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    Clinical Trial Results:
    Phase 2 Study of the Combination of Ibrutinib Plus Venetoclax in Subjects With Treatment-naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

    Summary
    EudraCT number
    		 2016-002293-12
    Trial protocol
    		 ES   IT  
    Global end of trial date
    27 Mar 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Dec 2024
    First version publication date
    11 Dec 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    PCYC-1142-CA
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02910583
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pharmacyclics LLC
    Sponsor organisation address
    1000 Gateway Boulevard, South San Francisco, United States, 94080
    Public contact
    Global Medical Services, AbbVie, 001 001 8006339110, abbvieclinicaltrials@abbvie.com
    Scientific contact
    Global Medical Services, AbbVie, 001 001 8006339110, abbvieclinicaltrials@abbvie.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    27 Mar 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Mar 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This is a multicenter, 2-cohort Phase 2 study assessing both minimal residual disease (MRD)-guided discontinuation and fixed duration therapy with the combination of ibrutinib + venetoclax in subjects with treatment-naïve CLL or SLL.
    Protection of trial subjects
    The study was conducted in accordance with the protocol ICH guidelines, applicable regulations and guidelines governing clinical study conduct and ethical principles that have their origin in the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Sep 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 77
    Country: Number of subjects enrolled
    Italy: 39
    Country: Number of subjects enrolled
    New Zealand: 21
    Country: Number of subjects enrolled
    Spain: 39
    Country: Number of subjects enrolled
    United States: 147
    Worldwide total number of subjects
    323
    EEA total number of subjects
    78
    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)
    237
    From 65 to 84 years
    86
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted at 39 centers in the United States (US), Australia, New Zealand, Spain, and Italy.

    Pre-assignment
    Screening details
    		 Upon completion of a pre-randomization phase, participants in the MRD Cohort with confirmed undetectable minimal residual disease (uMRD) were randomized to blinded ibrutinib or placebo. Subjects in the MRD Cohort with uMRD not confirmed were randomized to open-label ibrutinib or open-label ibrutinib + venetoclax.

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor
    Blinding implementation details
    Triple (Participant, Investigator, Outcomes Assessor) Participants with confirmed undetectable minimal residual disease (uMRD) in the MRD cohort are triple masked. Allocation was not randomized for the Fixed Duration (FD) cohort.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Fixed Duration (FD) Cohort: All Treated
    Arm description
    		 Subjects received 420mg Ibrutinib (IBR) for 3 cycles followed by combination treatment with IBR 420mg and Venetoclax (VEN) 400mg orally once daily on a continuous schedule for 12 cycles (1 cycle=28 days) or until disease progression or unacceptable toxicity, whichever was earlier. Subjects with confirmed progression per 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria after completing the FD regimen could be retreated with continuous single agent IBR until disease progression or unacceptable toxicity, whichever was earlier, because it is an established standard of care for relapsed chronic lymphocytic leukemia (CLL). For subjects with durable efficacy after IBR plus VEN (ie, time to progression after FD regimen is completed of >2 years), the IBR plus VEN FD treatment regimen may have been repeated based on Investigator’s clinical discretion and Medical Monitor’s approval. Retreatment was for 15 cycles, until disease progression or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ibrutinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Ibrutinib administered orally once daily (three 140 mg capsules)

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Venetoclax tablets will be administered orally once daily starting with a 5 week ramp up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg. After ramp up, venetoclax will be administered at 400 mg.

    Arm title
    		 Minimal Residual Disease (MRD) Cohort: All Treated
    Arm description
    		 Subjects received 420mg of single-agent Ibrutinib (IBR) for the first 3 cycles followed by IBR plus Venetoclax (VEN) combination treatment for at least 12 cycles (1 cycle=28 days) prior to randomization (pre-randomization phase). Subjects who completed the planned pre-randomization treatment are eligible to be randomized according to their confirmed undetectable minimal residual disease (uMRD) status: Subjects with confirmed uMRD were randomized to receive blinded IBR 420mg or placebo orally once daily on a continuous schedule until PD or unacceptable toxicity, whichever was earlier. Subjects with uMRD not confirmed were randomized to receive open-label IBR 420mg or open-label IBR 420mg plus VEN 400mg orally once daily on a continuous schedule until PD or unacceptable toxicity, whichever was earlier. The VEN could be administered cumulative from pre-randomization to randomization phase at the dose of 400mg/day for up to approximately 2 years, or earlier PD or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ibrutinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Ibrutinib administered orally once daily (three 140 mg capsules)

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Venetoclax tablets will be administered orally once daily starting with a 5 week ramp up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg. After ramp up, venetoclax will be administered at 400 mg.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo capsules to match ibrutinib administered orally once daily

    Number of subjects in period 1
    		Fixed Duration (FD) Cohort: All Treated Minimal Residual Disease (MRD) Cohort: All Treated
    Started
    159
    164
    Completed
    133
    150
    Not completed
    26
    14
         Consent withdrawn by subject
    12
    8
         Death
    7
    3
         Not Specified
    6
    3
         Lost to follow-up
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Fixed Duration (FD) Cohort: All Treated
    Reporting group description
    		 Subjects received 420mg Ibrutinib (IBR) for 3 cycles followed by combination treatment with IBR 420mg and Venetoclax (VEN) 400mg orally once daily on a continuous schedule for 12 cycles (1 cycle=28 days) or until disease progression or unacceptable toxicity, whichever was earlier. Subjects with confirmed progression per 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria after completing the FD regimen could be retreated with continuous single agent IBR until disease progression or unacceptable toxicity, whichever was earlier, because it is an established standard of care for relapsed chronic lymphocytic leukemia (CLL). For subjects with durable efficacy after IBR plus VEN (ie, time to progression after FD regimen is completed of >2 years), the IBR plus VEN FD treatment regimen may have been repeated based on Investigator’s clinical discretion and Medical Monitor’s approval. Retreatment was for 15 cycles, until disease progression or unacceptable toxicity.

    Reporting group title
    Minimal Residual Disease (MRD) Cohort: All Treated
    Reporting group description
    		 Subjects received 420mg of single-agent Ibrutinib (IBR) for the first 3 cycles followed by IBR plus Venetoclax (VEN) combination treatment for at least 12 cycles (1 cycle=28 days) prior to randomization (pre-randomization phase). Subjects who completed the planned pre-randomization treatment are eligible to be randomized according to their confirmed undetectable minimal residual disease (uMRD) status: Subjects with confirmed uMRD were randomized to receive blinded IBR 420mg or placebo orally once daily on a continuous schedule until PD or unacceptable toxicity, whichever was earlier. Subjects with uMRD not confirmed were randomized to receive open-label IBR 420mg or open-label IBR 420mg plus VEN 400mg orally once daily on a continuous schedule until PD or unacceptable toxicity, whichever was earlier. The VEN could be administered cumulative from pre-randomization to randomization phase at the dose of 400mg/day for up to approximately 2 years, or earlier PD or unacceptable toxicity.

    Reporting group values
    		 Fixed Duration (FD) Cohort: All Treated Minimal Residual Disease (MRD) Cohort: All Treated Total
    Number of subjects
    		 159 164 323
    Age categorical
    Units: Subjects
        <65
    		 114 123 237
        >=65
    		 45 41 86
    Gender categorical
    Units: Subjects
        Female
    		 53 61 114
        Male
    		 106 103 209
    Ethnicity (NIH/ OMB)
    Units: Subjects
        Hispanic or Latino
    		 5 11 16
        Not Hispanic or Latino
    		 149 150 299
        Unknown or Not Reported
    		 5 3 8
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 1 1
        Asian
    		 3 5 8
        Native Hawaiian or Other Pacific Islander
    		 1 0 1
        Black or African American
    		 1 2 3
        White
    		 147 147 294
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 7 9 16

    End points

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    End points reporting groups
    Reporting group title
    Fixed Duration (FD) Cohort: All Treated
    Reporting group description
    		 Subjects received 420mg Ibrutinib (IBR) for 3 cycles followed by combination treatment with IBR 420mg and Venetoclax (VEN) 400mg orally once daily on a continuous schedule for 12 cycles (1 cycle=28 days) or until disease progression or unacceptable toxicity, whichever was earlier. Subjects with confirmed progression per 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria after completing the FD regimen could be retreated with continuous single agent IBR until disease progression or unacceptable toxicity, whichever was earlier, because it is an established standard of care for relapsed chronic lymphocytic leukemia (CLL). For subjects with durable efficacy after IBR plus VEN (ie, time to progression after FD regimen is completed of >2 years), the IBR plus VEN FD treatment regimen may have been repeated based on Investigator’s clinical discretion and Medical Monitor’s approval. Retreatment was for 15 cycles, until disease progression or unacceptable toxicity.

    Reporting group title
    Minimal Residual Disease (MRD) Cohort: All Treated
    Reporting group description
    		 Subjects received 420mg of single-agent Ibrutinib (IBR) for the first 3 cycles followed by IBR plus Venetoclax (VEN) combination treatment for at least 12 cycles (1 cycle=28 days) prior to randomization (pre-randomization phase). Subjects who completed the planned pre-randomization treatment are eligible to be randomized according to their confirmed undetectable minimal residual disease (uMRD) status: Subjects with confirmed uMRD were randomized to receive blinded IBR 420mg or placebo orally once daily on a continuous schedule until PD or unacceptable toxicity, whichever was earlier. Subjects with uMRD not confirmed were randomized to receive open-label IBR 420mg or open-label IBR 420mg plus VEN 400mg orally once daily on a continuous schedule until PD or unacceptable toxicity, whichever was earlier. The VEN could be administered cumulative from pre-randomization to randomization phase at the dose of 400mg/day for up to approximately 2 years, or earlier PD or unacceptable toxicity.

    Subject analysis set title
    MRD/uMRD Confirmed: Randomized to Ibrutinib (Blinded)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects receive venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase). Subjects with confirmed uMRD are randomized to receive ibrutinib 420 mg orally once daily on a continuous schedule until MRD-positive relapse, disease progression (PD), or unacceptable toxicity, whichever was earlier. After MRD-positive relapse or disease progression (PD) by iwCLL criteria, subjects can reintroduce 400 mg venetoclax with a 5-week ramp up. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative), or earlier PD or unacceptable toxicity.

    Subject analysis set title
    MRD/uMRD Confirmed: Randomized to Placebo (Blinded)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase). Subjects with confirmed uMRD are randomized to receive placebo orally once daily on a continuous schedule until MRD-positive relapse, PD or unacceptable toxicity, whichever was earlier. If MRD-positive relapse or PD is confirmed after restaging per iwCLL criteria, subjects can first reintroduce oral daily ibrutinib with the option of subsequently reintroducing 400 mg venetoclax with a 5-week ramp up, if subsequent disease relapse per iwCLL criteria occurs after ibrutinib reintroduction. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative), or earlier PD or unacceptable toxicity.

    Subject analysis set title
    MRD/uMRD Not Confirmed: All Treated
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase). Subjects with uMRD not confirmed were randomized to receive open-label ibrutinib 420 mg or open-label ibrutinib 420 mg plus venetoclax 400 mg orally once daily on a continuous schedule until PD or unacceptable toxicity, whichever was earlier.

    Subject analysis set title
    MRD/uMRD Not Confirmed: Open-Label Ibrutinib
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase). Subjects with uMRD not confirmed were randomized to receive open-label ibrutinib 420 mg orally once daily on a continuous schedule until PD or unacceptable toxicity, whichever was earlier. In case of confirmed PD after restaging per iwCLL criteria, subjects can continue ibrutinib and reintroduce venetoclax treatment. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) or earlier PD or unacceptable toxicity.

    Subject analysis set title
    MRD/uMRD Not Confirmed: Open-Label Ibrutinib + Venetoclax
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase). Subjects with uMRD not confirmed were randomized to receive open-label ibrutinib 420 mg and venetoclax 400 mg orally once daily on a continuous schedule until PD or unacceptable toxicity, whichever was earlier. In case of confirmed PD after restaging per iwCLL criteria, subjects can continue ibrutinib and reintroduce venetoclax treatment. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) or earlier PD or unacceptable toxicity.

    Subject analysis set title
    FD Cohort/Non-Del 17p Population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects in the FD cohort without del 17p abnormality (according to non-missing baseline fluorescent in situ hybridization [FISH] results) received 420 mg of single agent ibrutinib for first 3 cycles followed by ibrutinib plus venetoclax combination treatment (ibrutinib 420 mg and venetoclax 400 mg orally once daily on a continuous schedule) for 12 cycles (a cycle is defined by 28 days) or until PD or unacceptable toxicity, whichever was earlier.

    Primary: MRD Cohort: 1-Year Disease-Free Survival (DFS) Rate in Confirmed uMRD Randomized Participants

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    End point title
    		 MRD Cohort: 1-Year Disease-Free Survival (DFS) Rate in Confirmed uMRD Randomized Participants
    End point description
    DFS is defined as time from randomization date to MRD-positive relapse, or disease progression per investigator assessment (per 2008 International Workshop for Chronic Lymphocytic Leukemia [IWCLL] criteria [Halleck et al]) or death from any cause, whichever occurred first. 1-year DFS estimated using Kaplan-Meier method at 12 months landmark time. Confirmed uMRD Randomized Population: all participants who achieved confirmed MRD-negative clinical response at the end of the pre-randomization phase, randomized to either blinded placebo arm or blinded ibrutinib arm.
    End point type
    Primary
    End point timeframe
    1 year after randomization
    End point values
    		 MRD/uMRD Confirmed: Randomized to Ibrutinib (Blinded) MRD/uMRD Confirmed: Randomized to Placebo (Blinded)
    Number of subjects analysed
    43
    43
    Units: percentage of subjects
        number (confidence interval 95%)
    100 (100 to 100)
    95.3 (82.7 to 98.8)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    MRD/uMRD Confirmed: Randomized to Ibrutinib (Blinded) v MRD/uMRD Confirmed: Randomized to Placebo (Blinded)
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1475 [1]
    Method
    		 Z test
    Parameter type
    		 Difference in Rates (ibrutinib vs. PBO)
    Point estimate
    4.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 10.9
    Notes
    [1] - P-value is from Z test for the difference of two proportions based on Kaplan-Meier estimates with standard error of each arm computed using Greenwood’s formula.

