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    Clinical Trial Results:
    A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel With or Without Bevacizumab Compared With Carboplatin + Paclitaxel + Bevacizumab in Chemotherapy-Naïve Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer

    Summary
    EudraCT number
    		 2014-003207-30
    Trial protocol
    		 LV   AT   DE   BE   ES   BG   NL   LT   PT   FR   SK   IT  
    Global end of trial date

    Results information
    Results version number
    		 v1
    This version publication date
    20 Sep 2020
    First version publication date
    20 Sep 2020
    Other versions
    		 v2

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GO29436
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02366143
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Hoffmann-La Roche
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland,
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 42 616878333, global.trial_information@roche.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Interim
    Date of interim/final analysis
    13 Sep 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    13 Sep 2019
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this trial was to evaluate the safety and efficacy of atezolizumab in combination with carboplatin+paclitaxel with or without bevacizumab compared with treatment with carboplatin+paclitaxel+bevacizumab in chemotherapy-naive patients with Stage IV non-squamous non-small cell lung cancer (NSCLC).
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 Mar 2015
    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: 88
    Country: Number of subjects enrolled
    Argentina: 10
    Country: Number of subjects enrolled
    Austria: 12
    Country: Number of subjects enrolled
    Belgium: 16
    Country: Number of subjects enrolled
    Bulgaria: 10
    Country: Number of subjects enrolled
    Brazil: 27
    Country: Number of subjects enrolled
    Canada: 6
    Country: Number of subjects enrolled
    Switzerland: 14
    Country: Number of subjects enrolled
    Chile: 44
    Country: Number of subjects enrolled
    Germany: 94
    Country: Number of subjects enrolled
    Spain: 138
    Country: Number of subjects enrolled
    France: 72
    Country: Number of subjects enrolled
    Italy: 50
    Country: Number of subjects enrolled
    Japan: 93
    Country: Number of subjects enrolled
    Lithuania: 3
    Country: Number of subjects enrolled
    Latvia: 17
    Country: Number of subjects enrolled
    Mexico: 9
    Country: Number of subjects enrolled
    Netherlands: 39
    Country: Number of subjects enrolled
    Peru: 9
    Country: Number of subjects enrolled
    Portugal: 23
    Country: Number of subjects enrolled
    Russian Federation: 37
    Country: Number of subjects enrolled
    Singapore: 9
    Country: Number of subjects enrolled
    Slovakia: 8
    Country: Number of subjects enrolled
    Taiwan: 34
    Country: Number of subjects enrolled
    Ukraine: 74
    Country: Number of subjects enrolled
    United States: 266
    Worldwide total number of subjects
    1202
    EEA total number of subjects
    482
    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)
    664
    From 65 to 84 years
    531
    85 years and over
    7

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 This study included chemotherapy-naive subjects with metastatic non-squamous non-small cell lung cancer (NSCLC).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm B
    Arm description
    		 Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab was administered as IV infusion at a dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle until loss of clinical benefit.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Paclitaxel was administered as IV infusion at a dose of 200 milligrams per square meter (mg/m^2) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin was administered at area under the concentration-time curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first.

    Investigational medicinal product name
    Bevacizumab
    Investigational medicinal product code
    Other name
    Avastin
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bevacizumab was administered as IV infusion at a dose of 15 milligrams per kilogram (mg/kg) on Day 1 of each 21-day cycle until progressive disease, unacceptable toxicity, or death.

    Arm title
    		 Arm A
    Arm description
    		 Atezolizumab+Paclitaxel+Carboplatin
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab was administered as IV infusion at a dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle until loss of clinical benefit.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Paclitaxel was administered as IV infusion at a dose of 200 milligrams per square meter (mg/m^2) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin was administered at area under the concentration-time curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first.

    Arm title
    		 Arm C
    Arm description
    		 Bevacizumab+Paclitaxel+Carboplatin
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Bevacizumab
    Investigational medicinal product code
    Other name
    Avastin
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bevacizumab was administered as IV infusion at a dose of 15 milligrams per kilogram (mg/kg) on Day 1 of each 21-day cycle until progressive disease, unacceptable toxicity, or death.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Paclitaxel was administered as IV infusion at a dose of 200 milligrams per square meter (mg/m^2) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin was administered at area under the concentration-time curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first.

    Number of subjects in period 1
    		Arm B Arm A Arm C
    Started
    400
    402
    400
    Completed
    0
    0
    0
    Not completed
    400
    402
    400
         Adverse event, serious fatal
    272
    275
    301
         On-Going in Study
    107
    101
    79
         Ineligible
    1
    -
    -
         PI Move and Site Closure
    -
    1
    1
         Physician decision
    2
    1
    1
         Consent withdrawn by subject
    15
    21
    16
         Lost to follow-up
    2
    1
    1
         Randomization Error
    -
    -
    1
         Increased Microscopic RBCS on Urinalysis
    1
    -
    -
         Protocol deviation
    -
    2
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm B
    Reporting group description
    		 Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin

    Reporting group title
    Arm A
    Reporting group description
    		 Atezolizumab+Paclitaxel+Carboplatin

    Reporting group title
    Arm C
    Reporting group description
    		 Bevacizumab+Paclitaxel+Carboplatin

    Reporting group values
    		 Arm B Arm A Arm C Total
    Number of subjects
    		 400 402 400 1202
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 215 223 226 664
        From 65-84 years
    		 182 178 171 531
        85 years and over
    		 3 1 3 7
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 63.0 ± 9.5 62.3 ± 9.2 63.1 ± 9.3 -
    Sex: Female, Male
    Units: Participants
        Female
    		 160 161 161 482
        Male
    		 240 241 239 720
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 3 0 1 4
        Asian
    		 56 48 46 150
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        Black or African American
    		 3 9 12 24
        White
    		 322 331 335 988
        More than one race
    		 3 4 0 7
        Unknown or Not Reported
    		 13 10 6 29
    Subject analysis sets

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis sets values
    		 Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Number of subjects
    336
    359
    337
    350
    338
    400
    400
    348
    190
    164
    192
    165
    185
    402
    224
    159
    347
    353
    331
    235
    196
    222
    197
    348
    356
    336
    400
    393
    394
    389
    376
    345
    28
    35
    24
    325
    348
    356
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    4.6 ±
    2.9 ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    Sex: Female, Male
    Units: Participants
        Female
        Male
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
        Asian
        Native Hawaiian or Other Pacific Islander
        Black or African American
        White
        More than one race
        Unknown or Not Reported

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Arm B
    Reporting group description
    		 Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin

    Reporting group title
    Arm A
    Reporting group description
    		 Atezolizumab+Paclitaxel+Carboplatin

    Reporting group title
    Arm C
    Reporting group description
    		 Bevacizumab+Paclitaxel+Carboplatin

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Subject analysis set title
    Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

    Subject analysis set title
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

    Primary: Progression Free Survival (PFS), as Determined by the Investigator in Arm B Versus Arm C in the Teff-high WT Population and ITT-WT Population

    		 Close Top of page
    End point title
    		 Progression Free Survival (PFS), as Determined by the Investigator in Arm B Versus Arm C in the Teff-high WT Population and ITT-WT Population
    End point description
    Progression Free Survival (PFS), as Determined by the Investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Arm B versus Arm C in the T-effector (Teff)-high wild type (WT) population and the intent-to-treat (ITT)-WT population.
    End point type
    Primary
    End point timeframe
    Baseline until disease progression or death, whichever occurs first until data cut-off on 15 September 2017 (up to approximately 29 months)
    End point values
    		 Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Number of subjects analysed
    336
    356
    Units: Months
    median (confidence interval 95%)
        Teff-high WT (Arm B n=155; Arm C=129)
    6.8 (5.9 to 7.4)
    11.3 (9.1 to 13.0)
        ITT-WT (Arm B n=356; Arm C=336)
    6.8 (6.0 to 7.1)
    8.3 (7.7 to 9.8)
    Statistical analysis title
    		 PFS Statistical Analysis
    Statistical analysis description
    ITT-WT population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 0.74
    Notes
    [1] - Stratified Analysis
    Statistical analysis title
    		 PFS Statistical Analysis
    Statistical analysis description
    Teff-high WT Population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    		 [2]
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.38
         upper limit
    		 0.68
    Notes
    [2] - Stratified Analysis

    Primary: Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population

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    End point title
    		 Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population
    End point description
    End point type
    Primary
    End point timeframe
    Baseline until death until data cut-off on 22 January 2018 (up to approximately 34 months)
    End point values
    		 Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    359
    337
    Units: Months
        median (confidence interval 95%)
    19.2 (17.0 to 23.8)
    14.7 (13.3 to 16.9)
    Statistical analysis title
    		 OS Statistical Analysis
    Statistical analysis description
    ITT-WT Population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    696
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.0164
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 0.96
    Notes
    [3] - Stratified Analysis

    Primary: Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population

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    End point title
    		 Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population
    End point description
    Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population
    End point type
    Primary
    End point timeframe
    Baseline until death (up approximately 53 months)
    End point values
    		 Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    350
    338
    Units: Months
        median (confidence interval 95%)
    19.0 (15.7 to 21.5)
    14.7 (12.9 to 17.1)
    Statistical analysis title
    		 OS Statistical Analysis
    Statistical analysis description
    ITT-WT Population
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    688
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    P-value
    		 = 0.0528
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.842
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.707
         upper limit
    		 1.002
    Notes
    [4] - Stratified Analysis

