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    Clinical Trial Results:
    A Randomized, Open-Label, Multicenter, Phase II Trial Evaluating the Safety and Activity of Pinatuzumab Vedotin (DCDT2980S) in Combination with Rituximab or Polatuzumab Vedotin (DCDS4501A) in Combination with Rituximab and a Non-Randomized Phase IB/II Evaluation of Polatuzumab Vedotin in Combination with Obinutuzumab in Patients with Relapsed or Refractory B-Cell NonHodgkin’s Lymphoma

    Summary
    EudraCT number
    2011-004377-84
    Trial protocol
    DE   IT   NL   FR  
    Global end of trial date

    Results information
    Results version number
    v1(current)
    This version publication date
    21 Mar 2018
    First version publication date
    21 Mar 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    GO27834
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01691898
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
    Scientific contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, 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
    10 Apr 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    08 Mar 2017
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    Safety, tolerability and anti-tumor activity of pinatuzumab vedotin combined with rituximab and polatuzumab vedotin combined with rituximab or obinutuzumab
    Protection of trial subjects
    The study was conducted in accordance with the principles of the “Declaration of Helsinki” and Good Clinical Practice (GCP) according to the regulations and procedures described in different sections of the protocol. Sponsor and the investigators strictly adhered to the stated provisions in these guidelines. This was documented by the investigator’s signature on the protocol agreeing to carry out all of its terms in accordance with the applicable regulations and law and to follow International Council for Harmonisation (ICH) GCP guidelines for good clinical practice.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    27 Sep 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Efficacy
    Long term follow-up duration
    2 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 23
    Country: Number of subjects enrolled
    Italy: 14
    Country: Number of subjects enrolled
    United States: 171
    Country: Number of subjects enrolled
    Canada: 16
    Country: Number of subjects enrolled
    Germany: 3
    Country: Number of subjects enrolled
    Netherlands: 3
    Worldwide total number of subjects
    230
    EEA total number of subjects
    43
    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)
    102
    From 65 to 84 years
    124
    85 years and over
    4

    Subject disposition

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    Recruitment
    Recruitment details
    For 4 participants the country was missing and these participants are currently reported under “United States”.

    Pre-assignment
    Screening details
    A total of 289 participants were screened, out of which, 230 participants were enrolled into the study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab
    Arm description
    Participants with relapsed or refractory (r/r) follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) received rituximab (RTX) at a dose of 375 milligrams per square meter (mg/m^2) administered via intravenous (IV) infusion on Day 1 and pinatuzumab vedotin at a dose of 2.4 milligrams per kilogram (mg/kg) administered via IV infusion on Day 2 for the first 2 cycles. RTX and pinatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle, in the absence of any infusion-related adverse events. Participants who developed disease progression (PD) were treated with RTX at 375 mg/m^2 and polatuzumab vedotin at 2.4 mg/kg via IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (maximum 17 cycles on an every-21-day schedule).
    Arm type
    Experimental

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    MabThera/Rituxan
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    RTX 375 mg/m^2 administered by IV infusion on Day 1 of every 21-day cycle.

    Investigational medicinal product name
    Pinatuzumab Vedotin
    Investigational medicinal product code
    Other name
    DCDT2980S
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pinatuzumab vedotin 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

    Investigational medicinal product name
    Polatuzumab Vedotin
    Investigational medicinal product code
    Other name
    DCDS4501A
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Polatuzumab vedotin 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

    Arm title
    Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Arm description
    Participants with r/r FL and DLBCL received RTX at a dose of 375 mg/m^2 administered via IV infusion on Day 1 and polatuzumab vedotin at a dose of 2.4 mg/kg administered via IV infusion on Day 2 for the first 2 cycles. RTX and polatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle, in the absence of any infusion-related adverse events. Participants who developed PD were treated with RTX at 375 mg/m^2 and pinatuzumab vedotin at 2.4 mg/kg via IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (maximum 17 cycles on an every-21-day schedule).
    Arm type
    Experimental

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    MabThera/Rituxan
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    RTX 375 mg/m^2 administered by IV infusion on Day 1 of every 21-day cycle.

    Investigational medicinal product name
    Polatuzumab Vedotin
    Investigational medicinal product code
    Other name
    DCDS4501A
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Polatuzumab vedotin 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

    Investigational medicinal product name
    Pinatuzumab Vedotin
    Investigational medicinal product code
    Other name
    DCDT2980S
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pinatuzumab vedotin 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

    Arm title
    Cohort C (FL): RTX + Polatuzumab
    Arm description
    Participants with r/r FL received RTX at a dose of 375 mg/m^2 administered via IV infusion on Day 1 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first 2 cycles. In the absence of any infusion-related adverse events, RTX and polatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle for up to a maximum of 1 year (17 cycles on an every-21-day schedule) or significant toxicity, disease progression, or withdrawal from study.
    Arm type
    Experimental

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    MabThera/Rituxan
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    RTX 375 mg/m^2 administered by IV infusion on Day 1 of every 21-day cycle.

    Investigational medicinal product name
    Polatuzumab Vedotin
    Investigational medicinal product code
    Other name
    DCDS4501A
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Polatuzumab vedotin 1.8 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

    Arm title
    Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab
    Arm description
    Participants with r/r FL and DLBCL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.
    Arm type
    Experimental

    Investigational medicinal product name
    Obinutuzumab
    Investigational medicinal product code
    Other name
    GA101, Gazyva, Gazyvaro
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Obinutuzumab 1000 mg administered by IV infusion on Days 1, 8, and 15 of first 21-Day cycle and on Day 1 of subsequent 21-day cycles for up to 8 cycles.

    Investigational medicinal product name
    Polatuzumab Vedotin
    Investigational medicinal product code
    Other name
    DCDS4501A
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Polatuzumab vedotin 1.8 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

    Arm title
    Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab
    Arm description
    Participants with r/r FL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.
    Arm type
    Experimental

    Investigational medicinal product name
    Obinutuzumab
    Investigational medicinal product code
    Other name
    GA101, Gazyva, Gazyvaro
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Obinutuzumab 1000 mg administered by IV infusion on Days 1, 8, and 15 of first 21-Day cycle and on Day 1 of subsequent 21-day cycles for up to 8 cycles.

    Investigational medicinal product name
    Polatuzumab Vedotin
    Investigational medicinal product code
    Other name
    DCDS4501A
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Polatuzumab vedotin 1.8 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

    Arm title
    Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab
    Arm description
    Participants with r/r DLBCL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.
    Arm type
    Experimental

    Investigational medicinal product name
    Obinutuzumab
    Investigational medicinal product code
    Other name
    GA101, Gazyva, Gazyvaro
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Obinutuzumab 1000 mg administered by IV infusion on Days 1, 8, and 15 of first 21-Day cycle and on Day 1 of subsequent 21-day cycles for up to 8 cycles.

    Investigational medicinal product name
    Polatuzumab Vedotin
    Investigational medicinal product code
    Other name
    DCDS4501A
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Polatuzumab vedotin 1.8 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

    Number of subjects in period 1
    Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Cohort C (FL): RTX + Polatuzumab Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab
    Started
    63
    59
    20
    9
    39
    40
    Completed
    3
    1
    2
    0
    0
    0
    Not completed
    60
    58
    18
    9
    39
    40
         Death
    31
    28
    4
    2
    5
    20
         Progression of Disease
    2
    3
    1
    -
    1
    2
         Unspecified
    -
    2
    1
    -
    -
    1
         Consent withdrawn by subject
    8
    5
    1
    1
    2
    3
         Ongoing in Study
    18
    19
    11
    5
    31
    14
         Adverse Event
    -
    1
    -
    1
    -
    -
         Lost to follow-up
    1
    -
    -
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab
    Reporting group description
    Participants with relapsed or refractory (r/r) follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) received rituximab (RTX) at a dose of 375 milligrams per square meter (mg/m^2) administered via intravenous (IV) infusion on Day 1 and pinatuzumab vedotin at a dose of 2.4 milligrams per kilogram (mg/kg) administered via IV infusion on Day 2 for the first 2 cycles. RTX and pinatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle, in the absence of any infusion-related adverse events. Participants who developed disease progression (PD) were treated with RTX at 375 mg/m^2 and polatuzumab vedotin at 2.4 mg/kg via IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (maximum 17 cycles on an every-21-day schedule).

    Reporting group title
    Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Reporting group description
    Participants with r/r FL and DLBCL received RTX at a dose of 375 mg/m^2 administered via IV infusion on Day 1 and polatuzumab vedotin at a dose of 2.4 mg/kg administered via IV infusion on Day 2 for the first 2 cycles. RTX and polatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle, in the absence of any infusion-related adverse events. Participants who developed PD were treated with RTX at 375 mg/m^2 and pinatuzumab vedotin at 2.4 mg/kg via IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (maximum 17 cycles on an every-21-day schedule).