    Primary: FD Cohort: Complete Response Rate (CRR; Complete Response/Complete Response With Incomplete Blood Count Recovery [CR/CRi]) Rate

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    End point title
    		 FD Cohort: Complete Response Rate (CRR; Complete Response/Complete Response With Incomplete Blood Count Recovery [CR/CRi]) Rate [2]
    End point description
    CR/CRi rate is defined as the percentage of participants achieving a best overall response of complete response (CR), CR with incomplete blood count recovery (CRi) per 2008 IWCLL criteria (halleck et al.) on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurred earlier. Per protocol, the primary analysis of the primary endpoint for the FD cohort was based on the FD Cohort, Non-Del 17p Population only.
    End point type
    Primary
    End point timeframe
    From the first dose of ibrutinib to the first confirmed PD, for a median follow-up of 69.0 months.
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Fixed Duration (FD) Cohort: All Treated FD Cohort/Non-Del 17p Population
    Number of subjects analysed
    159
    136
    Units: percentage of subjects
        number (confidence interval 95%)
    57.2 (49.5 to 64.9)
    58.1 (49.8 to 66.4)
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Fixed Duration (FD) Cohort: All Treated v FD Cohort/Non-Del 17p Population
    Number of subjects included in analysis
    295
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [3]
    Method
    		 asymptotic test for binomial proportion
    Confidence interval
    Notes
    [3] - One-sided P-value from asymptotic test for the binomial proportion (CRR <= 37% vs CRR > 37%).

    Secondary: MRD Cohort: CRR (CR/CRi Rate)

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    End point title
    		 MRD Cohort: CRR (CR/CRi Rate) [4]
    End point description
    CR/CRi rate is defined as the percentage of participants achieving a best overall response of CR or CRi per 2008 IWCLL criteria (Halleck et al.) on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurred earlier. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD Ibrutinib arm 69.1 months; Confirmed uMRD Placebo arm 67.4 months; uMRD Not Confirmed Ibrutinib arm 47.9 months; uMRD Not Confirmed Ibrutinib + Venetoclax arm 47.9 months.
    End point type
    Secondary
    End point timeframe
    From the first dose of ibrutinib to the first confirmed PD, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated MRD/uMRD Confirmed: Randomized to Ibrutinib (Blinded) MRD/uMRD Confirmed: Randomized to Placebo (Blinded) MRD/uMRD Not Confirmed: Open-Label Ibrutinib MRD/uMRD Not Confirmed: Open-Label Ibrutinib + Venetoclax
    Number of subjects analysed
    164
    43
    43
    31
    32
    Units: percentage of subjects
        number (confidence interval 95%)
    66.5 (59.2 to 73.7)
    79.1 (66.9 to 91.2)
    65.1 (50.9 to 79.4)
    77.4 (62.7 to 92.1)
    56.3 (39.1 to 73.4)
    No statistical analyses for this end point

    Secondary: MRD Cohort: Overall Response Rate (ORR)

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    End point title
    		 MRD Cohort: Overall Response Rate (ORR) [5]
    End point description
    ORR, defined as the percentage of participants achieving a best overall response of protocol-specified complete response (CR), CR with incomplete blood count recovery (CRi), nodular partial response (nPR), partial response (PR), or PR with lymphocytosis (PRL) evaluated in accordance with the 2008 IWCLL criteria (Halleck et al). Participants who did not have any postbaseline response assessment were considered as non-responders. This table is based on response assessments performed on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurs earlier. Kaplan-Meier estimate. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD Ibrutinib arm 69.1 months; Confirmed uMRD Placebo arm 67.4 months; uMRD Not Confirmed Ibrutinib arm 47.9 months; uMRD Not Confirmed Ibrutinib + Venetoclax arm 47.9 months.
    End point type
    Secondary
    End point timeframe
    From the first dose of ibrutinib to the first confirmed PD, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated MRD/uMRD Confirmed: Randomized to Ibrutinib (Blinded) MRD/uMRD Confirmed: Randomized to Placebo (Blinded) MRD/uMRD Not Confirmed: Open-Label Ibrutinib MRD/uMRD Not Confirmed: Open-Label Ibrutinib + Venetoclax
    Number of subjects analysed
    164
    43
    43
    31
    32
    Units: percentage of subjects
        number (confidence interval 95%)
    97.0 (94.3 to 99.6)
    100 (100 to 100)
    100 (100 to 100)
    100 (100 to 100)
    100 (100 to 100)
    No statistical analyses for this end point

    Secondary: MRD Cohort: Duration of Response (DOR) at 42 Months Landmark Time

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    End point title
    		 MRD Cohort: Duration of Response (DOR) at 42 Months Landmark Time [6]
    End point description
    Duration of response was calculated for participants achieving a response (CR, CRi, nPR, PR) based on 2008 IWCLL response criteria (Halleck et al.) and defined as the interval between the date of initial documentation of a response including PR with lymphocytosis, until disease progression (PD) or death from any cause, whichever occurred first. As the median DOR was not reached as of 67.0 months study follow-up, the Kaplan-Meier estimate of DOR at 42 months landmark time was presented. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD Ibrutinib arm 69.1 months; Confirmed uMRD Placebo arm 67.4 months; uMRD Not Confirmed Ibrutinib arm 47.9 months; uMRD Not Confirmed Ibrutinib + Venetoclax arm 47.9 months. MRD Cohort: Participants who achieved PR or better
    End point type
    Secondary
    End point timeframe
    From initial documentation of a response until PD or death from any cause, whichever occurs first, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated MRD/uMRD Confirmed: Randomized to Ibrutinib (Blinded) MRD/uMRD Confirmed: Randomized to Placebo (Blinded) MRD/uMRD Not Confirmed: Open-Label Ibrutinib MRD/uMRD Not Confirmed: Open-Label Ibrutinib + Venetoclax
    Number of subjects analysed
    159
    43
    43
    31
    32
    Units: Months
        number (confidence interval 95%)
    93.5 (88.2 to 96.4)
    97.6 (84.3 to 99.7)
    93.0 (79.7 to 97.7)
    96.7 (78.6 to 99.5)
    93.2 (75.5 to 98.3)
    No statistical analyses for this end point

    Secondary: MRD Cohort: MRD-Negativity Rate

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    End point title
    		 MRD Cohort: MRD-Negativity Rate [7]
    End point description
    MRD negativity rate is defined as the percentage of participants achieving MRD negativity, which is defined as <1 CLL cell per 10,000 leukocytes (<1 x 10^-4) as assessed by flow cytometry of a peripheral blood (PB) or bone marrow (BM) aspirate sample per central laboratory on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurs earlier. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD Ibrutinib arm 69.1 months; Confirmed uMRD Placebo arm 67.4 months; uMRD Not Confirmed Ibrutinib arm 47.9 months; uMRD Not Confirmed Ibrutinib + Venetoclax arm 47.9 months. MRD All Treated Population; participants with an assessment.
    End point type
    Secondary
    End point timeframe
    From randomization date until before any subsequent antineoplastic therapy, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated MRD/uMRD Not Confirmed: All Treated MRD/uMRD Not Confirmed: Open-Label Ibrutinib MRD/uMRD Not Confirmed: Open-Label Ibrutinib + Venetoclax
    Number of subjects analysed
    164
    63
    31
    32
    Units: percentage of subjects
    number (confidence interval 95%)
        PB or BM
    81.7 (75.8 to 87.6)
    65.1 (53.3 to 76.9)
    51.6 (34.0 to 69.2)
    78.1 (63.8 to 92.4)
        BM
    77.4 (71.0 to 83.8)
    55.6 (43.3 to 67.8)
    41.9 (24.6 to 59.3)
    68.8 (52.7 to 84.8)
        PB
    79.9 (73.7 to 86.0)
    60.3 (48.2 to 72.4)
    48.4 (30.8 to 66.0)
    71.9 (56.3 to 87.5)
    No statistical analyses for this end point

    Secondary: MRD Cohort: Tumor Lysis Syndrome (TLS) Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in)

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    End point title
    		 MRD Cohort: Tumor Lysis Syndrome (TLS) Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in) [8]
    End point description
    TLS risk reduction was summarized by the percentage of participants with TLS risk reduced from high at baseline to medium or low after ibrutinib lead-in. A reduction in TLS risk from high risk to medium or low risk is clinically meaningful because there is a reduction in the extent of TLS monitoring and risk of hospitalization. TLS risk category is defined as the tumor burden category, where: Low=All lymph nodes (LN) < 5 cm AND absolute lymphocyte count (ALC) < 25 x 10^9/L; Medium=Any LN 5 cm to < 10 cm OR ALC ≥ 25 x 10^9/L; High=Any LN ≥ 10 cm OR ALC ≥ 25 x10^9/L AND any LN ≥ 5 cm.
    End point type
    Secondary
    End point timeframe
    Baseline, and last post-baseline value on or prior to venetoclax first dose date (cycle 4 day 1) or, for participants who never received venetoclax, the post-baseline value closest to cycle 4 day 1 (i.e. 84 days after the first dose date of ibrutinib).
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated
    Number of subjects analysed
    40 [9]
    Units: percentage of subjects
        number (not applicable)
    90.0
    Notes
    [9] - MRD Cohort: All Treated Population with baseline TLS high risk
    No statistical analyses for this end point

    Secondary: MRD Cohort: Kaplan-Meier Estimate of Progression Free Survival (PFS) Rate at 48 Months Landmark Time

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    End point title
    		 MRD Cohort: Kaplan-Meier Estimate of Progression Free Survival (PFS) Rate at 48 Months Landmark Time [10]
    End point description
    PFS was defined as time from the first dose date of study treatment until disease progression (PD) or death from any cause, whichever occurs first. Assessment of PD was conducted in accordance with the 2008 IWCLL criteria (Halleck et al). As the median PFS was not reached as of the overall median 67.0 months study follow-up, the Kaplan-Meier estimate of PFS rate at 48 months landmark time was presented. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD Ibrutinib arm 69.1 months; Confirmed uMRD Placebo arm 67.4 months; uMRD Not Confirmed Ibrutinib arm 47.9 months; uMRD Not Confirmed Ibrutinib + Venetoclax arm 47.9 months.
    End point type
    Secondary
    End point timeframe
    From the first dose of ibrutinib to the first confirmed PD or death, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated MRD/uMRD Confirmed: Randomized to Ibrutinib (Blinded) MRD/uMRD Confirmed: Randomized to Placebo (Blinded) MRD/uMRD Not Confirmed: Open-Label Ibrutinib MRD/uMRD Not Confirmed: Open-Label Ibrutinib + Venetoclax
    Number of subjects analysed
    164
    43
    43
    31
    32
    Units: percentage of subjects
        number (confidence interval 95%)
    90.9 (85.1 to 94.5)
    97.6 (84.3 to 99.7)
    88.2 (73.9 to 94.9)
    93.3 (75.9 to 98.3)
    93.2 (75.5 to 98.3)
    No statistical analyses for this end point

    Secondary: MRD Cohort: Kaplan-Meier Estimate of Overall Survival (OS) Rate at 48 Months Landmark Time

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    End point title
    		 MRD Cohort: Kaplan-Meier Estimate of Overall Survival (OS) Rate at 48 Months Landmark Time [11]
    End point description
    OS is defined as the time from the first dose date of study treatment until date of death due to any cause. As the median OS was not reached as of the overall median 67.0 months study follow-up, the Kaplan-Meier estimate of OS rate at 48 months landmark time was presented. Median follow up duration for the individual MRD Cohort treatment arms: Confirmed uMRD: Randomized to Ibrutinib=69.1 months; Confirmed uMRD: Randomized to Placebo=67.4 months; uMRD Not Confirmed: Randomized to Open-Label Ibrutinib=47.9 months; uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax=47.9 months.
    End point type
    Secondary
    End point timeframe
    From the first dose of ibrutinib to time of death, for an overall median follow-up of 67.0 months. (Median follow up duration for the individual MRD Cohort treatment arms listed above.)
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated MRD/uMRD Confirmed: Randomized to Ibrutinib (Blinded) MRD/uMRD Confirmed: Randomized to Placebo (Blinded) MRD/uMRD Not Confirmed: Open-Label Ibrutinib MRD/uMRD Not Confirmed: Open-Label Ibrutinib + Venetoclax
    Number of subjects analysed
    164
    43
    43
    31
    32
    Units: percentage of subjects
        number (confidence interval 95%)
    98.0 (94.0 to 99.4)
    97.6 (84.3 to 99.7)
    100 (100 to 100)
    96.7 (78.6 to 99.5)
    100 (100 to 100)
    No statistical analyses for this end point