    Secondary: PFS, as Determined by the Independent Review Facility (IRF) in Arm B Versus Arm C in Teff-High-WT Population and ITT-WT Population

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    End point title
    		 PFS, as Determined by the Independent Review Facility (IRF) in Arm B Versus Arm C in Teff-High-WT Population and ITT-WT Population
    End point description
    PFS, as determined by the independent review facility (IRF) Using RECIST v1.1 in Arm B versus Arm C in the T-effector (Teff)-high wild type (WT) population and the intent-to-treat (ITT)-WT population.
    End point type
    Secondary
    End point timeframe
    Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)
    End point values
    		 Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Number of subjects analysed
    336
    356
    Units: Months
    median (confidence interval 95%)
        Teff-high WT Population (Arm B n=155; Arm C n=129)
    7.0 (6.1 to 8.1)
    10.7 (8.4 to 13.0)
        ITT-WT Population (Arm B n=356; Arm C n=336)
    7.0 (6.3 to 8.0)
    8.5 (7.7 to 9.7)
    Statistical analysis title
    		 PFS Statistical Analysis
    Statistical analysis description
    ITT-WT population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.0002
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 0.85
    Notes
    [5] - Stratified Analysis
    Statistical analysis title
    		 PFS Statistical Analysis
    Statistical analysis description
    Teff-high WT Population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    P-value
    		 = 0.0001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.564
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.418
         upper limit
    		 0.76
    Notes
    [6] - Stratified Analysis

    Secondary: PFS, as Determined by the Investigator in Arm B Versus Arm C in Teff High Population and ITT Population

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    End point title
    		 PFS, as Determined by the Investigator in Arm B Versus Arm C in Teff High Population and ITT Population
    End point description
    PFS, as determined by the investigator according to RECIST v1.1, in Arm B versus C in the Teff high population and ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)
    End point values
    		 Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    400
    400
    Units: Months
    median (confidence interval 95%)
        Teff-high (Arm B n=166; Arm C=148)
    11.3 (9.1 to 13.0)
    6.8 (5.8 to 7.3)
        ITT Population (Arm B n=400; Arm C=4008)
    8.3 (7.9 to 9.8)
    6.8 (6.0 to 7.1)
    Statistical analysis title
    		 PFS Statistical Analysis
    Statistical analysis description
    ITT Population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    800
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.517
         upper limit
    		 0.72
    Notes
    [7] - Stratified Analysis
    Statistical analysis title
    		 PFS Statistical Analysis
    Statistical analysis description
    Teff-high Population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    800
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.492
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.374
         upper limit
    		 0.649
    Notes
    [8] - Stratified Analysis

    Secondary: PFS, as Determined by the Investigator in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population

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    End point title
    		 PFS, as Determined by the Investigator in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population
    End point description
    PFS, as determined by the investigator according to RECIST v1.1, in Arm A versus B in the Teff high-WT population and ITT-WT population.
    End point type
    Secondary
    End point timeframe
    Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)
    End point values
    		 Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Number of subjects analysed
    348
    356
    Units: Months
    median (confidence interval 95%)
        Teff-high WT (Arm A n=161; Arm B n=155)
    6.3 (5.6 to 7.8)
    11.3 (9.1 to 13.0)
        ITT-WT (Arm A n=348; Arm C n=356)
    6.3 (5.6 to 7.0)
    8.3 (7.7 to 9.8)
    No statistical analyses for this end point

    Secondary: PFS, as Determined by the Investigator in Arm B Versus Arm C by PD-L1 Subgroup

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    End point title
    		 PFS, as Determined by the Investigator in Arm B Versus Arm C by PD-L1 Subgroup
    End point description
    PFS as Determined by the Investigator according to RECIST v1.1, in Arm B Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)
    End point type
    Secondary
    End point timeframe
    Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)
    End point values
    		 Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    190
    164
    Units: Months
    median (confidence interval 95%)
        TC2/3 or IC2/3 (Arm B n=129; Arm C n=115)
    11.1 (8.3 to 13.0)
    6.8 (5.8 to 7.7)
        TC1/2/3 or IC1/2/3 (Arm B n=190; Arm C n=164)
    11.0 (8.3 to 12.5)
    6.8 (5.8 to 7.3)
    Statistical analysis title
    		 PFS Statistical Analysis
    Statistical analysis description
    TC1/2/3 or IC1/2/3 Subgroup
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    354
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.486
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.386
         upper limit
    		 0.639
    Notes
    [9] - Stratified Analysis
    Statistical analysis title
    		 PFS Statistical Analysis
    Statistical analysis description
    TC2/3 or IC2/3 Subgroup
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    354
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [10]
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.471
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.352
         upper limit
    		 0.647
    Notes
    [10] - Stratified Analysis

    Secondary: OS in Arm B Versus Arm C by PD-L1 Subgroup

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    End point title
    		 OS in Arm B Versus Arm C by PD-L1 Subgroup
    End point description
    OS in Arm B Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)
    End point type
    Secondary
    End point timeframe
    Baseline until death (up to approximately 34 months)
    End point values
    		 Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    192
    165
    Units: Months
    median (confidence interval 95%)
        TC 2/3 or IC2/3 (Arm B n=129; Arm C n=116)
    22.2 (17.0 to 26.1)
    16.7 (10.5 to 24.2)
        TC1/2/3 or IC1/2/3 (Arm B n=192; Arm C n=165)
    22.5 (18.2 to 26.1)
    16.4 (11.2 to 22.9)
    Statistical analysis title
    		 OS Analysis by PD-L1 Subgroup
    Statistical analysis description
    TC2/3 or IC2/3, WT ITT
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    357
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [11]
    P-value
    		 = 0.2765
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.824
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 1.169
    Notes
    [11] - Unstratified Analysis
    Statistical analysis title
    		 OS Analysis by PD-L1 Subgroup
    Statistical analysis description
    TC1/2/3 or IC1/2/3, WT ITT
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    357
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [12]
    P-value
    		 = 0.0829
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.771
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.575
         upper limit
    		 1.035
    Notes
    [12] - Unstratified Analysis

    Secondary: OS in Arm A Versus Arm C by PD-L1 Subgroup

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    End point title
    		 OS in Arm A Versus Arm C by PD-L1 Subgroup
    End point description
    OS in Arm A Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)
    End point type
    Secondary
    End point timeframe
    Baseline until death (up approximately 53 months)
    End point values
    		 Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    165
    185
    Units: Months
    median (confidence interval 95%)
        TC2/3 or IC2/3 (Arm A n=124; Arm C n=116)
    17.0 (10.3 to 22.9)
    26.1 (20.5 to 40.0)
        TC1/2/3 or IC1/2/3 (Arm A n=185; Arm C n=165)
    16.0 (11.2 to 20.1)
    24.4 (20.2 to 28.1)
    Statistical analysis title
    		 OS by PD-L1 Subgroup
    Statistical analysis description
    TC2/3 or IC2/3 Population
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    350
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    P-value
    		 = 0.0097
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.662
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.484
         upper limit
    		 0.907
    Notes
    [13] - Unstratified Analysis
    Statistical analysis title
    		 OS by PD-L1 Subgroup
    Statistical analysis description
    TC1/2/3 or IC1/2/3 ITT-WT
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    350
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [14]
    P-value
    		 = 0.0073
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.709
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.551
         upper limit
    		 0.913
    Notes
    [14] - Unstratified Analysis

    Secondary: OS in Arm B Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population

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    End point title
    		 OS in Arm B Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population
    End point description
    Note: 999999=Not estimable
    End point type
    Secondary
    End point timeframe
    Baseline until death (up to approximately 34 months)
    End point values
    		 Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    400
    400
    Units: Months
    median (confidence interval 95%)
        Teff High-WT (Arm B n=156; Arm C n=129)
    25.0 (17.8 to 999999)
    16.7 (12.4 to 999999)
        Teff High Population (Arm B n=166; Arm C n=148)
    25.2 (19.1 to 999999)
    16.7 (12.4 to 999999)
        ITT Population (Arm B n=400; Arm C n=400)
    19.8 (17.4 to 24.2)
    14.9 (13.4 to 17.1)
    Statistical analysis title
    		 OS Statistical Analysis
    Statistical analysis description
    Teff high-WT
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    800
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [15]
    P-value
    		 = 0.2843
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.831
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.592
         upper limit
    		 1.167
    Notes
    [15] - Stratified Analysis
    Statistical analysis title
    		 OS Statistical Analysis
    Statistical analysis description
    Teff high
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    800
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [16]
    P-value
    		 = 0.1861
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.802
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.579
         upper limit
    		 1.113
    Notes
    [16] - Stratified Analysis
    Statistical analysis title
    		 OS Statistical Analysis
    Statistical analysis description
    ITT
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    800
    Analysis specification
    Pre-specified
    Analysis type
    		 [17]
    P-value
    		 = 0.006
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.764
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 0.926
    Notes
    [17] - Stratified Analysis

    Secondary: OS in Arm A Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population

