.2 ( 17.88 )
    82.6 ( 17.95 )
        Feelings about Side-Effects, Week 3
    74.5 ( 17.22 )
    69.1 ( 20.96 )
    73.3 ( 19.89 )
    72.5 ( 17.46 )
        Feelings about Side-Effects, Week 6
    74.6 ( 19.83 )
    69.9 ( 20.73 )
    69.0 ( 24.46 )
    69.7 ( 20.99 )
        Satisfaction with Therapy, Week 3
    84.4 ( 12.88 )
    82.6 ( 13.60 )
    87.2 ( 12.14 )
    86.6 ( 11.07 )
        Satisfaction with Therapy, Week 6
    84.2 ( 13.94 )
    84.6 ( 12.38 )
    87.4 ( 13.29 )
    87.2 ( 12.06 )
    No statistical analyses for this end point

    Secondary: Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13)

    		 Close Top of page
    End point title
    		 Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13)
    End point description
    The EORTC QLQ-LC13 was a lung-cancer-specific module comprising 13 questions to assess lung cancer symptoms (cough, haemoptysis, dyspnoea, and site-specific pain); treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia); and pain medication. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items. Higher scores on the global health status/QoL and functioning scales indicated better health status/QoL and function. Higher scores on the symptoms scales indicated greater symptom burden. The analysis was performed using a Mixed-effects model for repeated measures analysis on the change from baseline in PRO symptom score at each visit up to 9 months (281 days), including subjects, treatment, visit and treatment by visit interaction as explanatory variables, the baseline PRO score as a covariate along with the baseline PRO score by visit interaction, using an unstructured covariance structure.
    End point type
    Secondary
    End point timeframe
    Questionnaires completed at baseline, first 9 months, and at week 1, 2, 3, 4, 5, 6, 12, 18, 24, 30 and 36
    End point values
    		 Osimertinib 80 mg (Global Cohort) SoC EGFR-TKI (Global Cohort) Osimertinib 80 mg (China Cohort) SoC EGFR-TKI (China Cohort)
    Number of subjects analysed
    279
    277
    71
    65
    Units: Unit on scale
    least squares mean (confidence interval 95%)
        Dyspnoea, First 9 months
    -4.04 (-5.63 to -2.45)
    -4.14 (-5.73 to -2.54)
    -4.87 (-7.81 to -1.92)
    -4.82 (-8.01 to -1.63)
        Dyspnoea, week 1
    -3.46 (-5.12 to -1.81)
    -3.60 (-5.24 to -1.96)
    -1.61 (-5.03 to 1.81)
    0.68 (-3.03 to 4.39)
        Dyspnoea, week 2
    -3.94 (-5.87 to -2.00)
    -3.64 (-5.57 to -1.70)
    -2.27 (-6.01 to 1.48)
    -5.03 (-9.08 to -0.98)
        Dyspnoea, week 3
    -3.99 (-5.85 to -2.12)
    -3.27 (-5.14 to -1.41)
    -3.09 (-6.96 to 0.77)
    -5.55 (-9.69 to -1.42)
        Dyspnoea, week 4
    -4.81 (-6.59 to -3.02)
    -4.11 (-5.88 to -2.34)
    -5.35 (-8.72 to -1.99)
    -5.55 (-9.20 to -1.89)
        Dyspnoea, week 5
    -3.51 (-5.53 to -1.50)
    -5.19 (-7.22 to -3.17)
    -5.72 (-10.06 to -1.39)
    -5.76 (-10.32 to -1.20)
        Dyspnoea, week 6
    -4.51 (-6.47 to -2.56)
    -4.45 (-6.42 to -2.48)
    -4.83 (-8.53 to -1.12)
    -6.37 (-10.40 to -2.33)
        Dyspnoea, week 12
    -3.83 (-5.99 to -1.68)
    -5.75 (-7.96 to -3.54)
    -5.38 (-9.41 to -1.35)
    -6.67 (-11.04 to -2.30)
        Dyspnoea, week 18
    -4.97 (-7.18 to -2.76)
    -5.21 (-7.46 to -2.95)
    -7.67 (-11.54 to -3.79)
    -7.48 (-11.66 to -3.30)
        Dyspnoea, week 24
    -4.65 (-7.06 to -2.25)
    -4.56 (-7.02 to -2.09)
    -7.59 (-11.84 to -3.34)
    -5.67 (-10.27 to -1.08)
        Dyspnoea, week 30
    -3.89 (-6.34 to -1.45)
    -3.68 (-6.22 to -1.15)
    -5.81 (-10.59 to -1.02)
    -3.46 (-8.58 to 1.65)
        Dyspnoea, week 36
    -2.88 (-5.52 to -0.24)
    -2.04 (-4.83 to 0.75)
    -4.21 (-8.91 to 0.48)
    -2.18 (-7.28 to 2.93)
        Cough, First 9 months
    -10.97 (-12.77 to -9.17)
    -11.65 (-13.47 to -9.84)
    -13.75 (-17.17 to -10.33)
    -8.49 (-12.19 to -4.79)
        Cough, week 1
    -6.90 (-9.30 to -4.51)
    -4.83 (-7.20 to -2.46)
    -4.60 (-9.00 to -0.20)
    -3.69 (-8.46 to 1.07)
        Cough, week 2
    -9.04 (-11.58 to -6.49)
    -9.52 (-12.05 to -6.98)
    -12.26 (-17.15 to -7.37)
    -3.73 (-9.01 to 1.54)