    Secondary: MRD Cohort: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs

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    End point title
    		 MRD Cohort: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs [12]
    End point description
    An adverse event (AE) is any untoward medical occurrence, which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires unplanned in-patient hospitalization >24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. Severity of events were graded according to the Common Terminology Criteria for Adverse Events version 4.03: mild=grade 1, moderate=grade 2, severe=grade 3, life-threatening=grade 4, death=grade 5. Causal relation of study drug and event was assessed as not related, unlikely, possibly or probably related to the study drug.
    End point type
    Secondary
    End point timeframe
    From first dose until 30 days following last dose of study drug. Overall treatment duration for the MRD cohort was 45.1 months.
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated MRD/uMRD Confirmed: Randomized to Ibrutinib (Blinded) MRD/uMRD Confirmed: Randomized to Placebo (Blinded) MRD/uMRD Not Confirmed: Open-Label Ibrutinib MRD/uMRD Not Confirmed: Open-Label Ibrutinib + Venetoclax
    Number of subjects analysed
    164
    43
    43
    31
    32
    Units: percentage of subjects
    number (not applicable)
        Any TEAE
    100.0
    100.0
    100.0
    100.0
    100.0
        Any Grade >=3 TEAE
    75.6
    83.7
    72.1
    71.0
    78.1
        Any Ibrutinib (Ibr)-Related TEAE
    95.7
    97.7
    93.0
    96.8
    93.8
        Any Grade >=3 Ibrutinib-Related TEAE
    57.9
    55.8
    51.2
    61.3
    62.5
        Any Venetoclax (Ven)-Related TEAE
    81.1
    88.4
    76.7
    80.6
    96.9
        Any Grade >=3 Venetoclax-Related TEAE
    44.5
    51.2
    34.9
    45.2
    56.3
        Any TEAE Leading to Ibr or Ven Discontinuation
    15.9
    16.3
    0
    9.7
    12.5
        Any TEAE Leading to Ibr or Ven Discon: Ib Only
    10.4
    14.0
    0
    9.7
    3.1
        Any TEAE Leading to Ibr or Ven Discon: Ven Only
    1.2
    2.3
    0
    0
    0
        Any TEAE Leading to Ibr or Ven Discon: Ibr + Ven
    4.3
    0
    0
    0
    9.4
        Any TEAE Leading to Ibr or Ven Dose Reduction
    26.2
    23.3
    25.6
    25.8
    34.4
        Any TEAE Leading to Ibr Only Dose Reduction
    16.5
    16.3
    11.6
    19.4
    25.0
        Any TEAE Leading to Ven Only Dose Reduction
    4.9
    2.3
    11.6
    0
    3.1
        Any TEAE Leading to Both Ibr + Ven Dose Reduction
    4.9
    4.7
    2.3
    6.5
    6.3
        Any SAE
    34.1
    34.9
    32.6
    41.9
    37.5
        Any Grade >= 3 SAE
    28.7
    32.6
    27.9
    32.3
    28.1
        Any SAE Related to Ibr or Ven
    20.1
    18.6
    14.0
    25.8
    21.9
        Any Ibr-related SAE
    17.1
    14.0
    11.6
    22.6
    18.8
        Any Ven-related SAE
    6.7
    4.7
    7.0
    12.9
    6.3
        Fatal TEAE
    1.2
    2.3
    0
    3.2
    0
        Major Hemorrhage TEAE
    2.4
    2.3
    0
    3.2
    6.3
        Grade >= 3 Major Hemorrhage TEAE
    1.8
    2.3
    0
    3.2
    3.1
        Major Hemorrhage SAE
    2.4
    2.3
    0
    3.2
    6.3
    No statistical analyses for this end point

    Secondary: FD Cohort: ORR

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    End point title
    		 FD Cohort: ORR [13]
    End point description
    ORR is defined as the percentage of participants who achieve a best overall response CR, CRi, nPR, PR, or PRL as evaluated by investigator using 2008 IWCLL criteria (Halleck et al.). Participants who did not have any postbaseline response assessment were considered as non-responders. This table is based on response assessments performed on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurs earlier. Kaplan-Meier estimate.
    End point type
    Secondary
    End point timeframe
    From the first dose of ibrutinib to the first confirmed PD, for a median follow-up of 69.0 months.
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Fixed Duration (FD) Cohort: All Treated FD Cohort/Non-Del 17p Population
    Number of subjects analysed
    159
    136
    Units: percentage of subjects
        number (confidence interval 95%)
    96.2 (93.3 to 99.2)
    95.6 (92.1 to 99.0)
    No statistical analyses for this end point

    Secondary: FD Cohort: DOR at 60 Months Landmark Time

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    End point title
    		 FD Cohort: DOR at 60 Months Landmark Time [14]
    End point description
    Duration of response was calculated for participants achieving a response (CR, CRi, nPR, PR) based on 2008 IWCLL response criteria (Halleck et al.) and defined as the interval between the date of initial documentation of a response including PR with lymphocytosis, until disease progression (PD) or death from any cause, whichever occurred first. As the median DOR was not reached as of the median 27.9 months study follow-up, the Kaplan-Meier estimate of DOR at 60 months landmark time was presented.
    End point type
    Secondary
    End point timeframe
    From initial documentation of a response until PD or death from any cause, whichever occurs first, for a median follow-up of 69.0 months.
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Fixed Duration (FD) Cohort: All Treated FD Cohort/Non-Del 17p Population
    Number of subjects analysed
    153 [15]
    130 [16]
    Units: percentage of subjects
        number (confidence interval 95%)
    60.5 (52.0 to 68.0)
    63.6 (54.4 to 71.4)
    Notes
    [15] - FD Cohort: Participants who achieved PR or better.
    [16] - FD Cohort: Participants who achieved PR or better.
    No statistical analyses for this end point

    Secondary: FD Cohort: MRD Negativity Rate

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    End point title
    		 FD Cohort: MRD Negativity Rate [17]
    End point description
    MRD negativity rate is defined as the percentage of participants achieving MRD negativity, which is defined as <1 CLL cell per 10,000 leukocytes (<1 x 10^-4) as assessed by flow cytometry of a peripheral blood (PB) or bone marrow (BM) aspirate sample per central laboratory on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurs earlier.
    End point type
    Secondary
    End point timeframe
    From randomization date until before any subsequent antineoplastic therapy, for a median follow-up of 69.0 months.
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Fixed Duration (FD) Cohort: All Treated FD Cohort/Non-Del 17p Population
    Number of subjects analysed
    159
    136
    Units: percentage of subjects
    number (confidence interval 95%)
        BM or PB
    78.6 (72.2 to 85.0)
    78.7 (71.8 to 85.6)
        BM
    59.7 (52.1 to 67.4)
    61.8 (53.6 to 69.9)
        PB
    76.7 (70.2 to 83.3)
    76.5 (69.3 to 83.6)
    No statistical analyses for this end point

    Secondary: FD Cohort: Kaplan-Meier Estimate of PFS Rate at 66 Months Landmark Time

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    End point title
    		 FD Cohort: Kaplan-Meier Estimate of PFS Rate at 66 Months Landmark Time [18]
    End point description
    PFS was defined as time from the first dose date of study treatment until disease progression (PD) or death from any cause, whichever occurs first. Assessment of PD was conducted in accordance with the 2008 IWCLL criteria (Halleck et al). As the median PFS was not reached as of the median 69.0 months study follow-up, the Kaplan-Meier estimate of PFS rate at 66 months landmark time was presented.
    End point type
    Secondary
    End point timeframe
    From the first dose of ibrutinib to the first confirmed PD or death, for a median follow-up of 69.0 months.
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Fixed Duration (FD) Cohort: All Treated FD Cohort/Non-Del 17p Population
    Number of subjects analysed
    159
    136
    Units: percentage of subjects
        number (confidence interval 95%)
    60.2 (51.7 to 67.7)
    63.2 (54.1 to 71.0)
    No statistical analyses for this end point

    Secondary: FD Cohort: Kaplan-Meier Estimate of OS Rate at 66 Months Landmark Time

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    End point title
    		 FD Cohort: Kaplan-Meier Estimate of OS Rate at 66 Months Landmark Time [19]
    End point description
    OS is defined as the time from the first dose date of study treatment until date of death due to any cause. As the median OS was not reached as of the median 69.0 months study follow-up, the Kaplan-Meier estimate of OS rate at 66 months landmark time was presented.
    End point type
    Secondary
    End point timeframe
    From the first dose of ibrutinib to time of death, for a median follow-up of 69.0 months.
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Fixed Duration (FD) Cohort: All Treated FD Cohort/Non-Del 17p Population
    Number of subjects analysed
    159
    136
    Units: percentage of subjects
        number (confidence interval 95%)
    96.1 (91.4 to 98.2)
    96.9 (92.1 to 98.8)
    No statistical analyses for this end point

    Secondary: FD Cohort: TLS Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in)

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    End point title
    		 FD Cohort: TLS Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in) [20]
    End point description
    TLS risk reduction was summarized by the percentage of participants with TLS risk reduced from high at baseline to medium or low after ibrutinib lead-in. A reduction in TLS risk from high risk to medium or low risk is clinically meaningful because there is a reduction in the extent of TLS monitoring and risk of hospitalization. TLS risk category is defined as the tumor burden category, where: Low=All lymph nodes (LN) < 5 cm AND absolute lymphocyte count (ALC) < 25 x 10^9/L; Medium=Any LN 5 cm to < 10 cm OR ALC ≥ 25 x 10^9/L; High=Any LN ≥ 10 cm OR ALC ≥ 25 x10^9/L AND any LN ≥ 5 cm.
    End point type
    Secondary
    End point timeframe
    Baseline, and last post-baseline value on or prior to venetoclax first dose date (cycle 4 day 1) or, for participants who never received venetoclax, the post-baseline value closest to cycle 4 day 1 (i.e. 84 days after the first dose date of ibrutinib).
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Fixed Duration (FD) Cohort: All Treated
    Number of subjects analysed
    34 [21]
    Units: percentage of subjects
        number (not applicable)
    94.1
    Notes
    [21] - FD Cohort: All Treated Population with baseline TLS high risk
    No statistical analyses for this end point

    Secondary: FD Cohort: Percentage of Participants With TEAEs, Treatment-Emergent SAEs, and Discontinuations Due to TEAEs

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    End point title
    		 FD Cohort: Percentage of Participants With TEAEs, Treatment-Emergent SAEs, and Discontinuations Due to TEAEs [22]
    End point description
    An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires unplanned in-patient hospitalization >24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. Severity of events were graded according to the Common Terminology Criteria for Adverse Events version 4.03: mild=grade1, moderate=grade 2, severe=grade 3, life-threatening=grade 4, death=grade 5. Causal relation of study drug and event was assessed as not related, unlikely, possibly or probably related to the study drug.
    End point type
    Secondary
    End point timeframe
    From first dose until 30 days following last dose of study drug. Overall median treatment duration for the FD cohort was 13.8 months.
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Fixed Duration (FD) Cohort: All Treated
    Number of subjects analysed
    159
    Units: percentage of subjects
    number (not applicable)
        Any TEAE
    99.4
        Any Grade >=3 TEAE
    62.3
        Any Ibrutinib (Ibr)-Related TEAE
    92.5
        Any Grade >=3 Ibrutinib-Related TEAE
    44.7
        Any Venetoclax (Ven)-Related TEAE
    84.3
        Any Grade >=3 Venetoclax-Related TEAE
    45.3
        Any TEAE Leading to Ibr or Ven Discontinuation
    5.0
        Any TEAE Leading to Ibr or Ven Discon: Ibr Only
    3.1
        Any TEAE Leading to Ibr or Ven Discon: Ven Only
    0
        Any TEAE Leading to Ibr or Ven Discon: Ibr + Ven
    1.9
        Any TEAE Leading to Ibr or Ven Dose Reduction
    20.8
        Any TEAE Leading to Ibr Only Dose Reduction
    5.7
        Any TEAE Leading to Ven Only Dose Reduction
    11.3
        Any TEAE Leading to Both Ibr + Ven Dose Reduction
    3.8
        Any Grade >= 3 SAE
    20.1
        Any SAE Related to Ibr or Ven
    13.8
        Any Ibr-related SAE
    11.9
        Any Ven-related SAE
    8.8
        Fatal TEAE
    0.6
        Major Hemorrhage TEAE
    1.9
        Grade >= 3 Major Hemorrhage TEAE
    1.3
        Major Hemorrhage SAE
    1.3
        Any SAE
    23.3
    No statistical analyses for this end point

    Secondary: MRD Cohort: Pharmacokinetics (PK) of Ibrutinib When Dosed in Combination With Venetoclax: Observed Maximum Concentration (Cmax)

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    End point title
    		 MRD Cohort: Pharmacokinetics (PK) of Ibrutinib When Dosed in Combination With Venetoclax: Observed Maximum Concentration (Cmax) [23]
    End point description
    MRD Cohort: All treated participants who were evaluable for PK analysis. Data were collected for the MRD cohort only, and without regard to uMRD confirmation status/randomization group, as pre-specified for this analysis.
    End point type
    Secondary
    End point timeframe
    Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated
    Number of subjects analysed
    130 [24]
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    88.5 ( 74.3 )
    Notes
    [24] - MRD Cohort: All treated participants who were evaluable for PK analysis.
    No statistical analyses for this end point

    Secondary: MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Time to Cmax (Tmax); Time of Last Measurable Concentration (Tlast); Terminal Elimination Half-Life (t1/2,Term)

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    End point title
    		 MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Time to Cmax (Tmax); Time of Last Measurable Concentration (Tlast); Terminal Elimination Half-Life (t1/2,Term) [25]
    End point description
    MRD Cohort: All treated participants who were evaluable for each PK analysis. Data were collected for the MRD cohort only, and without regard to uMRD confirmation status/randomization group, as pre-specified for this analysis.
    End point type
    Secondary
    End point timeframe
    Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated
    Number of subjects analysed
    130 [26]
    Units: hours
    median (full range (min-max))
        tmax
    2.00 (0.970 to 7.00)
        tlast
    24.0 (5.75 to 24.0)
        t1/2term
    5.30 (1.47 to 10.5)
    Notes
    [26] - MRD Cohort: All treated participants who were evaluable for each PK analysis.
    No statistical analyses for this end point

    Secondary: MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Area Under the Plasma Concentration-Time Curve (AUC) Over the Last 24-hour Dosing Interval (AUC0-24h); AUC From Time Zero to the Time of Last Quantifiable Concentration (AUClast)

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    End point title
    		 MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Area Under the Plasma Concentration-Time Curve (AUC) Over the Last 24-hour Dosing Interval (AUC0-24h); AUC From Time Zero to the Time of Last Quantifiable Concentration (AUClast) [27]
    End point description
    MRD Cohort: All treated participants who were evaluable for each PK analysis. Data were collected for the MRD cohort only, and without regard to uMRD confirmation status/randomization group, as pre-specified for this analysis.
    End point type
    Secondary
    End point timeframe
    Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated
    Number of subjects analysed
    128 [28]
    Units: ng*h/mL
    geometric mean (geometric coefficient of variation)
        AUC0-24h
    504 ( 76.3 )
        AUClast
    480 ( 78.5 )
    Notes
    [28] - MRD Cohort: All treated participants who were evaluable for PK analysis.
    No statistical analyses for this end point

    Secondary: MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Terminal Elimination Rate Constant (λz)

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    End point title
    		 MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Terminal Elimination Rate Constant (λz) [29]
    End point description
    MRD Cohort: All treated participants who were evaluable for PK analysis. Data were collected for the MRD cohort only, and without regard to uMRD confirmation status/randomization group, as pre-specified for this analysis.
    End point type
    Secondary
    End point timeframe
    Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
    Notes
    [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated
    Number of subjects analysed
    91 [30]
    Units: 1/h
        geometric mean (geometric coefficient of variation)
    0.132 ( 44.5 )
    Notes
    [30] - MRD Cohort: All treated participants who were evaluable for PK analysis.
    No statistical analyses for this end point

