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    Clinical Trial Results:
    A Phase Ib/II, Open-Label Study Evaluating the Safety and Pharmacokinetics of GDC-0199 (ABT-199) in Combination With Rituximab (R) or Obinutuzumab (G) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Patients With B-Cell Non-Hodgkin’s Lymphoma (NHL) and Diffuse Large B-cell Lymphoma (DLBCL)

    Summary
    EudraCT number
    		 2013-003749-40
    Trial protocol
    		 FR   NL   HU   CZ   ES   AT  
    Global end of trial date

    Results information
    Results version number
    		 v2
    This version publication date
    05 May 2019
    First version publication date
    12 Jul 2018
    Other versions
    		 v1 , v3
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GO27878
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02055820
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Hoffmann-La Roche
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Scientific contact
    Medical Communications, Hoffmann-La Roche, +41 616878333, global.trial_information@roche.com
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Interim
    Date of interim/final analysis
    28 Jun 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Jun 2017
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    This is a multicenter, open-label, dose-finding study of venetoclax administered orally in combination with rituximab (R) or obinutuzumab (G) and standard doses of cyclophosphamide, doxorubicin, vincristine and oral prednisone (CHOP) in participants with Non-Hodgkin's Lymphoma (NHL). The study will consist of 2 stages: a dose-finding Phase Ib stage and a Phase II expansion stage. In the Phase I portion of the study, participants will be randomized to one of 2 treatment arms venetoclax in combination with R-CHOP (Arm A) and venetoclax in combination with G-CHOP (Arm B) and will explore the doses of venetoclax in combination with R-CHOP and G-CHOP. For the Phase II portion of the study, the venetoclax dose for venetoclax + R-CHOP is on a non-continuous dosing schedule as determined by the Phase Ib portion of the study based on safety and tolerability observed in participants treated in the dose escalation portion of the study.
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    17 Nov 2013
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy, Safety
    Long term follow-up duration
    		 2 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 18
    Country: Number of subjects enrolled
    Austria: 11
    Country: Number of subjects enrolled
    Canada: 19
    Country: Number of subjects enrolled
    Czech Republic: 25
    Country: Number of subjects enrolled
    Spain: 11
    Country: Number of subjects enrolled
    France: 63
    Country: Number of subjects enrolled
    Hungary: 12
    Country: Number of subjects enrolled
    Italy: 20
    Country: Number of subjects enrolled
    Netherlands: 8
    Country: Number of subjects enrolled
    United States: 77
    Worldwide total number of subjects
    264
    EEA total number of subjects
    150
    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)
    137
    From 65 to 84 years
    126
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 The data reported for participant flow is based on safety population, which includes all participants who received at least one dose of study medication. There were 53 sites involved in 10 countries.

    Pre-assignment
    Screening details
    		 Phase I: Patients must have histologically confirmed B‑cell NHL (never received R‑CHOP treatment), except MCL or SLL. Any relapsed/refractory patients should have received only a single previous treatment regimen Phase II: Patients must have previously untreated CD20‑positive DLBCL and IPI score must be 2-5.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Venetoclax + R-CHOP Arm
    Arm description
    		 Phase I: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle will consist of 21 days. Phase II: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle will consist of 21 days. For both phase I and II, participants with ongoing response without excessive toxicity may receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    Other name
    GDC-0199
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Venetoclax 200 to 800 milligrams (mg) tablets will be administered orally once daily (QD) on Days 4−10 of Cycle 1 and Days 1−10 of Cycles 2−8 during Phase I and MTD will be administered according to the same schedule during Phase II.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cyclophosphamide 750 milligrams per square meter (mg/m^2) administered intravenously (IV) on Day 1 of each 21-day cycle up to Cycle 6.

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 50 mg/m^2 administered IV on Day 1 of each 21-day cycle up to Cycle 6.

    Investigational medicinal product name
    Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vincristine 1.4 mg/m^2 (maximum 2 mg) administered IV on Day 1 of each 21-day cycle up to Cycle 6.

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Prednisone 100 mg per day orally on Days 1-5 of each 21-day cycle up to Cycle 6.

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

    Arm title
    		 Venetoclax + G-CHOP Arm
    Arm description
    		 Phase I: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle will consist of 21 days. Phase II: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle will consist of 21 days. For both phase I and II, participants with ongoing response without excessive toxicity may receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Obinutuzumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Obinutuzumab administered by IV infusion as an absolute dose of 1000 mg on Days 1, 8, 15 of Cycle 1 and Day 1 of Cycles 2-8 (cycle length = 21 days).

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    Other name
    GDC-0199
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Venetoclax 200 to 800 milligrams (mg) tablets will be administered orally once daily (QD) on Days 4−10 of Cycle 1 and Days 1−10 of Cycles 2−8 during Phase I and MTD will be administered according to the same schedule during Phase II.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cyclophosphamide 750 milligrams per square meter (mg/m^2) administered intravenously (IV) on Day 1 of each 21-day cycle up to Cycle 6.

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 50 mg/m^2 administered IV on Day 1 of each 21-day cycle up to Cycle 6.

    Investigational medicinal product name
    Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vincristine 1.4 mg/m^2 (maximum 2 mg) administered IV on Day 1 of each 21-day cycle up to Cycle 6.

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Prednisone 100 mg per day orally on Days 1-5 of each 21-day cycle up to Cycle 6.

    Number of subjects in period 1
    		Venetoclax + R-CHOP Arm Venetoclax + G-CHOP Arm
    Started
    232
    32
    Completed
    0
    0
    Not completed
    232
    32
         Adverse event, serious fatal
    19
    -
         Participants still in study
    200
    31
         Consent withdrawn by subject
    10
    1
         Lost to follow-up
    3
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Venetoclax + R-CHOP Arm
    Reporting group description
    		 Phase I: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle will consist of 21 days. Phase II: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle will consist of 21 days. For both phase I and II, participants with ongoing response without excessive toxicity may receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Reporting group title
    Venetoclax + G-CHOP Arm
    Reporting group description
    		 Phase I: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle will consist of 21 days. Phase II: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle will consist of 21 days. For both phase I and II, participants with ongoing response without excessive toxicity may receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Reporting group values
    		 Venetoclax + R-CHOP Arm Venetoclax + G-CHOP Arm Total
    Number of subjects
    		 232 32 264
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 61.3 ( 12.6 ) 61.1 ( 11.4 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 103 17 120
        Male
    		 129 15 144