        Cough, week 3
    -9.78 (-12.37 to -7.20)
    -10.24 (-12.82 to -7.65)
    -11.95 (-16.66 to -7.24)
    -5.56 (-10.57 to -0.54)
        Cough, week 4
    -11.25 (-13.87 to -8.63)
    -13.36 (-15.96 to -10.76)
    -12.78 (-17.80 to -7.77)
    -10.32 (-15.75 to -4.90)
        Cough, week 5
    -12.98 (-15.64 to -10.31)
    -13.55 (-16.21 to -10.88)
    -17.74 (-23.11 to -12.38)
    -9.20 (-14.84 to -3.55)
        Cough, week 6
    -11.88 (-14.56 to -9.19)
    -11.92 (-14.63 to -9.21)
    -16.92 (-22.36 to -11.48)
    -10.58 (-16.52 to -4.64)
        Cough, week 12
    -13.36 (-15.95 to -10.78)
    -13.57 (-16.24 to -10.90)
    -15.51 (-21.39 to -9.64)
    -8.04 (-14.41 to -1.67)
        Cough, week 18
    -12.31 (-15.25 to -9.37)
    -11.00 (-14.03 to -7.98)
    -11.79 (-17.19 to -6.40)
    -9.44 (-15.23 to -3.65)
        Cough, week 24
    -11.34 (-14.24 to -8.43)
    -13.16 (-16.17 to -10.14)
    -17.61 (-22.84 to -12.39)
    -14.92 (-20.56 to -9.29)
        Cough, week 30
    -10.34 (-13.21 to -7.46)
    -12.43 (-15.44 to -9.41)
    -15.45 (-21.46 to -9.45)
    -9.35 (-15.75 to -2.94)
        Cough, week 36
    -11.49 (-14.48 to -8.49)
    -14.62 (-17.85 to -11.39)
    -14.62 (-20.65 to -8.58)
    -8.55 (-15.14 to -1.96)
        Pain in Chest, First 9 months
    -6.62 (-8.24 to -5.01)
    -6.41 (-8.04 to -4.78)
    -2.79 (-5.84 to 0.26)
    -4.74 (-8.05 to -1.44)
        Pain in Chest, week 1
    -1.93 (-4.19 to 0.32)
    -4.26 (-6.50 to -2.03)
    -1.79 (-5.98 to 2.40)
    -4.16 (-8.71 to 0.38)
        Pain in Chest, week 2
    -5.94 (-8.13 to -3.74)
    -6.32 (-8.51 to -4.13)
    -4.76 (-8.63 to -0.89)
    -3.00 (-7.18 to 1.17)
        Pain in Chest, week 3
    -7.17 (-9.31 to -5.04)
    -5.36 (-7.49 to -3.23)
    -0.76 (-4.90 to 3.39)
    -4.77 (-9.18 to -0.36)
        Pain in Chest, week 4
    -7.45 (-9.60 to -5.29)
    -6.40 (-8.54 to -4.26)
    -2.13 (-6.32 to 2.07)
    -4.22 (-8.78 to 0.34)
        Pain in Chest, week 5
    -7.33 (-9.54 to -5.11)
    -6.98 (-9.20 to -4.76)
    -0.62 (-4.67 to 3.42)
    -6.82 (-11.05 to -2.60)
        Pain in Chest, week 6
    -4.99 (-7.30 to -2.68)
    -7.08 (-9.41 to -4.75)
    0.94 (-3.40 to 5.29)
    -6.26 (-11.00 to -1.52)
        Pain in Chest, week 12
    -7.28 (-9.56 to -5.01)
    -6.70 (-9.05 to -4.35)
    -3.71 (-8.77 to 1.35)
    -5.13 (-10.62 to 0.36)
        Pain in Chest, week 18
    -6.79 (-9.22 to -4.36)
    -7.90 (-10.40 to -5.41)
    -4.40 (-9.05 to 0.26)
    -7.24 (-12.23 to -2.25)
        Pain in Chest, week 24
    -7.72 (-10.26 to -5.18)
    -7.34 (-9.95 to -4.72)
    -5.66 (-10.48 to -0.84)
    -3.15 (-8.36 to 2.07)
        Pain in Chest, week 30
    -8.33 (-10.80 to -5.87)
    -6.60 (-9.18 to -4.02)
    -4.25 (-9.62 to 1.12)
    -4.02 (-9.76 to 1.72)
        Pain in Chest, week 36
    -7.94 (-10.59 to -5.30)
    -5.58 (-8.43 to -2.73)
    -3.56 (-9.42 to 2.30)
    -3.40 (-9.80 to 3.00)
    No statistical analyses for this end point

    Secondary: Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items (EORTC QLQ-C30)

    		 Close Top of page
    End point title
    		 Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items (EORTC QLQ-C30)
    End point description
    The EORTC QLQ-C30 cancer-specific questionnaire consisted of 30 questions, combined to produce 5 functional scales, 3 symptom scales, 6 individual items, and a global measure of health status/QoL. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, the functional scales, and the global health status/QoL scale in the EORTC QLQ-C30. Higher scores on the global health status and functioning scales indicated better health status/function. Higher scores on the symptoms scales indicated greater symptom burden. The analysis was performed using a Mixed-effects model for repeated measures analysis on the change from baseline in PRO symptom score at each visit up to 9 months (281 days), including subjects, treatment, visit and treatment by visit interaction as explanatory variables, the baseline PRO score as a covariate along with the baseline PRO score by visit interaction, using an unstructured covariance structure.