    Secondary: MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Apparent Total Clearance at Steady-State (CLss/F)

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    End point title
    		 MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Apparent Total Clearance at Steady-State (CLss/F) [31]
    End point description
    MRD Cohort: All treated participants who were evaluable for PK analysis. Data were collected for the MRD cohort only, and without regard to uMRD confirmation status/randomization group, as pre-specified for this analysis.
    End point type
    Secondary
    End point timeframe
    Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
    Notes
    [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated
    Number of subjects analysed
    128 [32]
    Units: L/h
        geometric mean (geometric coefficient of variation)
    833 ( 90.9 )
    Notes
    [32] - MRD Cohort: All treated participants who were evaluable for PK analysis.
    No statistical analyses for this end point

    Secondary: MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Cmax

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    End point title
    		 MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Cmax [33]
    End point description
    MRD Cohort: All treated participants who were evaluable for PK analysis. Data were collected for the MRD cohort only, and without regard to uMRD confirmation status/randomization group, as pre-specified for this analysis.
    End point type
    Secondary
    End point timeframe
    Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
    Notes
    [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated
    Number of subjects analysed
    131 [34]
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    3034 ( 56.3 )
    Notes
    [34] - MRD Cohort: All treated participants who were evaluable for PK analysis.
    No statistical analyses for this end point

    Secondary: MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Tmax

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    End point title
    		 MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Tmax [35]
    End point description
    MRD Cohort: All treated participants who were evaluable for PK analysis. Data were collected for the MRD cohort only, and without regard to uMRD confirmation status/randomization group, as pre-specified for this analysis.
    End point type
    Secondary
    End point timeframe
    Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
    Notes
    [35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated
    Number of subjects analysed
    131 [36]
    Units: hours
        median (full range (min-max))
    6.00 (0.00 to 8.08)
    Notes
    [36] - MRD Cohort: All treated participants who were evaluable for PK analysis.
    No statistical analyses for this end point

    Secondary: MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: AUC0-24h

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    End point title
    		 MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: AUC0-24h [37]
    End point description
    MRD Cohort: All treated participants who were evaluable for PK analysis. Data were collected for the MRD cohort only, and without regard to uMRD confirmation status/randomization group, as pre-specified for this analysis.
    End point type
    Secondary
    End point timeframe
    Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
    Notes
    [37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated
    Number of subjects analysed
    131 [38]
    Units: ng*h/mL
        geometric mean (geometric coefficient of variation)
    48993 ( 66.2 )
    Notes
    [38] - MRD Cohort: All treated participants who were evaluable for PK analysis.
    No statistical analyses for this end point

    Secondary: MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: CLss/F

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    End point title
    		 MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: CLss/F [39]
    End point description
    MRD Cohort: All treated participants who were evaluable for PK analysis. Data were collected for the MRD cohort only, and without regard to uMRD confirmation status/randomization group, as pre-specified for this analysis.
    End point type
    Secondary
    End point timeframe
    Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)
    Notes
    [39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data are summarized for this end point per protocol.
    End point values
    		 Minimal Residual Disease (MRD) Cohort: All Treated
    Number of subjects analysed
    131 [40]
    Units: L/h
        geometric mean (geometric coefficient of variation)
    8.16 ( 69.7 )
    Notes
    [40] - MRD Cohort: All treated participants who were evaluable for PK analysis.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose until 30 days following last dose of study drug. Overall median treatment duration was 45.1 months for the MRD cohort and 13.8 months for the FD cohort.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    MRD Cohort: Pre-Dose
    Reporting group description
    		 All reported AEs started prior to the first dose date of any study treatment in the MRD Cohort.

    Reporting group title
    FD Cohort: Pre-Dose
    Reporting group description
    		 All reported AEs that started prior to the first dose date of any study treatment in the FD Cohort.

    Reporting group title
    FD Cohort: All Subjects
    Reporting group description
    		 Subjects in the FD Cohort received 420mg of single agent ibrutinib for first 3 cycles followed by ibrutinib plus venetoclax combination treatment (ibrutinib 420mg and venetoclax 400mg orally once daily on a continuous schedule) for 12 cycles (1 cycle = 28 days) or until PD or unacceptable toxicity. 1. For subjects who did not receive any reintroduced treatment, includes all reported AEs started after the first dose date of the first-line treatment over the whole study course. 2. For subjects who received any reintroduced treatment, includes all reported AEs started after the first dose date of the first-line treatment and prior to the first dose date of the reintroduced treatment.

    Reporting group title
    MRD Cohort: Confirmed uMRD (IbrVen->Ibr)
    Reporting group description
    		 Subjects in the MRD Cohort with confirmed uMRD received 420mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (1 cycle = 28 days) prior to randomization (prerandomization phase). Subjects with confirmed uMRD were randomized to receive ibrutinib 420mg orally once daily on a continuous schedule until MRD-positive relapse, clinical PD, or unacceptable toxicity. 1. For subjects who did not receive any reintroduced treatment, includes all reported AEs started after the first dose date of the first-line treatment over the whole study course. 2. For subjects who received any reintroduced treatment, includes all reported AEs started after the first dose date of the first-line treatment and prior to the first dose date of the reintroduced treatment.

    Reporting group title
    MRD Cohort: All Subjects
    Reporting group description
    		 Subjects in the MRD Cohort received 420mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (1 cycle = 28 days) prior to randomization (pre-randomization phase). Subjects with confirmed uMRD were randomized to blinded ibrutinib 420mg or placebo orally once daily on a continuous schedule until PD or unacceptable toxicity. Subjects with uMRD not confirmed were randomized to open-label ibrutinib 420mg or open-label ibrutinib 420mg plus venetoclax 400mg orally once daily on a continuous schedule until PD or unacceptable toxicity. 1. For subjects who did not receive reintroduced treatment, includes all reported AEs started after the first dose date of the first-line treatment over the whole study course. 2. For subjects who received any reintroduced treatment, includes all reported AEs started after the first dose date of the first-line treatment and prior to the first dose date of the reintroduced treatment.

    Reporting group title
    MRD Cohort: Confirmed uMRD (IbrVen->Pbo)
    Reporting group description
    		 Subjects in the MRD Cohort with confirmed uMRD received 420mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (1 cycle = 28 days) prior to randomization (pre-randomization phase). Subjects with confirmed uMRD were randomized to receive placebo orally once daily on a continuous schedule until MRD-positive relapse, clinical PD or unacceptable toxicity. 1. For subjects who did not receive any reintroduced treatment, includes all reported AEs started after the first dose date of the first-line treatment over the whole study course. 2. For subjects who received any reintroduced treatment, includes all reported AEs started after the first dose date of the first-line treatment and prior to the first dose date of the reintroduced treatment.

    Reporting group title
    MRD Cohort: uMRD Not Confirmed (IbrVen->Ibr)
    Reporting group description
    		 Subjects in the MRD Cohort with uMRD not confirmed received 420mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (1 cycle = 28 days) prior to randomization (pre-randomization phase). Subjects with uMRD not confirmed were randomized to receive open-label ibrutinib 420 mg orally once daily on a continuous schedule until PD or unacceptable toxicity. 1. For subjects who did not receive any reintroduced treatment, includes all reported AEs started after the first dose date of the first-line treatment over the whole study course. 2. For subjects who received any reintroduced treatment, includes all reported AEs started after the first dose date of the first-line treatment and prior to the first dose date of the reintroduced treatment.

    Reporting group title
    MRD Cohort: uMRD Not Confirmed (IbrVen->IbrVen)
    Reporting group description
    		 Subjects in the MRD Cohort with uMRD not confirmed received 420mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (1 cycle = 28 days) prior to randomization (pre-randomization phase). Subjects with uMRD not confirmed were randomized to receive open-label ibrutinib 420 mg and venetoclax 400 mg orally once daily on a continuous schedule until PD or unacceptable toxicity. 1. For subjects who did not receive any reintroduced treatment, includes all reported AEs started after the first dose date of the first-line treatment over the whole study course. 2. For subjects who received any reintroduced treatment, includes all reported AEs started after the first dose date of the first-line treatment and prior to the first dose date of the reintroduced treatment.

    Reporting group title
    FD Cohort: Reintroduced Ibrutinib
    Reporting group description
    		 All reported AEs in the FD Cohort that started after the first dose date of reintroduced treatment with ibrutinib.

    Reporting group title
    FD Cohort: Reintroduced Ibr+Ven
    Reporting group description
    		 All reported AEs in the FD Cohort that started after the first dose date of reintroduced treatment with ibrutinib + venetoclax.

    Reporting group title
    MRD Cohort: Reintroduced Ibrutinib
    Reporting group description
    		 All reported AEs in the MRD Cohort that started after the first dose date of reintroduced treatment with ibrutinib.

    Reporting group title
    MRD Cohort: Reintroduced Ven + Continued Ibr
    Reporting group description
    		 All reported AEs in the MRD Cohort that started after the first dose date of reintroduced treatment with venetoclax and continued ibrutinib.

    Serious adverse events
    		 MRD Cohort: Pre-Dose FD Cohort: Pre-Dose FD Cohort: All Subjects MRD Cohort: Confirmed uMRD (IbrVen->Ibr) MRD Cohort: All Subjects MRD Cohort: Confirmed uMRD (IbrVen->Pbo) MRD Cohort: uMRD Not Confirmed (IbrVen->Ibr) MRD Cohort: uMRD Not Confirmed (IbrVen->IbrVen) FD Cohort: Reintroduced Ibrutinib FD Cohort: Reintroduced Ibr+Ven MRD Cohort: Reintroduced Ibrutinib MRD Cohort: Reintroduced Ven + Continued Ibr
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 164 (1.22%)
    1 / 159 (0.63%)
    37 / 159 (23.27%)
    15 / 43 (34.88%)
    63 / 164 (38.41%)
    14 / 43 (32.56%)
    13 / 31 (41.94%)
    12 / 32 (37.50%)
    6 / 18 (33.33%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         number of deaths (all causes)
    0
    0
    5
    1
    3
    0
    1
    0
    2
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    1
    1
    2
    0
    1
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BASAL CELL CARCINOMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    ENDOMETRIAL ADENOCARCINOMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    LUNG ADENOCARCINOMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    INVASIVE DUCTAL BREAST CARCINOMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    INVASIVE BREAST CARCINOMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 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
    0 / 0
    0 / 0
    MENINGIOMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    PROSTATE CANCER
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    MYELODYSPLASTIC SYNDROME
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    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
    0 / 0
    0 / 0
    RENAL CANCER
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    TRANSITIONAL CELL CARCINOMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    RENAL ONCOCYTOMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    Vascular disorders
    CIRCULATORY COLLAPSE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    HYPERTENSION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    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
    0 / 0
    0 / 0
    General disorders and administration site conditions
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    PAIN
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    SUDDEN DEATH
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    0 / 0
    0 / 0
         deaths 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
    0 / 0
    0 / 0
    SUDDEN CARDIAC DEATH
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    2 / 2
    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
    0 / 0
    0 / 0
    Immune system disorders
    ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY POSITIVE VASCULITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    HEAVY MENSTRUAL BLEEDING
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    PELVIC HAEMATOMA
         subjects affected / exposed
    0 / 164 (0.00%)
    1 / 159 (0.63%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ATELECTASIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    BRONCHOSPASM
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    2 / 164 (1.22%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    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
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    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
    0 / 0
    0 / 0
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    EMPHYSEMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    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 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY DISTRESS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    Psychiatric disorders
    ADJUSTMENT DISORDER WITH MIXED ANXIETY AND DEPRESSED MOOD
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    ANXIETY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    SCHIZOPHRENIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    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
    0 / 0
    0 / 0
    Investigations
    BLOOD PRESSURE DECREASED
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    INFLUENZA B VIRUS TEST POSITIVE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    FEMUR FRACTURE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    ROAD TRAFFIC ACCIDENT
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    SPINAL COMPRESSION FRACTURE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    MALFORMATION VENOUS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    Cardiac disorders
    ATRIAL FIBRILLATION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    2 / 43 (4.65%)
    5 / 164 (3.05%)
    1 / 43 (2.33%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    2 / 2
    7 / 7
    1 / 1
    3 / 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
    0 / 0
    0 / 0
    ANGINA PECTORIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    BRADYCARDIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    CARDIAC ARREST
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    CARDIAC FAILURE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 1
    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
    0 / 0
    0 / 0
    CORONARY ARTERY STENOSIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    DILATED CARDIOMYOPATHY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    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
    0 / 0
    0 / 0
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    PALPITATIONS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    PERICARDITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    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
    0 / 0
    0 / 0
    SINUS BRADYCARDIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    VENTRICULAR TACHYARRHYTHMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    Nervous system disorders
    ALTERED STATE OF CONSCIOUSNESS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    AMNESIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    EPILEPSY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    CEREBRAL VENOUS SINUS THROMBOSIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    CEREBRAL HAEMORRHAGE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    HEADACHE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    HEPATIC ENCEPHALOPATHY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    ISCHAEMIC STROKE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    SUBARACHNOID HAEMORRHAGE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    TRANSIENT ISCHAEMIC ATTACK
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    3 / 164 (1.83%)
    0 / 43 (0.00%)
    2 / 31 (6.45%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 3
    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
    0 / 0
    0 / 0
    VESTIBULAR MIGRAINE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    4 / 164 (2.44%)
    3 / 43 (6.98%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    3 / 4
    3 / 3
    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
    0 / 0
    0 / 0
    HAEMOLYSIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    NEUTROPENIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    2 / 31 (6.45%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    2 / 2
    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
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    VERTIGO
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    VERTIGO POSITIONAL
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    Eye disorders
    EYE HAEMORRHAGE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    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
    0 / 0
    0 / 0
    MACULAR OEDEMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    RETINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    2 / 164 (1.22%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    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
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    COLITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    OESOPHAGEAL SPASM
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    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
    0 / 0
    0 / 0
    PANCREATITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    VOMITING
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    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
    0 / 0
    0 / 0
    RETROPERITONEAL HAEMORRHAGE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    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
    0 / 0
    0 / 0
    Hepatobiliary disorders
    BILE DUCT STONE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    CHOLANGITIS ACUTE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    CHOLELITHIASIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    CHOLECYSTITIS ACUTE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    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
    0 / 0
    0 / 0
    HEPATITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    DERMATITIS BULLOUS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    Renal and urinary disorders
    RENAL COLIC
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    1 / 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
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    ARTHRITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    ARTHRALGIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    BACK PAIN
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    SPINAL SYNOVIAL CYST
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    OSTEOPOROSIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    Infections and infestations
    ABDOMINAL ABSCESS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    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
    0 / 0
    0 / 0
    ARTHRITIS INFECTIVE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    APPENDICITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    APPENDICEAL ABSCESS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 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
    0 / 0
    0 / 0
    BRONCHITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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 / 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
    0 / 0
    0 / 0
    CELLULITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 4
    0 / 1
    0 / 1
    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
    0 / 0
    0 / 0
    CAMPYLOBACTER INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    CELLULITIS ORBITAL
         subjects affected / exposed
    1 / 164 (0.61%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    2 / 164 (1.22%)
    2 / 43 (4.65%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 2
    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
    0 / 0
    0 / 0
    DIVERTICULITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    COVID-19 PNEUMONIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    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
    0 / 0
    0 / 0
    EMPYEMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    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
    0 / 0
    0 / 0
    ENCEPHALITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    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
    0 / 0
    0 / 0
    ESCHERICHIA BACTERAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    GASTROENTERITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    HERPES ZOSTER DISSEMINATED
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    INFLUENZA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    LOWER RESPIRATORY TRACT INFECTION BACTERIAL
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    LYMPHADENITIS BACTERIAL
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    PHARYNGITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    PILONIDAL DISEASE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    3 / 43 (6.98%)
    9 / 164 (5.49%)
    1 / 43 (2.33%)
    3 / 31 (9.68%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 4
    1 / 3
    4 / 9
    0 / 1
    2 / 3
    1 / 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
    0 / 0
    0 / 0
    PNEUMONIA BACTERIAL
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    PNEUMONIA LEGIONELLA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    PYELONEPHRITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    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
    0 / 0
    0 / 0
    PYOMYOSITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY SYNCYTIAL VIRUS BRONCHITIS
         subjects affected / exposed
    1 / 164 (0.61%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    SKIN INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    SALMONELLOSIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    STAPHYLOCOCCAL BACTERAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    STAPHYLOCOCCAL INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    VIRAL INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    VIRAL UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    WEST NILE VIRAL INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (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
    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
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    HYPONATRAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    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
    0 / 0
    0 / 0
    HYPERPHOSPHATAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    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
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 MRD Cohort: Pre-Dose FD Cohort: Pre-Dose FD Cohort: All Subjects MRD Cohort: Confirmed uMRD (IbrVen->Ibr) MRD Cohort: All Subjects MRD Cohort: Confirmed uMRD (IbrVen->Pbo) MRD Cohort: uMRD Not Confirmed (IbrVen->Ibr) MRD Cohort: uMRD Not Confirmed (IbrVen->IbrVen) FD Cohort: Reintroduced Ibrutinib FD Cohort: Reintroduced Ibr+Ven MRD Cohort: Reintroduced Ibrutinib MRD Cohort: Reintroduced Ven + Continued Ibr
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1 / 164 (0.61%)
    1 / 159 (0.63%)
    156 / 159 (98.11%)
    43 / 43 (100.00%)
    163 / 164 (99.39%)
    43 / 43 (100.00%)
    31 / 31 (100.00%)
    32 / 32 (100.00%)
    14 / 18 (77.78%)
    11 / 11 (100.00%)
    5 / 7 (71.43%)
    2 / 2 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    SQUAMOUS CELL CARCINOMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    2 / 43 (4.65%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    3
    3
    0
    0
    0
    1
    0
    0
    0
    MELANOCYTIC NAEVUS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    2 / 164 (1.22%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    0
    2
    1
    0
    0
    0
    0
    1
    0
    BASAL CELL CARCINOMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    4 / 43 (9.30%)
    12 / 164 (7.32%)
    5 / 43 (11.63%)
    1 / 31 (3.23%)
    2 / 32 (6.25%)
    1 / 18 (5.56%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    4
    6
    18
    5
    5
    2
    1
    1
    0
    0
    Vascular disorders
    HYPERTENSION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    24 / 159 (15.09%)
    15 / 43 (34.88%)
    45 / 164 (27.44%)
    11 / 43 (25.58%)
    9 / 31 (29.03%)
    8 / 32 (25.00%)
    2 / 18 (11.11%)
    5 / 11 (45.45%)
    3 / 7 (42.86%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    33
    26
    68
    16
    13
    10
    5
    7
    4
    0
    PHLEBITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    2
    0
    0
    0
    0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    9 / 159 (5.66%)
    2 / 43 (4.65%)
    12 / 164 (7.32%)
    3 / 43 (6.98%)
    2 / 31 (6.45%)
    3 / 32 (9.38%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    13
    2
    15
    4
    4
    3
    0
    1
    0
    0
    CHEST PAIN
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    2 / 43 (4.65%)
    6 / 164 (3.66%)
    1 / 43 (2.33%)
    2 / 31 (6.45%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    4
    2
    6
    1
    2
    1
    0
    0
    0
    0
    CHEST DISCOMFORT
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    1 / 43 (2.33%)
    7 / 164 (4.27%)
    2 / 43 (4.65%)
    4 / 31 (12.90%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    1
    8
    2
    5
    0
    0
    0
    0
    0
    CHILLS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    5 / 159 (3.14%)
    4 / 43 (9.30%)
    14 / 164 (8.54%)
    5 / 43 (11.63%)
    1 / 31 (3.23%)
    4 / 32 (12.50%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    5
    5
    19
    6
    1
    7
    0
    1
    1
    0
    INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    7 / 159 (4.40%)
    4 / 43 (9.30%)
    11 / 164 (6.71%)
    1 / 43 (2.33%)
    4 / 31 (12.90%)
    1 / 32 (3.13%)
    2 / 18 (11.11%)
    1 / 11 (9.09%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    7
    5
    12
    1
    4
    1
    3
    1
    1
    0
    FATIGUE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    39 / 159 (24.53%)
    14 / 43 (32.56%)
    56 / 164 (34.15%)
    21 / 43 (48.84%)
    10 / 31 (32.26%)
    7 / 32 (21.88%)
    1 / 18 (5.56%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    51
    25
    102
    37
    22
    12
    1
    1
    0
    0
    MALAISE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    7 / 159 (4.40%)
    1 / 43 (2.33%)
    6 / 164 (3.66%)
    3 / 43 (6.98%)
    1 / 31 (3.23%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    7
    2
    7
    3
    1
    1
    0
    0
    0
    0
    INJECTION SITE BRUISING
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    2 / 43 (4.65%)
    5 / 164 (3.05%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    2
    5
    1
    0
    2
    0
    0
    0
    0
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    4 / 164 (2.44%)
    0 / 43 (0.00%)
    3 / 31 (9.68%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    0
    5
    0
    4
    1
    0
    0
    0
    0
    OEDEMA PERIPHERAL
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    11 / 159 (6.92%)
    8 / 43 (18.60%)
    22 / 164 (13.41%)
    6 / 43 (13.95%)
    3 / 31 (9.68%)
    4 / 32 (12.50%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    12
    11
    34
    11
    4
    7
    0
    0
    0
    0
    PERIPHERAL SWELLING
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    11 / 159 (6.92%)
    0 / 43 (0.00%)
    6 / 164 (3.66%)
    2 / 43 (4.65%)
    2 / 31 (6.45%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    11
    0
    6
    2
    2
    2
    0
    0
    0
    0
    PAIN
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    0 / 43 (0.00%)
    9 / 164 (5.49%)
    2 / 43 (4.65%)
    5 / 31 (16.13%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    7
    0
    10
    2
    6
    2
    0
    0
    0
    0
    PYREXIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    22 / 159 (13.84%)
    10 / 43 (23.26%)
    31 / 164 (18.90%)
    4 / 43 (9.30%)
    3 / 31 (9.68%)
    10 / 32 (31.25%)
    2 / 18 (11.11%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    35
    12
    44
    7
    5
    13
    6
    0
    0
    0
    Immune system disorders
    SEASONAL ALLERGY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    7 / 164 (4.27%)
    2 / 43 (4.65%)
    2 / 31 (6.45%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    1
    7
    2
    2
    2
    0
    0
    0
    0
    Reproductive system and breast disorders
    BENIGN PROSTATIC HYPERPLASIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    3 / 164 (1.83%)
    1 / 43 (2.33%)
    2 / 31 (6.45%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    0
    3
    1
    2
    0
    0
    0
    0
    0
    ERECTILE DYSFUNCTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    3 / 43 (6.98%)
    7 / 164 (4.27%)
    0 / 43 (0.00%)
    2 / 31 (6.45%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    3
    7
    0
    2
    1
    0
    0
    0
    0
    HEAVY MENSTRUAL BLEEDING
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    1
    1
    0
    0
    0
    1
    0
    0
    0
    TESTICULAR SWELLING
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    0 / 43 (0.00%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    0
    2
    0
    0
    2
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    3 / 43 (6.98%)
    3 / 164 (1.83%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    4
    4
    0
    0
    0
    0
    0
    0
    0
    COUGH
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    28 / 159 (17.61%)
    15 / 43 (34.88%)
    46 / 164 (28.05%)
    17 / 43 (39.53%)
    8 / 31 (25.81%)
    4 / 32 (12.50%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    2 / 7 (28.57%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    34
    20
    63
    25
    10
    5
    1
    0
    2
    0
    DYSPNOEA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    11 / 159 (6.92%)
    11 / 43 (25.58%)
    22 / 164 (13.41%)
    6 / 43 (13.95%)
    3 / 31 (9.68%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    11
    12
    25
    6
    4
    0
    0
    0
    0
    0
    DYSPNOEA EXERTIONAL
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    2 / 43 (4.65%)
    5 / 164 (3.05%)
    3 / 43 (6.98%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    2
    5
    3
    0
    0
    1
    0
    0
    0
    EPISTAXIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    19 / 159 (11.95%)
    10 / 43 (23.26%)
    30 / 164 (18.29%)
    8 / 43 (18.60%)
    5 / 31 (16.13%)
    6 / 32 (18.75%)
    2 / 18 (11.11%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    27
    18
    51
    17
    8
    7
    2
    3
    0
    0
    HAEMOPTYSIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    0
    3
    0
    3
    0
    1
    0
    0
    0
    RHINITIS ALLERGIC
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    2 / 43 (4.65%)
    6 / 164 (3.66%)
    1 / 43 (2.33%)
    2 / 31 (6.45%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    4
    2
    6
    1
    2
    1
    0
    0
    0
    0
    RESPIRATORY TRACT CONGESTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    1
    2
    0
    0
    1
    0
    1
    0
    0
    PRODUCTIVE COUGH
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    5 / 43 (11.63%)
    7 / 164 (4.27%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    4
    5
    7
    1
    0
    0
    0
    0
    0
    0
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    17 / 159 (10.69%)
    10 / 43 (23.26%)
    39 / 164 (23.78%)
    9 / 43 (20.93%)
    9 / 31 (29.03%)
    10 / 32 (31.25%)
    2 / 18 (11.11%)
    1 / 11 (9.09%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    19
    16
    63
    15
    16
    14
    3
    1
    1
    0
    NASAL DRYNESS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    5 / 164 (3.05%)
    3 / 43 (6.98%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    1
    5
    3
    0
    1
    0
    0
    0
    0
    NASAL CONGESTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    7 / 43 (16.28%)
    18 / 164 (10.98%)
    4 / 43 (9.30%)
    4 / 31 (12.90%)
    1 / 32 (3.13%)
    2 / 18 (11.11%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    4
    8
    21
    5
    4
    1
    2
    0
    0
    0
    SINUS CONGESTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    5 / 43 (11.63%)
    10 / 164 (6.10%)
    2 / 43 (4.65%)
    3 / 31 (9.68%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    5
    10
    2
    3
    0
    0
    0
    0
    0
    Psychiatric disorders
    INSOMNIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    6 / 159 (3.77%)
    3 / 43 (6.98%)
    21 / 164 (12.80%)
    6 / 43 (13.95%)
    7 / 31 (22.58%)
    4 / 32 (12.50%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    6
    3
    22
    7
    7
    4
    0
    0
    0
    0
    DEPRESSION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    4 / 43 (9.30%)
    8 / 164 (4.88%)
    0 / 43 (0.00%)
    2 / 31 (6.45%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    4
    9
    0
    3
    1
    0
    0
    0
    0
    CONFUSIONAL STATE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    1 / 32 (3.13%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    1
    1
    1
    0
    0
    0
    ANXIETY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    4 / 43 (9.30%)
    13 / 164 (7.93%)
    2 / 43 (4.65%)
    5 / 31 (16.13%)
    2 / 32 (6.25%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    4
    14
    3
    5
    2
    1
    0
    0
    0
    AGITATION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    4 / 164 (2.44%)
    0 / 43 (0.00%)
    2 / 31 (6.45%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    1
    5
    0
    3
    0
    0
    0
    0
    0
    Investigations
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    7 / 159 (4.40%)
    5 / 43 (11.63%)
    16 / 164 (9.76%)
    4 / 43 (9.30%)
    3 / 31 (9.68%)
    4 / 32 (12.50%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    8
    6
    20
    4
    5
    5
    0
    1
    0
    0
    BLOOD BILIRUBIN INCREASED
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    6 / 159 (3.77%)
    1 / 43 (2.33%)
    7 / 164 (4.27%)
    0 / 43 (0.00%)
    5 / 31 (16.13%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    15
    1
    20
    0
    17
    2
    0
    0
    0
    0
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    6 / 159 (3.77%)
    4 / 43 (9.30%)
    17 / 164 (10.37%)
    5 / 43 (11.63%)
    4 / 31 (12.90%)
    3 / 32 (9.38%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    6
    7
    33
    6
    11
    5
    0
    1
    0
    0
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    9 / 159 (5.66%)
    5 / 43 (11.63%)
    17 / 164 (10.37%)
    5 / 43 (11.63%)
    4 / 31 (12.90%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    16
    5
    24
    6
    7
    5
    0
    0
    0
    0
    BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    3 / 43 (6.98%)
    3 / 164 (1.83%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    4
    4
    0
    0
    0
    0
    0
    0
    0
    WEIGHT DECREASED
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    6 / 159 (3.77%)
    5 / 43 (11.63%)
    8 / 164 (4.88%)
    2 / 43 (4.65%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    6
    5
    8
    2
    1
    0
    0
    0
    0
    0
    PLATELET COUNT DECREASED
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    8 / 159 (5.03%)
    5 / 43 (11.63%)
    9 / 164 (5.49%)
    2 / 43 (4.65%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    14
    8
    12
    2
    0
    0
    0
    0
    0
    0
    NEUTROPHIL COUNT DECREASED
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    16 / 159 (10.06%)
    2 / 43 (4.65%)
    5 / 164 (3.05%)
    2 / 43 (4.65%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    38
    2
    6
    2
    2
    0
    0
    1
    0
    0
    BLOOD THYROID STIMULATING HORMONE DECREASED
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    BLOOD LACTATE DEHYDROGENASE INCREASED
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    2 / 164 (1.22%)
    2 / 43 (4.65%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    0
    0
    0
    1
    0
    0
    WHITE BLOOD CELL COUNT DECREASED
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    7 / 159 (4.40%)
    0 / 43 (0.00%)
    4 / 164 (2.44%)
    0 / 43 (0.00%)
    2 / 31 (6.45%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    18
    0
    6
    0
    2
    4
    0
    1
    0
    0
    Injury, poisoning and procedural complications
    ARTHROPOD BITE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    5 / 159 (3.14%)
    1 / 43 (2.33%)
    4 / 164 (2.44%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    2 / 32 (6.25%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    5
    1
    5
    0
    0
    2
    1
    0
    0
    0
    HAND FRACTURE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    FALL
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    5 / 43 (11.63%)
    10 / 164 (6.10%)
    2 / 43 (4.65%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    6
    11
    2
    0
    1
    0
    0
    0
    0
    EYE CONTUSION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    3 / 164 (1.83%)
    1 / 43 (2.33%)
    2 / 31 (6.45%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    1
    2
    0
    0
    0
    0
    0
    CONTUSION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    24 / 159 (15.09%)
    10 / 43 (23.26%)
    40 / 164 (24.39%)
    12 / 43 (27.91%)
    10 / 31 (32.26%)
    6 / 32 (18.75%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    25
    14
    63
    20
    14
    13
    1
    0
    0
    0
    LIMB INJURY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    1 / 43 (2.33%)
    6 / 164 (3.66%)
    3 / 43 (6.98%)
    2 / 31 (6.45%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    1
    6
    3
    2
    0
    0
    0
    0
    0
    RIB FRACTURE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    3 / 164 (1.83%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    1
    3
    0
    0
    2
    0
    0
    0
    0
    SCRATCH
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    4 / 164 (2.44%)
    0 / 43 (0.00%)
    3 / 31 (9.68%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    0
    4
    0
    3
    1
    0
    0
    0
    0
    SKIN ABRASION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    1 / 43 (2.33%)
    9 / 164 (5.49%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    6 / 32 (18.75%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    5
    1
    10
    1
    0
    7
    0
    1
    0
    0
    SKIN LACERATION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    3 / 43 (6.98%)
    9 / 164 (5.49%)
    2 / 43 (4.65%)
    3 / 31 (9.68%)
    1 / 32 (3.13%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    3
    9
    2
    3
    1
    1
    0
    0
    0
    WOUND HAEMORRHAGE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    3 / 164 (1.83%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    3 / 32 (9.38%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    3
    2
    0
    0
    0
    Cardiac disorders
    ATRIAL FIBRILLATION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    5 / 159 (3.14%)
    2 / 43 (4.65%)
    13 / 164 (7.93%)
    3 / 43 (6.98%)
    3 / 31 (9.68%)
    3 / 32 (9.38%)
    2 / 18 (11.11%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    7
    2
    18
    3
    3
    5
    2
    0
    0
    0
    PALPITATIONS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    15 / 159 (9.43%)
    11 / 43 (25.58%)
    27 / 164 (16.46%)
    8 / 43 (18.60%)
    1 / 31 (3.23%)
    6 / 32 (18.75%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    17
    18
    39
    11
    1
    8
    0
    0
    0
    0
    SINUS TACHYCARDIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    0 / 43 (0.00%)
    4 / 164 (2.44%)
    2 / 43 (4.65%)
    0 / 31 (0.00%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    4
    0
    4
    2
    0
    2
    0
    0
    0
    0
    SINUS BRADYCARDIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    2 / 43 (4.65%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    6
    6
    0
    0
    0
    0
    0
    1
    0
    Nervous system disorders
    BRAIN FOG
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    HYPOAESTHESIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    3 / 43 (6.98%)
    12 / 164 (7.32%)
    4 / 43 (9.30%)
    4 / 31 (12.90%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    3
    15
    5
    6
    1
    0
    0
    0
    0
    HEADACHE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    39 / 159 (24.53%)
    15 / 43 (34.88%)
    52 / 164 (31.71%)
    18 / 43 (41.86%)
    8 / 31 (25.81%)
    9 / 32 (28.13%)
    1 / 18 (5.56%)
    2 / 11 (18.18%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    55
    27
    92
    32
    16
    14
    2
    2
    0
    0
    DYSGEUSIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    1 / 43 (2.33%)
    5 / 164 (3.05%)
    2 / 43 (4.65%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    1
    6
    3
    1
    0
    1
    0
    0
    0
    DIZZINESS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    27 / 159 (16.98%)
    10 / 43 (23.26%)
    32 / 164 (19.51%)
    9 / 43 (20.93%)
    5 / 31 (16.13%)
    6 / 32 (18.75%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    34
    14
    45
    11
    9
    9
    0
    0
    0
    0
    CAROTID ARTERIOSCLEROSIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    MEMORY IMPAIRMENT
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    3 / 43 (6.98%)
    4 / 164 (2.44%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    4
    5
    0
    1
    0
    0
    0
    0
    0
    PARAESTHESIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    6 / 159 (3.77%)
    4 / 43 (9.30%)
    14 / 164 (8.54%)
    4 / 43 (9.30%)
    4 / 31 (12.90%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    6
    4
    18
    6
    6
    2
    0
    0
    0
    0
    PERIPHERAL SENSORY NEUROPATHY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    3 / 43 (6.98%)
    4 / 164 (2.44%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    4
    5
    0
    0
    1
    0
    0
    1
    0
    SCIATICA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    5 / 164 (3.05%)
    1 / 43 (2.33%)
    1 / 31 (3.23%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    1
    5
    1
    1
    2
    0
    0
    0
    0
    SYNCOPE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    2 / 43 (4.65%)
    7 / 164 (4.27%)
    0 / 43 (0.00%)
    2 / 31 (6.45%)
    3 / 32 (9.38%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    2
    7
    0
    2
    3
    1
    0
    0
    0
    TREMOR
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    3 / 43 (6.98%)
    3 / 164 (1.83%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    5
    5
    0
    0
    0
    0
    0
    0
    0
    NEUROPATHY PERIPHERAL
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    4 / 164 (2.44%)
    2 / 43 (4.65%)
    0 / 31 (0.00%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    2
    0
    2
    0
    0
    0
    0
    Blood and lymphatic system disorders
    INCREASED TENDENCY TO BRUISE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    35 / 159 (22.01%)
    12 / 43 (27.91%)
    41 / 164 (25.00%)
    7 / 43 (16.28%)
    11 / 31 (35.48%)
    8 / 32 (25.00%)
    1 / 18 (5.56%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    44
    19
    62
    9
    19
    11
    1
    1
    0
    0
    ANAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    1 / 159 (0.63%)
    10 / 159 (6.29%)
    5 / 43 (11.63%)
    14 / 164 (8.54%)
    0 / 43 (0.00%)
    3 / 31 (9.68%)
    5 / 32 (15.63%)
    2 / 18 (11.11%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    2
    17
    10
    26
    0
    7
    7
    3
    0
    0
    0
    LYMPHOCYTOSIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    0
    1
    0
    0
    1
    1
    0
    0
    0
    IRON DEFICIENCY ANAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    2 / 43 (4.65%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    3
    3
    0
    0
    0
    1
    0
    0
    0
    NEUTROPENIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    65 / 159 (40.88%)
    24 / 43 (55.81%)
    71 / 164 (43.29%)
    15 / 43 (34.88%)
    12 / 31 (38.71%)
    14 / 32 (43.75%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    169
    107
    246
    36
    29
    54
    0
    0
    0
    0
    SPONTANEOUS HAEMATOMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    1 / 43 (2.33%)
    4 / 164 (2.44%)
    0 / 43 (0.00%)
    2 / 31 (6.45%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    4
    3
    13
    0
    4
    6
    0
    0
    0
    0
    THROMBOCYTOPENIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    21 / 159 (13.21%)
    9 / 43 (20.93%)
    33 / 164 (20.12%)
    5 / 43 (11.63%)
    5 / 31 (16.13%)
    10 / 32 (31.25%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    38
    21
    72
    9
    12
    23
    0
    2
    0
    0
    Ear and labyrinth disorders
    DEAFNESS NEUROSENSORY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    VERTIGO
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    2 / 43 (4.65%)
    9 / 164 (5.49%)
    2 / 43 (4.65%)
    2 / 31 (6.45%)
    3 / 32 (9.38%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    4
    2
    12
    4
    2
    4
    0
    0
    0
    0
    Eye disorders
    CONJUNCTIVAL HYPERAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    CATARACT
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    2 / 43 (4.65%)
    5 / 164 (3.05%)
    2 / 43 (4.65%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    2
    6
    3
    0
    1
    0
    0
    1
    0
    RETINAL DETACHMENT
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    2
    0
    0
    0
    DRY EYE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    2 / 43 (4.65%)
    8 / 164 (4.88%)
    2 / 43 (4.65%)
    1 / 31 (3.23%)
    3 / 32 (9.38%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    2
    8
    2
    1
    3
    1
    0
    0
    0
    RETINAL TEAR
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    0
    0
    3
    0
    0
    0
    VISION BLURRED
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    4 / 43 (9.30%)
    13 / 164 (7.93%)
    1 / 43 (2.33%)
    3 / 31 (9.68%)
    4 / 32 (12.50%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    6
    15
    1
    3
    4
    0
    0
    0
    0
    UVEITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    VITREOUS HAEMORRHAGE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    2
    0
    0
    0
    Gastrointestinal disorders
    ABDOMINAL DISCOMFORT
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    5 / 43 (11.63%)
    10 / 164 (6.10%)
    1 / 43 (2.33%)
    1 / 31 (3.23%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    5
    5
    12
    1
    2
    3
    0
    0
    0
    0
    ABDOMINAL DISTENSION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    10 / 159 (6.29%)
    4 / 43 (9.30%)
    15 / 164 (9.15%)
    5 / 43 (11.63%)
    4 / 31 (12.90%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    11
    6
    21
    9
    4
    0
    1
    0
    0
    0
    ABDOMINAL PAIN
         subjects affected / exposed
    0 / 164 (0.00%)
    1 / 159 (0.63%)
    13 / 159 (8.18%)
    8 / 43 (18.60%)
    28 / 164 (17.07%)
    10 / 43 (23.26%)
    2 / 31 (6.45%)
    6 / 32 (18.75%)
    2 / 18 (11.11%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    1
    16
    9
    34
    11
    2
    8
    2
    0
    0
    1
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    14 / 159 (8.81%)
    7 / 43 (16.28%)
    25 / 164 (15.24%)
    5 / 43 (11.63%)
    7 / 31 (22.58%)
    5 / 32 (15.63%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    15
    9
    34
    6
    13
    5
    0
    1
    0
    0
    APHTHOUS ULCER
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    8 / 159 (5.03%)
    1 / 43 (2.33%)
    7 / 164 (4.27%)
    5 / 43 (11.63%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    10
    1
    10
    8
    0
    1
    0
    0
    1
    0
    COLITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    CONSTIPATION
         subjects affected / exposed
    0 / 164 (0.00%)
    1 / 159 (0.63%)
    25 / 159 (15.72%)
    11 / 43 (25.58%)
    34 / 164 (20.73%)
    8 / 43 (18.60%)
    9 / 31 (29.03%)
    6 / 32 (18.75%)
    1 / 18 (5.56%)
    2 / 11 (18.18%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    31
    14
    47
    11
    12
    10
    1
    2
    0
    0
    DRY MOUTH
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    6 / 159 (3.77%)
    4 / 43 (9.30%)
    8 / 164 (4.88%)
    2 / 43 (4.65%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    6
    4
    8
    2
    0
    1
    0
    0
    1
    0
    DIARRHOEA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    99 / 159 (62.26%)
    34 / 43 (79.07%)
    119 / 164 (72.56%)
    28 / 43 (65.12%)
    23 / 31 (74.19%)
    28 / 32 (87.50%)
    3 / 18 (16.67%)
    4 / 11 (36.36%)
    2 / 7 (28.57%)
    2 / 2 (100.00%)
         occurrences all number
    0
    0
    203
    91
    435
    72
    56
    201
    6
    7
    3
    3
    DYSPEPSIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    29 / 159 (18.24%)
    10 / 43 (23.26%)
    30 / 164 (18.29%)
    5 / 43 (11.63%)
    7 / 31 (22.58%)
    7 / 32 (21.88%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    38
    11
    40
    9
    12
    7
    0
    0
    0
    0
    FLATULENCE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    6 / 159 (3.77%)
    1 / 43 (2.33%)
    9 / 164 (5.49%)
    3 / 43 (6.98%)
    1 / 31 (3.23%)
    3 / 32 (9.38%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    6
    1
    9
    3
    1
    3
    0
    0
    0
    0
    DYSPHAGIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    1 / 43 (2.33%)
    3 / 164 (1.83%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    5
    1
    4
    1
    0
    2
    1
    0
    0
    0
    GASTRITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    4 / 43 (9.30%)
    7 / 164 (4.27%)
    1 / 43 (2.33%)
    1 / 31 (3.23%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    4
    7
    1
    1
    1
    0
    0
    0
    0
    HAEMORRHOIDAL HAEMORRHAGE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    2 / 43 (4.65%)
    5 / 164 (3.05%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    2
    5
    1
    0
    2
    0
    0
    0
    0
    GLOSSODYNIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    2 / 31 (6.45%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    3
    0
    0
    0
    0
    0
    GINGIVAL BLEEDING
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    2 / 43 (4.65%)
    7 / 164 (4.27%)
    1 / 43 (2.33%)
    4 / 31 (12.90%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    2
    8
    1
    5
    0
    0
    0
    0
    0
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    0 / 164 (0.00%)
    1 / 159 (0.63%)
    16 / 159 (10.06%)
    10 / 43 (23.26%)
    30 / 164 (18.29%)
    4 / 43 (9.30%)
    6 / 31 (19.35%)
    7 / 32 (21.88%)
    2 / 18 (11.11%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    1
    19
    11
    36
    6
    9
    7
    2
    1
    0
    2
    HAEMORRHOIDS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    4 / 164 (2.44%)
    3 / 43 (6.98%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    1
    4
    3
    0
    0
    0
    0
    1
    0
    INGUINAL HERNIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    2 / 43 (4.65%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    4
    2
    2
    0
    0
    0
    0
    1
    0
    0
    LIP BLISTER
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    1
    2
    0
    1
    0
    1
    0
    0
    0
    MOUTH HAEMORRHAGE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    1
    0
    MOUTH ULCERATION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    24 / 159 (15.09%)
    6 / 43 (13.95%)
    19 / 164 (11.59%)
    4 / 43 (9.30%)
    6 / 31 (19.35%)
    3 / 32 (9.38%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    30
    8
    31
    4
    10
    9
    0
    0
    0
    0
    ORAL PAIN
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    4 / 164 (2.44%)
    1 / 43 (2.33%)
    2 / 31 (6.45%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    1
    4
    1
    2
    0
    0
    0
    0
    0
    NAUSEA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    68 / 159 (42.77%)
    21 / 43 (48.84%)
    80 / 164 (48.78%)
    20 / 43 (46.51%)
    20 / 31 (64.52%)
    12 / 32 (37.50%)
    1 / 18 (5.56%)
    2 / 11 (18.18%)
    0 / 7 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    0
    97
    40
    136
    29
    36
    22
    1
    3
    0
    1
    PROCTALGIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    SALIVARY GLAND ENLARGEMENT
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    RECTAL HAEMORRHAGE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    0 / 43 (0.00%)
    4 / 164 (2.44%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    3 / 32 (9.38%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    0
    4
    1
    0
    3
    0
    0
    0
    0
    STOMATITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    21 / 159 (13.21%)
    9 / 43 (20.93%)
    28 / 164 (17.07%)
    8 / 43 (18.60%)
    6 / 31 (19.35%)
    3 / 32 (9.38%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    33
    13
    61
    14
    11
    20
    0
    0
    1
    0
    VOMITING
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    33 / 159 (20.75%)
    13 / 43 (30.23%)
    42 / 164 (25.61%)
    6 / 43 (13.95%)
    7 / 31 (22.58%)
    11 / 32 (34.38%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    0
    48
    26
    73
    10
    16
    14
    0
    0
    0
    1
    TOOTHACHE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    2 / 43 (4.65%)
    7 / 164 (4.27%)
    1 / 43 (2.33%)
    1 / 31 (3.23%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    2
    7
    1
    1
    2
    0
    0
    0
    0
    Hepatobiliary disorders
    HYPERBILIRUBINAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    1 / 43 (2.33%)
    2 / 164 (1.22%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    2
    3
    1
    0
    0
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    BLISTER
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    2 / 43 (4.65%)
    7 / 164 (4.27%)
    2 / 43 (4.65%)
    2 / 31 (6.45%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    4
    2
    7
    2
    2
    1
    0
    0
    0
    0
    ALOPECIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    6 / 159 (3.77%)
    3 / 43 (6.98%)
    9 / 164 (5.49%)
    2 / 43 (4.65%)
    0 / 31 (0.00%)
    3 / 32 (9.38%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    6
    3
    9
    2
    0
    3
    0
    0
    0
    0
    ACNE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    3 / 43 (6.98%)
    6 / 164 (3.66%)
    1 / 43 (2.33%)
    1 / 31 (3.23%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    4
    4
    7
    1
    1
    1
    0
    0
    0
    0
    BLOOD BLISTER
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    6 / 159 (3.77%)
    0 / 43 (0.00%)
    5 / 164 (3.05%)
    4 / 43 (9.30%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    7
    0
    5
    4
    0
    0
    0
    0
    0
    0
    DERMATITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    0 / 43 (0.00%)
    3 / 164 (1.83%)
    1 / 43 (2.33%)
    1 / 31 (3.23%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    0
    4
    1
    2
    1
    0
    1
    0
    0
    DERMATITIS ACNEIFORM
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    2 / 43 (4.65%)
    4 / 164 (2.44%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    2
    4
    0
    0
    2
    0
    0
    0
    0
    DERMATITIS BULLOUS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    1
    0
    1
    0
    DRY SKIN
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    16 / 159 (10.06%)
    10 / 43 (23.26%)
    25 / 164 (15.24%)
    7 / 43 (16.28%)
    3 / 31 (9.68%)
    5 / 32 (15.63%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    18
    13
    28
    7
    3
    5
    1
    0
    1
    0
    ECCHYMOSIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    7 / 43 (16.28%)
    12 / 164 (7.32%)
    0 / 43 (0.00%)
    3 / 31 (9.68%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    4
    10
    16
    0
    4
    2
    0
    0
    0
    0
    ECZEMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    0 / 43 (0.00%)
    4 / 164 (2.44%)
    1 / 43 (2.33%)
    1 / 31 (3.23%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    5
    0
    4
    1
    1
    2
    0
    0
    0
    0
    ERYTHEMA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    8 / 159 (5.03%)
    2 / 43 (4.65%)
    13 / 164 (7.93%)
    4 / 43 (9.30%)
    2 / 31 (6.45%)
    5 / 32 (15.63%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    8
    2
    18
    6
    4
    6
    0
    0
    0
    0
    HYPERHIDROSIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    0 / 43 (0.00%)
    7 / 164 (4.27%)
    3 / 43 (6.98%)
    1 / 31 (3.23%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    6
    0
    8
    3
    1
    3
    0
    0
    0
    0
    NIGHT SWEATS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    5 / 159 (3.14%)
    4 / 43 (9.30%)
    15 / 164 (9.15%)
    3 / 43 (6.98%)
    5 / 31 (16.13%)
    3 / 32 (9.38%)
    1 / 18 (5.56%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    5
    5
    18
    3
    6
    4
    1
    1
    0
    0
    NAIL RIDGING
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    5 / 164 (3.05%)
    3 / 43 (6.98%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    1
    5
    3
    0
    1
    0
    0
    0
    0
    HYPERKERATOSIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    0
    0
    0
    1
    0
    0
    ONYCHOCLASIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    14 / 159 (8.81%)
    5 / 43 (11.63%)
    22 / 164 (13.41%)
    5 / 43 (11.63%)
    5 / 31 (16.13%)
    6 / 32 (18.75%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    14
    5
    23
    6
    5
    6
    0
    0
    0
    0
    PRURITUS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    17 / 159 (10.69%)
    7 / 43 (16.28%)
    21 / 164 (12.80%)
    2 / 43 (4.65%)
    3 / 31 (9.68%)
    8 / 32 (25.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    19
    9
    30
    3
    4
    13
    0
    0
    1
    0
    PETECHIAE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    17 / 159 (10.69%)
    5 / 43 (11.63%)
    25 / 164 (15.24%)
    3 / 43 (6.98%)
    6 / 31 (19.35%)
    8 / 32 (25.00%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    23
    6
    35
    6
    9
    11
    0
    1
    0
    0
    PSORIASIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    1 / 43 (2.33%)
    2 / 164 (1.22%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    2
    3
    1
    0
    0
    1
    0
    0
    0
    RASH
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    10 / 159 (6.29%)
    5 / 43 (11.63%)
    19 / 164 (11.59%)
    4 / 43 (9.30%)
    3 / 31 (9.68%)
    6 / 32 (18.75%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    12
    5
    23
    5
    5
    7
    0
    0
    0
    0
    RASH ERYTHEMATOUS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    9 / 159 (5.66%)
    3 / 43 (6.98%)
    13 / 164 (7.93%)
    4 / 43 (9.30%)
    2 / 31 (6.45%)
    3 / 32 (9.38%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    11
    5
    16
    5
    2
    3
    0
    0
    0
    0
    RASH MACULAR
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    0 / 43 (0.00%)
    3 / 164 (1.83%)
    0 / 43 (0.00%)
    2 / 31 (6.45%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    0
    4
    0
    3
    1
    0
    0
    0
    0
    RASH MACULO-PAPULAR
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    27 / 159 (16.98%)
    9 / 43 (20.93%)
    29 / 164 (17.68%)
    10 / 43 (23.26%)
    5 / 31 (16.13%)
    5 / 32 (15.63%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    32
    12
    38
    11
    9
    6
    0
    0
    0
    0
    SKIN ATROPHY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    3
    0
    0
    0
    0
    SKIN DISCOLOURATION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    0 / 43 (0.00%)
    4 / 164 (2.44%)
    1 / 43 (2.33%)
    3 / 31 (9.68%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    5
    0
    4
    1
    3
    0
    0
    0
    0
    0
    SKIN FISSURES
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    5 / 159 (3.14%)
    3 / 43 (6.98%)
    9 / 164 (5.49%)
    3 / 43 (6.98%)
    1 / 31 (3.23%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    6
    3
    9
    3
    1
    2
    0
    0
    0
    0
    SKIN FRAGILITY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    3 / 164 (1.83%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    1
    2
    0
    0
    0
    0
    SKIN LESION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    8 / 159 (5.03%)
    4 / 43 (9.30%)
    13 / 164 (7.93%)
    3 / 43 (6.98%)
    1 / 31 (3.23%)
    4 / 32 (12.50%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    8
    7
    16
    3
    1
    4
    0
    1
    0
    0
    SKIN MASS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    0 / 43 (0.00%)
    4 / 164 (2.44%)
    4 / 43 (9.30%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    0
    5
    5
    0
    0
    0
    0
    0
    0
    Renal and urinary disorders
    HAEMATURIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    9 / 159 (5.66%)
    3 / 43 (6.98%)
    12 / 164 (7.32%)
    2 / 43 (4.65%)
    3 / 31 (9.68%)
    4 / 32 (12.50%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    9
    3
    14
    2
    5
    4
    0
    0
    0
    0
    NEPHROLITHIASIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    4 / 43 (9.30%)
    6 / 164 (3.66%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    5
    7
    0
    1
    0
    0
    0
    0
    0
    POLLAKIURIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    2 / 43 (4.65%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    2
    2
    0
    0
    0
    1
    0
    0
    0
    Endocrine disorders
    HYPOTHYROIDISM
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    3 / 43 (6.98%)
    6 / 164 (3.66%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    3
    6
    1
    0
    2
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    JOINT STIFFNESS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    1 / 43 (2.33%)
    5 / 164 (3.05%)
    2 / 43 (4.65%)
    2 / 31 (6.45%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    1
    5
    2
    2
    0
    0
    0
    0
    0
    FOOT DEFORMITY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    1
    0
    0
    0
    BONE PAIN
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    5 / 43 (11.63%)
    9 / 164 (5.49%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    5
    8
    12
    0
    1
    2
    0
    0
    0
    0
    BACK PAIN
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    20 / 159 (12.58%)
    11 / 43 (25.58%)
    42 / 164 (25.61%)
    9 / 43 (20.93%)
    10 / 31 (32.26%)
    9 / 32 (28.13%)
    2 / 18 (11.11%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    22
    12
    57
    14
    17
    11
    5
    1
    0
    0
    ARTHRALGIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    52 / 159 (32.70%)
    23 / 43 (53.49%)
    82 / 164 (50.00%)
    20 / 43 (46.51%)
    17 / 31 (54.84%)
    16 / 32 (50.00%)
    2 / 18 (11.11%)
    1 / 11 (9.09%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    84
    48
    162
    40
    28
    34
    3
    1
    1
    0
    OSTEOARTHRITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    3 / 43 (6.98%)
    9 / 164 (5.49%)
    2 / 43 (4.65%)
    3 / 31 (9.68%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    3
    9
    2
    3
    1
    0
    0
    0
    0
    NECK PAIN
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    5 / 159 (3.14%)
    3 / 43 (6.98%)
    12 / 164 (7.32%)
    3 / 43 (6.98%)
    3 / 31 (9.68%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    7
    3
    12
    3
    3
    2
    0
    0
    0
    0
    MYALGIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    23 / 159 (14.47%)
    9 / 43 (20.93%)
    31 / 164 (18.90%)
    9 / 43 (20.93%)
    7 / 31 (22.58%)
    3 / 32 (9.38%)
    1 / 18 (5.56%)
    2 / 11 (18.18%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    30
    18
    46
    11
    8
    3
    1
    3
    1
    0
    MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    0 / 43 (0.00%)
    6 / 164 (3.66%)
    2 / 43 (4.65%)
    0 / 31 (0.00%)
    4 / 32 (12.50%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    0
    6
    2
    0
    4
    0
    0
    0
    0
    PAIN IN EXTREMITY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    21 / 159 (13.21%)
    5 / 43 (11.63%)
    31 / 164 (18.90%)
    9 / 43 (20.93%)
    8 / 31 (25.81%)
    8 / 32 (25.00%)
    3 / 18 (16.67%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    25
    5
    39
    12
    8
    13
    3
    0
    0
    0
    MUSCLE SPASMS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    47 / 159 (29.56%)
    13 / 43 (30.23%)
    43 / 164 (26.22%)
    11 / 43 (25.58%)
    10 / 31 (32.26%)
    7 / 32 (21.88%)
    1 / 18 (5.56%)
    2 / 11 (18.18%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    66
    20
    61
    17
    11
    11
    1
    2
    1
    0
    PERIARTHRITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    2 / 164 (1.22%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    0
    2
    1
    0
    1
    1
    0
    0
    0
    SPINAL PAIN
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    3 / 164 (1.83%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    2
    4
    0
    0
    2
    0
    0
    0
    0
    Infections and infestations
    BRONCHITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    5 / 159 (3.14%)
    2 / 43 (4.65%)
    7 / 164 (4.27%)
    1 / 43 (2.33%)
    3 / 31 (9.68%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    6
    2
    7
    1
    3
    1
    0
    0
    0
    0
    CELLULITIS
         subjects affected / exposed
    1 / 164 (0.61%)
    0 / 159 (0.00%)
    7 / 159 (4.40%)
    3 / 43 (6.98%)
    14 / 164 (8.54%)
    7 / 43 (16.28%)
    0 / 31 (0.00%)
    4 / 32 (12.50%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    7
    3
    19
    7
    0
    9
    0
    0
    0
    0
    CAMPYLOBACTER GASTROENTERITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    CONJUNCTIVITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    5 / 159 (3.14%)
    1 / 43 (2.33%)
    8 / 164 (4.88%)
    2 / 43 (4.65%)
    2 / 31 (6.45%)
    2 / 32 (6.25%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    6
    2
    9
    2
    2
    2
    1
    0
    0
    0
    EYE INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    0 / 43 (0.00%)
    4 / 164 (2.44%)
    1 / 43 (2.33%)
    1 / 31 (3.23%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    0
    7
    4
    1
    2
    0
    0
    0
    0
    FOLLICULITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    4 / 43 (9.30%)
    7 / 164 (4.27%)
    2 / 43 (4.65%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    10
    13
    2
    1
    0
    0
    1
    0
    0
    FUNGAL SKIN INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    3 / 43 (6.98%)
    5 / 164 (3.05%)
    1 / 43 (2.33%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    3
    5
    1
    1
    0
    0
    0
    0
    0
    COVID-19
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    8 / 159 (5.03%)
    14 / 43 (32.56%)
    29 / 164 (17.68%)
    13 / 43 (30.23%)
    2 / 31 (6.45%)
    0 / 32 (0.00%)
    3 / 18 (16.67%)
    2 / 11 (18.18%)
    3 / 7 (42.86%)
    1 / 2 (50.00%)
         occurrences all number
    0
    0
    9
    18
    38
    18
    2
    0
    4
    2
    4
    1
    CYSTITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    2 / 164 (1.22%)
    1 / 43 (2.33%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    0
    3
    2
    1
    0
    1
    0
    0
    0
    FURUNCLE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    2 / 31 (6.45%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    2
    0
    0
    0
    0
    0
    GASTROENTERITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    6 / 159 (3.77%)
    4 / 43 (9.30%)
    8 / 164 (4.88%)
    1 / 43 (2.33%)
    2 / 31 (6.45%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    7
    4
    8
    1
    2
    1
    0
    0
    0
    0
    INFLUENZA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    10 / 159 (6.29%)
    7 / 43 (16.28%)
    13 / 164 (7.93%)
    4 / 43 (9.30%)
    1 / 31 (3.23%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    10
    10
    16
    4
    1
    1
    0
    0
    0
    0
    INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    HERPES ZOSTER
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    8 / 164 (4.88%)
    0 / 43 (0.00%)
    2 / 31 (6.45%)
    5 / 32 (15.63%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    0
    9
    0
    2
    5
    1
    0
    0
    0
    LOCALISED INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    7 / 159 (4.40%)
    4 / 43 (9.30%)
    8 / 164 (4.88%)
    1 / 43 (2.33%)
    2 / 31 (6.45%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    8
    5
    11
    1
    4
    1
    0
    1
    0
    0
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    1 / 43 (2.33%)
    6 / 164 (3.66%)
    0 / 43 (0.00%)
    4 / 31 (12.90%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    4
    1
    7
    0
    4
    0
    0
    0
    0
    0
    NASOPHARYNGITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    12 / 159 (7.55%)
    7 / 43 (16.28%)
    26 / 164 (15.85%)
    6 / 43 (13.95%)
    8 / 31 (25.81%)
    5 / 32 (15.63%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    16
    11
    33
    7
    9
    6
    0
    0
    0
    0
    NOROVIRUS INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    ONYCHOMYCOSIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    1 / 43 (2.33%)
    5 / 164 (3.05%)
    2 / 43 (4.65%)
    0 / 31 (0.00%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    1
    6
    3
    0
    2
    0
    0
    1
    0
    ORAL HERPES
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    7 / 159 (4.40%)
    3 / 43 (6.98%)
    8 / 164 (4.88%)
    2 / 43 (4.65%)
    0 / 31 (0.00%)
    3 / 32 (9.38%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    8
    5
    10
    2
    0
    3
    1
    0
    0
    0
    OTITIS MEDIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    4 / 164 (2.44%)
    3 / 43 (6.98%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    1
    4
    3
    0
    0
    0
    0
    0
    0
    PHARYNGITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    0 / 43 (0.00%)
    3 / 164 (1.83%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    5
    0
    3
    0
    1
    2
    0
    0
    0
    0
    PARONYCHIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    5 / 43 (11.63%)
    14 / 164 (8.54%)
    2 / 43 (4.65%)
    3 / 31 (9.68%)
    4 / 32 (12.50%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    5
    10
    23
    2
    3
    8
    2
    0
    0
    0
    PNEUMONIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    5 / 159 (3.14%)
    2 / 43 (4.65%)
    5 / 164 (3.05%)
    2 / 43 (4.65%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    5
    2
    5
    2
    0
    1
    0
    0
    1
    0
    PNEUMONIA BACTERIAL
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    0
    0
    1
    0
    0
    0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    8 / 164 (4.88%)
    6 / 43 (13.95%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    5
    14
    8
    0
    1
    0
    1
    0
    0
    PROSTATIC ABSCESS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    RHINITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    3 / 43 (6.98%)
    5 / 164 (3.05%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    5
    7
    0
    1
    1
    0
    0
    0
    0
    SIALOADENITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    1 / 43 (2.33%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    1
    0
    0
    0
    TINEA PEDIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    2 / 31 (6.45%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    2
    0
    0
    0
    0
    0
    STAPHYLOCOCCAL INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    2 / 43 (4.65%)
    2 / 164 (1.22%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    2
    2
    0
    0
    0
    1
    0
    0
    0
    SKIN INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    4 / 159 (2.52%)
    1 / 43 (2.33%)
    6 / 164 (3.66%)
    2 / 43 (4.65%)
    1 / 31 (3.23%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    4
    1
    7
    3
    1
    2
    0
    0
    1
    0
    SINUSITIS
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    10 / 159 (6.29%)
    7 / 43 (16.28%)
    23 / 164 (14.02%)
    4 / 43 (9.30%)
    7 / 31 (22.58%)
    4 / 32 (12.50%)
    1 / 18 (5.56%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    17
    11
    38
    7
    11
    8
    1
    1
    0
    0
    TOOTH INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    7 / 164 (4.27%)
    4 / 43 (9.30%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    1
    8
    5
    0
    1
    0
    0
    0
    0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    39 / 159 (24.53%)
    21 / 43 (48.84%)
    73 / 164 (44.51%)
    22 / 43 (51.16%)
    14 / 31 (45.16%)
    11 / 32 (34.38%)
    2 / 18 (11.11%)
    2 / 11 (18.18%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    50
    44
    138
    48
    24
    15
    2
    2
    2
    0
    URINARY TRACT INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    12 / 159 (7.55%)
    8 / 43 (18.60%)
    23 / 164 (14.02%)
    6 / 43 (13.95%)
    6 / 31 (19.35%)
    3 / 32 (9.38%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    17
    15
    40
    11
    8
    6
    1
    0
    1
    0
    VIRAL INFECTION
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    1 / 43 (2.33%)
    6 / 164 (3.66%)
    1 / 43 (2.33%)
    1 / 31 (3.23%)
    3 / 32 (9.38%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    1
    8
    1
    2
    4
    0
    0
    0
    0
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    7 / 159 (4.40%)
    6 / 43 (13.95%)
    19 / 164 (11.59%)
    8 / 43 (18.60%)
    4 / 31 (12.90%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    9
    7
    23
    8
    6
    2
    0
    0
    0
    0
    ELECTROLYTE IMBALANCE
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    0 / 43 (0.00%)
    0 / 164 (0.00%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    GOUT
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    3 / 159 (1.89%)
    0 / 43 (0.00%)
    4 / 164 (2.44%)
    0 / 43 (0.00%)
    1 / 31 (3.23%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    3
    0
    8
    0
    4
    3
    0
    2
    0
    0
    HYPERGLYCAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    1 / 159 (0.63%)
    6 / 159 (3.77%)
    2 / 43 (4.65%)
    9 / 164 (5.49%)
    6 / 43 (13.95%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    7
    3
    12
    8
    1
    0
    0
    0
    0
    0
    HYPERKALAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    1 / 159 (0.63%)
    5 / 159 (3.14%)
    3 / 43 (6.98%)
    12 / 164 (7.32%)
    2 / 43 (4.65%)
    4 / 31 (12.90%)
    3 / 32 (9.38%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    5
    6
    15
    2
    4
    3
    0
    0
    0
    0
    HYPERPHOSPHATAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    7 / 159 (4.40%)
    4 / 43 (9.30%)
    8 / 164 (4.88%)
    3 / 43 (6.98%)
    1 / 31 (3.23%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    9
    4
    11
    4
    3
    0
    1
    0
    0
    0
    HYPERURICAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    12 / 159 (7.55%)
    7 / 43 (16.28%)
    15 / 164 (9.15%)
    2 / 43 (4.65%)
    1 / 31 (3.23%)
    4 / 32 (12.50%)
    1 / 18 (5.56%)
    1 / 11 (9.09%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    21
    11
    25
    2
    2
    7
    1
    1
    0
    0
    HYPOCALCAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    2 / 159 (1.26%)
    2 / 43 (4.65%)
    7 / 164 (4.27%)
    1 / 43 (2.33%)
    2 / 31 (6.45%)
    1 / 32 (3.13%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    2
    7
    1
    2
    1
    0
    0
    0
    0
    HYPOGLYCAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    2 / 43 (4.65%)
    6 / 164 (3.66%)
    0 / 43 (0.00%)
    3 / 31 (9.68%)
    1 / 32 (3.13%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    2
    6
    0
    3
    1
    1
    0
    0
    0
    HYPOKALAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    7 / 159 (4.40%)
    3 / 43 (6.98%)
    11 / 164 (6.71%)
    3 / 43 (6.98%)
    2 / 31 (6.45%)
    2 / 32 (6.25%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    8
    8
    20
    5
    3
    3
    1
    0
    0
    0
    HYPOPHOSPHATAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    5 / 159 (3.14%)
    3 / 43 (6.98%)
    3 / 164 (1.83%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    0 / 32 (0.00%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    8
    3
    3
    0
    0
    0
    2
    0
    0
    0
    HYPONATRAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    7 / 159 (4.40%)
    0 / 43 (0.00%)
    1 / 164 (0.61%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    1 / 32 (3.13%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    12
    0
    2
    0
    0
    2
    1
    0
    0
    0
    HYPOMAGNESAEMIA
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    0 / 159 (0.00%)
    3 / 43 (6.98%)
    7 / 164 (4.27%)
    1 / 43 (2.33%)
    1 / 31 (3.23%)
    2 / 32 (6.25%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    0
    5
    15
    1
    2
    7
    1
    0
    0
    0
    IRON DEFICIENCY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    5 / 159 (3.14%)
    2 / 43 (4.65%)
    8 / 164 (4.88%)
    3 / 43 (6.98%)
    1 / 31 (3.23%)
    2 / 32 (6.25%)
    1 / 18 (5.56%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    6
    2
    9
    3
    1
    3
    1
    0
    0
    0
    VITAMIN B12 DEFICIENCY
         subjects affected / exposed
    0 / 164 (0.00%)
    0 / 159 (0.00%)
    1 / 159 (0.63%)
    1 / 43 (2.33%)
    3 / 164 (1.83%)
    0 / 43 (0.00%)
    0 / 31 (0.00%)
    2 / 32 (6.25%)
    0 / 18 (0.00%)
    0 / 11 (0.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    1
    3
    0
    0
    2
    0
    0
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    25 Sep 2017
    Protocol Amendment 1 Summary of Changes: • Defined MRD cohort and added a FD cohort study to evaluate the depth of response after 15 months fixed duration of therapy, in addition to the current MRD cohort assessing discontinuation based on MRD status. • Included contraception up to 90 days for women of child-bearing age post-treatment in order to align with both venetoclax and ibrutinib products' current labelling. • Excluded subjects with uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura. • Included updates to align language with current version of the ibrutinib IB.
    29 Nov 2018
    Protocol Amendment 2 Summary of Changes: • Included collection and storage of imaging for the MRD cohort in addition to the FD cohort. • Included collection of BM slides for the FD cohort in addition to the MRD cohort. • Combined endpoints for the MRD cohort pre-randomization and randomization phases. • Added DOR and TLS risk reduction as secondary endpoints. • Updated concomitant use with CYP3A inhibitor section. • Included updates to align language with the current ibrutinib IB.
    11 Sep 2019
    Protocol Amendment 3 Summary of Changes: • Extended duration of study to enable extended follow-up in the FD cohort. • Increased frequency of efficacy assessment visits without CT scans in FD cohort. • Clarified duration of therapy and duration of study for the MRD cohort. • Clarified timing of primary analyses for FD and MRD cohorts. • Clarified choice and duration of reintroduction therapy for both MRD and FD cohorts. • Reduced frequency of both reintroduction visits and CT scans, CT assessments in response to follow-up visits. • Clarified response to ibrutinib reintroduction as an exploratory endpoint in the MRD and FD cohorts. • Added an additional MRD assessment (added Cycle 28 in FD cohort) and additional biomarker assessments.
    02 Dec 2022
    Protocol Amendment 4 Summary of Changes: • Extended study duration to enable longer follow-up in the FD cohort. • Included other editorial and administrative changes. • Include the updated recommendations that are intended to improve tolerability for continued ibrutinib treatment in the study protocol. • Update risks to cardiac arrhythmia section.

    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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