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    End point title
    		 OS in Arm A Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline until death (up approximately 53 months)
    End point values
    		 Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    400
    402
    Units: Months
    median (confidence interval 95%)
        Teff-high WT (Arm A n=163; Arm C n=130)
    16.3 (11.2 to 22.3)
    21.3 (17.6 to 26.3)
        Teff-high Population (Arm A n=177; Arm C n=148)
    16.7 (11.4 to 21.6)
    21.0 (17.1 to 26.0)
        ITT Population (Arm A n=402; Arm C n=400)
    15.0 (13.4 to 17.1)
    19.0 (16.3 to 21.5)
    Statistical analysis title
    		 OS Statistical Analysis
    Statistical analysis description
    Teff high-WT
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    802
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [18]
    P-value
    		 = 0.0894
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.786
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.595
         upper limit
    		 1.038
    Notes
    [18] - Stratified Analysis
    Statistical analysis title
    		 OS Statistical Analysis
    Statistical analysis description
    Teff high
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    802
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [19]
    P-value
    		 = 0.1276
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.815
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.626
         upper limit
    		 1.061
    Notes
    [19] - Stratified Analysis
    Statistical analysis title
    		 OS Statistical Analysis
    Statistical analysis description
    ITT
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    802
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [20]
    P-value
    		 = 0.0681
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.861
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.733
         upper limit
    		 1.011
    Notes
    [20] - Stratified Analysis

    Secondary: OS in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population

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    End point title
    		 OS in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline until death (up approximately 53 months)
    End point values
    		 Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm A (Atezolizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    359
    350
    Units: Months
    median (confidence interval 95%)
        Teff High-WT (Arm A n=163; Arm B n=156)
    25.8 (19.1 to 32.6)
    21.3 (17.6 to 26.3)
        ITT-WT (Arm A n=350; Arm B n=359)
    19.5 (17.0 to 22.2)
    19.0 (15.7 to 21.5)
    Statistical analysis title
    		 OS Statistical Analysis
    Statistical analysis description
    Teff high-WT ITT
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Number of subjects included in analysis
    709
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [21]
    P-value
    		 = 0.4599
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.901
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.683
         upper limit
    		 1.188
    Notes
    [21] - Stratified Analysis

    Secondary: Duration of Response (DOR), as Determined By Investigator in Arm B Versus Arm C

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    End point title
    		 Duration of Response (DOR), as Determined By Investigator in Arm B Versus Arm C
    End point description
    DOR, as determined by investigator according to RECIST v1.1 in Arm B versus Arm C in the Teff high-WT population and the ITT-WT population.
    End point type
    Secondary
    End point timeframe
    Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)
    End point values
    		 Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    224
    159
    Units: Months
    median (confidence interval 95%)
        Teff high-WT (Arm B n=106; Arm C n=68)
    11.2 (9.7 to 15.7)
    5.7 (4.9 to 7.0)
        ITT-WT (Arm B n=224; Arm C n=159)
    9.0 (6.9 to 11.4)
    5.7 (5.1 to 6.5)
    Statistical analysis title
    		 DOR Statistical Analysis
    Statistical analysis description
    ITT-WT
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    383
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [22]
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.523
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.406
         upper limit
    		 0.675
    Notes
    [22] - Stratified Analysis
    Statistical analysis title
    		 DOR Statistical Analysis
    Statistical analysis description
    Teff-high WT
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    383
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [23]
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.283
         upper limit
    		 0.624
    Notes
    [23] - Stratified Analysis

    Secondary: Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator in the Teff-High-WT Population and ITT-WT Population

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    End point title
    		 Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator in the Teff-High-WT Population and ITT-WT Population
    End point description
    Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator using RECIST v1.1 in the Teff-High-WT population and ITT-WT population.
    End point type
    Secondary
    End point timeframe
    Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)
    End point values
    		 Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    347
    353
    331
    Units: Percentage
    number (not applicable)
        Teff-high WT (Arm A n=161; Arm B n=153)
    54.0
    69.3
    53.5
        ITT-WT (Arm A n=347; Arm B n=353)
    49.3
    63.5
    48.0
    No statistical analyses for this end point

    Secondary: OS Rates at Years 1 and 2 in Arm B Versus Arm C

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    End point title
    		 OS Rates at Years 1 and 2 in Arm B Versus Arm C
    End point description
    OS at 1- and 2-year landmark timepoints in Teff-high WT population and ITT-WT population.
    End point type
    Secondary
    End point timeframe
    Years 1 and 2 (up to approximately 34 months)
    End point values
    		 Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    235
    196
    Units: Percentage
    number (confidence interval 95%)
        1-Year Teff-high WT (Arm B n=105; Arm C n=71)
    68.63 (61.28 to 75.98)
    58.74 (50.03 to 67.45)
        1-Year ITT-WT (Arm B n=235; Arm C n=196)
    67.32 (62.41 to 72.22)
    60.63 (55.34 to 65.93)
        2-Year Teff-high WT (Arm B n=21; Arm C n=15)
    52.03 (43.12 to 60.94)
    41.70 (31.55 to 51.85)
        2-Year ITT-WT (Arm B n=34; Arm C n=29)
    43.42 (36.94 to 49.90)
    33.71 (27.44 to 39.98)
    Statistical analysis title
    		 OS Rate at Year 1 Statistical Analysis
    Statistical analysis description
    1-Year ITT-WT Population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    431
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [24]
    P-value
    		 = 0.0697
    Method
    		 Z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    6.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.54
         upper limit
    		 13.9
    Notes
    [24] - Stratified Analysis
    Statistical analysis title
    		 OS Rate at Year 2 Statistical Analysis
    Statistical analysis description
    2-Year ITT-WT Population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    431
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [25]
    P-value
    		 = 0.0347
    Method
    		 Z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    9.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 18.73
    Notes
    [25] - Stratified Analysis
    Statistical analysis title
    		 OS Rate at Year 1 Statistical Analysis
    Statistical analysis description
    1-Year Teff-high WT Population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    431
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [26]
    P-value
    		 = 0.089
    Method
    		 Z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    9.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.51
         upper limit
    		 21.29
    Notes
    [26] - Stratified Analysis
    Statistical analysis title
    		 OS Rate at Year 2 Statistical Analysis
    Statistical analysis description
    2-Year Teff-high WT Population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    431
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [27]
    P-value
    		 = 0.1336
    Method
    		 Z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    10.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.17
         upper limit
    		 23.84
    Notes
    [27] - Stratified Analysis

    Secondary: OS Rates at Years 1 and 2 in Arm A Versus Arm C

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    End point title
    		 OS Rates at Years 1 and 2 in Arm A Versus Arm C
    End point description
    OS at 1- and 2-year landmark timepoints in Teff-high WT population and ITT-WT population.
    End point type
    Secondary
    End point timeframe
    Years 1 and 2 (up to approximately 53 months)
    End point values
    		 Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    222
    197
    Units: Percentage
    number (confidence interval 95%)
        1-Year Teff-high WT (Arm A n=110; Arm C n=72)
    67.48 (60.29 to 74.68)
    56.92 (48.32 to 65.53)
        2-Year Teff-high WT (Arm A n=75; Arm C n=49)
    46.01 (38.36 to 53.66)
    38.74 (30.26 to 47.22)
        1-Year ITT-WT (Arm A n=222; Arm C n=1972)
    64.06 (59.02 to 69.11)
    59.89 (54.61 to 65.17)
        2-Year ITT-WT (Arm A n=143; Arm C n=104)
    41.45 (36.26 to 46.64)
    31.79 (26.75 to 36.82)
    Statistical analysis title
    		 OS Rate at Year 1
    Statistical analysis description
    1-Year ITT-WT Population
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [28]
    P-value
    		 = 0.2624
    Method
    		 Z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    4.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.13
         upper limit
    		 11.48
    Notes
    [28] - Stratified Analysis
    Statistical analysis title
    		 OS Rate at Year 2
    Statistical analysis description
    2-Year ITT-WT Population
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [29]
    P-value
    		 = 0.0088
    Method
    		 Z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    9.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.43
         upper limit
    		 16.9
    Notes
    [29] - Stratified Analysis
    Statistical analysis title
    		 OS Rate at Year 1
    Statistical analysis description
    1-Year Teff-high WT Population
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [30]
    P-value
    		 = 0.0649
    Method
    		 Z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    10.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.65
         upper limit
    		 21.77
    Notes
    [30] - Stratified Analysis
    Statistical analysis title
    		 OS Rate at Year 2
    Statistical analysis description
    2-Year Teff-high WT Population
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [31]
    P-value
    		 = 0.212
    Method
    		 Z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    7.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.15
         upper limit
    		 18.69
    Notes
    [31] - Stratified Analysis

    Secondary: Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms Determined by European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Score