    End point type
    Secondary
    End point timeframe
    Questionnaires completed at baseline, first 9 months, and at week 6, 12, 18, 24, 30, and 36.
    End point values
    		 Osimertinib 80 mg (Global Cohort) SoC EGFR-TKI (Global Cohort) Osimertinib 80 mg (China Cohort) SoC EGFR-TKI (China Cohort)
    Number of subjects analysed
    279
    277
    71
    65
    Units: Unit on scale
    least squares mean (confidence interval 95%)
        Fatigue, First 9 months
    -5.48 (-7.45 to -3.52)
    -4.72 (-6.74 to -2.69)
    -5.65 (-9.33 to -1.98)
    -5.79 (-9.58 to -2.00)
        Fatigue, week 6
    -4.13 (-6.35 to -1.91)
    -5.78 (-8.02 to -3.54)
    -1.73 (-6.05 to 2.58)
    -6.81 (-11.30 to -2.33)
        Fatigue, week 12
    -5.11 (-7.31 to -2.91)
    -6.52 (-8.81 to -4.23)
    -5.40 (-9.51 to -1.29)
    -6.36 (-10.61 to -2.12)
        Fatigue, week 18
    -6.83 (-9.21 to -4.44)
    -5.77 (-8.23 to -3.31)
    -6.64 (-11.26 to -2.03)
    -7.90 (-12.61 to -3.19)
        Fatigue, week 24
    -6.18 (-8.75 to -3.61)
    -4.96 (-7.63 to -2.28)
    -8.92 (-13.30 to -4.54)
    -3.87 (-8.32 to 0.58)
        Fatigue, week 30
    -5.19 (-7.94 to -2.43)
    -3.26 (-6.16 to -0.35)
    -4.43 (-9.53 to 0.68)
    -6.31 (-11.53 to -1.10)
        Fatigue, week 36
    -5.47 (-8.31 to -2.63)
    -2.00 (-2.00 to 1.04)
    -6.78 (-12.38 to -1.19)
    -3.46 (-9.28 to 2.36)
        Appetite Loss, First 9 months
    -6.15 (-8.39 to -3.90)
    -5.64 (-7.96 to -3.32)
    1.18 (-2.78 to 5.14)
    -1.73 (-5.80 to 2.34)
        Appetite Loss, week 6
    -4.54 (-7.36 to -1.72)
    -5.67 (-8.52 to -2.83)
    3.20 (-1.60 to 8.01)
    -6.27 (-11.26 to -1.27)
        Appetite Loss, week 12
    -6.52 (-9.43 to -3.62)
    -6.95 (-9.98 to -3.91)
    1.58 (-3.23 to 6.39)
    -1.44 (-6.41 to 3.53)
        Appetite Loss, week 18
    -7.27 (-10.09 to -4.45)
    -6.84 (-9.75 to -3.92)
    1.42 (-4.38 to 7.22)
    -4.43 (-10.35 to 1.48)
        Appetite Loss, week 24
    -7.14 (-10.27 to -4.01)
    -5.08 (-8.35 to -1.81)
    -2.26 (-7.74 to 3.22)
    0.24 (-5.29 to 5.78)
        Appetite Loss, week 30
    -4.50 (-7.74 to -1.26)
    -4.17 (-7.60 to -0.74)
    2.19 (-3.28 to 7.65)
    -1.83 (-7.36 to 3.70)
        Appetite Loss, week 36
    -6.90 (-10.00 to -3.81)
    -5.15 (-8.49 to -1.81)
    0.98 (-5.28 to 7.24)
    3.36 (-3.15 to 9.86)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All adverse events (AEs) were collected from the time of signature of informed consent throughout the Treatment Period and including the safety follow-up period.The safety follow-up period was defined as 28 days after study drug was discontinued.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Osimertinib 80 mg (Global Cohort)
    Reporting group description
    		 Randomized participants received Osimertinib 80 mg orally once daily (QD)

    Reporting group title
    SoC EGFR-TKI (China Cohort)
    Reporting group description
    		 Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.

    Reporting group title
    SoC EGFR-TKI (Global Cohort)
    Reporting group description
    		 Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.