    End points

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    End points reporting groups
    Reporting group title
    Venetoclax + R-CHOP Arm
    Reporting group description
    		 Phase I: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle will consist of 21 days. Phase II: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle will consist of 21 days. For both phase I and II, participants with ongoing response without excessive toxicity may receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Reporting group title
    Venetoclax + G-CHOP Arm
    Reporting group description
    		 Phase I: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle will consist of 21 days. Phase II: Participants will receive 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle will consist of 21 days. For both phase I and II, participants with ongoing response without excessive toxicity may receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 200 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 400 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 600 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + G-CHOP 800 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + G-CHOP 200 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + G-CHOP 400 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + G-CHOP 600 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 800 mg Phase II
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + Rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 800 mg Phase II
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + Rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 100 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 200 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 400 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + G-CHOP 800 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 800 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 200 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 400 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 600 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 800 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + G-CHOP 400 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + G-CHOP 600 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All participants in the study. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All participants in the study. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All participants in the study. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All participants in the study. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All participants in the study. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All participants in the study. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All participants in the study. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 800 mg Phase II
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + Rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 800 mg A
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + G-CHOP 800 mg A
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + G-CHOP 800 mg B
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Subject analysis set title
    Venetoclax + R-CHOP 800mg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Primary: Safety: Number of Participants With Dose-Limiting Toxicities (DLTs)

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    End point title
    		 Safety: Number of Participants With Dose-Limiting Toxicities (DLTs) [1]
    End point description
    DLTs were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0). Decrease in B cells, lymphopenia, and leukopenia caused by lymphopenia were not considered DLTs but instead were expected outcomes of study treatment. Any Grade >/= 3 adverse event, that was attributed to having a reasonable possibility of being related to the combined administration of venetoclax plus R-CHOP or G-CHOP, that could not be attributed by the investigator to an alternative, clearly identifiable cause such as tumor progression, concurrent illness or medical condition, or concomitant medication and that occurred during the DLT observation period (start of venetoclax treatment through end of Cycle 2) was considered a DLT for dose-escalation purposes. Grade 3 or 4 neutropenia or thrombocytopenia identified on Day 1 of Cycle 2 or 3, resulting in dose delay were considered DLTs.
    End point type
    Primary
    End point timeframe
    Start of venetoclax administration (Cycle 1 Day 4 or 3 days after first CHOP dose) up to end of Cycle 2 (cycle length = 21 days)
    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: Descriptive statistics only
    End point values
    		 Venetoclax + R-CHOP 200 mg Venetoclax + R-CHOP 400 mg Venetoclax + R-CHOP 600 mg Venetoclax + G-CHOP 200 mg Venetoclax + G-CHOP 400 mg Venetoclax + G-CHOP 600 mg Venetoclax + G-CHOP 800 mg A Venetoclax + G-CHOP 800 mg B Venetoclax + R-CHOP 800mg
    Number of subjects analysed
    7
    3
    8
    7
    7
    6
    6
    6
    6
    Units: Participants
    1
    0
    1
    2
    1
    1
    0
    0
    0
    No statistical analyses for this end point

    Primary: Percentage of Participants With Complete Response (CR) Defined by Positron Emission Tomography-Computed Tomography (PET-CT) Scan Using the Modified Lugano Classification assessed by Independent Review Committee (IRC)

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    End point title
    		 Percentage of Participants With Complete Response (CR) Defined by Positron Emission Tomography-Computed Tomography (PET-CT) Scan Using the Modified Lugano Classification assessed by Independent Review Committee (IRC) [2]
    End point description
    CR was defined as follows according to modified Lugano classification for PET-CT-based response: Lymph nodes and extra-lymphatic sites with score 1, 2, or 3 with or without a residual mass on 5-point scale with 1) no uptake above background; 2) uptake </= mediastinum; 3) uptake < mediastinum but </= liver. No evidence of fluorodeoxyglucose (FDG)-uptake disease in marrow. If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. Intent-to-treat. All participants who enrolled in the study were included in the ITT population.
    End point type
    Primary
    End point timeframe
    Baseline up to end of treatment (up to approximately 36 months)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics only
    End point values
    		 Venetoclax + R-CHOP 800 mg Phase II
    Number of subjects analysed
    211 [3]
    Units: Percentage of participants
        number (confidence interval 95%)
    68.2 (61.50 to 74.47)
    Notes
    [3] - All participants who enrolled in the study were included in the ITT population
    No statistical analyses for this end point

    Primary: Percentage of Participants With CR Defined by PET/CT Scan in Dual Expressor Diffuse Large B-Cell Lymphoma (DE-DLBCL) Participants assessed by IRC

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    End point title
    		 Percentage of Participants With CR Defined by PET/CT Scan in Dual Expressor Diffuse Large B-Cell Lymphoma (DE-DLBCL) Participants assessed by IRC [4]
    End point description
    CR was defined as follows according to modified Lugano classification for PET/CT-based response: Lymph nodes and extra-lymphatic sites with score 1, 2, or 3 with or without a residual mass on 5-point scale with 1) no uptake above background; 2) uptake </= mediastinum; 3) uptake < mediastinum but </= liver. No evidence of fluorodeoxyglucose (FDG)-uptake disease in marrow. If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample.
    End point type
    Primary
    End point timeframe
    Baseline up to end of treatment (up to approximately 36 months)
    Notes
    [4] - 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: Descriptive statistics only
    End point values
    		 Venetoclax + R-CHOP 800 mg Phase II
    Number of subjects analysed
    81 [5]
    Units: Percentage of participants
        number (confidence interval 95%)
    66.7 (55.32 to 76.76)
    Notes
    [5] - All participants who enrolled in the study were included in the ITT population
    No statistical analyses for this end point

    Secondary: Venetoclax Plasma PK: Area Under the Plasma Concentration-Time Curve (AUC)

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    End point title
    		 Venetoclax Plasma PK: Area Under the Plasma Concentration-Time Curve (AUC)
    End point description
    AUC was calculated based on measurement of venetoclax concentration in plasma over time. Data are reported as hour*micrograms per milliliter (hr*mcg/mL). PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample. 99999=N/A
    End point type
    Secondary
    End point timeframe
    Predose (within 30 minutes) & 2, 4, 6, 8 hours (Hr) postdose on Cycle 1 Day 4; predose (within 30 minutes) and 8 Hr postdose on Cycle 1 Day 8; predose (within 30 minutes) on Cycle 2, 3, 4 Day 10 (cycle length = 21 days)
    End point values
    		 Venetoclax + R-CHOP 600 mg Venetoclax + G-CHOP 200 mg Venetoclax + G-CHOP 400 mg Venetoclax + G-CHOP 600 mg Venetoclax + R-CHOP 100 mg Venetoclax + R-CHOP 200 mg Venetoclax + R-CHOP 400 mg Venetoclax + G-CHOP 800 mg Venetoclax + R-CHOP 800 mg
    Number of subjects analysed
    8
    7
    7
    6
    1
    6
    4
    10
    124
    Units: hr*mcg/mL
        arithmetic mean (standard deviation)
    3.70 ( 1.59 )
    2.55 ( 1.13 )
    4.33 ( 1.31 )
    5.13 ( 2.41 )
    .66 ( 99999 )
    2.51 ( .97 )
    3.87 ( 2.41 )
    6.20 ( 1.71 )
    4.51 ( 2.32 )
    No statistical analyses for this end point

    Secondary: Venetoclax Plasma PK: Time to Maximum Observed Plasma Concentration (Tmax)