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    End point title
    		 Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms Determined by European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Score
    End point description
    EORTC QLQ-C30 is a validated & reliable self-report measure that consists of 30 questions that assess 5 aspects of patient functioning, 3 symptom scales, health/quality of life,and 6 single items. EORTC QLQ-C30 is scored according to the EORTC scoring manual. All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL;however a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al.1998). Dyspnea in Teff-high WT (Arm A n=161; Arm B n=155; Arm C n= 129). Dyspnea ITT-WT (Arm A n=348; Arm B n=356; Arm C n= 336) Note: 999999=not estimable
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 29 months
    End point values
    		 Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Number of subjects analysed
    336
    348
    356
    Units: Months
    median (confidence interval 95%)
        Dyspnea in Teff-high WT
    999999 (999999 to 999999)
    999999 (999999 to 999999)
    999999 (999999 to 999999)
        Dyspnea ITT-WT
    999999 (999999 to 999999)
    999999 (999999 to 999999)
    999999 (999999 to 999999)
    Statistical analysis title
    		 TTD EORTC QLQ-C30 Score
    Statistical analysis description
    Teff-high WT Population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [32]
    P-value
    		 = 0.6899
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.909
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.571
         upper limit
    		 1.45
    Notes
    [32] - Stratified Analysis
    Statistical analysis title
    		 TTD EORTC QLQ-C30 Score
    Statistical analysis description
    Teff-high WT Population
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [33]
    P-value
    		 = 0.1043
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.671
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.413
         upper limit
    		 1.089
    Notes
    [33] - Stratified Analysis
    Statistical analysis title
    		 TTD EORTC QLQ-C30 Score
    Statistical analysis description
    ITT WT
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [34]
    P-value
    		 = 0.173
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.232
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.912
         upper limit
    		 1.665
    Notes
    [34] - Stratified Analysis
    Statistical analysis title
    		 TTD EORTC QLQ-C30 Score
    Statistical analysis description
    ITT WT
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [35]
    P-value
    		 = 0.6145
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.084
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.792
         upper limit
    		 1.483
    Notes
    [35] - Stratified Analysis

    Secondary: TTD in Patient-Reported Lung Cancer Symptoms as Determined by EORTC Quality-of-Life Questionnaire-Core Lung Cancer Module 13 (QLQ-LC13) Score

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    End point title
    		 TTD in Patient-Reported Lung Cancer Symptoms as Determined by EORTC Quality-of-Life Questionnaire-Core Lung Cancer Module 13 (QLQ-LC13) Score
    End point description
    QLQ-LC13 incorporates 1 multiple-item scale & a series of single items.EORTC scales & single-item measures are linearly transformed so that each score has a range of 0-100.A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL;a high score for a symptom scale or item represents a high level of symptomatology or problems.Cough in Teff-high WT(Arm A n=161;Arm B n=155;Arm C n=129).Dyspnea in Teff-high WT(Arm A n=161;Arm B n=155;Arm C n=129).Chest Pain in Teff-high WT (Arm A n=161;Arm B n=155;Arm C n=129).Arm and/or Shoulder Pain in Teff-high WT (Arm A n=161;Arm B n=155; Arm C n=129).Cough in ITT-WT(Arm A n=348;Arm B n=356;Arm C n=336).Dyspnea in ITT-WT (Arm A n=348; Arm B n=356;Arm C n=336).Arm and/or Shoulder Pain in ITT-WT(Arm A n=348;Arm B n=356;Arm C n=336).Pain in Chest in ITT-WT(Arm A n=348;Arm B n=356;Arm C n=336).Note: 999999=not estimable
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 29 months
    End point values
    		 Arm C (Bevacizumab+Paclitaxel+Carboplatin) Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Number of subjects analysed
    336
    348
    356
    Units: Months
    median (confidence interval 95%)
        Cough in Teff-high WT
    999999 (999999 to 999999)
    999999 (999999 to 999999)
    999999 (21.0 to 999999)
        Dyspnea in Teff-high WT
    999999 (6.3 to 999999)
    999999 (5.6 to 999999)
    999999 (999999 to 999999)
        Chest Pain in Teff-high WT
    18.4 (18.4 to 999999)
    999999 (999999 to 999999)
    22.2 (22.2 to 999999)
        Arm and/or Shoulder Pain in Teff-high WT
    999999 (12.7 to 999999)
    999999 (18.3 to 999999)
    19.5 (12.5 to 999999)
        Cough in ITT-WT
    999999 (999999 to 999999)
    999999 (999999 to 999999)
    999999 (21.0 to 999999)
        Dyspnea in ITT-WT
    999999 (10.0 to 999999)
    21.9 (9.7 to 999999)
    999999 (999999 to 999999)
        Arm and/or Shoulder Pain in ITT-WT
    999999 (999999 to 999999)
    999999 (18.3 to 999999)
    19.5 (15.2 to 999999)
        Pain in Chest in ITT-WT
    999999 (18.4 to 999999)
    999999 (999999 to 999999)
    999999 (22.2 to 999999)
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Cough for Teff-high WT ITT population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [36]
    P-value
    		 = 0.8816
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.041
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.614
         upper limit
    		 1.763
    Notes
    [36] - Stratified Analysis
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Cough for Teff-high WT ITT Population
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [37]
    P-value
    		 = 0.2995
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.741
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.419
         upper limit
    		 1.309
    Notes
    [37] - Stratified Analysis
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Dyspnea in Teff-high WT Population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [38]
    P-value
    		 = 0.7578
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.936
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.616
         upper limit
    		 1.422
    Notes
    [38] - Stratified Analysis
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Dyspnea in Teff-high WT Population
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [39]
    P-value
    		 = 0.847
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.041
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.694
         upper limit
    		 1.56
    Notes
    [39] - Stratified Analysis
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Pain in Chest in Teff-high WT Population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [40]
    P-value
    		 = 0.1289
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.659
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.383
         upper limit
    		 1.133
    Notes
    [40] - Stratified Analysis
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Pain in Chest in Teff-high WT Population
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [41]
    P-value
    		 = 0.2381
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.729
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 1.235
    Notes
    [41] - Stratified Analysis
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Arm and/or Shoulder Pain in Teff-high WT
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [42]
    P-value
    		 = 0.7163
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.685
         upper limit
    		 1.732
    Notes
    [42] - Stratified Analysis
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Arm and/or Shoulder Pain in Teff-high WT
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [43]
    P-value
    		 = 0.1502
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.693
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 1.145
    Notes
    [43] - Stratified Analysis
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Cough in ITT-WT Population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [44]
    P-value
    		 = 0.9568
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.713
         upper limit
    		 1.43
    Notes
    [44] - Stratified Analysis
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Cough in ITT-WT Population
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [45]
    P-value
    		 = 0.5377
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.891
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.619
         upper limit
    		 1.284
    Notes
    [45] - Stratified Analysis
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Dyspnea in ITT-WT Population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [46]
    P-value
    		 = 0.4012
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.893
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.685
         upper limit
    		 1.163
    Notes
    [46] - Stratified Analysis
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Dyspnea in ITT-WT Population
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [47]
    P-value
    		 = 0.7149
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.809
         upper limit
    		 1.363
    Notes
    [47] - Stratified Analysis
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Arm and/or Shoulder Pain in ITT-WT
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [48]
    P-value
    		 = 0.7126
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.057
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.786
         upper limit
    		 1.422
    Notes
    [48] - Stratified Analysis
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Arm and/or Shoulder Pain in ITT-WT
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [49]
    P-value
    		 = 0.6053
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.921
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.675
         upper limit
    		 1.258
    Notes
    [49] - Stratified Analysis
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Pain in Chest in ITT-WT Population
    Comparison groups
    Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [50]
    P-value
    		 = 0.3134
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.829
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.576
         upper limit
    		 1.194
    Notes
    [50] - Stratified Analysis
    Statistical analysis title
    		 TTD by EORTC QLQ-LC13 Score
    Statistical analysis description
    Pain in Chest in ITT-WT Population
    Comparison groups
    Arm A (Atezolizumab+Paclitaxel+Carboplatin) v Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [51]
    P-value
    		 = 0.6115
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.633
         upper limit
    		 1.309
    Notes
    [51] - Stratified Analysis

    Secondary: Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale

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    End point title
    		 Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale
    End point description
    The SILC scale was used to assess patient-reported severity of lung cancer symptoms (chest pain, dyspnea, and cough). The SILC scale is a 9-item content validated self-report measure of lung cancer symptoms. It measures severity of cough, dyspnea, and chest pain with a symptom severity score. The SILC questionnaire comprises three individual symptoms (dyspnea, cough, chest pain) and are scored at the individual symptom level, thus have a dyspnea score, chest pain score, and cough score. Each individual symptom score is calculated as the average of responses for the symptom items [e.g. Chest Pain Score=mean (item 1; item 2)]. An increase in score is suggestive of a worsening in symptomology (i.e. frequency or severity). A score change of ≥0.3 points for the dyspnea and cough symptom scores is considered to be clinically significant; whereas a score change of ≥0.5 points for the chest pain score is considered to be clinically significant. Note: 999999=not available.
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 29 months
    End point values
    		 Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    0 [52]
    0 [53]
    0 [54]
    Units: Months
    median (confidence interval 95%)
        Teff-high WT
    ( to )
    ( to )
    ( to )
        ITT WT
    ( to )
    ( to )
    ( to )
    Notes
    [52] - No analysis due to psychometric properties in NSCLC population are being determined & quality issue.
    [53] - No analysis due to psychometric properties in NSCLC population are being determined & quality issue.
    [54] - No analysis due to psychometric properties in NSCLC population are being determined & quality issue.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Adverse Events

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    End point title
    		 Percentage of Participants With Adverse Events
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 63 months
    End point values
    		 Arm B Arm A Arm C
    Number of subjects analysed
    0 [55]
    0 [56]
    0 [57]
    Units: Percentage
    Notes
    [55] - This will be reported at the time of final results posting.
    [56] - This will be reported at the time of final results posting.
    [57] - This will be reported at the time of final results posting.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab

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    End point title
    		 Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 29 months
    End point values
    		 Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Number of subjects analysed
    389
    376
    Units: Percentage of Participants
        number (not applicable)
    4.6
    2.9
    No statistical analyses for this end point

    Secondary: Maximum Observed Serum Concentration (Cmax) of Atezolizumab in Arm A and Arm B

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    End point title
    		 Maximum Observed Serum Concentration (Cmax) of Atezolizumab in Arm A and Arm B
    End point description
    The predose samples will be collected on the same day of treatment administration. The infusion duration of atezolizumab will be of 30-60 minutes.
    End point type
    Secondary
    End point timeframe
    Day 1 of Cycle 1 and 3 (Cycle length=21 days)
    End point values
    		 Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Number of subjects analysed
    378
    364
    Units: mcg/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1 (Arm A n=378, Arm B n=364)
    410 ± 157
    414 ± 127
        Cycle 3 Day 1 (Arm A n=310, Arm B n=302)
    498 ± 160
    540 ± 198
    No statistical analyses for this end point

    Secondary: Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Arm A and Arm B

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    End point title
    		 Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Arm A and Arm B
    End point description
    Note: 999999=not available
    End point type
    Secondary
    End point timeframe
    Day 21 of Cycles 1, 2 3, and 7 (Cycle length=21 days)
    End point values
    		 Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
    Number of subjects analysed
    354
    345
    Units: mcg/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 21 (Arm A n=354; Arm B n=345)
    76.4 ± 37.7
    80.8 ± 41.4
        Cycle 2 Day 21 (Arm A n=322; Arm B n=319)
    119 ± 55.7
    130 ± 57.1
        Cycle 3 Day 21 (Arm A n=312; Arm B n=307)
    146 ± 58.9
    160 ± 102
        Cycle 7 Day 21 (Arm A n=230; Arm B n=249)
    219 ± 89.6
    220 ± 99.0
    No statistical analyses for this end point

    Secondary: Plasma Concentrations for Carboplatin in Arm A, Arm B, and Arm C

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    End point title
    		 Plasma Concentrations for Carboplatin in Arm A, Arm B, and Arm C
    End point description
    Note: 999999=not available. BEOI=Before end of infusion. AI=After infusion.
    End point type
    Secondary
    End point timeframe
    Predose (same day of treatment administration), 5-10 minutes before end of carboplatin infusion, 1 h after carboplatin infusion (infusion duration=15 to 30 minutes) on D1 of Cy1,3 (Cycle length=21 days)
    End point values
    		 Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    28
    35
    24
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cy1D1 Pre-dose (Arm A n=28;Arm B n=35;Arm C n=24)
    999999 ± 999999
    999999 ± 999999
    999999 ± 999999
        Cy1D1 BEOI (Arm A n=26;Arm B n=32;Arm C n=24)
    18300 ± 9610
    18300 ± 11900
    17200 ± 9860
        Cy1D1 AI (Arm A n=26;Arm B n=31;Arm C n=22)
    11700 ± 5570
    13900 ± 14300
    10100 ± 5320
        Cy2D21 (Arm A n=19;Arm B n=27;Arm C n=17)
    176 ± 82.9
    190 ± 113
    143 ± 73.0
        Cy3D1 BEOI (Arm A n=18;Arm B n=28;Arm C n=16)
    20900 ± 8330
    18700 ± 9410
    20600 ± 12900
        Cy3D1 AI (Arm A n=20;Arm B n=27;Arm C n=17)
    11700 ± 6990
    12200 ± 7480
    10400 ± 4150
    No statistical analyses for this end point

    Secondary: Plasma Concentrations for Paclitaxel in Arm A, Arm B, and Arm C

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    End point title
    		 Plasma Concentrations for Paclitaxel in Arm A, Arm B, and Arm C
    End point description
    Note: 999999=not available. BEOI=Before end of infusion. AI=After infusion
    End point type
    Secondary
    End point timeframe
    Predose (same day of treatment administration), 5-10 minutes before end of paclitaxel infusion, 1 h after paclitaxel infusion (infusion duration=3 h) on D1 of Cy1,3 (Cycle length=21 days)
    End point values
    		 Arm A (Atezolizumab+Paclitaxel+Carboplatin) Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    28
    35
    24
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cy1D1 Pre-dose (Arm A n=28; Arm B n=35;Arm C n=24)
    999999 ± 999999
    999999 ± 999999
    999999 ± 999999
        Cy1D1 BEOI (Arm A n=26;Arm B n=34;Arm C n=24)
    4850 ± 2800
    6440 ± 3640
    5560 ± 2590
        Cy1D1 AI (Arm A n=27;Arm B n=32;Arm C n=23)
    2300 ± 2790
    2490 ± 3020
    1980 ± 1780
        Cy2D21 (Arm A n=2;Arm B n=3; Arm C n=0)
    999999 ± 999999
    999999 ± 999999
    999999 ± 999999
        Cy3D1 BEOI (Arm A n=19; Arm B n=25; Arm C n=16)
    5810 ± 3610
    7810 ± 4510
    7810 ± 5160
        Cy3D1 AI (Arm A n=19;Arm B n=27;Arm C n=17)
    1800 ± 1660
    2990 ± 5830
    1930 ± 1380
    No statistical analyses for this end point

    Secondary: Cmax of Bevacizumab in Arm B and Arm C

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    End point title
    		 Cmax of Bevacizumab in Arm B and Arm C
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length=21 days)
    End point values
    		 Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    205
    215
    Units: mcg/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1 (Arm A n=205; Arm C n=215)
    329 ± 129
    323 ± 95.0
        Cycle 3 Day 1 (Arm A n=154; Arm C n=168)
    413 ± 126
    430 ± 123
    No statistical analyses for this end point

    Secondary: Cmin of Bevacizumab in Arm B and Arm C

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    End point title
    		 Cmin of Bevacizumab in Arm B and Arm C
    End point description
    Note: 999999=not available
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 and Cycle 2 Day 21 (Cycle length=21 days)
    End point values
    		 Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Arm C (Bevacizumab+Paclitaxel+Carboplatin)
    Number of subjects analysed
    325
    348
    Units: mcg/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1 (Arm A n=325; Arm B n=348)
    999999 ± 999999
    999999 ± 999999
        Cycle 2 Day 21 (Arm A n=280; Arm B n=316)
    98.0 ± 50.9
    90.4 ± 36.8
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the first study drug to the data cutoff date 13 Sept 2019 (up to approximately 53 months)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Arm B
    Reporting group description
    		 Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin

    Reporting group title
    Arm C
    Reporting group description
    		 Bevacizumab+Paclitaxel+Carboplatin

    Reporting group title
    Arm A
    Reporting group description
    		 Atezolizumab+Paclitaxel+Carboplatin