    Reporting group title
    Osimertinib 80 mg (China Cohort)
    Reporting group description
    		 Randomized participants received Osimertinib 80 mg orally once daily (QD)

    Serious adverse events
    		 Osimertinib 80 mg (Global Cohort) SoC EGFR-TKI (China Cohort) SoC EGFR-TKI (Global Cohort) Osimertinib 80 mg (China Cohort)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    74 / 279 (26.52%)
    12 / 65 (18.46%)
    76 / 277 (27.44%)
    25 / 71 (35.21%)
         number of deaths (all causes)
    155
    44
    166
    45
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Endometrial adenocarcinoma
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Histiocytic necrotising lymphadenitis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian fibroma
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Desmoid tumour
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Circulatory collapse
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Aortic dissection
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Condition aggravated
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 65 (0.00%)
    2 / 277 (0.72%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug withdrawal syndrome
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    General physical health deterioration
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 279 (1.08%)
    0 / 65 (0.00%)
    2 / 277 (0.72%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Uterine polyp
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 65 (0.00%)
    2 / 277 (0.72%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 65 (1.54%)
    4 / 277 (1.44%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    4 / 279 (1.43%)
    1 / 65 (1.54%)
    3 / 277 (1.08%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    4 / 4
    1 / 1
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    4 / 279 (1.43%)
    1 / 65 (1.54%)
    3 / 277 (1.08%)
    3 / 71 (4.23%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 65 (0.00%)
    2 / 277 (0.72%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    4 / 279 (1.43%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pulmonary haemorrhage
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    2 / 277 (0.72%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Tonsillolith
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Acute psychosis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Investigations
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 279 (0.36%)
    1 / 65 (1.54%)
    2 / 277 (0.72%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    1 / 279 (0.36%)
    1 / 65 (1.54%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    2 / 277 (0.72%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural pneumothorax
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound complication
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Poisoning
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bundle branch block left
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Myocardial infarction
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Tachyarrhythmia
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Nervous system disorders
    Brain oedema
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral motor neuropathy
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 65 (1.54%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral ventricle dilatation
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 65 (1.54%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood disorder
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 65 (1.54%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    3 / 279 (1.08%)
    0 / 65 (0.00%)
    4 / 277 (1.44%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    3 / 4
    0 / 0
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Enterocolitis
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mouth ulceration
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    2 / 277 (0.72%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    5 / 277 (1.81%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    4 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Duodenal ulcer
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 65 (1.54%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Drug-induced liver injury
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    3 / 277 (1.08%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 65 (1.54%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis acneiform
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    2 / 277 (0.72%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxic epidermal necrolysis
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erythema nodosum
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 279 (0.36%)
    1 / 65 (1.54%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 65 (1.54%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridial infection
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    2 / 277 (0.72%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Enteritis infectious
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection viral
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perineal abscess
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngotonsillitis
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural infection
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    9 / 279 (3.23%)
    1 / 65 (1.54%)
    7 / 277 (2.53%)
    3 / 71 (4.23%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 1
    1 / 7
    1 / 3
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Salmonella bacteraemia
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 279 (1.08%)
    0 / 65 (0.00%)
    3 / 277 (1.08%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenoviral upper respiratory infection
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 65 (1.54%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis C
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia pseudomonal
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus bronchitis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 65 (0.00%)
    2 / 277 (0.72%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    4 / 279 (1.43%)
    0 / 65 (0.00%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperuricaemia
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour lysis syndrome
         subjects affected / exposed
    0 / 279 (0.00%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    1 / 71 (1.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 65 (0.00%)
    0 / 277 (0.00%)
    0 / 71 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Osimertinib 80 mg (Global Cohort) SoC EGFR-TKI (China Cohort) SoC EGFR-TKI (Global Cohort) Osimertinib 80 mg (China Cohort)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    273 / 279 (97.85%)
    64 / 65 (98.46%)
    269 / 277 (97.11%)
    69 / 71 (97.18%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
         subjects affected / exposed
    14 / 279 (5.02%)
    0 / 65 (0.00%)
    7 / 277 (2.53%)
    0 / 71 (0.00%)
         occurrences all number
    18
    0
    7
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    15 / 279 (5.38%)
    5 / 65 (7.69%)
    10 / 277 (3.61%)
    4 / 71 (5.63%)
         occurrences all number
    18
    5
    12
    5
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    45 / 279 (16.13%)
    6 / 65 (9.23%)
    34 / 277 (12.27%)
    7 / 71 (9.86%)
         occurrences all number
    53
    8
    41
    9
    Pyrexia
         subjects affected / exposed
    29 / 279 (10.39%)
    3 / 65 (4.62%)
    10 / 277 (3.61%)
    2 / 71 (2.82%)
         occurrences all number
    37
    4
    12
    2
    Oedema peripheral
         subjects affected / exposed
    16 / 279 (5.73%)
    0 / 65 (0.00%)
    24 / 277 (8.66%)
    3 / 71 (4.23%)
         occurrences all number
    19
    0
    27
    4
    Asthenia
         subjects affected / exposed
    25 / 279 (8.96%)
    3 / 65 (4.62%)
    9 / 277 (3.25%)
    5 / 71 (7.04%)
         occurrences all number
    34
    3
    9
    5
    Chest discomfort
         subjects affected / exposed
    5 / 279 (1.79%)
    8 / 65 (12.31%)
    2 / 277 (0.72%)
    6 / 71 (8.45%)
         occurrences all number
    5
    10
    2
    7
    Non-cardiac chest pain
         subjects affected / exposed
    18 / 279 (6.45%)
    5 / 65 (7.69%)
    17 / 277 (6.14%)
    8 / 71 (11.27%)
         occurrences all number
    18
    5
    17
    12
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    60 / 279 (21.51%)
    11 / 65 (16.92%)
    50 / 277 (18.05%)
    14 / 71 (19.72%)
         occurrences all number
    77
    14
    60
    21
    Dyspnoea
         subjects affected / exposed
    40 / 279 (14.34%)
    5 / 65 (7.69%)
    21 / 277 (7.58%)
    10 / 71 (14.08%)
         occurrences all number
    47
    5
    21
    12
    Epistaxis
         subjects affected / exposed
    21 / 279 (7.53%)
    0 / 65 (0.00%)
    14 / 277 (5.05%)
    3 / 71 (4.23%)
         occurrences all number
    54
    0
    28
    8
    Haemoptysis
         subjects affected / exposed
    7 / 279 (2.51%)
    3 / 65 (4.62%)
    16 / 277 (5.78%)
    3 / 71 (4.23%)
         occurrences all number
    7
    3
    16
    3
    Pleural effusion
         subjects affected / exposed
    0 / 279 (0.00%)
    2 / 65 (3.08%)
    0 / 277 (0.00%)
    6 / 71 (8.45%)
         occurrences all number
    0
    2
    0
    6
    Productive cough
         subjects affected / exposed
    13 / 279 (4.66%)
    2 / 65 (3.08%)
    6 / 277 (2.17%)
    5 / 71 (7.04%)
         occurrences all number
    19
    2
    6
    7
    Oropharyngeal pain
         subjects affected / exposed
    14 / 279 (5.02%)
    1 / 65 (1.54%)
    12 / 277 (4.33%)
    1 / 71 (1.41%)
         occurrences all number
    19
    1
    15
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    31 / 279 (11.11%)
    5 / 65 (7.69%)
    21 / 277 (7.58%)
    6 / 71 (8.45%)
         occurrences all number
    31
    5
    24
    8
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    27 / 279 (9.68%)
    28 / 65 (43.08%)
    68 / 277 (24.55%)
    11 / 71 (15.49%)
         occurrences all number
    32
    38
    82
    15
    Alanine aminotransferase increased
         subjects affected / exposed
    18 / 279 (6.45%)
    29 / 65 (44.62%)
    72 / 277 (25.99%)
    6 / 71 (8.45%)
         occurrences all number
    18
    39
    85
    7
    Electrocardiogram QT prolonged
         subjects affected / exposed
    27 / 279 (9.68%)
    3 / 65 (4.62%)
    12 / 277 (4.33%)
    6 / 71 (8.45%)
         occurrences all number
    46