    Reporting group title
    Cohort C (FL): RTX + Polatuzumab
    Reporting group description
    Participants with r/r FL received RTX at a dose of 375 mg/m^2 administered via IV infusion on Day 1 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first 2 cycles. In the absence of any infusion-related adverse events, RTX and polatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle for up to a maximum of 1 year (17 cycles on an every-21-day schedule) or significant toxicity, disease progression, or withdrawal from study.

    Reporting group title
    Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab
    Reporting group description
    Participants with r/r FL and DLBCL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.

    Reporting group title
    Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab
    Reporting group description
    Participants with r/r FL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.

    Reporting group title
    Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab
    Reporting group description
    Participants with r/r DLBCL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.

    Reporting group values
    Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Cohort C (FL): RTX + Polatuzumab Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab Total
    Number of subjects
    63 59 20 9 39 40 230
    Age Categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    65.1 ± 11.1 65.5 ± 13.6 61.0 ± 9.9 67.7 ± 9.7 63.8 ± 11.6 65.2 ± 15.3 -
    Gender Categorical
    Units: Subjects
        Female
    27 24 8 2 16 18 95
        Male
    36 35 12 7 23 22 135

    End points

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    End points reporting groups
    Reporting group title
    Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab
    Reporting group description
    Participants with relapsed or refractory (r/r) follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) received rituximab (RTX) at a dose of 375 milligrams per square meter (mg/m^2) administered via intravenous (IV) infusion on Day 1 and pinatuzumab vedotin at a dose of 2.4 milligrams per kilogram (mg/kg) administered via IV infusion on Day 2 for the first 2 cycles. RTX and pinatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle, in the absence of any infusion-related adverse events. Participants who developed disease progression (PD) were treated with RTX at 375 mg/m^2 and polatuzumab vedotin at 2.4 mg/kg via IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (maximum 17 cycles on an every-21-day schedule).

    Reporting group title
    Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Reporting group description
    Participants with r/r FL and DLBCL received RTX at a dose of 375 mg/m^2 administered via IV infusion on Day 1 and polatuzumab vedotin at a dose of 2.4 mg/kg administered via IV infusion on Day 2 for the first 2 cycles. RTX and polatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle, in the absence of any infusion-related adverse events. Participants who developed PD were treated with RTX at 375 mg/m^2 and pinatuzumab vedotin at 2.4 mg/kg via IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (maximum 17 cycles on an every-21-day schedule).

    Reporting group title
    Cohort C (FL): RTX + Polatuzumab
    Reporting group description
    Participants with r/r FL received RTX at a dose of 375 mg/m^2 administered via IV infusion on Day 1 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first 2 cycles. In the absence of any infusion-related adverse events, RTX and polatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle for up to a maximum of 1 year (17 cycles on an every-21-day schedule) or significant toxicity, disease progression, or withdrawal from study.

    Reporting group title
    Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab
    Reporting group description
    Participants with r/r FL and DLBCL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.

    Reporting group title
    Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab
    Reporting group description
    Participants with r/r FL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.

    Reporting group title
    Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab
    Reporting group description
    Participants with r/r DLBCL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.

    Subject analysis set title
    Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with r/r DLBCL received RTX at a dose of 375 mg/m^2 administered via IV infusion on Day 1 and pinatuzumab vedotin at a dose of 2.4 mg/kg administered via IV infusion on Day 2 for the first 2 cycles. RTX and pinatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle, in the absence of any infusion-related adverse events. Participants who developed PD were treated with RTX at 375 mg/m^2 and polatuzumab vedotin at 2.4 mg/kg via IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (maximum 17 cycles on an every-21-day schedule).

    Subject analysis set title
    Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with r/r FL received RTX at a dose of 375 mg/m^2 administered via IV infusion on Day 1 and pinatuzumab vedotin at a dose of 2.4 mg/kg administered via IV infusion on Day 2 for the first 2 cycles. RTX and pinatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle, in the absence of any infusion-related adverse events. Participants who developed PD were treated with RTX at 375 mg/m^2 and polatuzumab vedotin at 2.4 mg/kg via IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (maximum 17 cycles on an every-21-day schedule).

    Subject analysis set title
    Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with r/r DLBCL received RTX at a dose of 375 mg/m^2 administered via IV infusion on Day 1 and polatuzumab vedotin at a dose of 2.4 mg/kg administered via IV infusion on Day 2 for the first 2 cycles. RTX and polatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle, in the absence of any infusion-related adverse events. Participants who developed PD were treated with RTX at 375 mg/m^2 and pinatuzumab vedotin at 2.4 mg/kg via IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (maximum 17 cycles on an every-21-day schedule).

    Subject analysis set title
    Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with r/r FL received RTX at a dose of 375 mg/m^2 administered via IV infusion on Day 1 and polatuzumab vedotin at a dose of 2.4 mg/kg administered via IV infusion on Day 2 for the first 2 cycles. RTX and polatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle, in the absence of any infusion-related adverse events. Participants who developed PD were treated with RTX at 375 mg/m^2 and pinatuzumab vedotin at 2.4 mg/kg via IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (maximum 17 cycles on an every-21-day schedule).

    Subject analysis set title
    Cohort E (DLBCL): Obinutuzumab + Polatuzumab
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with r/r DLBCL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.

    Subject analysis set title
    Cohort E (FL): Obinutuzumab + Polatuzumab
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with r/r FL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.

    Subject analysis set title
    Cohort E + Cohort G (FL): Obinutuzumab + Polatuzumab
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with r/r FL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.

    Subject analysis set title
    Cohort E + Cohort H (DLBCL): Obinutuzumab + Polatuzumab
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with r/r DLBCL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.

    Primary: Percentage of Participants with a Best Overall Response (OR) of Complete Response (CR) or Partial Response (PR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)

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    End point title
    Percentage of Participants with a Best Overall Response (OR) of Complete Response (CR) or Partial Response (PR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C) [1] [2]
    End point description
    Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments greater than or equal to (>/=) 4 weeks after initial documentation. CR was defined as disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. PR was defined as >/=50 percent (%) decrease in sum of the products of greatest diameters (SPD) of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a >/=50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease. Analysis was performed on efficacy-evaluable population, which included all participants with baseline measurable disease and at least one post-baseline tumor assessment.
    End point type
    Primary
    End point timeframe
    Baseline up to 12 months after the last dose of study treatment (up to approximately 3.5 years)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    20
    42
    21
    39
    20
    Units: percentage of participants
        number (confidence interval 90%)
    75.0 (54.44 to 89.59)
    59.5 (45.67 to 72.32)
    61.9 (41.72 to 79.43)
    53.8 (39.58 to 67.65)
    70.0 (49.22 to 86.04)
    No statistical analyses for this end point

    Primary: Duration of Objective Response (DOR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)

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    End point title
    Duration of Objective Response (DOR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C) [3] [4]
    End point description
    Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014). DOR was defined as the time from the initial documentation of a CR or PR to the time of PD or death. CR was defined as disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. PR was defined as >/=50% decrease in SPD of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a >/=50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease. PD was defined as appearance of any new lesion more than 1.5 centimeters (cm) in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node. Analysis was performed on efficacy-evaluable population participants who achieved objective response.
    End point type
    Primary
    End point timeframe
    First occurrence of objective response up to PD/relapse or death due to any cause, whichever occurred first (up to approximately 3.5 years)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    15
    25
    13
    21
    14
    Units: months
        median (full range (min-max))
    12.85 (0.03 to 22.11)
    6.24 (0.89 to 22.57)
    6.47 (0.03 to 23.52)
    13.37 (0.03 to 35.68)
    9.36 (0.03 to 19.35)
    No statistical analyses for this end point

    Primary: Percentage of Participants with CR at End of Treatment (EOT) Based on Positron Emission Tomographic/Computed Tomography (PET/CT) Assessment Determined by Independent Review Committee (IRC) per Lugano 2014 Response Criteria: Cohorts E, G, and H