    Serious adverse events
    		 Arm B Arm C Arm A
    Total subjects affected by serious adverse events
         subjects affected / exposed
    187 / 393 (47.58%)
    142 / 394 (36.04%)
    169 / 400 (42.25%)
         number of deaths (all causes)
    272
    301
    275
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ADENOCARCINOMA GASTRIC
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    B-CELL LYMPHOMA
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLADDER TRANSITIONAL CELL CARCINOMA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MARROW HYPERPLASIA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MENINGIOMA
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    METASTASES TO MENINGES
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TUMOUR PAIN
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TUMOUR PSEUDOPROGRESSION
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    ANEURYSM
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    AORTIC DISSECTION
         subjects affected / exposed
    2 / 393 (0.51%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    ARTERIAL OCCLUSIVE DISEASE
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    2 / 393 (0.51%)
    1 / 394 (0.25%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETIC VASCULAR DISORDER
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EMBOLISM
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EMBOLISM VENOUS
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMATOMA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERTENSION
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOTENSION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LYMPHOEDEMA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ORTHOSTATIC HYPOTENSION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL ARTERIAL OCCLUSIVE DISEASE
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL ARTERY THROMBOSIS
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL ISCHAEMIA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL VASCULAR DISORDER
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    THROMBOSIS
         subjects affected / exposed
    2 / 393 (0.51%)
    1 / 394 (0.25%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    VENOUS THROMBOSIS LIMB
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    VERTEBROPLASTY
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CATHETER SITE ERYTHEMA
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHEST PAIN
         subjects affected / exposed
    4 / 393 (1.02%)
    6 / 394 (1.52%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 7
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COMPLICATION ASSOCIATED WITH DEVICE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEATH
         subjects affected / exposed
    2 / 393 (0.51%)
    2 / 394 (0.51%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    GENERAL PHYSICAL HEALTH DETERIORATION
         subjects affected / exposed
    2 / 393 (0.51%)
    2 / 394 (0.51%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFUSION SITE EXTRAVASATION
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MUCOSAL INFLAMMATION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OEDEMA PERIPHERAL
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PAIN
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    7 / 393 (1.78%)
    1 / 394 (0.25%)
    6 / 400 (1.50%)
         occurrences causally related to treatment / all
    2 / 7
    0 / 1
    3 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    ANAPHYLACTIC REACTION
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DRUG HYPERSENSITIVITY
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERSENSITIVITY
         subjects affected / exposed
    1 / 393 (0.25%)
    2 / 394 (0.51%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY DISTRESS SYNDROME
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    ACUTE RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    3 / 400 (0.75%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    BRONCHOSTENOSIS
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    3 / 393 (0.76%)
    2 / 394 (0.51%)
    3 / 400 (0.75%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    COUGH
         subjects affected / exposed
    3 / 393 (0.76%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    2 / 393 (0.51%)
    6 / 394 (1.52%)
    4 / 400 (1.00%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EPISTAXIS
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMOPTYSIS
         subjects affected / exposed
    8 / 393 (2.04%)
    2 / 394 (0.51%)
    3 / 400 (0.75%)
         occurrences causally related to treatment / all
    3 / 8
    1 / 2
    0 / 4
         deaths causally related to treatment / all
    3 / 3
    0 / 1
    0 / 1
    HICCUPS
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOXIA
         subjects affected / exposed
    2 / 393 (0.51%)
    1 / 394 (0.25%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    IMMUNE-MEDIATED PNEUMONITIS
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTERSTITIAL LUNG DISEASE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    PLEURAL EFFUSION
         subjects affected / exposed
    0 / 393 (0.00%)
    2 / 394 (0.51%)
    3 / 400 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PLEURISY
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PLEURITIC PAIN
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    PNEUMONITIS
         subjects affected / exposed
    7 / 393 (1.78%)
    0 / 394 (0.00%)
    8 / 400 (2.00%)
         occurrences causally related to treatment / all
    7 / 7
    0 / 0
    8 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMOTHORAX
         subjects affected / exposed
    0 / 393 (0.00%)
    2 / 394 (0.51%)
    4 / 400 (1.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    5 / 393 (1.27%)
    8 / 394 (2.03%)
    7 / 400 (1.75%)
         occurrences causally related to treatment / all
    2 / 5
    5 / 8
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    2 / 2
    0 / 0
    PULMONARY HAEMORRHAGE
         subjects affected / exposed
    2 / 393 (0.51%)
    4 / 394 (1.02%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 4
    0 / 0
         deaths causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
    PULMONARY NECROSIS
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PULMONARY OEDEMA
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    ALCOHOL WITHDRAWAL SYNDROME
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANXIETY
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BIPOLAR DISORDER
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CONFUSIONAL STATE
         subjects affected / exposed
    1 / 393 (0.25%)
    2 / 394 (0.51%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DELIRIUM
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DELUSION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MENTAL STATUS CHANGES
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PSYCHOTIC DISORDER
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUICIDAL IDEATION
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLOOD PRESSURE INCREASED
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLOOD LACTATE DEHYDROGENASE INCREASED
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    C-REACTIVE PROTEIN INCREASED
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GENERAL PHYSICAL CONDITION ABNORMAL
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATIC ENZYME INCREASED
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LIPASE INCREASED
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEUTROPHIL COUNT DECREASED
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PLATELET COUNT DECREASED
         subjects affected / exposed
    2 / 393 (0.51%)
    2 / 394 (0.51%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TRANSAMINASES INCREASED
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TROPONIN INCREASED
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WEIGHT DECREASED
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WHITE BLOOD CELL COUNT DECREASED
         subjects affected / exposed
    2 / 393 (0.51%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    ACCIDENTAL OVERDOSE
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FALL
         subjects affected / exposed
    2 / 393 (0.51%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FEMUR FRACTURE
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FRACTURE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HIP FRACTURE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFUSION RELATED REACTION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    3 / 400 (0.75%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HUMERUS FRACTURE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROCEDURAL COMPLICATION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    RIB FRACTURE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROCEDURAL PAIN
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPINAL COMPRESSION FRACTURE
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WOUND COMPLICATION
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    STERNAL FRACTURE
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    ACUTE MYOCARDIAL INFARCTION
         subjects affected / exposed
    2 / 393 (0.51%)
    3 / 394 (0.76%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    ATRIAL FIBRILLATION
         subjects affected / exposed
    2 / 393 (0.51%)
    1 / 394 (0.25%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATRIAL FLUTTER
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATRIOVENTRICULAR BLOCK SECOND DEGREE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CARDIAC ARREST
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    CARDIAC FAILURE
         subjects affected / exposed
    2 / 393 (0.51%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    CARDIAC FAILURE CONGESTIVE
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CORONARY ARTERY DISEASE
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LEFT VENTRICULAR DYSFUNCTION
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    MYOCARDIAL ISCHAEMIA
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERICARDIAL EFFUSION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERICARDITIS
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    TACHYARRHYTHMIA
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VENTRICULAR TACHYCARDIA
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    ATAXIA
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBRAL HAEMORRHAGE
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBRAL INFARCTION
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    CEREBRAL ISCHAEMIA
         subjects affected / exposed
    2 / 393 (0.51%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    CEREBROVASCULAR ACCIDENT
         subjects affected / exposed
    5 / 393 (1.27%)
    1 / 394 (0.25%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    3 / 5
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    COGNITIVE DISORDER
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEPRESSED LEVEL OF CONSCIOUSNESS
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIZZINESS
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIZZINESS POSTURAL
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENCEPHALOPATHY
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DYSAESTHESIA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FOCAL DYSCOGNITIVE SEIZURES
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMORRHAGE INTRACRANIAL
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    HEADACHE
         subjects affected / exposed
    2 / 393 (0.51%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ISCHAEMIC STROKE
         subjects affected / exposed
    1 / 393 (0.25%)
    4 / 394 (1.02%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    LOSS OF CONSCIOUSNESS
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    METABOLIC ENCEPHALOPATHY
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEUROPATHY PERIPHERAL
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PARTIAL SEIZURES
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL SENSORY NEUROPATHY
         subjects affected / exposed
    0 / 393 (0.00%)
    2 / 394 (0.51%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME
         subjects affected / exposed
    0 / 393 (0.00%)
    2 / 394 (0.51%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    PRESYNCOPE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SEIZURE
         subjects affected / exposed
    5 / 393 (1.27%)
    1 / 394 (0.25%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SOMNOLENCE
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPINAL CORD COMPRESSION
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SYNCOPE
         subjects affected / exposed
    1 / 393 (0.25%)
    2 / 394 (0.51%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TRANSIENT ISCHAEMIC ATTACK
         subjects affected / exposed
    2 / 393 (0.51%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    5 / 393 (1.27%)
    4 / 394 (1.02%)
    5 / 400 (1.25%)
         occurrences causally related to treatment / all
    5 / 5
    4 / 4
    5 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BONE MARROW FAILURE
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    27 / 393 (6.87%)
    17 / 394 (4.31%)
    13 / 400 (3.25%)
         occurrences causally related to treatment / all
    28 / 30
    16 / 18
    13 / 13
         deaths causally related to treatment / all
    3 / 3
    0 / 0
    0 / 0
    LEUKOPENIA
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEUTROPENIA
         subjects affected / exposed
    4 / 393 (1.02%)
    2 / 394 (0.51%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    4 / 4
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NORMOCHROMIC ANAEMIA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PANCYTOPENIA
         subjects affected / exposed
    1 / 393 (0.25%)
    3 / 394 (0.76%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPONTANEOUS HAEMATOMA
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    THROMBOCYTOPENIA
         subjects affected / exposed
    6 / 393 (1.53%)
    2 / 394 (0.51%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    6 / 6
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    OPTIC NEUROPATHY
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    1 / 393 (0.25%)
    3 / 394 (0.76%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL PAIN LOWER
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COLITIS
         subjects affected / exposed
    6 / 393 (1.53%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    5 / 6
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COLITIS ISCHAEMIC
         subjects affected / exposed
    1 / 393 (0.25%)
    2 / 394 (0.51%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CONSTIPATION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    10 / 393 (2.54%)
    3 / 394 (0.76%)
    8 / 400 (2.00%)
         occurrences causally related to treatment / all
    6 / 11
    3 / 3
    7 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIVERTICULAR PERFORATION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DUODENAL ULCER
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DYSPHAGIA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FAECALOMA
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FOOD POISONING
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTRIC HAEMORRHAGE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTRITIS
         subjects affected / exposed
    4 / 393 (1.02%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GLOSSODYNIA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ILEUS PARALYTIC
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INGUINAL HERNIA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL ANGINA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    INTESTINAL HAEMORRHAGE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL INFARCTION
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL ISCHAEMIA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    INTESTINAL OBSTRUCTION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    INTESTINAL PERFORATION
         subjects affected / exposed
    0 / 393 (0.00%)
    2 / 394 (0.51%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    IRRITABLE BOWEL SYNDROME
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINE PERFORATION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    7 / 393 (1.78%)
    3 / 394 (0.76%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    6 / 7
    3 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OESOPHAGEAL FOOD IMPACTION
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS ACUTE
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VOMITING
         subjects affected / exposed
    5 / 393 (1.27%)
    3 / 394 (0.76%)
    4 / 400 (1.00%)
         occurrences causally related to treatment / all
    4 / 5
    3 / 3
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    CHOLANGITIS
         subjects affected / exposed
    3 / 393 (0.76%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHOLANGITIS ACUTE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHOLELITHIASIS
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATITIS
         subjects affected / exposed
    2 / 393 (0.51%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATOMEGALY
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATOTOXICITY
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    DERMATITIS
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ERYTHEMA MULTIFORME
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    3 / 400 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PEMPHIGOID
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RASH
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    3 / 400 (0.75%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RASH MACULO-PAPULAR
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    3 / 393 (0.76%)
    3 / 394 (0.76%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GLOMERULONEPHROPATHY
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMATURIA
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEPHROLITHIASIS
         subjects affected / exposed
    2 / 393 (0.51%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PRERENAL FAILURE
         subjects affected / exposed
    2 / 393 (0.51%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL FAILURE
         subjects affected / exposed
    3 / 393 (0.76%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL IMPAIRMENT
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL INJURY
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TUBULOINTERSTITIAL NEPHRITIS
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT OBSTRUCTION
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    ADRENAL INSUFFICIENCY
         subjects affected / exposed
    2 / 393 (0.51%)
    1 / 394 (0.25%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ADRENOCORTICAL INSUFFICIENCY ACUTE
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIABETES INSIPIDUS
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOPHYSITIS
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOTHYROIDISM
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SECONDARY ADRENOCORTICAL INSUFFICIENCY
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BACK PAIN
         subjects affected / exposed
    2 / 393 (0.51%)
    3 / 394 (0.76%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BONE PAIN
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COMPARTMENT SYNDROME
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FLANK PAIN
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MUSCULAR WEAKNESS
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MYALGIA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OSTEOLYSIS
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PAIN IN EXTREMITY
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SOFT TISSUE NECROSIS
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPINAL PAIN
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VERTEBRAL FORAMINAL STENOSIS
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    ABDOMINAL SEPSIS
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANAL ABSCESS
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BACTERAEMIA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BACTERIAL INFECTION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BONE ABSCESS
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRONCHITIS
         subjects affected / exposed
    3 / 393 (0.76%)
    2 / 394 (0.51%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BURSITIS INFECTIVE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CELLULITIS
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHRONIC SINUSITIS
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CLOSTRIDIUM DIFFICILE INFECTION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEVICE RELATED INFECTION
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EMPYEMA
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIVERTICULITIS
         subjects affected / exposed
    1 / 393 (0.25%)
    1 / 394 (0.25%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENCEPHALITIS
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENTERITIS INFECTIOUS
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENDOCARDITIS BACTERIAL
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENTEROCOLITIS BACTERIAL
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FEBRILE INFECTION
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROENTERITIS
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROENTERITIS CLOSTRIDIAL
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMORRHAGIC PNEUMONIA
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATITIS A
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATITIS C
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HERPES ZOSTER
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFECTED SKIN ULCER
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFECTION
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFECTIOUS PLEURAL EFFUSION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFLUENZA
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    KLEBSIELLA SEPSIS
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINE INFECTION
         subjects affected / exposed
    2 / 393 (0.51%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    3 / 400 (0.75%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LUNG INFECTION
         subjects affected / exposed
    2 / 393 (0.51%)
    1 / 394 (0.25%)
    4 / 400 (1.00%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEUTROPENIC SEPSIS
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OSTEOMYELITIS
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PARAINFLUENZAE VIRUS INFECTION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PAROTITIS
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    26 / 393 (6.62%)
    17 / 394 (4.31%)
    17 / 400 (4.25%)
         occurrences causally related to treatment / all
    7 / 28
    3 / 18
    4 / 19
         deaths causally related to treatment / all
    0 / 1
    1 / 3
    0 / 2
    PNEUMONIA ADENOVIRAL
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA BACTERIAL
         subjects affected / exposed
    3 / 393 (0.76%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROSTATIC ABSCESS
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PYOPNEUMOTHORAX
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY SYNCYTIAL VIRUS BRONCHITIS
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY SYNCYTIAL VIRUS INFECTION
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    4 / 393 (1.02%)
    2 / 394 (0.51%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    RESPIRATORY TRACT INFECTION FUNGAL
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SALMONELLOSIS
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SCROTAL ABSCESS
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    3 / 393 (0.76%)
    5 / 394 (1.27%)
    3 / 400 (0.75%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 5
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
    SEPTIC SHOCK
         subjects affected / exposed
    2 / 393 (0.51%)
    0 / 394 (0.00%)
    2 / 400 (0.50%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    STAPHYLOCOCCAL BACTERAEMIA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    STAPHYLOCOCCAL INFECTION
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TOOTH ABSCESS
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    3 / 393 (0.76%)
    2 / 394 (0.51%)
    4 / 400 (1.00%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VASCULAR DEVICE INFECTION
         subjects affected / exposed
    2 / 393 (0.51%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VIRAL INFECTION
         subjects affected / exposed
    3 / 393 (0.76%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    2 / 393 (0.51%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEHYDRATION
         subjects affected / exposed
    7 / 393 (1.78%)
    6 / 394 (1.52%)
    3 / 400 (0.75%)
         occurrences causally related to treatment / all
    7 / 9
    3 / 6
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FAILURE TO THRIVE
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERCALCAEMIA
         subjects affected / exposed
    0 / 393 (0.00%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERGLYCAEMIA
         subjects affected / exposed
    0 / 393 (0.00%)
    1 / 394 (0.25%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOKALAEMIA
         subjects affected / exposed
    2 / 393 (0.51%)
    0 / 394 (0.00%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPONATRAEMIA
         subjects affected / exposed
    2 / 393 (0.51%)
    1 / 394 (0.25%)
    1 / 400 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOPHOSPHATAEMIA
         subjects affected / exposed
    1 / 393 (0.25%)
    0 / 394 (0.00%)
    0 / 400 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Arm B Arm C Arm A
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    375 / 393 (95.42%)
    381 / 394 (96.70%)
    385 / 400 (96.25%)
    Vascular disorders
    HYPERTENSION
         subjects affected / exposed
    103 / 393 (26.21%)
    87 / 394 (22.08%)
    16 / 400 (4.00%)
         occurrences all number
    147
    102
    16
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    84 / 393 (21.37%)
    80 / 394 (20.30%)
    75 / 400 (18.75%)
         occurrences all number
    143
    107
    122
    CHEST PAIN
         subjects affected / exposed
    35 / 393 (8.91%)
    28 / 394 (7.11%)
    38 / 400 (9.50%)
         occurrences all number
    37
    32
    45
    FATIGUE
         subjects affected / exposed
    136 / 393 (34.61%)
    107 / 394 (27.16%)
    110 / 400 (27.50%)
         occurrences all number
    156
    125
    127
    MALAISE
         subjects affected / exposed
    27 / 393 (6.87%)
    12 / 394 (3.05%)
    21 / 400 (5.25%)
         occurrences all number
    43
    14
    28
    MUCOSAL INFLAMMATION
         subjects affected / exposed
    37 / 393 (9.41%)
    24 / 394 (6.09%)
    10 / 400 (2.50%)
         occurrences all number
    41
    27
    10
    OEDEMA PERIPHERAL
         subjects affected / exposed
    34 / 393 (8.65%)
    19 / 394 (4.82%)
    29 / 400 (7.25%)
         occurrences all number
    41
    20
    33
    PAIN
         subjects affected / exposed
    26 / 393 (6.62%)
    17 / 394 (4.31%)
    22 / 400 (5.50%)
         occurrences all number
    31
    17
    23
    PYREXIA
         subjects affected / exposed
    67 / 393 (17.05%)
    34 / 394 (8.63%)
    52 / 400 (13.00%)
         occurrences all number
    88
    44
    63
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    85 / 393 (21.63%)
    77 / 394 (19.54%)
    81 / 400 (20.25%)
         occurrences all number
    104
    94
    95
    DYSPHONIA
         subjects affected / exposed
    27 / 393 (6.87%)
    18 / 394 (4.57%)
    11 / 400 (2.75%)
         occurrences all number
    27
    19
    12
    DYSPNOEA
         subjects affected / exposed
    66 / 393 (16.79%)
    60 / 394 (15.23%)
    85 / 400 (21.25%)
         occurrences all number
    79
    66
    105
    EPISTAXIS
         subjects affected / exposed
    67 / 393 (17.05%)
    86 / 394 (21.83%)
    17 / 400 (4.25%)
         occurrences all number
    88
    108
    22
    HAEMOPTYSIS
         subjects affected / exposed
    21 / 393 (5.34%)
    18 / 394 (4.57%)
    15 / 400 (3.75%)
         occurrences all number
    24
    21
    26
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    22 / 393 (5.60%)
    10 / 394 (2.54%)
    9 / 400 (2.25%)
         occurrences all number
    25
    10
    10
    Psychiatric disorders
    ANXIETY
         subjects affected / exposed
    31 / 393 (7.89%)
    22 / 394 (5.58%)
    21 / 400 (5.25%)
         occurrences all number
    31
    23
    21
    DEPRESSION
         subjects affected / exposed
    25 / 393 (6.36%)
    12 / 394 (3.05%)
    15 / 400 (3.75%)
         occurrences all number
    26
    12
    15
    INSOMNIA
         subjects affected / exposed
    41 / 393 (10.43%)
    38 / 394 (9.64%)
    50 / 400 (12.50%)
         occurrences all number
    42
    41
    56
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    30 / 393 (7.63%)
    20 / 394 (5.08%)
    23 / 400 (5.75%)
         occurrences all number
    44
    24
    27
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    30 / 393 (7.63%)
    18 / 394 (4.57%)
    22 / 400 (5.50%)
         occurrences all number
    47
    19
    29
    NEUTROPHIL COUNT DECREASED
         subjects affected / exposed
    49 / 393 (12.47%)
    34 / 394 (8.63%)
    33 / 400 (8.25%)
         occurrences all number
    86
    72
    64
    PLATELET COUNT DECREASED
         subjects affected / exposed
    57 / 393 (14.50%)
    44 / 394 (11.17%)
    40 / 400 (10.00%)
         occurrences all number
    84
    76
    58
    WEIGHT DECREASED
         subjects affected / exposed
    52 / 393 (13.23%)
    42 / 394 (10.66%)
    27 / 400 (6.75%)
         occurrences all number
    56
    46
    30
    WHITE BLOOD CELL COUNT DECREASED
         subjects affected / exposed
    26 / 393 (6.62%)
    20 / 394 (5.08%)
    17 / 400 (4.25%)
         occurrences all number
    42
    39
    27
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    27 / 393 (6.87%)
    26 / 394 (6.60%)
    27 / 400 (6.75%)
         occurrences all number
    33
    31
    38
    DYSGEUSIA
         subjects affected / exposed
    24 / 393 (6.11%)
    19 / 394 (4.82%)
    15 / 400 (3.75%)
         occurrences all number
    27
    24
    16
    HEADACHE
         subjects affected / exposed
    70 / 393 (17.81%)
    53 / 394 (13.45%)
    41 / 400 (10.25%)
         occurrences all number
    87
    65
    49
    NEUROPATHY PERIPHERAL
         subjects affected / exposed
    92 / 393 (23.41%)
    67 / 394 (17.01%)
    104 / 400 (26.00%)
         occurrences all number
    105
    77
    116
    PARAESTHESIA
         subjects affected / exposed
    53 / 393 (13.49%)
    44 / 394 (11.17%)
    37 / 400 (9.25%)
         occurrences all number
    59
    50
    42
    PERIPHERAL SENSORY NEUROPATHY
         subjects affected / exposed
    65 / 393 (16.54%)
    54 / 394 (13.71%)
    58 / 400 (14.50%)
         occurrences all number
    73
    59
    65
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    115 / 393 (29.26%)
    104 / 394 (26.40%)
    145 / 400 (36.25%)
         occurrences all number
    133
    124
    182
    LEUKOPENIA
         subjects affected / exposed
    14 / 393 (3.56%)
    14 / 394 (3.55%)
    20 / 400 (5.00%)
         occurrences all number
    20
    17
    35
    NEUTROPENIA
         subjects affected / exposed
    72 / 393 (18.32%)
    70 / 394 (17.77%)
    60 / 400 (15.00%)
         occurrences all number
    111
    107
    85
    THROMBOCYTOPENIA
         subjects affected / exposed
    52 / 393 (13.23%)
    45 / 394 (11.42%)
    48 / 400 (12.00%)
         occurrences all number
    73
    64
    77
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    36 / 393 (9.16%)
    20 / 394 (5.08%)
    28 / 400 (7.00%)
         occurrences all number
    48
    24
    35
    CONSTIPATION
         subjects affected / exposed
    122 / 393 (31.04%)
    92 / 394 (23.35%)
    102 / 400 (25.50%)
         occurrences all number
    151
    115
    126
    DIARRHOEA
         subjects affected / exposed
    124 / 393 (31.55%)
    98 / 394 (24.87%)
    81 / 400 (20.25%)
         occurrences all number
    218
    133
    134
    DRY MOUTH
         subjects affected / exposed
    21 / 393 (5.34%)
    6 / 394 (1.52%)
    13 / 400 (3.25%)
         occurrences all number
    23
    6
    16
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    20 / 393 (5.09%)
    9 / 394 (2.28%)
    11 / 400 (2.75%)
         occurrences all number
    20
    11
    13
    NAUSEA
         subjects affected / exposed
    149 / 393 (37.91%)
    124 / 394 (31.47%)
    129 / 400 (32.25%)
         occurrences all number
    223
    177
    207
    STOMATITIS
         subjects affected / exposed
    54 / 393 (13.74%)
    24 / 394 (6.09%)
    23 / 400 (5.75%)
         occurrences all number
    72
    30
    27
    VOMITING
         subjects affected / exposed
    71 / 393 (18.07%)
    67 / 394 (17.01%)
    68 / 400 (17.00%)
         occurrences all number
    99
    105
    91
    Skin and subcutaneous tissue disorders
    ALOPECIA
         subjects affected / exposed
    188 / 393 (47.84%)
    180 / 394 (45.69%)
    180 / 400 (45.00%)
         occurrences all number
    195
    183
    182
    DRY SKIN
         subjects affected / exposed
    29 / 393 (7.38%)
    9 / 394 (2.28%)
    23 / 400 (5.75%)
         occurrences all number
    31
    9
    26
    PRURITUS
         subjects affected / exposed
    54 / 393 (13.74%)
    25 / 394 (6.35%)
    50 / 400 (12.50%)
         occurrences all number
    70
    27
    68
    RASH
         subjects affected / exposed
    70 / 393 (17.81%)
    28 / 394 (7.11%)
    71 / 400 (17.75%)
         occurrences all number
    90
    34
    94
    Renal and urinary disorders
    PROTEINURIA
         subjects affected / exposed
    79 / 393 (20.10%)
    63 / 394 (15.99%)
    9 / 400 (2.25%)
         occurrences all number
    123
    81
    13
    Endocrine disorders
    HYPOTHYROIDISM
         subjects affected / exposed
    50 / 393 (12.72%)
    13 / 394 (3.30%)
    33 / 400 (8.25%)
         occurrences all number
    56
    13
    39
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    108 / 393 (27.48%)
    88 / 394 (22.34%)
    94 / 400 (23.50%)
         occurrences all number
    175
    135
    145
    BACK PAIN
         subjects affected / exposed
    56 / 393 (14.25%)
    43 / 394 (10.91%)
    50 / 400 (12.50%)
         occurrences all number
    66
    49
    69
    BONE PAIN
         subjects affected / exposed
    23 / 393 (5.85%)
    19 / 394 (4.82%)
    16 / 400 (4.00%)
         occurrences all number
    31
    19
    18
    MUSCLE SPASMS
         subjects affected / exposed
    20 / 393 (5.09%)
    7 / 394 (1.78%)
    10 / 400 (2.50%)
         occurrences all number
    24
    8
    10
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    48 / 393 (12.21%)
    36 / 394 (9.14%)
    36 / 400 (9.00%)
         occurrences all number
    58
    39
    43
    MYALGIA
         subjects affected / exposed
    68 / 393 (17.30%)
    53 / 394 (13.45%)
    66 / 400 (16.50%)
         occurrences all number
    116
    81
    103
    PAIN IN EXTREMITY
         subjects affected / exposed
    49 / 393 (12.47%)
    33 / 394 (8.38%)
    44 / 400 (11.00%)
         occurrences all number
    62
    44
    50
    Infections and infestations
    BRONCHITIS
         subjects affected / exposed
    28 / 393 (7.12%)
    16 / 394 (4.06%)
    14 / 400 (3.50%)
         occurrences all number
    37
    17
    15
    NASOPHARYNGITIS
         subjects affected / exposed
    25 / 393 (6.36%)
    17 / 394 (4.31%)
    31 / 400 (7.75%)
         occurrences all number
    32
    18
    48
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    36 / 393 (9.16%)
    16 / 394 (4.06%)
    23 / 400 (5.75%)
         occurrences all number
    52
    20
    42
    URINARY TRACT INFECTION
         subjects affected / exposed
    35 / 393 (8.91%)
    28 / 394 (7.11%)
    37 / 400 (9.25%)
         occurrences all number
    55
    37
    50
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    117 / 393 (29.77%)
    86 / 394 (21.83%)
    100 / 400 (25.00%)
         occurrences all number
    155
    102
    128
    DEHYDRATION
         subjects affected / exposed
    33 / 393 (8.40%)
    15 / 394 (3.81%)
    7 / 400 (1.75%)
         occurrences all number
    42
    16
    7
    HYPOKALAEMIA
         subjects affected / exposed
    36 / 393 (9.16%)
    16 / 394 (4.06%)
    24 / 400 (6.00%)
         occurrences all number
    47
    18
    30
    HYPOMAGNESAEMIA
         subjects affected / exposed
    55 / 393 (13.99%)
    25 / 394 (6.35%)
    37 / 400 (9.25%)
         occurrences all number
    76
    29
    48
    HYPONATRAEMIA
         subjects affected / exposed
    23 / 393 (5.85%)
    17 / 394 (4.31%)
    13 / 400 (3.25%)
         occurrences all number
    32
    20
    14

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Nov 2014
    Protocol was amended to change test product MPDL3280A to atezolizumab.
    31 May 2016
    Protocol was amended to include additional secondary end point to evaluate efficacy of atezolizumab as measured by investigator-assessed time to response (TTR) accordinto RECIST v1.1 for the ITT population, the TC1/2/3 or IC1/2/3 population, and the TC2/3 or IC2/3 population.

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

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

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