    4
    15
    11
    Weight decreased
         subjects affected / exposed
    20 / 279 (7.17%)
    8 / 65 (12.31%)
    20 / 277 (7.22%)
    17 / 71 (23.94%)
         occurrences all number
    24
    9
    24
    23
    White blood cell count decreased
         subjects affected / exposed
    27 / 279 (9.68%)
    6 / 65 (9.23%)
    5 / 277 (1.81%)
    29 / 71 (40.85%)
         occurrences all number
    51
    10
    6
    70
    Blood alkaline phosphatase increased
         subjects affected / exposed
    7 / 279 (2.51%)
    4 / 65 (6.15%)
    15 / 277 (5.42%)
    6 / 71 (8.45%)
         occurrences all number
    7
    6
    19
    6
    Platelet count decreased
         subjects affected / exposed
    14 / 279 (5.02%)
    1 / 65 (1.54%)
    3 / 277 (1.08%)
    20 / 71 (28.17%)
         occurrences all number
    18
    2
    4
    31
    Neutrophil count decreased
         subjects affected / exposed
    12 / 279 (4.30%)
    3 / 65 (4.62%)
    2 / 277 (0.72%)
    17 / 71 (23.94%)
         occurrences all number
    29
    4
    2
    35
    Lymphocyte count decreased
         subjects affected / exposed
    9 / 279 (3.23%)
    3 / 65 (4.62%)
    1 / 277 (0.36%)
    11 / 71 (15.49%)
         occurrences all number
    9
    4
    1
    14
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    10 / 279 (3.58%)
    7 / 65 (10.77%)
    2 / 277 (0.72%)
    6 / 71 (8.45%)
         occurrences all number
    11
    10
    2
    7
    Blood bilirubin increased
         subjects affected / exposed
    7 / 279 (2.51%)
    6 / 65 (9.23%)
    13 / 277 (4.69%)
    2 / 71 (2.82%)
         occurrences all number
    13
    9
    18
    3
    Blood albumin decreased
         subjects affected / exposed
    1 / 279 (0.36%)
    3 / 65 (4.62%)
    2 / 277 (0.72%)
    5 / 71 (7.04%)
         occurrences all number
    2
    4
    3
    9
    Blood creatinine increased
         subjects affected / exposed
    11 / 279 (3.94%)
    2 / 65 (3.08%)
    4 / 277 (1.44%)
    5 / 71 (7.04%)
         occurrences all number
    14
    2
    5
    7
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    3 / 279 (1.08%)
    2 / 65 (3.08%)
    3 / 277 (1.08%)
    5 / 71 (7.04%)
         occurrences all number
    3
    3
    4
    5
    Haemoglobin decreased
         subjects affected / exposed
    4 / 279 (1.43%)
    4 / 65 (6.15%)
    2 / 277 (0.72%)
    2 / 71 (2.82%)
         occurrences all number
    4
    4
    2
    2
    Blood uric acid increased
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 65 (1.54%)
    0 / 277 (0.00%)
    4 / 71 (5.63%)
         occurrences all number
    0
    3
    0
    7
    Injury, poisoning and procedural complications
    Injury, poisoning and procedural complications
         subjects affected / exposed
    33 / 279 (11.83%)
    1 / 65 (1.54%)
    29 / 277 (10.47%)
    3 / 71 (4.23%)
         occurrences all number
    43
    1
    33
    3
    Cardiac disorders
    Left ventricular dysfunction
         subjects affected / exposed
    0 / 279 (0.00%)
    5 / 65 (7.69%)
    2 / 277 (0.72%)
    2 / 71 (2.82%)
         occurrences all number
    0
    5
    2
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    39 / 279 (13.98%)
    4 / 65 (6.15%)
    25 / 277 (9.03%)
    7 / 71 (9.86%)
         occurrences all number
    53
    6
    29
    7
    Dysgeusia
         subjects affected / exposed
    18 / 279 (6.45%)
    0 / 65 (0.00%)
    9 / 277 (3.25%)
    0 / 71 (0.00%)
         occurrences all number
    19
    0
    9
    0
    Dizziness
         subjects affected / exposed
    22 / 279 (7.89%)
    4 / 65 (6.15%)
    12 / 277 (4.33%)
    3 / 71 (4.23%)
         occurrences all number
    25
    5
    13
    3
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    44 / 279 (15.77%)
    11 / 65 (16.92%)
    26 / 277 (9.39%)
    27 / 71 (38.03%)
         occurrences all number
    53
    12
    32
    38
    Thrombocytopenia
         subjects affected / exposed
    26 / 279 (9.32%)
    1 / 65 (1.54%)
    0 / 277 (0.00%)
    7 / 71 (9.86%)
         occurrences all number
    37
    1
    0
    11
    Leukopenia
         subjects affected / exposed
    21 / 279 (7.53%)
    2 / 65 (3.08%)
    3 / 277 (1.08%)
    12 / 71 (16.90%)
         occurrences all number
    34
    3
    3
    27
    Neutropenia
         subjects affected / exposed
    21 / 279 (7.53%)
    2 / 65 (3.08%)
    1 / 277 (0.36%)
    12 / 71 (16.90%)
         occurrences all number
    35
    2
    1
    24
    Bone marrow failure
         subjects affected / exposed
    1 / 279 (0.36%)
    4 / 65 (6.15%)
    1 / 277 (0.36%)
    4 / 71 (5.63%)
         occurrences all number
    3
    7
    2
    13
    Ear and labyrinth disorders
    Ear and labyrinth disorders
         subjects affected / exposed
    17 / 279 (6.09%)
    1 / 65 (1.54%)
    14 / 277 (5.05%)
    1 / 71 (1.41%)
         occurrences all number
    22
    1
    16
    1
    Eye disorders
    Dry eye
         subjects affected / exposed
    21 / 279 (7.53%)
    1 / 65 (1.54%)
    21 / 277 (7.58%)
    2 / 71 (2.82%)
         occurrences all number
    50
    2
    42
    4
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    167 / 279 (59.86%)
    19 / 65 (29.23%)
    159 / 277 (57.40%)
    17 / 71 (23.94%)
         occurrences all number
    262
    31
    246
    32
    Stomatitis
         subjects affected / exposed