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    End point title
    Percentage of Participants with CR at End of Treatment (EOT) Based on Positron Emission Tomographic/Computed Tomography (PET/CT) Assessment Determined by Independent Review Committee (IRC) per Lugano 2014 Response Criteria: Cohorts E, G, and H [5] [6]
    End point description
    Tumor response assessment was performed by an IRC according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake less than or equal to [</=] mediastinum), or 3 (uptake less than [<] mediastinum but </=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method. Analysis was performed on efficacy-evaluable population. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Primary
    End point timeframe
    6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Results were reported descriptively and were not planned to be analyzed for statistically significant differences between groups.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab Cohort E (DLBCL): Obinutuzumab + Polatuzumab Cohort E (FL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    34
    27
    4
    2
    Units: percentage of participants
        number (confidence interval 90%)
    35.3 (21.79 to 50.82)
    0 (0.0 to 10.50)
    0 (0.0 to 52.71)
    50.0 (2.53 to 97.47)
    No statistical analyses for this end point

    Secondary: Number of Participants with Anti-Drug Antibodies (ADA) to Pinatuzumab Vedotin

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    End point title
    Number of Participants with Anti-Drug Antibodies (ADA) to Pinatuzumab Vedotin [7]
    End point description
    The number of participants with positive results for ADA against pinatuzumab vedotin at Baseline and at any of the post-baseline assessment time-points (overall 1.5 years) was reported. Participants positive at any post-baseline time points: post-baseline evaluable participants determined to have “Treatment-induced ADAs” or “Treatment-enhanced ADA”. Treatment-induced ADA: participant with negative or missing Baseline ADA result(s) and at least 1 positive post-Baseline ADA result. Treatment-enhanced ADA: participant with positive ADA result at Baseline who has >/=1 post Baseline titer results that are at least 0.60 titer unit greater than the Baseline result. Analysis was performed on safety-evaluable population, which included all participants who received at least 1 dose of study treatment (pinatuzumab vedotin). Here, 'Number of Subjects Analysed'=participants evaluable for this outcome measure; ‘n'=participants evaluable at specified time points for each group, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, post-baseline (up to approximately 1.5 years)
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    60
    1
    Units: participants
        Baseline (n=60, 0)
    2
    0
        Post-baseline (n=56, 1)
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants with ADA to Polatuzumab Vedotin

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    End point title
    Number of Participants with ADA to Polatuzumab Vedotin
    End point description
    The number of participants with positive results for ADA against polatuzumab vedotin at Baseline and at any of the post-baseline assessment time-points (overall 1.5 years) was reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have “Treatment-induced ADAs” or “Treatment-enhanced ADA” during the study. Treatment-induced ADA: participant with negative or missing Baseline ADA result(s) and at least 1 positive post-Baseline ADA result. Treatment-enhanced ADA: participant with positive ADA result at Baseline who has >/=1 post Baseline titer results that are at least 0.60 titer unit greater than the Baseline result. Analysis was performed on safety-evaluable population (only participants who received polatuzumab vedotin). Here, 'Number of Subjects Analysed'=participants evaluable for this outcome measure and ‘n'=participants evaluable at specified time points for each group, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, post-baseline (up to approximately 1.5 years)
    End point values
    Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Cohort C (FL): RTX + Polatuzumab Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    2
    59
    20
    8
    37
    36
    Units: participants
        Baseline (n=0,59,20,8,37,36)
    0
    1
    0
    0
    0
    0
        Post-baseline (n=2,53,20,6,36,36)
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants with ADA to Obinutuzumab

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    End point title
    Number of Participants with ADA to Obinutuzumab [8]
    End point description
    The number of participants with positive results for ADA against obinutuzumab at Baseline and at any of the post-baseline assessment time-points (overall 1.5 years) was reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have “Treatment-induced ADAs” or “Treatment-enhanced ADA” during the study. Treatment-induced ADA: participant with negative or missing Baseline ADA result(s) and at least 1 positive post-Baseline ADA result. Treatment-enhanced ADA: participant with positive ADA result at Baseline who has >/=1 post Baseline titer results that are at least 0.60 titer unit greater than the Baseline result. Analysis was performed on safety-evaluable population (only participants who received obinutuzumab). Here, 'Number of Subjects Analysed'=participants evaluable for this outcome measure and ‘n'=participants evaluable at specified time points for each group, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, post-baseline (up to approximately 1.5 years)
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    9
    37
    39
    Units: participants
        Baseline (n=9,37,39)
    1
    2
    0
        Post-baseline (n=6,36,37)
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Participants with PD as Determined by Modified Response and Progression Criteria for NHL or Death due to any Cause: Rituximab Containing Regimens (Arms A and B, Cohort C)

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    End point title
    Percentage of Participants with PD as Determined by Modified Response and Progression Criteria for NHL or Death due to any Cause: Rituximab Containing Regimens (Arms A and B, Cohort C) [9]
    End point description
    Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments >/=4 weeks after initial documentation. PD was defined as appearance of any new lesion more than 1.5 cm in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node. Analysis was performed on efficacy-evaluable population.
    End point type
    Secondary
    End point timeframe
    Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 3.5 years)
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    20
    42
    21
    39
    20
    Units: percentage of participants
        number (not applicable)
    60.0
    85.7
    52.4
    76.9
    55.0
    No statistical analyses for this end point

    Secondary: Progression-free Survival (PFS) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)

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    End point title
    Progression-free Survival (PFS) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C) [10]
    End point description
    Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments >/=4 weeks after initial documentation. PD was defined as appearance of any new lesion more than 1.5 cm in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node. PFS was defined as the time from the date of randomization to the date of PD or death from any cause, whichever occurred first. In absence of PD or death, PFS was censored at the date of the last tumor assessment. Participants with no post-baseline tumor assessment were censored on the date of randomization or date of enrollment. The median PFS was estimated using Kaplan-Meier estimates and the 95% CI for median was computed using the method of Brookmeyer and Crowley. Analysis was performed on efficacy-evaluable population.
    End point type
    Secondary
    End point timeframe
    Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 3.5 years)
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    20
    42
    21
    39
    20
    Units: months
        median (confidence interval 95%)
    18.103 (11.598 to 30.259)
    5.388 (3.943 to 10.579)
    12.682 (8.936 to 27.466)
    5.552 (4.304 to 12.780)
    15.277 (12.189 to 25.133)
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Died due to any Cause: Rituximab Containing Regimens (Arms A and B, Cohort C)

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    End point title
    Percentage of Participants who Died due to any Cause: Rituximab Containing Regimens (Arms A and B, Cohort C) [11]
    End point description
    Percentage of participants who died due to any cause was reported. Analysis was performed on efficacy-evaluable population.
    End point type
    Secondary
    End point timeframe
    Baseline up to death due to any cause (from baseline up to data cut-off date, up to approximately 4.5 years)
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    20
    42
    21
    39
    20
    Units: percentage of participants
        number (not applicable)
    20.0
    66.7
    23.8
    61.5
    15.0
    No statistical analyses for this end point

    Secondary: Overall Survival (OS): Rituximab Containing Regimens (Arms A and B, Cohort C)

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    End point title
    Overall Survival (OS): Rituximab Containing Regimens (Arms A and B, Cohort C) [12]
    End point description
    OS was defined as the time from the date of randomization or enrollment to the date of death from any cause. The median OS was estimated using Kaplan-Meier estimates and the 95% CI for median was computed using the method of Brookmeyer and Crowley. Analysis was performed on efficacy-evaluable population. The data ‘99.999 (9.9999 to 999.99)’ in the results signifies that median and corresponding CI could not be calculated because very few participants (<50%) had the event of interest.
    End point type
    Secondary
    End point timeframe
    Baseline up to death due to any cause (from baseline up to data cut-off date, up to approximately 4.5 years)
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    20
    42
    21
    39
    20
    Units: months
        median (confidence interval 95%)
    99.999 (9.9999 to 999.99)
    16.493 (7.458 to 32.460)
    99.999 (44.025 to 999.99)
    18.760 (10.415 to 38.571)
    99.999 (9.9999 to 999.99)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With CR at EOT Based on PET/CT Assessment as Determined by Investigator per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)

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    End point title
    Percentage of Participants With CR at EOT Based on PET/CT Assessment as Determined by Investigator per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H) [13]
    End point description
    Tumor response assessment was performed by the investigator according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Analysis was performed on efficacy-evaluable population. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab Cohort E (DLBCL): Obinutuzumab + Polatuzumab Cohort E (FL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    36
    33
    4
    3
    Units: percentage of participants
        number (confidence interval 90%)
    33.3 (20.49 to 48.34)
    15.2 (6.17 to 29.25)
    25.0 (1.27 to 75.14)
    66.7 (13.54 to 98.30)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with OR at EOT Based on PET/CT Assessment as Determined by IRC per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)