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    End point title
    		 Venetoclax Plasma PK: Time to Maximum Observed Plasma Concentration (Tmax)
    End point description
    Tmax was determined based on measurement of venetoclax concentrations in plasma over time. PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample. 99999=N/A
    End point type
    Secondary
    End point timeframe
    Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4; predose (within 30 minutes) and 8 Hr postdose on Cycle 1 Day 8; predose (within 30 minutes) on Cycle 2, 3, 4 Day 10 (cycle length = 21 days)
    End point values
    		 Venetoclax + R-CHOP 600 mg Venetoclax + G-CHOP 200 mg Venetoclax + G-CHOP 400 mg Venetoclax + G-CHOP 600 mg Venetoclax + R-CHOP 100 mg Venetoclax + R-CHOP 200 mg Venetoclax + R-CHOP 400 mg Venetoclax + G-CHOP 800 mg Venetoclax + R-CHOP 800 mg
    Number of subjects analysed
    8
    7
    7
    6
    1
    6
    4
    10
    124
    Units: Hour
        arithmetic mean (standard deviation)
    5.52 ( 2.07 )
    5.72 ( 1.42 )
    6.56 ( 1.51 )
    5.30 ( 2.38 )
    4.0 ( 99999 )
    4.59 ( 1.08 )
    6.50 ( 1.91 )
    5.79 ( 1.47 )
    5.53 ( 1.55 )
    No statistical analyses for this end point

    Secondary: Venetoclax Plasma PK: Maximum Observed Plasma Concentration (Cmax)

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    End point title
    		 Venetoclax Plasma PK: Maximum Observed Plasma Concentration (Cmax)
    End point description
    Cmax was determined based on measurement of venetoclax concentrations in plasma over time. Data are reported as micrograms per milliliter. PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample. 99999=N/A
    End point type
    Secondary
    End point timeframe
    Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4; predose (within 30 minutes) and 8 Hr postdose on Cycle 1 Day 8; predose (within 30 minutes) on Cycle 2, 3, 4 Day 10 (cycle length = 21 days)
    End point values
    		 Venetoclax + R-CHOP 600 mg Venetoclax + G-CHOP 200 mg Venetoclax + G-CHOP 400 mg Venetoclax + G-CHOP 600 mg Venetoclax + R-CHOP 100 mg Venetoclax + R-CHOP 200 mg Venetoclax + R-CHOP 400 mg Venetoclax + G-CHOP 800 mg Venetoclax + R-CHOP 800 mg
    Number of subjects analysed
    8
    7
    7
    6
    1
    6
    4
    10
    124
    Units: Ug/ML
        arithmetic mean (standard deviation)
    .85 ( .33 )
    .52 ( .21 )
    1.26 ( .30 )
    1.00 ( .58 )
    .09 ( 99999 )
    .58 ( .32 )
    .92 ( .64 )
    1.54 ( .37 )
    1.15 ( .48 )
    No statistical analyses for this end point

    Secondary: Venetoclax Plasma PK: Minimum Plasma Concentration (Cmin) within the Dosing Interval

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    End point title
    		 Venetoclax Plasma PK: Minimum Plasma Concentration (Cmin) within the Dosing Interval
    End point description
    Cmin was determined based on measurement of venetoclax concentrations in plasma over time. PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample.
    End point type
    Secondary
    End point timeframe
    Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4; predose (within 30 minutes) and 8 Hr postdose on Cycle 1 Day 8; predose (within 30 minutes) on Cycle 2, 3, 4 Day 10 (cycle length = 21 days)
    End point values
    		 Venetoclax + G-CHOP 800 mg Venetoclax + G-CHOP 200 mg Venetoclax + R-CHOP 100 mg Venetoclax + R-CHOP 200 mg Venetoclax + R-CHOP 400 mg Venetoclax + R-CHOP 600 mg Venetoclax + R-CHOP 800 mg Venetoclax + G-CHOP 400 mg Venetoclax + G-CHOP 600 mg
    Number of subjects analysed
    6
    7
    1
    3
    2
    4
    126
    5
    5
    Units: mcg/mL
        arithmetic mean (standard deviation)
    0.628 ( 0.395 )
    0.134 ( 0.107 )
    0.0714 ( 0.00 )
    0.522 ( 0.441 )
    0.253 ( 0.247 )
    0.387 ( 0.141 )
    0.640 ( 0.451 )
    0.395 ( 0.381 )
    0.612 ( 0.535 )
    No statistical analyses for this end point

    Secondary: Prednisone Plasma PK: AUC

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    End point title
    		 Prednisone Plasma PK: AUC
    End point description
    AUC was determined based on measurement of Predisone concentrations in plasma over time. PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample.
    End point type
    Secondary
    End point timeframe
    Predose (within 30 minutes) and 0.5, 1, 2, 4, 6 Hr after prednisone dose on Day 1 of Cycle 1 and 2 (cycle length = 21 days)
    End point values
    		 Venetoclax
    Number of subjects analysed
    54
    Units: hr*mcg/mL
    arithmetic mean (standard deviation)
        Cycle 1, Day 1|
    195 ( 72.8 )
        Cycle 2, Day 1|
    184 ( 81.2 )
    No statistical analyses for this end point

    Secondary: Prednisone Plasma PK: Tmax

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    End point title
    		 Prednisone Plasma PK: Tmax
    End point description
    Tmax was determined based on measurement of Predisone concentrations in plasma over time. PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample.
    End point type
    Secondary
    End point timeframe
    Predose (within 30 minutes) and 0.5, 1, 2, 4, 6 Hr after prednisone dose on Day 1 of Cycle 1 and 2 (cycle length = 21 days)
    End point values
    		 Venetoclax
    Number of subjects analysed
    54
    Units: Hour
    arithmetic mean (standard deviation)
        Cycle 1, Day 1|
    2.19 ( 1.61 )
        Cycle 2, Day 1|
    3.80 ( 2.52 )
    No statistical analyses for this end point

    Secondary: Prednisone Plasma PK: Cmax

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    End point title
    		 Prednisone Plasma PK: Cmax
    End point description
    Cmax was determined based on measurement of Predisone concentrations in plasma over time. PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample.
    End point type
    Secondary
    End point timeframe
    Predose (within 30 minutes) and 0.5, 1, 2, 4, 6 Hr after prednisone dose on Day 1 of Cycle 1 and 2 (cycle length = 21 days)
    End point values
    		 Venetoclax
    Number of subjects analysed
    54
    Units: Ng/ML
    arithmetic mean (standard deviation)
        Cycle 1, Day 1|
    49.9 ( 28.7 )
        Cycle 2, Day 1|
    43.2 ( 17.6 )
    No statistical analyses for this end point

    Secondary: Rituximab PK: Cmax

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    End point title
    		 Rituximab PK: Cmax
    End point description
    Cmax was determined based on measurement of Rituximab concentrations in plasma over time. PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample.
    End point type
    Secondary
    End point timeframe
    Predose (within 30 minutes) on Day 1 of Cycles 1-8; end of infusion (infusion duration = 2-3 hours) on Cycle 1 Day 1; anytime during end of treatment (6-9 weeks after Cycle 8 Day 1) (cycle length = 21 days)
    End point values
    		 Venetoclax
    Number of subjects analysed
    7
    Units: mcg/mL
        arithmetic mean (standard deviation)
    173 ( 39.4 )
    No statistical analyses for this end point

    Secondary: Rituximab PK: Cmin within the Dosing Interval

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    End point title
    		 Rituximab PK: Cmin within the Dosing Interval
    End point description
    Cmin was determined based on measurement of Rituximab concentrations in plasma over time. PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample.
    End point type
    Secondary
    End point timeframe
    Predose (within 30 minutes) on Day 1 of Cycles 1-8; end of infusion (infusion duration = 2-3 hours) on Cycle 1 Day 1 (cycle length = 21 days)
    End point values
    		 Venetoclax
    Number of subjects analysed
    8
    Units: mcg/mL
        arithmetic mean (standard deviation)
    26.1 ( 13 )
    No statistical analyses for this end point

    Secondary: Obinutuzumab PK: Cmax

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    End point title
    		 Obinutuzumab PK: Cmax
    End point description
    Cmax was determined based on measurement of Obinutuzumab concentrations in plasma over time. PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample.
    End point type
    Secondary
    End point timeframe
    Predose (within 30 minutes) on Day 1 of Cycles 1-8; predose (within 30 minutes) and end of infusion (infusion duration = 3 Hr) on Day 1 of Cycles 1 and 2; anytime during end of treatment (6-9 weeks after Cycle 8 Day 1) (cycle length = 21 days)
    End point values
    		 Venetoclax
    Number of subjects analysed
    10
    Units: mcg/mL
        arithmetic mean (standard deviation)
    326 ( 76 )
    No statistical analyses for this end point

    Secondary: Cyclophosphamide PK: Cmax

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    End point title
    		 Cyclophosphamide PK: Cmax
    End point description
    Cmax was determined based on measurement of Cyclophosphamide concentrations in plasma over time. PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample.
    End point type
    Secondary
    End point timeframe
    Predose (within 30 minutes) and end of infusion (infusion duration = 30 minutes) on Day 1 of Cycles 1 and 2 (cycle length = 21 days)
    End point values
    		 Venetoclax
    Number of subjects analysed
    36
    Units: mcg/mL
        arithmetic mean (standard deviation)
    32.1 ( 7.51 )
    No statistical analyses for this end point

    Secondary: Doxorubicin PK: Cmax

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    End point title
    		 Doxorubicin PK: Cmax
    End point description
    Cmax was determined based on measurement of Doxorubicin concentrations in plasma over time. PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample.
    End point type
    Secondary
    End point timeframe
    Predose (within 30 minutes) and end of infusion (infusion duration = 15-30 minutes) on Day 1 of Cycles 1 and 2 (cycle length = 21 days)
    End point values
    		 Venetoclax
    Number of subjects analysed
    24
    Units: mcg/mL
        arithmetic mean (standard deviation)
    1260 ( 911 )
    No statistical analyses for this end point

    Secondary: Vincristine PK: Cmax

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    End point title
    		 Vincristine PK: Cmax
    End point description
    Cmax was determined based on measurement of Rituximab concentrations in plasma over time. PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample.
    End point type
    Secondary
    End point timeframe
    Predose (within 30 minutes) and end of infusion (infusion duration = 10 minutes) on Day 1 of Cycles 1 and 2 (cycle length = 21 days)
    End point values
    		 Venetoclax
    Number of subjects analysed
    28
    Units: mcg/mL
        arithmetic mean (standard deviation)
    54.0 ( 44.6 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Objective Response Defined as Partial Response (PR) or Complete Response (CR) Using the Modified Lugano Classification

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    End point title
    		 Percentage of Participants With Objective Response Defined as Partial Response (PR) or Complete Response (CR) Using the Modified Lugano Classification
    End point description
    Objective Response defined as PR (partial response) or CR (complete response) at end of treatment. CR: Lymph nodes and extra-lymphatic sites with score 1, 2 or 3 on a 5-point scale (with a higher score being a worse outcome). No evidence of fluorodeoxyglucose (FDG)-uptake disease in marrow. If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: Lymph nodes and extralymphatic sites with score of 4 or 5 on the 5-point scale with reduced uptake compared with baseline and residual mass(es) of any size. CT-based response criteria for PR must also be met. No new lesions. In bone marrow residual uptake could be higher than in normal marrow but must be reduced compared with baseline; persistent focal changes in the marrow to be considered for further evaluation with magnetic resonance imaging (MRI) or biopsy or an interval scan. OR=PR+CR
    End point type
    Secondary
    End point timeframe
    Baseline up to disease progression or death due to any cause, whichever occurs first (up to approximately 36 months)
    End point values
    		 Venetoclax + R-CHOP 800 mg Phase II
    Number of subjects analysed
    211 [6]
    Units: Percentage of Participants
        number (confidence interval 95%)
    81.5 (75.61 to 86.51)
    Notes
    [6] - All participants who enrolled in the study were included in the ITT population.
    No statistical analyses for this end point

    Secondary: Percentage of Participants who are Alive and Without Disease Progression at Month 12

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    End point title
    		 Percentage of Participants who are Alive and Without Disease Progression at Month 12
    End point description
    Progressive disease (PD) was determined using the modified Lugano classification criteria. For PET-CT-based PD: Score 4 (uptake moderately > liver) or 5 (uptake markedly higher than liver and/or new lesions) with an increase in intensity of uptake from baseline in target nodes and nodal lesions, new FDG-uptake foci of extranodal lesions consistent with lymphoma at interim or end-of-treatment assessment, no non-measured lesions, new FDG-uptake foci consistent with lymphoma, new or recurrent FDG-uptake foci in bone marrow. For CT-based PD: >/= 50% decrease in SPD of up to 6 target measureable nodes and extranodal sites; non-measured lesion should be absent/normal, have regressed, but not increased; no new lesions. All participants who enrolled in the study were included in the ITT population
    End point type
    Secondary
    End point timeframe
    Month 12
    End point values
    		 Venetoclax + R-CHOP 200 mg Venetoclax + R-CHOP 400 mg Venetoclax + R-CHOP 600 mg Venetoclax + G-CHOP 200 mg Venetoclax + G-CHOP 400 mg Venetoclax + G-CHOP 600 mg Venetoclax + R-CHOP 800 mg Phase II Venetoclax + G-CHOP 800 mg A Venetoclax + G-CHOP 800 mg B Venetoclax + R-CHOP 800mg
    Number of subjects analysed
    7
    3
    8
    7
    7
    6
    211
    6
    6
    4
    Units: Percentage of Participants
        number (confidence interval 95%)
    85.71 (59.79 to 100.00)
    100.00 (100.00 to 100.00)
    87.50 (64.58 to 100.00)
    100.00 (100.00 to 100.00)
    75.00 (32.57 to 100.00)
    100.00 (100.00 to 100.00)
    83.62 (76.97 to 90.27)
    100.00 (100.00 to 100.00)
    100.00 (100.00 to 100.00)
    66.67 (28.95 to 100.00)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With CR Defined by Computed Tomography (CT) Scan Using the Modified Lugano Classification

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    End point title
    		 Percentage of Participants With CR Defined by Computed Tomography (CT) Scan Using the Modified Lugano Classification
    End point description
    CR was defined as follows according to modified Lugano classification for CT-based response: Target nodes/nodal masses must have regressed to </= 1.5 cm in longest transverse diameter of a lesion (LDi), no extra-lymphatic sites of disease, absence of non-measured lesions, organ enlargement must have regressed to normal, no new lesions, and if the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. All participants who enrolled in the study were included in the ITT population
    End point type
    Secondary
    End point timeframe
    Baseline up to disease progression or death due to any cause, whichever occurs first (up to approximately 36 months)
    End point values
    		 Venetoclax + R-CHOP 800 mg Phase II
    Number of subjects analysed
    211
    Units: Percentage of Participants
        number (confidence interval 95%)
    37.4 (30.89 to 44.35)
    No statistical analyses for this end point

    Secondary: Safety: Percentage of Participants With Adverse Events

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    End point title
    		 Safety: Percentage of Participants With Adverse Events
    End point description
    An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. All patients who enrolled in the study and received any amount of venetoclax or R-CHOP/G-CHOP were included in the safety population.
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 36 months
    End point values
    		 Venetoclax + R-CHOP 200 mg Venetoclax + R-CHOP 400 mg Venetoclax + R-CHOP 600 mg Venetoclax + G-CHOP 200 mg Venetoclax + G-CHOP 400 mg Venetoclax + G-CHOP 600 mg Venetoclax + R-CHOP 800 mg Phase II Venetoclax + G-CHOP 800 mg A Venetoclax + G-CHOP 800 mg B Venetoclax + R-CHOP 800mg
    Number of subjects analysed
    7
    3
    8
    7
    7
    6
    208
    6
    6
    6
    Units: Percentage of Participants
        number (not applicable)
    100.00
    100.00
    100.00
    100.00
    100.00
    100.00
    98.6
    100.0
    100.00
    100.00
    No statistical analyses for this end point

    Secondary: Safety: Percentage of Participants Maintaining Relative Dose Intensity of CHOP Chemotherapy

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    End point title
    		 Safety: Percentage of Participants Maintaining Relative Dose Intensity of CHOP Chemotherapy
    End point description
    Maintenance of relative dose intensity was defined as a dose intensity of >/= 90%. All patients who enrolled in the study and received any amount of venetoclax or R-CHOP/G-CHOP were included in the safety population.
    End point type
    Secondary
    End point timeframe
    Baseline up to Cycle 6 (cycle length = 21 days)
    End point values
    		 Venetoclax + R-CHOP Arm Venetoclax + G-CHOP Arm
    Number of subjects analysed
    232
    32
    Units: Percentage of participants
    number (not applicable)
        Cyclophosphamide|
    89.5
    77.4
        Doxorubicin|
    88.6
    77.4
        Vincristine|
    86.6
    78.1
        Prednisone|
    87.4
    81.3
    No statistical analyses for this end point

    Secondary: Relative Dose Intensity of Venetoclax

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    End point title
    		 Relative Dose Intensity of Venetoclax
    End point description
    Dose intensity was categorized as < 80%, 80% to < 85%, 85% to < 90%, or >/= 90%. All patients who enrolled in the study and received any amount of venetoclax or R-CHOP/G-CHOP were included in the safety population
    End point type
    Secondary
    End point timeframe
    Baseline up to Cycle 6 (cycle length = 21 days)
    End point values
    		 Venetoclax + R-CHOP 200 mg Venetoclax + R-CHOP 400 mg Venetoclax + R-CHOP 600 mg Venetoclax + G-CHOP 200 mg Venetoclax + G-CHOP 400 mg Venetoclax + G-CHOP 600 mg Venetoclax + R-CHOP 800 mg Phase II Venetoclax + G-CHOP 800 mg A Venetoclax + G-CHOP 800 mg B Venetoclax + R-CHOP 800mg
    Number of subjects analysed
    7
    3
    8
    7
    7
    6
    208
    6
    6
    6
    Units: Percentage of Partcipants
    number (not applicable)
        <80%|
    71.4
    0.00
    12.5
    100.00
    14.3
    50.0
    26.0
    83.3
    100.00
    0.00
        80-<85%|
    0.00
    0.00
    12.5
    0.00
    14.3
    16.7
    3.4
    0.00
    0.00
    0.00
        85-<90%|
    0.00
    0.00
    12.5
    0.00
    0.00
    0.00
    2.9
    16.7
    0.00
    0.00
        >=90%|
    28.6
    100.00
    62.5
    0.00
    71.4
    33.3
    67.6
    0.00
    0.00
    0.00
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to approximately 50 months
    Adverse event reporting additional description
    Safety population: All participants, who were enrolled in the study and received any amount of venetoclax or R-CHOP/G-CHOP, were included in the safety population.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Venetoclax+R-CHOP 200 mg
    Reporting group description
    		 Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Reporting group title
    Venetoclax+R-CHOP 400 mg
    Reporting group description
    		 Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Reporting group title
    Venetoclax+R-CHOP 600 mg
    Reporting group description
    		 Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Reporting group title
    Venetoclax+R-CHOP 800 mg
    Reporting group description
    		 Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Reporting group title
    Venetoclax+R-CHOP 800 mg Phase II
    Reporting group description
    		 Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Reporting group title
    Venetoclax+G-CHOP 200 mg
    Reporting group description
    		 Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Reporting group title
    Venetoclax+G-CHOP 400 mg
    Reporting group description
    		 Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Reporting group title
    Venetoclax+G-CHOP 600 mg
    Reporting group description
    		 Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Reporting group title
    Venetoclax+G-CHOP 800 mg A
    Reporting group description
    		 Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Reporting group title
    Venetoclax+G-CHOP 800 mg B
    Reporting group description
    		 Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.

    Serious adverse events
    		 Venetoclax+R-CHOP 200 mg Venetoclax+R-CHOP 400 mg Venetoclax+R-CHOP 600 mg Venetoclax+R-CHOP 800 mg Venetoclax+R-CHOP 800 mg Phase II Venetoclax+G-CHOP 200 mg Venetoclax+G-CHOP 400 mg Venetoclax+G-CHOP 600 mg Venetoclax+G-CHOP 800 mg A Venetoclax+G-CHOP 800 mg B
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 7 (71.43%)
    2 / 3 (66.67%)
    3 / 8 (37.50%)
    3 / 6 (50.00%)
    114 / 208 (54.81%)
    5 / 7 (71.43%)
    4 / 7 (57.14%)
    3 / 6 (50.00%)
    5 / 6 (83.33%)
    5 / 6 (83.33%)
         number of deaths (all causes)
    1
    0
    1
    2
    15
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Embolism
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inflammation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    7 / 208 (3.37%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    6 / 7
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypogammaglobulinaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Organising pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Productive cough
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Biopsy salivary gland
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood potassium increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    C−reactive protein increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 3
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    2 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post lumbar puncture syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    6 / 208 (2.88%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    3 / 6
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Carotid sinus syndrome
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglossal nerve paresis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 3
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Agranulocytosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    4 / 4
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    3 / 7 (42.86%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    2 / 6 (33.33%)
    60 / 208 (28.85%)
    2 / 7 (28.57%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    5 / 5
    0 / 0
    3 / 3
    3 / 3
    90 / 94
    2 / 2
    2 / 2
    0 / 0
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemolytic anaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    17 / 208 (8.17%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    21 / 21
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Optic neuropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 4
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticular perforation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal stenosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric dilatation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric perforation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric stenosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer perforation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileal perforation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal stenosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    5 / 208 (2.40%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    4 / 5
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug−induced liver injury
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash maculo−papular
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint swelling
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium colitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia pyelonephritis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis norovirus
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes simplex
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 4
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 3
    0 / 0
    1 / 1
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis viral
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral herpes
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    8 / 208 (3.85%)
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    6 / 8
    1 / 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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomonas infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Root canal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    7 / 208 (3.37%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    6 / 7
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection pseudomonal
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour lysis syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Venetoclax+R-CHOP 200 mg Venetoclax+R-CHOP 400 mg Venetoclax+R-CHOP 600 mg Venetoclax+R-CHOP 800 mg Venetoclax+R-CHOP 800 mg Phase II Venetoclax+G-CHOP 200 mg Venetoclax+G-CHOP 400 mg Venetoclax+G-CHOP 600 mg Venetoclax+G-CHOP 800 mg A Venetoclax+G-CHOP 800 mg B
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 7 (100.00%)
    3 / 3 (100.00%)
    8 / 8 (100.00%)
    6 / 6 (100.00%)
    205 / 208 (98.56%)
    7 / 7 (100.00%)
    7 / 7 (100.00%)
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Papillary thyroid cancer
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Vascular disorders
    Hot flush
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    3 / 208 (1.44%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    3
    0
    0
    0
    1
    0
    Hypotension
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    13 / 208 (6.25%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    15
    1
    0
    0
    2
    0
    Thrombophlebitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    3 / 208 (1.44%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    3
    1
    0
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    3 / 8 (37.50%)
    0 / 6 (0.00%)
    33 / 208 (15.87%)
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    2
    3
    0
    41
    2
    0
    1
    0
    0
    Chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    11 / 208 (5.29%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    11
    0
    0
    0
    0
    1
    Chills
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    11 / 208 (5.29%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    13
    0
    0
    0
    0
    0
    Fatigue
         subjects affected / exposed
    5 / 7 (71.43%)
    0 / 3 (0.00%)
    3 / 8 (37.50%)
    2 / 6 (33.33%)
    80 / 208 (38.46%)
    5 / 7 (71.43%)
    2 / 7 (28.57%)
    2 / 6 (33.33%)
    3 / 6 (50.00%)
    1 / 6 (16.67%)
         occurrences all number
    5
    0
    3
    4
    113
    7
    2
    2
    4
    1
    Gait disturbance
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Malaise
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    6 / 208 (2.88%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    0
    6
    2
    0
    0
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    1 / 6 (16.67%)
    20 / 208 (9.62%)
    1 / 7 (14.29%)
    3 / 7 (42.86%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    2
    1
    32
    1
    3
    0
    1
    0
    Non−cardiac chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Oedema
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    3 / 208 (1.44%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    4
    0
    0
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    0 / 6 (0.00%)
    24 / 208 (11.54%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    3 / 6 (50.00%)
    1 / 6 (16.67%)
         occurrences all number
    2
    0
    2
    0
    29
    0
    1
    0
    3
    1
    Pyrexia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    2 / 6 (33.33%)
    49 / 208 (23.56%)
    0 / 7 (0.00%)
    5 / 7 (71.43%)
    2 / 6 (33.33%)
    1 / 6 (16.67%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    1
    2
    67
    0
    7
    2
    2
    2
    Unevaluable event
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Feeling abnormal
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    5
    1
    0
    0
    0
    0
    Infusion site extravasation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    6 / 208 (2.88%)
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    0
    0
    7
    1
    1
    0
    1
    2
    Immune system disorders
    Hypogammaglobulinaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Hypersensitivity
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Reproductive system and breast disorders
    Breast pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Testicular pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Vaginal discharge
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    Vulvovaginal dryness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    3 / 8 (37.50%)
    1 / 6 (16.67%)
    52 / 208 (25.00%)
    3 / 7 (42.86%)
    3 / 7 (42.86%)
    0 / 6 (0.00%)
    3 / 6 (50.00%)
    2 / 6 (33.33%)
         occurrences all number
    2
    0
    4
    1
    71
    3
    3
    0
    5
    2
    Dyspnoea
         subjects affected / exposed
    3 / 7 (42.86%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    22 / 208 (10.58%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    4
    2
    0
    1
    24
    0
    1
    0
    1
    1
    Dyspnoea exertional
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    1 / 6 (16.67%)
    4 / 208 (1.92%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    1
    4
    0
    0
    0
    0
    0
    Hiccups
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    5
    0
    0
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 6 (16.67%)
    11 / 208 (5.29%)
    2 / 7 (28.57%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    1
    1
    11
    2
    1
    0
    4
    1
    Rhinorrhoea
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    13 / 208 (6.25%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    0
    0
    13
    1
    0
    1
    0
    1
    Sinus pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Vocal cord dysfunction
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Wheezing
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Pleural effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    Productive cough
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    7 / 208 (3.37%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    7
    0
    0
    0
    0
    1
    Epistaxis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    3 / 208 (1.44%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    1
    0
    0
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    10 / 208 (4.81%)
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    13
    1
    1
    0
    0
    0
    Pleuritic pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    9 / 208 (4.33%)
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    9
    3
    1
    0
    0
    1
    Depression
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    5
    0
    1
    0
    0
    0
    Insomnia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    1 / 6 (16.67%)
    15 / 208 (7.21%)
    2 / 7 (28.57%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    3
    1
    18
    2
    3
    0
    0
    1
    Mood swings
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Investigations
    Blood potassium increased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    32 / 208 (15.38%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    1 / 6 (16.67%)
         occurrences all number
    3
    0
    0
    1
    33
    0
    1
    0
    2
    1
    Weight increased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    3 / 208 (1.44%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    3
    0
    0
    0
    1
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Blood magnesium decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Computerised tomogram thorax abnormal
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Ejection fraction decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    0
    0
    0
    0
    Urine output decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    White blood cell count decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Hand fracture
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Infusion related reaction
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 3 (66.67%)
    1 / 8 (12.50%)
    2 / 6 (33.33%)
    44 / 208 (21.15%)
    4 / 7 (57.14%)
    1 / 7 (14.29%)
    2 / 6 (33.33%)
    2 / 6 (33.33%)
    3 / 6 (50.00%)
         occurrences all number
    1
    2
    1
    3
    48
    4
    1
    2
    3
    4
    Muscle strain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Thermal burn
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Tracheal obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Fall
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    0
    0
    1
    0
    Procedural pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Congenital, familial and genetic disorders
    Ichthyosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Atrial fibrillation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    7 / 208 (3.37%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    0
    8
    1
    0
    0
    0
    1
    Palpitations
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    8 / 208 (3.85%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    8
    0
    1
    0
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    3 / 208 (1.44%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    0
    3
    0
    0
    0
    0
    1
    Cardiac failure
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    Nervous system disorders
    Carotid sinus syndrome
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Cognitive disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Disturbance in attention
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Dizziness
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    1 / 6 (16.67%)
    23 / 208 (11.06%)
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
         occurrences all number
    1
    0
    2
    1
    31
    1
    1
    0
    0
    2
    Dysgeusia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    1 / 6 (16.67%)
    23 / 208 (11.06%)
    1 / 7 (14.29%)
    3 / 7 (42.86%)
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    4 / 6 (66.67%)
         occurrences all number
    0
    1
    1
    1
    28
    1
    3
    1
    2
    4
    Headache
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    3 / 8 (37.50%)
    1 / 6 (16.67%)
    27 / 208 (12.98%)
    3 / 7 (42.86%)
    3 / 7 (42.86%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    3
    1
    30
    5
    3
    1
    0
    0
    Memory impairment
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    3 / 8 (37.50%)
    3 / 6 (50.00%)
    27 / 208 (12.98%)
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    2 / 6 (33.33%)
         occurrences all number
    2
    2
    3
    3
    33
    0
    2
    1
    1
    3
    Paraesthesia
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    18 / 208 (8.65%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    1
    25
    0
    1
    0
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    3 / 7 (42.86%)
    1 / 3 (33.33%)
    2 / 8 (25.00%)
    2 / 6 (33.33%)
    14 / 208 (6.73%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    3
    1
    2
    2
    14
    0
    1
    1
    1
    1
    Presyncope
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    Syncope
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    8
    0
    0
    0
    0
    0
    Ageusia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    1
    0
    0
    0
    0
    Lethargy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Peripheral motor neuropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    1
    1
    Post herpetic neuralgia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 7 (57.14%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    2 / 6 (33.33%)
    72 / 208 (34.62%)
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    5 / 6 (83.33%)
    4 / 6 (66.67%)
         occurrences all number
    9
    0
    1
    3
    116
    1
    1
    4
    8
    5
    Febrile neutropenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 6 (16.67%)
    13 / 208 (6.25%)
    0 / 7 (0.00%)
    4 / 7 (57.14%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    3
    17
    0
    7
    0
    1
    0
    Haemolytic anaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Leukopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    24 / 208 (11.54%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    48
    0
    0
    1
    0
    0
    Neutropenia
         subjects affected / exposed
    4 / 7 (57.14%)
    2 / 3 (66.67%)
    5 / 8 (62.50%)
    2 / 6 (33.33%)
    130 / 208 (62.50%)
    2 / 7 (28.57%)
    4 / 7 (57.14%)
    5 / 6 (83.33%)
    6 / 6 (100.00%)
    2 / 6 (33.33%)
         occurrences all number
    9
    8
    15
    9
    356
    2
    17
    13
    12
    10
    Pancytopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 6 (16.67%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    0
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    4 / 7 (57.14%)
    1 / 3 (33.33%)
    2 / 8 (25.00%)
    0 / 6 (0.00%)
    54 / 208 (25.96%)
    2 / 7 (28.57%)
    3 / 7 (42.86%)
    2 / 6 (33.33%)
    4 / 6 (66.67%)
    2 / 6 (33.33%)
         occurrences all number
    7
    2
    4
    0
    88
    3
    7
    6
    14
    5
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    Tinnitus
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    Eye disorders
    Dry eye
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    4
    0
    0
    0
    0
    0
    Lacrimation increased
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    3 / 208 (1.44%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    0
    3
    0
    0
    1
    0
    0
    Vision blurred
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    7 / 208 (3.37%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    7
    0
    0
    0
    0
    0
    Photophobia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Vitreous floaters
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Eye pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    14 / 208 (6.73%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    0
    15
    0
    1
    0
    1
    0
    Abdominal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 6 (16.67%)
    31 / 208 (14.90%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    3 / 6 (50.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    39
    0
    1
    1
    4
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    7 / 208 (3.37%)
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    13
    1
    1
    0
    1
    0
    Constipation
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 3 (66.67%)
    3 / 8 (37.50%)
    2 / 6 (33.33%)
    67 / 208 (32.21%)
    6 / 7 (85.71%)
    3 / 7 (42.86%)
    2 / 6 (33.33%)
    2 / 6 (33.33%)
    1 / 6 (16.67%)
         occurrences all number
    1
    2
    3
    2
    78
    7
    3
    2
    2
    1
    Diarrhoea
         subjects affected / exposed
    3 / 7 (42.86%)
    2 / 3 (66.67%)
    2 / 8 (25.00%)
    3 / 6 (50.00%)
    79 / 208 (37.98%)
    5 / 7 (71.43%)
    3 / 7 (42.86%)
    2 / 6 (33.33%)
    2 / 6 (33.33%)
    1 / 6 (16.67%)
         occurrences all number
    10
    4
    2
    5
    136
    5
    6
    3
    4
    1
    Dyspepsia
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    22 / 208 (10.58%)
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    0
    1
    27
    1
    1
    1
    0
    0
    Dysphagia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    7 / 208 (3.37%)
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    1
    9
    1
    1
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    2 / 6 (33.33%)
    6 / 208 (2.88%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    2
    7
    0
    0
    0
    1
    0
    Gingival pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    1
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    15 / 208 (7.21%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    17
    0
    1
    0
    0
    0
    Mouth ulceration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    6 / 208 (2.88%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    6
    0
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    3 / 7 (42.86%)
    2 / 3 (66.67%)
    1 / 8 (12.50%)
    5 / 6 (83.33%)
    108 / 208 (51.92%)
    3 / 7 (42.86%)
    4 / 7 (57.14%)
    3 / 6 (50.00%)
    5 / 6 (83.33%)
    4 / 6 (66.67%)
         occurrences all number
    3
    4
    1
    7
    172
    5
    7
    4
    10
    6
    Oral pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    3 / 208 (1.44%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    1
    3
    0
    0
    0
    0
    0
    Proctalgia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    2
    0
    0
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    2 / 6 (33.33%)
    23 / 208 (11.06%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    2
    1
    1
    2
    28
    0
    0
    1
    0
    1
    Toothache
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    3 / 208 (1.44%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    3
    1
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    2 / 6 (33.33%)
    63 / 208 (30.29%)
    5 / 7 (71.43%)
    4 / 7 (57.14%)
    0 / 6 (0.00%)
    4 / 6 (66.67%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    1
    6
    110
    5
    8
    0
    6
    1
    Abdominal discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    3 / 208 (1.44%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    0
    1
    0
    Dental caries
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Dental cyst
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Dry mouth
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    5 / 208 (2.40%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    5
    0
    0
    2
    1
    0
    Flatulence
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    1
    0
    0
    0
    Gastric ulcer
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    3 / 208 (1.44%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    5
    1
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    3 / 6 (50.00%)
    27 / 208 (12.98%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    3
    28
    0
    0
    1
    0
    0
    Dry skin
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    8 / 208 (3.85%)
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    9
    0
    2
    0
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    3 / 208 (1.44%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    1
    3
    0
    0
    0
    1
    0
    Nail discolouration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 6 (16.67%)
    3 / 208 (1.44%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    1
    3
    0
    1
    0
    0
    0
    Night sweats
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    4
    0
    0
    0
    0
    0
    Pigmentation disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Pruritus
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    6 / 208 (2.88%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    0
    0
    8
    0
    0
    1
    2
    0
    Rash
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    9 / 208 (4.33%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    9
    0
    0
    0
    0
    0
    Rash maculo−papular
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    6 / 208 (2.88%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    1
    6
    1
    0
    2
    0
    0
    Ecchymosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Nail disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Purpura
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Skin hyperpigmentation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Renal and urinary disorders
    Bladder hypertrophy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Dysuria
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    3 / 208 (1.44%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    1
    3
    0
    0
    0
    0
    0
    Urinary tract pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Haematuria
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Nocturia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    1
    0
    Pollakiuria
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    Renal failure
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Urinary incontinence
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    22 / 208 (10.58%)
    1 / 7 (14.29%)
    2 / 7 (28.57%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    4
    0
    0
    1
    23
    1
    3
    3
    0
    0
    Bone pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    10 / 208 (4.81%)
    2 / 7 (28.57%)
    1 / 7 (14.29%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    1
    11
    2
    2
    2
    0
    1
    Back pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    2 / 6 (33.33%)
    29 / 208 (13.94%)
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    2
    35
    0
    2
    1
    0
    1
    Muscle spasms
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    4
    0
    0
    0
    0
    0
    Muscular weakness
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    10 / 208 (4.81%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    2
    0
    0
    1
    10
    0
    1
    0
    1
    1
    Myalgia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 6 (16.67%)
    12 / 208 (5.77%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    1
    1
    17
    1
    0
    0
    1
    1
    Pain in extremity
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    5 / 208 (2.40%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    5
    0
    0
    0
    0
    1
    Pain in jaw
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    3 / 208 (1.44%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    0
    0
    1
    Infections and infestations
    Anorectal infection
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Bronchitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    15 / 208 (7.21%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    2
    0
    16
    0
    1
    1
    0
    1
    Campylobacter gastroenteritis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Escherichia bacteraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    Herpes simplex
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    8 / 208 (3.85%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    0
    0
    9
    0
    1
    0
    0
    1
    Oral candidiasis
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    9 / 208 (4.33%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    2
    0
    0
    0
    11
    0
    0
    1
    1
    1
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    0 / 208 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    5 / 208 (2.40%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    5
    0
    0
    0
    1
    0
    Pneumonia klebsiella
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Pseudomonal bacteraemia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 6 (16.67%)
    11 / 208 (5.29%)
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    0
    1
    14
    2
    0
    1
    2
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    17 / 208 (8.17%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    24
    0
    0
    0
    0
    0
    Vulvovaginal candidiasis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Device related infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    1
    1
    Influenza
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    1
    0
    Lung infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    5 / 208 (2.40%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    6
    1
    0
    0
    0
    0
    Oral herpes
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    5 / 208 (2.40%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    6
    0
    0
    0
    1
    0
    Candida infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    1
    0
    0
    0
    Cellulitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    Cellulitis orbital
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    1
    0
    Enterovirus infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    Erysipelas
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Furuncle
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Oral fungal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    7 / 208 (3.37%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    7
    0
    0
    2
    0
    0
    Sinusitis bacterial
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Skin infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    3 / 208 (1.44%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    1
    0
    0
    0
    Staphylococcal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    Tooth abscess
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    1 / 6 (16.67%)
    41 / 208 (19.71%)
    2 / 7 (28.57%)
    2 / 7 (28.57%)
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    1 / 6 (16.67%)
         occurrences all number
    1
    1
    1
    1
    44
    2
    2
    1
    2
    1
    Dehydration
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    7 / 208 (3.37%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    12
    0
    0
    0
    0
    0
    Hyperuricaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    Hypocalcaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    3 / 208 (1.44%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    4
    0
    0
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    3 / 7 (42.86%)
    1 / 3 (33.33%)
    2 / 8 (25.00%)
    0 / 6 (0.00%)
    33 / 208 (15.87%)
    1 / 7 (14.29%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    4
    1
    2
    0
    43
    1
    2
    0
    1
    1
    Hypomagnesaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    10 / 208 (4.81%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    6
    0
    0
    0
    12
    0
    0
    0
    0
    0
    Hyponatraemia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    2
    0
    0
    0
    4
    0
    0
    0
    0
    1
    Hypophosphataemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 6 (0.00%)
    6 / 208 (2.88%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    8
    0
    0
    0
    0
    0
    Tumour lysis syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    1 / 208 (0.48%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    1
    0
    Fluid retention
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    0
    1
    0
    Gout
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    1
    Hyperphosphataemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    2 / 208 (0.96%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    0
    1
    0
    0
    Hypochloraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    0 / 208 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Hyperkalaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 6 (0.00%)
    4 / 208 (1.92%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    1
    1
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Jan 2014
    Changes that allow for symmetry in the treatment of patients receiving rituximab or obinutuzumab in case of hepatitis B reactivation. Changes to clarify that either antibody should be held in case of serious infection. clarification that patients with mantle cell lymphoma (MCL) and small lymphocytic lymphoma (SLL) were not eligible for the dose escalation portion of the study for safety reasons.
    23 May 2014
    Changes amended following identification of higher incidence of thrombocytopenia and hemorrhagic events in patients receiving obinutuzumab. Guidelines for management of patients with thrombocytopenia, especially during the first cycle have been added.
    01 Oct 2014
    An exploratory analysis of minimal residual disease has been added. Language has been added indicating the possibility of continued cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) treatment for up to eight cycles in selected patients who are tolerating therapy well and for whom it is felt by the investigator to be appropriate. Response criteria have been updated to be consistent with the 2014 Lugano Classification. Safety language has been updated.
    24 Apr 2015
    GDC-0199 dosing schedule updated. Characterization of the pharmacokinetics of the cyclophosphamide, doxorubicin and vincristine (CHO) components was deleted from the Pharmacokinetic Objectives as detailed characterization cannot be achieved with the current PK sampling scheme.
    07 Dec 2015
    An interim safety analysis has been added after 20 patients in the R-CHOP arm in the Phase II portion of the study have completed two cycles of treatment in order to confirm the safety and tolerability of the combination therapy at the venetoclax. The primary objectives of Phase II of the study have been modified to include assessment of efficacy of R-CHOP+ Venetoclax in patients with co-expression of both Bcl-2 and c-Myc. The term PET/CT will be replaced with PET-CT throughout the protocol.
    10 Oct 2016
    Venetoclax nonclinical toxicology section updated based on recent data findings. Twelve month Progression Free Survival (PFS) was added as a secondary efficacy objective. Information was added regarding the decision to not open Arm B in Phase II in DLBCL on the basis of information from the GOYA study results.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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