    82 / 279 (29.39%)
    1 / 65 (1.54%)
    60 / 277 (21.66%)
    1 / 71 (1.41%)
         occurrences all number
    118
    1
    73
    6
    Nausea
         subjects affected / exposed
    55 / 279 (19.71%)
    7 / 65 (10.77%)
    55 / 277 (19.86%)
    10 / 71 (14.08%)
         occurrences all number
    66
    7
    81
    13
    Constipation
         subjects affected / exposed
    51 / 279 (18.28%)
    3 / 65 (4.62%)
    39 / 277 (14.08%)
    4 / 71 (5.63%)
         occurrences all number
    64
    5
    44
    5
    Vomiting
         subjects affected / exposed
    40 / 279 (14.34%)
    5 / 65 (7.69%)
    28 / 277 (10.11%)
    10 / 71 (14.08%)
         occurrences all number
    50
    7
    36
    12
    Dry mouth
         subjects affected / exposed
    12 / 279 (4.30%)
    3 / 65 (4.62%)
    15 / 277 (5.42%)
    0 / 71 (0.00%)
         occurrences all number
    12
    3
    15
    0
    Abdominal pain
         subjects affected / exposed
    12 / 279 (4.30%)
    3 / 65 (4.62%)
    17 / 277 (6.14%)
    2 / 71 (2.82%)
         occurrences all number
    13
    3
    18
    2
    Mouth ulceration
         subjects affected / exposed
    12 / 279 (4.30%)
    7 / 65 (10.77%)
    4 / 277 (1.44%)
    12 / 71 (16.90%)
         occurrences all number
    20
    11
    4
    20
    Toothache
         subjects affected / exposed
    3 / 279 (1.08%)
    4 / 65 (6.15%)
    1 / 277 (0.36%)
    0 / 71 (0.00%)
         occurrences all number
    3
    4
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    16 / 279 (5.73%)
    2 / 65 (3.08%)
    13 / 277 (4.69%)
    0 / 71 (0.00%)
         occurrences all number
    19
    2
    15
    0
    Dyspepsia
         subjects affected / exposed
    8 / 279 (2.87%)
    1 / 65 (1.54%)
    14 / 277 (5.05%)
    0 / 71 (0.00%)
         occurrences all number
    12
    1
    17
    0
    Hepatobiliary disorders
    Hepatic function abnormal
         subjects affected / exposed
    2 / 279 (0.72%)
    5 / 65 (7.69%)
    7 / 277 (2.53%)
    2 / 71 (2.82%)
         occurrences all number
    2
    6
    8
    3
    Drug-induced liver injury
         subjects affected / exposed
    0 / 279 (0.00%)
    6 / 65 (9.23%)
    2 / 277 (0.72%)
    2 / 71 (2.82%)
         occurrences all number
    0
    7
    2
    3
    Skin and subcutaneous tissue disorders
    Dermatitis acneiform
         subjects affected / exposed
    73 / 279 (26.16%)
    9 / 65 (13.85%)
    135 / 277 (48.74%)
    14 / 71 (19.72%)
         occurrences all number
    97
    11
    177
    15
    Dry skin
         subjects affected / exposed
    92 / 279 (32.97%)
    8 / 65 (12.31%)
    92 / 277 (33.21%)
    4 / 71 (5.63%)
         occurrences all number
    104
    8
    100
    4
    Pruritus
         subjects affected / exposed
    50 / 279 (17.92%)
    4 / 65 (6.15%)
    44 / 277 (15.88%)
    5 / 71 (7.04%)
         occurrences all number
    74
    7
    61
    6
    Alopecia
         subjects affected / exposed
    22 / 279 (7.89%)
    5 / 65 (7.69%)
    35 / 277 (12.64%)
    1 / 71 (1.41%)
         occurrences all number
    22
    6
    35
    1
    Skin fissures
         subjects affected / exposed
    18 / 279 (6.45%)
    0 / 65 (0.00%)
    16 / 277 (5.78%)
    3 / 71 (4.23%)
         occurrences all number
    21
    0
    18
    3
    Rash
         subjects affected / exposed
    17 / 279 (6.09%)
    1 / 65 (1.54%)
    14 / 277 (5.05%)
    1 / 71 (1.41%)
         occurrences all number
    19
    1
    20
    1
    Rash macular
         subjects affected / exposed
    15 / 279 (5.38%)
    0 / 65 (0.00%)
    12 / 277 (4.33%)
    0 / 71 (0.00%)
         occurrences all number
    16
    0
    22
    0
    Rash papular
         subjects affected / exposed
    18 / 279 (6.45%)
    3 / 65 (4.62%)
    10 / 277 (3.61%)
    4 / 71 (5.63%)
         occurrences all number
    30
    6
    11
    4
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    4 / 279 (1.43%)
    3 / 65 (4.62%)
    7 / 277 (2.53%)
    5 / 71 (7.04%)
         occurrences all number
    5
    3
    7
    9
    Rash maculo-papular
         subjects affected / exposed
    38 / 279 (13.62%)
    12 / 65 (18.46%)
    46 / 277 (16.61%)
    10 / 71 (14.08%)
         occurrences all number
    52
    14
    63
    10
    Erythema
         subjects affected / exposed
    14 / 279 (5.02%)
    0 / 65 (0.00%)
    11 / 277 (3.97%)
    0 / 71 (0.00%)
         occurrences all number
    16
    0
    14
    0
    Onychoclasis
         subjects affected / exposed
    15 / 279 (5.38%)
    0 / 65 (0.00%)
    5 / 277 (1.81%)
    1 / 71 (1.41%)
         occurrences all number
    16
    0
    5
    1
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    5 / 279 (1.79%)
    7 / 65 (10.77%)
    1 / 277 (0.36%)
    9 / 71 (12.68%)
         occurrences all number
    5
    11
    1
    11
    Haematuria
         subjects affected / exposed
    5 / 279 (1.79%)
    5 / 65 (7.69%)
    8 / 277 (2.89%)
    8 / 71 (11.27%)
         occurrences all number
    12
    10
    18
    22
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    35 / 279 (12.54%)
    6 / 65 (9.23%)
    29 / 277 (10.47%)
    7 / 71 (9.86%)
         occurrences all number
    41
    10
    35
    8
    Arthralgia
         subjects affected / exposed
    23 / 279 (8.24%)
    3 / 65 (4.62%)
    21 / 277 (7.58%)
    3 / 71 (4.23%)
         occurrences all number