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    End point title
    Percentage of Participants with OR at EOT Based on PET/CT Assessment as Determined by IRC per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H) [14]
    End point description
    Tumor response assessment was performed by an IRC according to modified Lugano classification using PET/CT scan. OR was defined as a response of CR or PR. CR: a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR: a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. 90% CI was calculated using Clopper-Pearson method. Analysis was performed on efficacy-evaluable population; 'Number of Subjects Analysed'=participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab Cohort E (DLBCL): Obinutuzumab + Polatuzumab Cohort E (FL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    34
    27
    4
    2
    Units: percentage of participants
        number (confidence interval 90%)
    64.7 (49.18 to 78.21)
    18.5 (7.59 to 35.06)
    25.0 (1.27 to 75.14)
    100.0 (22.36 to 100.00)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with OR at EOT Based on PET/CT Assessment as Determined by the Investigator per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)

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    End point title
    Percentage of Participants with OR at EOT Based on PET/CT Assessment as Determined by the Investigator per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H) [15]
    End point description
    Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT scan. OR was defined as a response of CR or PR. CR: a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR: a score 4 (uptake moderately >liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. 90% CI for was calculated using Clopper-Pearson method. Analysis was performed on efficacy-evaluable population; 'Number of Subjects Analysed'=participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab Cohort E (DLBCL): Obinutuzumab + Polatuzumab Cohort E (FL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    36
    33
    4
    3
    Units: percentage of participants
        number (confidence interval 90%)
    63.9 (48.83 to 77.15)
    21.2 (10.40 to 36.18)
    25.0 (1.27 to 75.14)
    66.7 (13.54 to 98.30)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with CR at EOT Based on CT Assessment Alone as Determined by IRC per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)

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    End point title
    Percentage of Participants with CR at EOT Based on CT Assessment Alone as Determined by IRC per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)
    End point description
    Tumor response assessment was performed by an IRC according to modified Lugano classification using CT scan. CR was defined as reduction of longest transverse diameter (LDi) of target nodes/nodal masses to less than or equal to (</=) 1.5 cm, no extralymphatic sites of disease, absence of non-measured lesions and new lesions, reduction of enlarged organs to normal, and normal/IHC-negative bone marrow morphology. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Analysis was performed on efficacy-evaluable population. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
    End point values
    Cohort E + Cohort G (FL): Obinutuzumab + Polatuzumab Cohort E + Cohort H (DLBCL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    36
    31
    Units: percentage of participants
        number (confidence interval 90%)
    13.9 (5.6 to 27.0)
    6.5 (1.2 to 19.0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with CR at EOT Based on CT Assessment Alone as Determined by Investigator per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)

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    End point title
    Percentage of Participants with CR at EOT Based on CT Assessment Alone as Determined by Investigator per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)
    End point description
    Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. CR was defined as reduction of LDi of target nodes/nodal masses to </=1.5 cm, no extralymphatic sites of disease, absence of non-measured lesions and new lesions, reduction of enlarged organs to normal, and normal/IHC-negative bone marrow morphology. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Analysis was performed on efficacy-evaluable population. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
    End point values
    Cohort E + Cohort G (FL): Obinutuzumab + Polatuzumab Cohort E + Cohort H (DLBCL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    39
    37
    Units: percentage of participants
        number (confidence interval 90%)
    20.5 (10.6 to 34.0)
    10.8 (3.8 to 23.1)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with OR at EOT Based on CT Assessment Alone as Determined by IRC per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)

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    End point title
    Percentage of Participants with OR at EOT Based on CT Assessment Alone as Determined by IRC per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)
    End point description
    Tumor response assessment was performed by an IRC according to modified Lugano classification using CT scan. OR was defined as a response of CR or PR. CR was defined as reduction of LDi of target nodes/nodal masses to </=1.5 cm, no extralymphatic sites of disease, absence of non-measured lesions and new lesions, reduction of enlarged organs to normal, and normal/IHC-negative bone marrow morphology. PR was defined as >/=50% decrease in SPD of up to 6 target measurable nodes and extra-nodal sites; absence/reduction/no increase in size of non-measured lesions; reduction in length of spleen by at least >50% beyond normal; and no new lesions. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Analysis was performed on efficacy-evaluable population. Here, 'Number of Subjects Analysed'=participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
    End point values
    Cohort E + Cohort G (FL): Obinutuzumab + Polatuzumab Cohort E + Cohort H (DLBCL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    36
    31
    Units: percentage of participants
        number (confidence interval 90%)
    66.7 (51.7 to 79.5)
    25.8 (13.5 to 41.8)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with OR at EOT Based on CT Assessment Alone as Determined by Investigator per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)

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    End point title
    Percentage of Participants with OR at EOT Based on CT Assessment Alone as Determined by Investigator per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)
    End point description
    Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR was defined as a response of CR or PR. CR was defined as reduction of LDi of target nodes/nodal masses to </=1.5 cm, no extralymphatic sites of disease, absence of non-measured lesions and new lesions, reduction of enlarged organs to normal, and normal/IHC-negative bone marrow morphology. PR was defined as >/=50% decrease in SPD of up to 6 target measurable nodes and extra-nodal sites; absence/reduction/no increase in size of non-measured lesions; reduction in length of spleen by at least >50% beyond normal; and no new lesions. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Analysis was performed on efficacy-evaluable population. Here, 'Number of Subjects Analysed'=participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
    End point values
    Cohort E + Cohort G (FL): Obinutuzumab + Polatuzumab Cohort E + Cohort H (DLBCL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    39
    37
    Units: percentage of participants
        number (confidence interval 90%)
    64.1 (49.7 to 76.8)
    21.6 (11.2 to 35.6)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Best OR Based on PET/CT or CT Assessment as Determined by Investigator per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)

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    End point title
    Percentage of Participants with Best OR Based on PET/CT or CT Assessment as Determined by Investigator per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H) [16]
    End point description
    Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT or CT scan. Best OR was defined as a response of CR or PR. CR: a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR: a score 4 (uptake moderately >liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. 90% CI was calculated using Clopper-Pearson method. Analysis was performed on efficacy-evaluable population; 'Number of Subjects Analysed'=participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Baseline up to disease progression or death, whichever occurred first (up to approximately 2.5 years)
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab Cohort E (DLBCL): Obinutuzumab + Polatuzumab Cohort E (FL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    39
    39
    5
    4
    Units: percentage of participants
        number (confidence interval 90%)
    74.4 (60.40 to 85.38)
    43.6 (30.0 to 57.94)
    20.0 (1.02 to 65.74)
    50.0 (9.76 to 90.24)
    No statistical analyses for this end point

    Secondary: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)

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    End point title
    Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C) [17]
    End point description
    AUCinf for rituximab was estimated from serum concentration data using non-compartmental analysis. Analysis was performed on all participants with measurable pharmacokinetic (PK) concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 days)
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    15
    25
    15
    26
    11
    Units: day*micrograms (mcg)/milliliter (mL)
        arithmetic mean (standard deviation)
    2660 ± 879
    5640 ± 8320
    3350 ± 1180
    4200 ± 2620
    3910 ± 2480
    No statistical analyses for this end point

    Secondary: Maximum Observed Serum Concentration (Cmax) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)

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    End point title
    Maximum Observed Serum Concentration (Cmax) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C) [18]
    End point description
    Cmax for rituximab was estimated from serum concentration data using non-compartmental analysis. Analysis was performed on all participants with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 days)
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    18
    36
    18
    35
    16
    Units: mcg/mL
        arithmetic mean (standard deviation)
    227 ± 32.4
    217 ± 61.5
    225 ± 40.9
    232 ± 72.7
    228 ± 83.3
    No statistical analyses for this end point

    Secondary: Systemic Clearance (CL) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)

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    End point title
    Systemic Clearance (CL) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C) [19]
    End point description
    CL for rituximab was estimated from serum concentration data using non-compartmental analysis. Analysis was performed on all participants with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 days)
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    15
    25
    15
    26
    11
    Units: mL/day/meter-square (m^2)
        arithmetic mean (standard deviation)
    158.57 ± 60.47
    113.97 ± 61.41
    124.53 ± 41.12
    116.26 ± 59.99
    134.31 ± 97.45
    No statistical analyses for this end point

    Secondary: Half-Life (t1/2) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)

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    End point title
    Half-Life (t1/2) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C) [20]
    End point description
    t1/2 for rituximab was estimated from serum concentration data using non-compartmental analysis. Analysis was performed on all participants with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure. Time Frame: Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1-4 and every 4th Cycle thereafter (approximately up to 1.5 years); Day 8, Day 15 of Cycle 1 and 3; 30 Days after last infusion; 2, 4, & 6 months after treatment completion visit (approximately up to 1.5 years, Cycle length= 21 days).
    End point type
    Secondary
    End point timeframe
    Day 1 up to 1.5 years (detailed timeframe is provided in the Description)
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    15
    25
    15
    26
    11
    Units: days
        arithmetic mean (standard deviation)
    14.4 ± 3.62
    35.3 ± 56.3
    18.7 ± 6.23
    25.6 ± 18.0
    19.8 ± 7.34
    No statistical analyses for this end point

    Secondary: Volume of Distribution at Steady State (Vss) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)

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    End point title
    Volume of Distribution at Steady State (Vss) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C) [21]
    End point description
    Vss for rituximab was estimated from serum concentration data using non-compartmental analysis. Analysis was performed on all participants with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure. Time Frame: Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1-4 and every 4th Cycle thereafter (approximately up to 1.5 years); Day 8, Day 15 of Cycle 1 and 3; 30 Days after last infusion; 2, 4, & 6 months after treatment completion visit (approximately up to 1.5 years, Cycle length= 21 days)
    End point type
    Secondary
    End point timeframe
    Day 1 up to 1.5 years (detailed timeframe is provided in the end point description)
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    15
    25
    15
    26
    11
    Units: mL/m^2
        arithmetic mean (standard deviation)
    2654.46 ± 413.19
    2901.85 ± 1009.31
    2802.96 ± 678.33
    2988.90 ± 788.89
    2839.26 ± 730.10
    No statistical analyses for this end point

    Secondary: AUCinf of Total Antibody for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab

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    End point title
    AUCinf of Total Antibody for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab
    End point description
    AUCinf of total antibody for pinatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with Monomethyl Auristatin E (MMAE)-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody. Analysis was performed on all participants who received pinatuzumab vedotin (Arm A) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab
    Number of subjects analysed
    27
    15
    Units: day*mcg/mL
        arithmetic mean (standard deviation)
    309 ± 67.7
    315 ± 111
    No statistical analyses for this end point

    Secondary: AUCinf of Antibody Conjugated Monomethyl Auristatin E (acMMAE) for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab

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    End point title
    AUCinf of Antibody Conjugated Monomethyl Auristatin E (acMMAE) for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab
    End point description
    AUCinf of acMMAE for pinatuzumab was estimated from plasma concentration data using non-compartmental analysis. Antibody conjugated MMAE is the total concentration of MMAE that was conjugated to the antibody. Analysis was performed on all participants who received pinatuzumab vedotin (Arm A) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab
    Number of subjects analysed
    39
    17
    Units: day*nanogram (ng)/mL
        arithmetic mean (standard deviation)
    2840 ± 555
    3110 ± 828
    No statistical analyses for this end point

    Secondary: Area Under the Concentration-Time Curve from Time Zero To Last Measurable Concentration (AUClast) of Unconjugated MMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab

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    End point title
    Area Under the Concentration-Time Curve from Time Zero To Last Measurable Concentration (AUClast) of Unconjugated MMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab
    End point description
    AUClast of unconjugated MMAE was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody. Analysis was performed on all participants who received pinatuzumab vedotin (Arm A) with measurable PK concentrations.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab
    Number of subjects analysed
    39
    21
    Units: day*ng/mL
        arithmetic mean (standard deviation)
    34.2 ± 24.0
    33.5 ± 17.5
    No statistical analyses for this end point

    Secondary: Cmax of Total Antibody for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab

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    End point title
    Cmax of Total Antibody for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab
    End point description
    Cmax of total antibody for pinatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody. Analysis was performed on all participants who received pinatuzumab vedotin (Arm A) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab
    Number of subjects analysed
    39
    20
    Units: mcg/mL
        arithmetic mean (standard deviation)
    42.5 ± 11.6
    48.3 ± 9.34
    No statistical analyses for this end point

    Secondary: Cmax of acMMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab

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    End point title
    Cmax of acMMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab
    End point description
    Cmax of acMMAE for pinatuzumab was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody. Analysis was performed on all participants who received pinatuzumab vedotin (Arm A) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab
    Number of subjects analysed
    38
    21
    Units: ng/mL
        arithmetic mean (standard deviation)
    850 ± 222
    994 ± 190
    No statistical analyses for this end point

    Secondary: Cmax of Unconjugated MMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab

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    End point title
    Cmax of Unconjugated MMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab
    End point description
    Cmax of unconjugated MMAE was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody. Analysis was performed on all participants who received pinatuzumab vedotin (Arm A) with measurable PK concentrations.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab
    Number of subjects analysed
    39
    21
    Units: ng/mL
        arithmetic mean (standard deviation)
    4.39 ± 3.15
    4.20 ± 2.32
    No statistical analyses for this end point

    Secondary: AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab

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    End point title
    AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab
    End point description
    AUCinf of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 2.4 mg/kg in combination with rituximab (Arm B) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    26
    17
    Units: day*mcg/mL
        arithmetic mean (standard deviation)
    412 ± 108
    428 ± 106
    No statistical analyses for this end point

    Secondary: AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab

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    End point title
    AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab
    End point description
    AUCinf of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 2.4 mg/kg in combination with rituximab (Arm B) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    30
    17
    Units: day*ng/mL
        arithmetic mean (standard deviation)
    3660 ± 843
    3510 ± 1160
    No statistical analyses for this end point

    Secondary: AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab

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    End point title
    AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab
    End point description
    AUClast of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 2.4 mg/kg in combination with rituximab (Arm B) with measurable PK concentrations.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    39
    18
    Units: day*ng/mL
        arithmetic mean (standard deviation)
    31.7 ± 17.2
    29.5 ± 25.0
    No statistical analyses for this end point

    Secondary: Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab

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    End point title
    Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab
    End point description
    Cmax of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 2.4 mg/kg in combination with rituximab (Arm B) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    38
    16
    Units: mcg/mL
        arithmetic mean (standard deviation)
    51.9 ± 12.3
    55.9 ± 12.8
    No statistical analyses for this end point

    Secondary: Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab

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    End point title
    Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab
    End point description
    Cmax of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 2.4 mg/kg in combination with rituximab (Arm B) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    38
    17
    Units: ng/mL
        arithmetic mean (standard deviation)
    948 ± 204
    968 ± 268
    No statistical analyses for this end point

    Secondary: Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab

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    End point title
    Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination with Rituximab
    End point description
    Cmax of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 2.4 mg/kg in combination with rituximab (Arm B) with measurable PK concentrations.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Number of subjects analysed
    39
    18
    Units: ng/mL
        arithmetic mean (standard deviation)
    3.72 ± 1.98
    3.29 ± 2.71
    No statistical analyses for this end point

    Secondary: AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Rituximab

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    End point title
    AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Rituximab [22]
    End point description
    AUCinf of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 1.8 mg/kg in combination with rituximab (Cohort C) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab
    Number of subjects analysed
    17
    Units: day*mcg/mL
        arithmetic mean (standard deviation)
    258 ± 84.1
    No statistical analyses for this end point

    Secondary: AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Rituximab

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    End point title
    AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Rituximab [23]
    End point description
    AUCinf of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 1.8 mg/kg in combination with rituximab (Cohort C) with measurable PK concentrations. Here, 'Number of Subjects Analyzed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab
    Number of subjects analysed
    15
    Units: day*ng/mL
        arithmetic mean (standard deviation)
    2600 ± 630
    No statistical analyses for this end point

    Secondary: AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Rituximab

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    End point title
    AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Rituximab [24]
    End point description
    AUClast of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 1.8 mg/kg in combination with rituximab (Cohort C) with measurable PK concentrations.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab
    Number of subjects analysed
    20
    Units: day*ng/mL
        arithmetic mean (standard deviation)
    17.7 ± 9.39
    No statistical analyses for this end point

    Secondary: Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Rituximab

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    End point title
    Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Rituximab [25]
    End point description
    Cmax of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 1.8 mg/kg in combination with rituximab (Cohort C) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab
    Number of subjects analysed
    19
    Units: mcg/mL
        arithmetic mean (standard deviation)
    42.2 ± 7.92
    No statistical analyses for this end point

    Secondary: Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Rituximab

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    End point title
    Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Rituximab [26]
    End point description
    Cmax of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 1.8 mg/kg in combination with rituximab (Cohort C) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab
    Number of subjects analysed
    17
    Units: ng/mL
        arithmetic mean (standard deviation)
    787 ± 113
    No statistical analyses for this end point

    Secondary: Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Rituximab

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    End point title
    Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Rituximab [27]
    End point description
    Cmax of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 1.8 mg/kg in combination with rituximab (Cohort C) with measurable PK concentrations.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Reported analysis was planned to be carried out in the indicated arms only.
    End point values
    Cohort C (FL): RTX + Polatuzumab
    Number of subjects analysed
    20
    Units: ng/mL
        arithmetic mean (standard deviation)
    2.02 ± 1.34
    No statistical analyses for this end point

    Secondary: AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Obinutuzumab

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    End point title
    AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Obinutuzumab
    End point description
    AUCinf of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 1.8 mg/kg in combination with obinutuzumab (Cohort E+H and E+G) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Cohort E + Cohort G (FL): Obinutuzumab + Polatuzumab Cohort E + Cohort H (DLBCL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    30
    27
    Units: day*mcg/mL
        arithmetic mean (standard deviation)
    215 ± 102
    218 ± 89.1
    No statistical analyses for this end point

    Secondary: AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Obinutuzumab

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    End point title
    AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Obinutuzumab
    End point description
    AUCinf of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 1.8 mg/kg in combination with obinutuzumab (Cohort E+H and E+G) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Cohort E + Cohort G (FL): Obinutuzumab + Polatuzumab Cohort E + Cohort H (DLBCL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    29
    26
    Units: day*ng/mL
        arithmetic mean (standard deviation)
    2340 ± 875
    2440 ± 665
    No statistical analyses for this end point

    Secondary: AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Obinutuzumab

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    End point title
    AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Obinutuzumab
    End point description
    AUClast of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 1.8 mg/kg in combination with obinutuzumab (Cohort E+H and E+G) with measurable PK concentrations.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Cohort E + Cohort G (FL): Obinutuzumab + Polatuzumab Cohort E + Cohort H (DLBCL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    41
    40
    Units: day*ng/mL
        arithmetic mean (standard deviation)
    22.3 ± 9.46
    27.9 ± 21.3
    No statistical analyses for this end point

    Secondary: Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Obinutuzumab

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    End point title
    Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Obinutuzumab
    End point description
    Cmax of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 1.8 mg/kg in combination with obinutuzumab (Cohort E+H and E+G) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Cohort E + Cohort G (FL): Obinutuzumab + Polatuzumab Cohort E + Cohort H (DLBCL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    38
    37
    Units: mcg/mL
        arithmetic mean (standard deviation)
    34.2 ± 7.89
    35.0 ± 9.89
    No statistical analyses for this end point

    Secondary: Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Obinutuzumab

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    End point title
    Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Obinutuzumab
    End point description
    Cmax of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 1.8 mg/kg in combination with obinutuzumab (Cohort E+H and E+G) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Cohort E + Cohort G (FL): Obinutuzumab + Polatuzumab Cohort E + Cohort H (DLBCL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    33
    33
    Units: ng/mL
        arithmetic mean (standard deviation)
    694 ± 161
    711 ± 155
    No statistical analyses for this end point

    Secondary: Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Obinutuzumab

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    End point title
    Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination with Obinutuzumab
    End point description
    Cmax of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody. Analysis was performed on all participants who received polatuzumab vedotin at dose level 1.8 mg/kg in combination with obinutuzumab (Cohort E+H and E+G) with measurable PK concentrations.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Cohort E + Cohort G (FL): Obinutuzumab + Polatuzumab Cohort E + Cohort H (DLBCL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    41
    40
    Units: ng/mL
        arithmetic mean (standard deviation)
    2.80 ± 1.30
    3.62 ± 3.73
    No statistical analyses for this end point

    Secondary: Cmax of Obinutuzumab: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)

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    End point title
    Cmax of Obinutuzumab: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)
    End point description
    Cmax of obinutuzumab was estimated from serum concentration data using non-compartmental analysis. Analysis was performed on all participants who received obinutuzumab (Cohort E+H and E+G) with measurable PK concentrations. Here, 'Number of Subjects Analysed' signifies the number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
    End point values
    Cohort E + Cohort G (FL): Obinutuzumab + Polatuzumab Cohort E + Cohort H (DLBCL): Obinutuzumab + Polatuzumab
    Number of subjects analysed
    35
    40
    Units: mcg/mL
        arithmetic mean (standard deviation)
    330 ± 87.9
    340 ± 95.0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to 30 days after the last dose of study treatment (up to approximately 12 months for rituximab-containing regimens [Arms A and B, Cohort C] and 24 weeks for Cohorts E, G, and H)
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab
    Reporting group description
    Participants with relapsed or refractory [r/r] FL and DLBCL received rituximab (RTX) at a dose of 375 milligrams per square meter (mg/m^2) administered via intravenous (IV) infusion on Day 1 and pinatuzumab vedotin at a dose of 2.4 milligrams per kilogram (mg/kg) administered via IV infusion on Day 2 for the first 2 cycles. RTX and pinatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle, in the absence of any infusion-related adverse events. Participants who developed disease progression (PD) were treated with RTX at 375 mg/m^2 and polatuzumab vedotin at 2.4 mg/kg via IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (maximum 17 cycles on an every-21-day schedule).

    Reporting group title
    Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab
    Reporting group description
    Participants with r/r FL and DLBCL received RTX at a dose of 375 mg/m^2 administered via IV infusion on Day 1 and polatuzumab vedotin at a dose of 2.4 mg/kg administered via IV infusion on Day 2 for the first 2 cycles. RTX and polatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle, in the absence of any infusion-related adverse events. Participants who developed PD were treated with RTX at 375 mg/m^2 and pinatuzumab vedotin at 2.4 mg/kg via IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (maximum 17 cycles on an every-21-day schedule).

    Reporting group title
    Cohort C (FL): RTX + Polatuzumab
    Reporting group description
    Participants with r/r FL received RTX at a dose of 375 mg/m^2 administered via IV infusion on Day 1 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first 2 cycles. In the absence of any infusion-related adverse events, RTX and polatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle for up to a maximum of 1 year (17 cycles on an every-21-day schedule) or significant toxicity, disease progression, or withdrawal from study.

    Reporting group title
    Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab
    Reporting group description
    Participants with r/r FL and DLBCL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.

    Reporting group title
    Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab
    Reporting group description
    Participants with r/r FL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.

    Reporting group title
    Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab
    Reporting group description
    Participants with r/r DLBCL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.

    Serious adverse events
    Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Cohort C (FL): RTX + Polatuzumab Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    27 / 63 (42.86%)
    21 / 59 (35.59%)
    7 / 20 (35.00%)
    3 / 9 (33.33%)
    8 / 39 (20.51%)
    17 / 40 (42.50%)
         number of deaths (all causes)
    33
    27
    4
    2
    5
    21
         number of deaths resulting from adverse events
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Ganglioneuroma
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Axillary pain
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    2 / 63 (3.17%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 63 (3.17%)
    1 / 59 (1.69%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural Haematoma
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound secretion
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Cardiac failure congestive
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    1 / 9 (11.11%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Coagulopathy
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    2 / 63 (3.17%)
    2 / 59 (3.39%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    1 / 2
    3 / 3
    1 / 2
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 63 (1.59%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary congestion
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral motor neuropathy
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 63 (1.59%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colonic fistula
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fistula of small intestine
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric perforation
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hernial eventration
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal perforation
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct obstruction
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic steatosis
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular injury
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatomegaly
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 63 (3.17%)
    2 / 59 (3.39%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Bone pain
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour lysis syndrome
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridial sepsis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 63 (4.76%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral diarrhoea
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Cohort C (FL): RTX + Polatuzumab Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    63 / 63 (100.00%)
    58 / 59 (98.31%)
    20 / 20 (100.00%)
    9 / 9 (100.00%)
    37 / 39 (94.87%)
    38 / 40 (95.00%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    4 / 39 (10.26%)
    1 / 40 (2.50%)
         occurrences all number
    1
    0
    0
    0
    5
    1
    Haematoma
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    Hypertension
         subjects affected / exposed
    0 / 63 (0.00%)
    3 / 59 (5.08%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    Hypotension
         subjects affected / exposed
    4 / 63 (6.35%)
    1 / 59 (1.69%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    4 / 40 (10.00%)
         occurrences all number
    4
    1
    1
    0
    2
    5
    Orthostatic hypotension
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Surgical and medical procedures
    Thrombolysis
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign neoplasm of skin
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    5
    0
    0
    0
    Immune system disorders
    Hypogammaglobulinaemia
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    Seasonal allergy
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    11 / 63 (17.46%)
    16 / 59 (27.12%)
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    3 / 39 (7.69%)
    8 / 40 (20.00%)
         occurrences all number
    14
    26
    0
    1
    4
    9
    Chest pain
         subjects affected / exposed
    4 / 63 (6.35%)
    6 / 59 (10.17%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    5
    7
    2
    0
    0
    1
    Chills
         subjects affected / exposed
    5 / 63 (7.94%)
    4 / 59 (6.78%)
    3 / 20 (15.00%)
    0 / 9 (0.00%)
    8 / 39 (20.51%)
    5 / 40 (12.50%)
         occurrences all number
    7
    6
    6
    0
    9
    6
    Fatigue
         subjects affected / exposed
    32 / 63 (50.79%)
    34 / 59 (57.63%)
    13 / 20 (65.00%)
    5 / 9 (55.56%)
    20 / 39 (51.28%)
    11 / 40 (27.50%)
         occurrences all number
    49
    51
    19
    6
    26
    12
    Feeling hot
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Gait disturbance
         subjects affected / exposed
    1 / 63 (1.59%)
    3 / 59 (5.08%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    2 / 40 (5.00%)
         occurrences all number
    1
    4
    2
    0
    1
    3
    Influenza like illness
         subjects affected / exposed
    0 / 63 (0.00%)
    8 / 59 (13.56%)
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
         occurrences all number
    0
    14
    0
    1
    1
    0
    Malaise
         subjects affected / exposed
    1 / 63 (1.59%)
    2 / 59 (3.39%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
         occurrences all number
    1
    3
    1
    0
    2
    1
    Nodule
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    6 / 63 (9.52%)
    8 / 59 (13.56%)
    3 / 20 (15.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    3 / 40 (7.50%)
         occurrences all number
    8
    11
    4
    0
    3
    4
    Pain
         subjects affected / exposed
    5 / 63 (7.94%)
    1 / 59 (1.69%)
    3 / 20 (15.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    5
    2
    4
    0
    0
    1
    Peripheral swelling
         subjects affected / exposed
    1 / 63 (1.59%)
    2 / 59 (3.39%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
         occurrences all number
    1
    2
    0
    0
    2
    0
    Pyrexia
         subjects affected / exposed
    15 / 63 (23.81%)
    9 / 59 (15.25%)
    5 / 20 (25.00%)
    2 / 9 (22.22%)
    5 / 39 (12.82%)
    3 / 40 (7.50%)
         occurrences all number
    19
    12
    20
    2
    5
    3
    Unevaluable event
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Psychiatric disorders
    Adjustment disorder with depressed mood
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Anxiety
         subjects affected / exposed
    2 / 63 (3.17%)
    5 / 59 (8.47%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
         occurrences all number
    2
    6
    1
    0
    2
    1
    Depression
         subjects affected / exposed
    3 / 63 (4.76%)
    4 / 59 (6.78%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    1 / 40 (2.50%)
         occurrences all number
    4
    4
    1
    0
    1
    1
    Hallucination olfactory
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Insomnia
         subjects affected / exposed
    15 / 63 (23.81%)
    8 / 59 (13.56%)
    3 / 20 (15.00%)
    1 / 9 (11.11%)
    1 / 39 (2.56%)
    6 / 40 (15.00%)
         occurrences all number
    16
    12
    3
    1
    1
    6
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Contusion
         subjects affected / exposed
    1 / 63 (1.59%)
    1 / 59 (1.69%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    1
    1
    1
    0
    0
    2
    Excoriation
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Fall
         subjects affected / exposed
    1 / 63 (1.59%)
    2 / 59 (3.39%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    3 / 39 (7.69%)
    2 / 40 (5.00%)
         occurrences all number
    2
    2
    0
    0
    3
    2
    Infusion related reaction
         subjects affected / exposed
    3 / 63 (4.76%)
    1 / 59 (1.69%)
    2 / 20 (10.00%)
    1 / 9 (11.11%)
    7 / 39 (17.95%)
    3 / 40 (7.50%)
         occurrences all number
    5
    1
    3
    1
    8
    3
    Procedural pain
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Radiation skin injury
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 63 (3.17%)
    2 / 59 (3.39%)
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    3 / 39 (7.69%)
    1 / 40 (2.50%)
         occurrences all number
    2
    9
    0
    1
    3
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 63 (3.17%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    4 / 39 (10.26%)
    2 / 40 (5.00%)
         occurrences all number
    2
    2
    0
    0
    5
    2
    Blood creatinine increased
         subjects affected / exposed
    2 / 63 (3.17%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    1 / 39 (2.56%)
    1 / 40 (2.50%)
         occurrences all number
    2
    1
    0
    1
    1
    3
    Blood potassium decreased
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    2
    0
    0
    0
    Lipase increased
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
         occurrences all number
    0
    0
    0
    0
    3
    1
    Neutrophil count decreased
         subjects affected / exposed
    0 / 63 (0.00%)
    4 / 59 (6.78%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    6
    0
    0
    0
    1
    Platelet count decreased
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 39 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    1
    0
    1
    0
    3
    Protein total decreased
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Weight decreased
         subjects affected / exposed
    6 / 63 (9.52%)
    7 / 59 (11.86%)
    3 / 20 (15.00%)
    1 / 9 (11.11%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    9
    7
    4
    1
    0
    0
    Weight increased
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    White blood cell count decreased
         subjects affected / exposed
    1 / 63 (1.59%)
    4 / 59 (6.78%)
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
         occurrences all number
    2
    7
    0
    1
    4
    1
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    1 / 39 (2.56%)
    1 / 40 (2.50%)
         occurrences all number
    2
    0
    0
    1
    1
    2
    Cardiac tamponade
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Pericardial effusion
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Tachycardia
         subjects affected / exposed
    3 / 63 (4.76%)
    3 / 59 (5.08%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
         occurrences all number
    3
    3
    0
    0
    4
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    9 / 63 (14.29%)
    15 / 59 (25.42%)
    3 / 20 (15.00%)
    1 / 9 (11.11%)
    7 / 39 (17.95%)
    7 / 40 (17.50%)
         occurrences all number
    10
    16
    6
    1
    7
    8
    Dysphonia
         subjects affected / exposed
    1 / 63 (1.59%)
    2 / 59 (3.39%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    2 / 40 (5.00%)
         occurrences all number
    1
    2
    1
    0
    3
    2
    Dyspnoea
         subjects affected / exposed
    11 / 63 (17.46%)
    11 / 59 (18.64%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    5 / 39 (12.82%)
    8 / 40 (20.00%)
         occurrences all number
    13
    14
    4
    0
    5
    9
    Dyspnoea exertional
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    1 / 40 (2.50%)
         occurrences all number
    1
    0
    2
    0
    1
    2
    Epistaxis
         subjects affected / exposed
    3 / 63 (4.76%)
    1 / 59 (1.69%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    2 / 40 (5.00%)
         occurrences all number
    3
    1
    2
    0
    2
    2
    Hiccups
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Hypoxia
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    2 / 40 (5.00%)
         occurrences all number
    0
    1
    0
    0
    2
    2
    Nasal congestion
         subjects affected / exposed
    4 / 63 (6.35%)
    2 / 59 (3.39%)
    2 / 20 (10.00%)
    1 / 9 (11.11%)
    5 / 39 (12.82%)
    3 / 40 (7.50%)
         occurrences all number
    4
    2
    3
    1
    5
    3
    Oropharyngeal pain
         subjects affected / exposed
    6 / 63 (9.52%)
    0 / 59 (0.00%)
    3 / 20 (15.00%)
    1 / 9 (11.11%)
    2 / 39 (5.13%)
    3 / 40 (7.50%)
         occurrences all number
    7
    0
    3
    1
    2
    3
    Orthopnoea
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Pleural effusion
         subjects affected / exposed
    2 / 63 (3.17%)
    0 / 59 (0.00%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    2
    0
    3
    0
    0
    1
    Productive cough
         subjects affected / exposed
    1 / 63 (1.59%)
    3 / 59 (5.08%)
    4 / 20 (20.00%)
    2 / 9 (22.22%)
    4 / 39 (10.26%)
    2 / 40 (5.00%)
         occurrences all number
    1
    3
    5
    2
    4
    2
    Pulmonary congestion
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    3 / 63 (4.76%)
    0 / 59 (0.00%)
    2 / 20 (10.00%)
    2 / 9 (22.22%)
    1 / 39 (2.56%)
    2 / 40 (5.00%)
         occurrences all number
    3
    0
    2
    2
    1
    2
    Sinus congestion
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    1
    0
    1
    0
    Sneezing
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    9 / 63 (14.29%)
    10 / 59 (16.95%)
    1 / 20 (5.00%)
    2 / 9 (22.22%)
    4 / 39 (10.26%)
    4 / 40 (10.00%)
         occurrences all number
    9
    12
    1
    2
    4
    4
    Lymphadenopathy
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    1
    0
    2
    0
    Neutropenia
         subjects affected / exposed
    19 / 63 (30.16%)
    15 / 59 (25.42%)
    8 / 20 (40.00%)
    4 / 9 (44.44%)
    8 / 39 (20.51%)
    8 / 40 (20.00%)
         occurrences all number
    49
    31
    16
    7
    12
    16
    Thrombocytopenia
         subjects affected / exposed
    3 / 63 (4.76%)
    2 / 59 (3.39%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    4 / 39 (10.26%)
    4 / 40 (10.00%)
         occurrences all number
    9
    3
    0
    0
    5
    8
    Nervous system disorders
    Carpal tunnel syndrome
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Cluster headache
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Cognitive disorder
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Cubital tunnel syndrome
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Dizziness
         subjects affected / exposed
    7 / 63 (11.11%)
    10 / 59 (16.95%)
    3 / 20 (15.00%)
    0 / 9 (0.00%)
    6 / 39 (15.38%)
    4 / 40 (10.00%)
         occurrences all number
    7
    13
    5
    0
    7
    4
    Dysgeusia
         subjects affected / exposed
    2 / 63 (3.17%)
    6 / 59 (10.17%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    4 / 39 (10.26%)
    1 / 40 (2.50%)
         occurrences all number
    2
    6
    1
    0
    4
    1
    Headache
         subjects affected / exposed
    10 / 63 (15.87%)
    8 / 59 (13.56%)
    6 / 20 (30.00%)
    1 / 9 (11.11%)
    10 / 39 (25.64%)
    6 / 40 (15.00%)
         occurrences all number
    15
    14
    7
    1
    10
    6
    Hypoaesthesia
         subjects affected / exposed
    3 / 63 (4.76%)
    2 / 59 (3.39%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    1 / 40 (2.50%)
         occurrences all number
    3
    3
    2
    0
    1
    2
    Memory impairment
         subjects affected / exposed
    1 / 63 (1.59%)
    3 / 59 (5.08%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    3
    2
    0
    0
    0
    Nerve compression
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    23 / 63 (36.51%)
    27 / 59 (45.76%)
    6 / 20 (30.00%)
    1 / 9 (11.11%)
    8 / 39 (20.51%)
    8 / 40 (20.00%)
         occurrences all number
    46
    40
    15
    1
    13
    9
    Paraesthesia
         subjects affected / exposed
    5 / 63 (7.94%)
    1 / 59 (1.69%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    4 / 39 (10.26%)
    3 / 40 (7.50%)
         occurrences all number
    6
    8
    2
    0
    7
    4
    Peripheral motor neuropathy
         subjects affected / exposed
    2 / 63 (3.17%)
    5 / 59 (8.47%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    4 / 39 (10.26%)
    0 / 40 (0.00%)
         occurrences all number
    2
    6
    3
    0
    4
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    16 / 63 (25.40%)
    17 / 59 (28.81%)
    11 / 20 (55.00%)
    2 / 9 (22.22%)
    7 / 39 (17.95%)
    2 / 40 (5.00%)
         occurrences all number
    21
    30
    22
    2
    10
    6
    Restless legs syndrome
         subjects affected / exposed
    3 / 63 (4.76%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    3 / 39 (7.69%)
    1 / 40 (2.50%)
         occurrences all number
    4
    1
    0
    0
    5
    1
    Syncope
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    Tremor
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
         occurrences all number
    0
    2
    1
    0
    2
    1
    Eye disorders
    Dry eye
         subjects affected / exposed
    2 / 63 (3.17%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    3 / 39 (7.69%)
    0 / 40 (0.00%)
         occurrences all number
    3
    0
    0
    0
    3
    0
    Eye pain
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Lacrimation increased
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Vision blurred
         subjects affected / exposed
    6 / 63 (9.52%)
    2 / 59 (3.39%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
         occurrences all number
    11
    2
    2
    0
    3
    1
    Visual impairment
         subjects affected / exposed
    1 / 63 (1.59%)
    1 / 59 (1.69%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
         occurrences all number
    2
    1
    0
    0
    2
    0
    Ear and labyrinth disorders
    Ear discomfort
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Ear pain
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    Vertigo
         subjects affected / exposed
    2 / 63 (3.17%)
    1 / 59 (1.69%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    0 / 40 (0.00%)
         occurrences all number
    2
    1
    1
    0
    4
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    2 / 63 (3.17%)
    3 / 59 (5.08%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    1 / 40 (2.50%)
         occurrences all number
    2
    3
    1
    0
    1
    1
    Abdominal distension
         subjects affected / exposed
    1 / 63 (1.59%)
    2 / 59 (3.39%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    3 / 39 (7.69%)
    4 / 40 (10.00%)
         occurrences all number
    1
    2
    0
    0
    4
    5
    Abdominal pain
         subjects affected / exposed
    11 / 63 (17.46%)
    11 / 59 (18.64%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    4 / 39 (10.26%)
    3 / 40 (7.50%)
         occurrences all number
    15
    15
    2
    0
    4
    6
    Abdominal pain lower
         subjects affected / exposed
    2 / 63 (3.17%)
    1 / 59 (1.69%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
         occurrences all number
    2
    1
    1
    0
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 63 (1.59%)
    4 / 59 (6.78%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    5 / 39 (12.82%)
    4 / 40 (10.00%)
         occurrences all number
    1
    4
    2
    0
    5
    4
    Constipation
         subjects affected / exposed
    18 / 63 (28.57%)
    14 / 59 (23.73%)
    5 / 20 (25.00%)
    0 / 9 (0.00%)
    14 / 39 (35.90%)
    8 / 40 (20.00%)
         occurrences all number
    21
    18
    6
    0
    14
    8
    Diarrhoea
         subjects affected / exposed
    28 / 63 (44.44%)
    25 / 59 (42.37%)
    5 / 20 (25.00%)
    3 / 9 (33.33%)
    13 / 39 (33.33%)
    14 / 40 (35.00%)
         occurrences all number
    42
    43
    7
    3
    17
    23
    Dry mouth
         subjects affected / exposed
    5 / 63 (7.94%)
    5 / 59 (8.47%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
         occurrences all number
    5
    6
    1
    0
    2
    1
    Dyspepsia
         subjects affected / exposed
    4 / 63 (6.35%)
    8 / 59 (13.56%)
    3 / 20 (15.00%)
    0 / 9 (0.00%)
    5 / 39 (12.82%)
    3 / 40 (7.50%)
         occurrences all number
    4
    9
    3
    0
    5
    3
    Dysphagia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    1 / 40 (2.50%)
         occurrences all number
    1
    0
    2
    0
    1
    1
    Gastritis
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Gastrointestinal pain
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 59 (0.00%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    2
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    4 / 63 (6.35%)
    0 / 59 (0.00%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    1 / 40 (2.50%)
         occurrences all number
    5
    0
    2
    0
    1
    1
    Haemorrhoids
         subjects affected / exposed
    2 / 63 (3.17%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    2
    0
    1
    0
    0
    0
    Nausea
         subjects affected / exposed
    20 / 63 (31.75%)
    25 / 59 (42.37%)
    11 / 20 (55.00%)
    0 / 9 (0.00%)
    11 / 39 (28.21%)
    14 / 40 (35.00%)
         occurrences all number
    27
    37
    14
    0
    14
    15
    Toothache
         subjects affected / exposed
    0 / 63 (0.00%)
    2 / 59 (3.39%)
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    1 / 39 (2.56%)
    0 / 40 (0.00%)
         occurrences all number
    0
    2
    2
    0
    1
    0
    Vomiting
         subjects affected / exposed
    11 / 63 (17.46%)
    13 / 59 (22.03%)
    3 / 20 (15.00%)
    0 / 9 (0.00%)
    8 / 39 (20.51%)
    5 / 40 (12.50%)
         occurrences all number
    13
    17
    8
    0
    8
    5
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 63 (1.59%)
    3 / 59 (5.08%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    4
    1
    0
    0
    0
    Nocturia
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    Urinary hesitation
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Actinic keratosis
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Alopecia
         subjects affected / exposed
    10 / 63 (15.87%)
    7 / 59 (11.86%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    2 / 39 (5.13%)
    1 / 40 (2.50%)
         occurrences all number
    11
    7
    1
    0
    2
    1
    Brow ptosis
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Dermatitis
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 59 (0.00%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Dermatitis acneiform
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 59 (1.69%)
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 39 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Dry skin
         subjects affected / exposed
    3 / 63 (4.76%)
    0 / 59 (0.00%)
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    3 / 39 (7.69%)
    2 / 40 (5.00%)
     &nb