    25
    5
    27
    3
    Musculoskeletal pain
         subjects affected / exposed
    28 / 279 (10.04%)
    3 / 65 (4.62%)
    14 / 277 (5.05%)
    4 / 71 (5.63%)
         occurrences all number
    32
    3
    16
    5
    Myalgia
         subjects affected / exposed
    19 / 279 (6.81%)
    0 / 65 (0.00%)
    14 / 277 (5.05%)
    0 / 71 (0.00%)
         occurrences all number
    23
    0
    15
    0
    Muscle spasms
         subjects affected / exposed
    24 / 279 (8.60%)
    0 / 65 (0.00%)
    13 / 277 (4.69%)
    3 / 71 (4.23%)
         occurrences all number
    27
    0
    18
    4
    Pain in extremity
         subjects affected / exposed
    19 / 279 (6.81%)
    3 / 65 (4.62%)
    6 / 277 (2.17%)
    7 / 71 (9.86%)
         occurrences all number
    24
    4
    6
    7
    Musculoskeletal chest pain
         subjects affected / exposed
    19 / 279 (6.81%)
    1 / 65 (1.54%)
    7 / 277 (2.53%)
    2 / 71 (2.82%)
         occurrences all number
    20
    1
    7
    2
    Infections and infestations
    Paronychia
         subjects affected / exposed
    89 / 279 (31.90%)
    2 / 65 (3.08%)
    84 / 277 (30.32%)
    9 / 71 (12.68%)
         occurrences all number
    228
    6
    230
    24
    Upper respiratory tract infection
         subjects affected / exposed
    36 / 279 (12.90%)
    2 / 65 (3.08%)
    23 / 277 (8.30%)
    9 / 71 (12.68%)
         occurrences all number
    54
    2
    26
    12
    Conjunctivitis
         subjects affected / exposed
    18 / 279 (6.45%)
    4 / 65 (6.15%)
    21 / 277 (7.58%)
    1 / 71 (1.41%)
         occurrences all number
    44
    8
    48
    2
    Pneumonia
         subjects affected / exposed
    18 / 279 (6.45%)
    2 / 65 (3.08%)
    4 / 277 (1.44%)
    2 / 71 (2.82%)
         occurrences all number
    25
    2
    5
    2
    Urinary tract infection
         subjects affected / exposed
    16 / 279 (5.73%)
    8 / 65 (12.31%)
    12 / 277 (4.33%)
    8 / 71 (11.27%)
         occurrences all number
    28
    12
    12
    14
    Urinary tract infection bacterial
         subjects affected / exposed
    12 / 279 (4.30%)
    4 / 65 (6.15%)
    9 / 277 (3.25%)
    5 / 71 (7.04%)
         occurrences all number
    15
    4
    9
    6
    Influenza
         subjects affected / exposed
    14 / 279 (5.02%)
    0 / 65 (0.00%)
    5 / 277 (1.81%)
    3 / 71 (4.23%)
         occurrences all number
    14
    0
    7
    3
    Lung infection
         subjects affected / exposed
    11 / 279 (3.94%)
    4 / 65 (6.15%)
    2 / 277 (0.72%)
    2 / 71 (2.82%)
         occurrences all number
    11
    5
    2
    2
    Nasopharyngitis
         subjects affected / exposed
    31 / 279 (11.11%)
    1 / 65 (1.54%)
    16 / 277 (5.78%)
    6 / 71 (8.45%)
         occurrences all number
    64
    1
    23
    16
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    64 / 279 (22.94%)
    8 / 65 (12.31%)
    56 / 277 (20.22%)
    10 / 71 (14.08%)
         occurrences all number
    78
    8
    64
    12
    Hypokalaemia
         subjects affected / exposed
    13 / 279 (4.66%)
    8 / 65 (12.31%)
    19 / 277 (6.86%)
    12 / 71 (16.90%)
         occurrences all number
    18
    8
    22
    18
    Hypoalbuminaemia
         subjects affected / exposed
    9 / 279 (3.23%)
    6 / 65 (9.23%)
    8 / 277 (2.89%)
    12 / 71 (16.90%)
         occurrences all number
    13
    6
    12
    21
    Hypocalcaemia
         subjects affected / exposed
    7 / 279 (2.51%)
    7 / 65 (10.77%)
    7 / 277 (2.53%)
    7 / 71 (9.86%)
         occurrences all number
    8
    9
    9
    9
    Hyponatraemia
         subjects affected / exposed
    15 / 279 (5.38%)
    0 / 65 (0.00%)
    9 / 277 (3.25%)
    9 / 71 (12.68%)
         occurrences all number
    19
    0
    16
    14
    Hypoproteinaemia
         subjects affected / exposed
    0 / 279 (0.00%)
    3 / 65 (4.62%)
    1 / 277 (0.36%)
    5 / 71 (7.04%)
         occurrences all number
    0
    3
    1
    10
    Hyperglycaemia
         subjects affected / exposed
    7 / 279 (2.51%)
    2 / 65 (3.08%)
    8 / 277 (2.89%)
    4 / 71 (5.63%)
         occurrences all number
    9
    2
    10
    4

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Mar 2018
    Amendment 3: - The length of time for male and female patients that reliable methods of contraception should be used after discontinuation of study treatment, - QTc interval prolongation with signs and symptoms of serious arrhythmia, and AEs of CTCAE grade 3, - Procedures prior to primary PFS analysis for cross-over patients were clarified, -new text was added to provide guidance on patient procedures after primary PFS analysis and up to final OS analysis; -Changes to the protocol and informed consent form section updated to outline the new process for changes to the CSP, -Removal of template guidance text for Japan that was not removed prior to finalization of the clinical study protocol.

    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.
    There were 19 Chinese subjects who were included in both the global and China cohort which gives a total of 692 participants instead of a total of 673 subjects.
    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.

    European Medicines Agency © 1995-Wed Apr 01 11:24:53 CEST 2026 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA