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    Clinical Trial Results:
    An Open-label, Phase 1/2 Study of MEDI-551, a Humanized Monoclonal Antibody Directed Against CD19, in Adult Subjects With Relapsed or Refractory Advanced B-cell Malignancies

    Summary
    EudraCT number
    		 2009-016378-34
    Trial protocol
    		 BE   FR  
    Global end of trial date
    21 Mar 2019

    Results information
    Results version number
    		 v2(current)
    This version publication date
    20 Jun 2020
    First version publication date
    05 Apr 2020
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MI-CP204
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00983619
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    MedImmune, LLC
    Sponsor organisation address
    One MedImmune Way, Gaithersburg, United States, 20878
    Public contact
    Shahram Rahimian, MedImmune, LLC, +1 800-236-9933, information.center@astrazeneca.com
    Scientific contact
    Shahram Rahimian, MedImmune, LLC, +1 800-236-9933, information.center@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    12 Apr 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Mar 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Mar 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the safety and tolerability, describe any dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or optimum biological dose (OBD) or highest protocol-defined doses (in the absence of exceeding the MTD) for MEDI-551 as monotherapy and in combination with rituximab in participants with relapsed or refractory advanced B-cell malignancies (chronic lymphocytic leukemia [CLL], including small lymphocytic lymphoma [SLL], diffuse large B-cell lymphoma [DLBCL], and follicular lymphoma [FL]).
    Protection of trial subjects
    The conduct of this clinical study met all local and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Conference on Harmonization guideline: Good Clinical Practice, and applicable regulatory requirements. Participants signed an informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 Apr 2010
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 6 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 115
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    Belgium: 11
    Country: Number of subjects enrolled
    Italy: 5
    Country: Number of subjects enrolled
    Spain: 4
    Worldwide total number of subjects
    136
    EEA total number of subjects
    20
    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)
    54
    From 65 to 84 years
    76
    85 years and over
    6

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 137 participants were screened, out of which 1 participant never received the study treatment. A total of 136 participants received study treatment.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Part A-MEDI-551 0.5 mg/kg
    Arm description
    		 Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI-551
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MEDI-551 0.5 mg/kg administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Arm title
    		 Part A-MEDI-551 1 mg/kg
    Arm description
    		 Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI-551
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MEDI-551 1 mg/kg administered IV once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Arm title
    		 Part A-MEDI-551 2 mg/kg
    Arm description
    		 Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI-551
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MEDI-551 2 mg/kg administered IV on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Arm title
    		 Part A-MEDI-551 4 mg/kg
    Arm description
    		 Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI-551
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MEDI-551 4 mg/kg administered IV on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Arm title
    		 Part A-MEDI-551 8 mg/kg
    Arm description
    		 Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI-551
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MEDI-551 8 mg/kg administered IV on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Arm title
    		 Part A-MEDI-551 12 mg/kg
    Arm description
    		 Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI-551
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MEDI-551 12 mg/kg administered IV on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Arm title
    		 Part B-MEDI-551 6 mg/kg
    Arm description
    		 Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI-551
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MEDI-551 6 mg/kg administered IV weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Arm title
    		 Part B-MEDI-551 12 mg/kg
    Arm description
    		 Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI-551
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MEDI-551 12 mg/kg administered IV weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Arm title
    		 Part B-MEDI-551 24 mg/kg
    Arm description
    		 Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI-551
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MEDI-551 24 mg/kg administered IV weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Arm title
    		 Part C-MEDI-551 8 mg/kg + rituximab
    Arm description
    		 Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Rituximab 375 mg/m^2 administered IV on Days 1, 8, 15, and 22 (28- day cycle). The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdraws consent.

    Investigational medicinal product name
    MEDI-551
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MEDI-551 8 mg/kg administered IV on Days 2 and 8 during Cycle 1 and thereafter on Day 1 from Cycle 2 of each 28-day cycle until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdraws consent.

    Arm title
    		 Part C-MEDI-551 12 mg/kg + rituximab
    Arm description
    		 Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI-551
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MEDI-551 12 mg/kg administered IV on Days 2 and 8 during Cycle 1 and thereafter on Day 1 from Cycle 2 of each 28-day cycle until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdraws.

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Rituximab 375 mg/m^2 administered IV on Days 1, 8, 15, and 22 (28- day cycle). The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdraws consent.

    Arm title
    		 Part D-MEDI-551 12 mg/kg
    Arm description
    		 Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI-551
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MEDI-551 12 mg/kg administered IV on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experiences unacceptable toxicity, disease progression, reached CR or consent withdrawal.

    Number of subjects in period 1
    		Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg
    Started
    3
    4
    3
    6
    3
    76
    3
    3
    1
    3
    17
    14
    Completed
    0
    0
    0
    1
    0
    9
    0
    1
    0
    0
    6
    3
    Not completed
    3
    4
    3
    5
    3
    67
    3
    2
    1
    3
    11
    11
         Adverse event, serious fatal
    -
    2
    2
    1
    2
    30
    1
    -
    1
    2
    9
    8
         Consent withdrawn by subject
    2
    1
    1
    3
    1
    23
    -
    -
    -
    -
    1
    1
         Not specified
    1
    -
    -
    1
    -
    12
    2
    2
    -
    1
    1
    -
         Lost to follow-up
    -
    1
    -
    -
    -
    2
    -
    -
    -
    -
    -
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part A-MEDI-551 0.5 mg/kg
    Reporting group description
    		 Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part A-MEDI-551 1 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part A-MEDI-551 2 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part A-MEDI-551 4 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part A-MEDI-551 8 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part A-MEDI-551 12 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part B-MEDI-551 6 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part B-MEDI-551 12 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part B-MEDI-551 24 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part C-MEDI-551 8 mg/kg + rituximab
    Reporting group description
    		 Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.

    Reporting group title
    Part C-MEDI-551 12 mg/kg + rituximab
    Reporting group description
    		 Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.

    Reporting group title
    Part D-MEDI-551 12 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.

    Reporting group values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg Total
    Number of subjects
    		 3 4 3 6 3 76 3 3 1 3 17 14 136
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 1 1 1 4 2 35 2 0 0 1 3 4 54
        From 65-84 years
    		 1 2 2 2 1 39 1 3 1 2 12 10 76
        85 years and over
    		 1 1 0 0 0 2 0 0 0 0 2 0 6
    Age Continuous
    Here, the arbitrary number "999" signifies standard deviation not reported as only one participant was evaluable for the specified arm.
    Units: years
        arithmetic mean (standard deviation)
    		 66.0 ( 19.5 ) 69.5 ( 12.5 ) 64.7 ( 18.3 ) 63.8 ( 12.7 ) 60.0 ( 12.1 ) 64.4 ( 11.2 ) 61.3 ( 20.8 ) 70.0 ( 7.0 ) 78.0 ( 999 ) 68.0 ( 11.8 ) 69.4 ( 10.8 ) 67.9 ( 11.0 ) -
    Sex: Female, Male
    Units:
        Male
    		 1 4 2 4 2 46 2 2 0 2 7 9 81
        Female
    		 2 0 1 2 1 30 1 1 1 1 10 5 55
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0 0 0 0 0 0 0 0
        Asian
    		 0 0 0 0 0 0 0 0 0 0 1 0 1
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0 0 0 0 0 0 0 0
        Black or African American
    		 0 1 0 1 0 5 0 1 0 0 0 0 8
        White
    		 3 3 3 5 3 68 3 2 1 2 15 14 122
        More than one race
    		 0 0 0 0 0 0 0 0 0 0 0 0 0
        Unknown or Not Reported
    		 0 0 0 0 0 3 0 0 0 1 1 0 5
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 0 0 0 0 6 0 0 0 0 0 0 6
        Not Hispanic or Latino
    		 3 4 3 6 3 70 3 3 1 3 17 14 130
        Unknown or Not Reported
    		 0 0 0 0 0 0 0 0 0 0 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Part A-MEDI-551 0.5 mg/kg
    Reporting group description
    		 Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part A-MEDI-551 1 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part A-MEDI-551 2 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part A-MEDI-551 4 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part A-MEDI-551 8 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part A-MEDI-551 12 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part B-MEDI-551 6 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part B-MEDI-551 12 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part B-MEDI-551 24 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part C-MEDI-551 8 mg/kg + rituximab
    Reporting group description
    		 Participants received IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.

    Reporting group title
    Part C-MEDI-551 12 mg/kg + rituximab
    Reporting group description
    		 Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdrew consent.

    Reporting group title
    Part D-MEDI-551 12 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached CR or withdrew consent.

    Subject analysis set title
    Part A-MEDI-551
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of MEDI 551 0.5 or 1 mg/kg (both, once every week in 4-week cycles), or 2, or 4, or 8, or 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Subject analysis set title
    Part B-MEDI-551
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of MEDI- 551 6 or 12 mg/kg weekly for 4 weeks during Cycle 1 (both from Days 1, 8, 15, and 22) or 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Subject analysis set title
    Part C-MEDI-551 + Rituximab
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of MEDI- 551 8 or 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 or 12 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdraws consent.

    Subject analysis set title
    Part A-MEDI-551 12 mg/kg (expansion)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Primary: Optimal Biologic Dose of MEDI-551 for Part A

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    End point title
    		 Optimal Biologic Dose of MEDI-551 for Part A [1]
    End point description
    Optimal biologic dose (OBD) was defined as the dose lower than the maximum tolerated dose (MTD), used for dose expansion. The MTD is defined as the highest dose at which less than equal to (<=) 1 out of 6 participants experience a dose limiting toxicities (DLT) from the time of first administration of MEDI-551 through the first 28-day cycle. The DLT evaluable population was analysed for this endpoint, which included all participants in the dose-escalation phase who received at least 1 full cycle of MEDI-551 and completed safety follow-up through the DLT evaluable period (from the time of first administration of MEDI-551 through the first 28-day of cycle 1).
    End point type
    Primary
    End point timeframe
    Day 1 to Day 28 of Cycle 1
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    End point values
    		 Part A-MEDI-551
    Number of subjects analysed
    95
    Units: mg/Kg
    12
    No statistical analyses for this end point

    Primary: Highest protocol-defined dose for Part B

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    End point title
    		 Highest protocol-defined dose for Part B [2]
    End point description
    Highest protocol-defined dose is dose of MEDI-551 in the absence of exceeding the MTD in participants with relapsed or rituximab-refractory chronic lymphocytic leukemia (defined as those with less than a partial response (PR) or progression within 6 months after completing therapy with rituximab). The MTD is defined as the highest dose at which <= 1 out of 6 participants experience a DLT from the time of first administration of MEDI-551 through the first 28-day cycle.
    End point type
    Primary
    End point timeframe
    Day 1 to Day 28 of Cycle 1
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    End point values
    		 Part B-MEDI-551
    Number of subjects analysed
    7
    Units: mg/Kg
    24
    No statistical analyses for this end point

    Primary: Highest protocol-defined dose for Part C

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    End point title
    		 Highest protocol-defined dose for Part C [3]
    End point description
    Highest protocol-defined dose is the dose of MEDI-551 in combination with rituximab at the MTD or the highest protocol-defined dose in the absence of exceeding the MTD in participants with aggressive lymphomas. The MTD is defined as the highest dose at which <= 1 out of 6 participants experience a DLT from the time of first administration of MEDI-551 through the first 28-day cycle.
    End point type
    Primary
    End point timeframe
    Day 1 to Day 28 of Cycle 1
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    End point values
    		 Part C-MEDI-551 + Rituximab
    Number of subjects analysed
    20
    Units: mg/kg
    12
    No statistical analyses for this end point

    Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part A, Part B, and Part C

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    End point title
    		 Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part A, Part B, and Part C [4] [5]
    End point description
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. The safety population was analysed for this endpoint, which included all participants who received any treatment of MEDI-551.
    End point type
    Primary
    End point timeframe
    Day 1 through 90-Day Post Last Dose (Approximately 9 years)
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab
    Number of subjects analysed
    3
    4
    3
    6
    3
    76
    3
    3
    1
    3
    17
    Units: Participants
        TEAEs
    3
    4
    3
    6
    3
    76
    3
    3
    1
    3
    17
        TESAEs
    1
    1
    2
    1
    1
    23
    1
    2
    1
    1
    9
    No statistical analyses for this end point

    Primary: Number of Participants With Dose Limiting Toxicities of MEDI-551 in Part A, Part B, and Part C

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    End point title
    		 Number of Participants With Dose Limiting Toxicities of MEDI-551 in Part A, Part B, and Part C [6] [7]
    End point description
    A dose limiting toxicities (DLT) for arm A, B, and C was defined as MEDI-551 (or rituximab for Arm C) treatment-related AE of any toxicity grade that led to an inability to receive a full cycle of MEDI-551 (or rituximab for Arm C) or any Grade 3 or higher toxicity (except Grade 3 fever, transient Grade 3 rigors or chills, Grade 3 tumor lysis syndrome, any Grade 3 or 4 electrolyte alteration, any Grade 3 liver function test elevation,>= Grade 3 or 4 lymphopenia or leukopenia, <= Grade 4 neutropenia, <= Grade 4 thrombocytopenia, <= Grade 4 anemia, and Grade 3 infusion-related reaction and infusion reaction), during DLT evaluable period.
    End point type
    Primary
    End point timeframe
    Day 1 to Day 28 of Cycle 1
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab
    Number of subjects analysed
    3
    4
    3
    6
    3
    76
    3
    3
    1
    3
    17
    Units: Participants
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part A, Part B, and Part C

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    End point title
    		 Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part A, Part B, and Part C [8] [9]
    End point description
    Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine. The safety population was analysed for this endpoint, which included all participants who received any treatment of MEDI-551.
    End point type
    Primary
    End point timeframe
    Day 1 through 90-Day Post Last Dose (Approximately 9 years)
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab
    Number of subjects analysed
    3
    4
    3
    6
    3
    76
    3
    3
    1
    3
    17
    Units: Participants
        Anemia
    0
    2
    0
    0
    1
    6
    0
    1
    1
    0
    4
        Blood fibrinogen decreased
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
        Blood fibrinogen increased
    0
    1
    0
    0
    0
    1
    0
    1
    0
    0
    0
        Febrile neutropenia
    0
    0
    0
    0
    0
    2
    0
    1
    0
    0
    1
        Hematocrit decreased
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Hemoglobin increased
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
        Leukopenia
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
        Lymphocyte count decreased
    0
    1
    0
    0
    0
    0
    0
    0
    1
    0
    2
        Lymphopenia
    0
    0
    0
    0
    0
    2
    0
    1
    0
    0
    0
        Myelocytosis
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
        Neutropenia
    0
    0
    0
    1
    1
    14
    1
    1
    0
    1
    2
        Neutrophil count abnormal
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Neutrophil count decreased
    1
    1
    0
    1
    0
    5
    0
    1
    1
    0
    2
        Platelet count decreased
    0
    0
    0
    0
    0
    2
    0
    1
    1
    0
    1
        Red blood cell count decreased
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Reticulocytosis
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
        Thrombocytopenia
    0
    1
    0
    3
    0
    6
    0
    1
    0
    0
    2
        White blood cell count decreased
    0
    0
    0
    1
    1
    3
    0
    2
    1
    0
    2
        Hypergammaglobulinemia
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
        Activated PTT prolonged
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
        Leukocytosis
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
        Alanine aminotransferase increased
    0
    1
    0
    0
    0
    3
    0
    0
    1
    0
    1
        Aspartate aminotransferase increased
    0
    1
    0
    0
    0
    4
    0
    0
    1
    0
    1
        Blood alkaline phosphatase increased
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    2
        Blood chloride decreased
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Blood creatinine increased
    0
    0
    1
    0
    0
    1
    0
    1
    1
    0
    2
        Blood glucose decreased
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
        Blood glucose increased
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
        Blood lactate dehydrogenase increased
    0
    0
    0
    0
    0
    2
    0
    0
    1
    0
    1
        Blood potassium decreased
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
        Blood urea increased
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Blood uric acid increased
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
        Gamma-glutamyl transferase increased
    0
    0
    0
    0
    0
    3
    0
    0
    0
    0
    0
        Hyperbilirubinemia
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
        Hypercalcemia
    0
    0
    0
    0
    0
    4
    0
    0
    0
    0
    1
        Hyperglycemia
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    2
        Hyperkalemia
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Hyperuricemia
    1
    1
    0
    0
    0
    2
    0
    0
    1
    0
    1
        Hypocalcemia
    0
    2
    0
    0
    0
    0
    0
    1
    1
    0
    2
        Hypoglycemia
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    1
        Hypokalemia
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    1
        Hypomagnesemia
    0
    0
    0
    0
    0
    2
    0
    1
    0
    0
    1
        Hyponatremia
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    2
        Protein total decreased
    0
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
        Blood albumin decreased
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
        Hypernatremia
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    2
        Hypoalbuminemia
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    2
        Haematuria
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    2
        Dysuria
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    2
        Pollakiuria
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
        Hemoglobinuria
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
        Hydronephrosis
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
        Urinary incontinence
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part A, Part B, and Part C

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    End point title
    		 Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part A, Part B, and Part C [10] [11]
    End point description
    Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure, pulse rate, respiratory rate, and pulse oximetry). The safety population was analysed for this endpoint, which included all participants who received any treatment of MEDI-551.
    End point type
    Primary
    End point timeframe
    Day 1 through 90-Day Post Last Dose (Approximately 9 years)
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab
    Number of subjects analysed
    3
    4
    3
    6
    3
    76
    3
    3
    1
    3
    17
    Units: Participants
        Bradycardia
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Chills
    0
    0
    0
    1
    0
    5
    0
    1
    0
    0
    1
        Dyspnea
    0
    1
    1
    1
    0
    10
    0
    2
    1
    0
    4
        Hypertension
    2
    1
    0
    0
    0
    8
    0
    2
    0
    0
    2
        Hypotension
    1
    3
    1
    0
    0
    4
    0
    0
    1
    0
    2
        Orthostatic hypotension
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
        Palpitations
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
        Pyrexia
    0
    0
    1
    2
    0
    16
    1
    1
    0
    0
    3
        Systolic hypertension
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
        Tachycardia
    0
    0
    0
    0
    0
    6
    1
    0
    0
    0
    1
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part A, Part B, and Part C

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    End point title
    		 Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part A, Part B, and Part C [12] [13]
    End point description
    Number of participants with abnormal electrocardiograms (ECGs) reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, axis, and QT intervals from the primary lead of the digital 12-lead ECG. The safety population was analysed for this endpoint, which included all participants who received any treatment of MEDI-551.
    End point type
    Primary
    End point timeframe
    Day 1 through 90-Day Post Last Dose (Approximately 9 years)
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab
    Number of subjects analysed
    3
    4
    3
    6
    3
    76
    3
    3
    1
    3
    17
    Units: Participants
        Sinus bradycardia
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Atrial fibrillation
    0
    0
    0
    0
    0
    3
    0
    1
    0
    0
    0
        Mitral valve incompetence
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
        Supraventricular extrasystoles
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
        Tricuspid valve incompetence
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
        ECG QT prolonged
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    1
        Atrial flutter
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
        Atrial tachycardia
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
        supraventricular tachycardia
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    No statistical analyses for this end point

    Primary: Percentage of Participants With Complete Response for Part B, Part C, and Part D

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    End point title
    		 Percentage of Participants With Complete Response for Part B, Part C, and Part D [14] [15]
    End point description
    Complete response (CR) is defined as disappearance of all evidence of disease according to International Working Group criteria (IWG). For nodal masses; fluorodeoxyglucose (FDG)-avid or polyethylene terephthalate (PET) positive prior to therapy; mass of any size permitted if PET negative .Variably FDG-avid or PET negative; regression to normal size on computed tomography (CT). For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry (IHC) was negative. Evaluable population for efficacy was analysed for this endpoint, which included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.
    End point type
    Primary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (EOT) (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    3
    3
    0 [16]
    3
    16
    13
    Units: Percentage of Participants
        number (confidence interval 95%)
    33.3 (0.8 to 90.6)
    0 (0.0 to 70.8)
    ( to )
    33.3 (0.8 to 90.6)
    18.8 (4.0 to 45.6)
    0 (0.0 to 24.7)
    Notes
    [16] - No participants were analysed for the specified arm.
    No statistical analyses for this end point

    Primary: Percentage of Participants With Partial Response for Part B, Part C, and Part D

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    End point title
    		 Percentage of Participants With Partial Response for Part B, Part C, and Part D [17] [18]
    End point description
    The partial response (PR) is defined as regression of measurable disease and no new sites according to IWG criteria. Nodal masses: >= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy. Evaluable population for efficacy was analysed for this endpoint, which included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.
    End point type
    Primary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    3
    3
    0 [19]
    3
    16
    13
    Units: Percentage of Participants
        number (not applicable)
    33.3
    33.3
    33.3
    25.0
    23.1
    Notes
    [19] - No participants were analysed for the specified arm.
    No statistical analyses for this end point

    Primary: Duration of Complete Response for Part B, Part C, and Part D

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    End point title
    		 Duration of Complete Response for Part B, Part C, and Part D [20] [21]
    End point description
    Duration of CR is from the first documentation of a CR to the time of progressive disease/relapse according to IWG criteria. The CR is disappearance of all evidence of disease according to IWG criteria. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. Kaplan-Meier method was used to evaluate duration of CR. Evaluable population for efficacy was analysed for this endpoint, which included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. Duration of CR is calculated for participants with CR. Here, the arbitrary number "20.999" signifies that median was not estimable because insufficient number of participants had events.
    End point type
    Primary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    1 [22]
    0 [23]
    0 [24]
    1 [25]
    3
    0 [26]
    Units: Months
        median (full range (min-max))
    5.6 (5.6 to 5.6)
    ( to )
    ( to )
    0.3 (0.3 to 0.3)
    20.999 (20.0 to 38.4)
    ( to )
    Notes
    [22] - An arbitrary value for median is reported as 5.6 (Median was not calculated, as < 3 participants).
    [23] - No participants were analysed, as no response was observed in this specified arm.
    [24] - No participants were analysed for the specified arm.
    [25] - An arbitrary value for median is reported as 0.3 (Median was not calculated, as < 3 participants).
    [26] - No participants were analysed, as no response was observed in this specified arm.
    No statistical analyses for this end point

    Primary: Percentage of Participants With Objective Response Rate for Part B, Part C, and Part D

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    End point title
    		 Percentage of Participants With Objective Response Rate for Part B, Part C, and Part D [27] [28]
    End point description
    ORR is proportion of participants with CR or partial response (PR) as per IWG criteria. CR is disappearance of all evidence of disease (Nodal masses: FDG-avid/PET positive prior to therapy; mass of any size permitted if PET negative; FDG-avid or PET negative - regression to normal size on CT; spleen nodules disappeared; cleared bone marrow infiltrate on repeat biopsy; IHC was negative if unknown by morphology). PR is regression of measurable disease and no new sites as: Nodal masses: >= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes: a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site; b) FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules. Bone marrow: irrelevant if positive prior to therapy. Evaluable population for efficacy is used for this endpoint.
    End point type
    Primary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [28] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    3
    3
    0 [29]
    3
    16
    13
    Units: Percentage of participants
        number (confidence interval 95%)
    66.7 (9.4 to 99.2)
    33.3 (0.8 to 90.6)
    ( to )
    66.7 (9.4 to 99.2)
    43.8 (19.8 to 70.1)
    23.1 (5.0 to 53.8)
    Notes
    [29] - No participant was analysed for the specified arm.
    No statistical analyses for this end point

    Primary: Duration of Objective Response for Part B, Part C, and Part D

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    End point title
    		 Duration of Objective Response for Part B, Part C, and Part D [30] [31]
    End point description
    Duration of objective response (DOR) is the first documentation of objective response to the first documented progressive disease (PD) or relapse according to IWG criteria. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate DOR. Evaluable population for efficacy was analysed for this endpoint. The DOR were calculated for participants with objective response. Here, the arbitrary numbers "38.9999 and 1.9999" signifies that median was not estimable because insufficient number of participants had events.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [30] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    2
    1
    0 [32]
    2
    7
    3
    Units: Months
        median (full range (min-max))
    38.9999 (38.9 to 47.2)
    27.5 (27.5 to 27.5)
    ( to )
    3.7 (2.4 to 3.7)
    1.9999 (1.0 to 44.7)
    3.7 (1.9 to 27.2)
    Notes
    [32] - No participant was analysed for the specified arm.
    No statistical analyses for this end point

    Primary: Percentage of Participants With Disease Control Rate for Part B, Part C, and Part D

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    End point title
    		 Percentage of Participants With Disease Control Rate for Part B, Part C, and Part D [33] [34]
    End point description
    Disease control includes CR, PR, or stable disease (SD) for at least 8 weeks according to IWG criteria. The CR is disappearance of all evidence of disease. Nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. Spleen; not palpable, nodules disappeared. Bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. PR is regression of measurable disease and no new sites. Nodal masses: >= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules. Bone marrow: irrelevant if positive prior to therapy. SD is failure to attain CR/PR or PD. Evaluable population for efficacy was analysed for this endpoint.
    End point type
    Primary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [34] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    3
    3
    0 [35]
    3
    11
    6
    Units: Percentage of participants
        number (confidence interval 95%)
    100 (29.2 to 100)
    100 (29.2 to 100)
    ( to )
    100 (29.2 to 100)
    68.8 (41.3 to 89.0)
    46.2 (19.2 to 74.9)
    Notes
    [35] - No participant was analysed for the specified arm.
    No statistical analyses for this end point

    Primary: Duration of Disease Control for Part B, Part C, and Part D

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    End point title
    		 Duration of Disease Control for Part B, Part C, and Part D [36] [37]
    End point description
    Duration of disease control is defined as the time period from start of MEDI-551 administration to the event of PD/relapse. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate duration of disease control. Evaluable population for efficacy was analysed for this endpoint. Duration of disease control is calculated for the participants with objective response or stable disease response. The arbitrary number "9.9999" signifies that median was not estimable because insufficient number of participants had events.
    End point type
    Primary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    3
    3
    0 [38]
    3
    11
    6
    Units: Months
        median (full range (min-max))
    9.9999 (9.7 to 50.9)
    29.8 (22.6 to 39.5)
    ( to )
    5.5 (4.2 to 5.5)
    14.6 (1.7 to 46.5)
    3.8 (3.5 to 29.0)
    Notes
    [38] - No participant was analysed for the specified arm.
    No statistical analyses for this end point

    Primary: Time to Response for Part B, Part C, and Part D

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    End point title
    		 Time to Response for Part B, Part C, and Part D [39] [40]
    End point description
    Time to response (TTR) is measured from the start of MEDI-551 administration to the first documentation of response (CR or PR) and assessed in participants who have achieved objective response. Kaplan-Meier method was used to evaluate TTR. Evaluable population for efficacy was analysed for this endpoint, which included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. TTR were calculated for the participants with objective response.
    End point type
    Primary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [40] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    2
    1
    0 [41]
    2
    7
    3
    Units: Months
        median (full range (min-max))
    6.5 (3.7 to 9.2)
    12.0 (12.0 to 12.0)
    ( to )
    1.8 (1.7 to 1.8)
    2.0 (1.7 to 17.3)
    1.8 (1.6 to 1.9)
    Notes
    [41] - No participant was analysed for the specified arm.
    No statistical analyses for this end point

    Primary: Progression Free Survival for Part B, Part C, and Part D

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    End point title
    		 Progression Free Survival for Part B, Part C, and Part D [42] [43]
    End point description
    Progression-free survival (PFS) is measured from the start of MEDI-551 treatment until the first documentation of disease progression, relapse or death, whichever occurs first. The PFS was censored on the date of last disease assessment for participants who have no documented PD/relapse or death prior to data cutoff, dropout, or the initiation of alternative anticancer therapy. Kaplan-Meier method was used to evaluate PFS. Evaluable population for efficacy was analysed for this endpoint, which included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. Here, the arbitrary number "9.9999" signifies that median was not estimable because insufficient number of participants had events.
    End point type
    Primary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [42] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [43] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    3
    3
    0 [44]
    3
    16
    13
    Units: Months
        median (full range (min-max))
    9.9999 (9.7 to 50.9)
    29.8 (22.6 to 39.5)
    ( to )
    5.5 (4.2 to 5.5)
    3.5 (0.7 to 46.5)
    2.0 (0.7 to 29.0)
    Notes
    [44] - No participant was analysed for the specified arm.
    No statistical analyses for this end point

    Primary: Overall Survival for Part B, Part C, and Part D

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    End point title
    		 Overall Survival for Part B, Part C, and Part D [45] [46]
    End point description
    Overall survival (OS) is measured from the start of MEDI-551 treatment until death. For participants who are alive at the end of study or lost to follow-up, OS will be censored on the last date when participants were known to be alive. Kaplan-Meier method was used to evaluate OS. Evaluable population for efficacy was analysed for this endpoint, which included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. Here, the arbitrary number "19.9999 and 37.9999" signifies that median was not estimable because insufficient number of participants had events.
    End point type
    Primary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [45] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [46] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    3
    3
    0 [47]
    3
    16
    13
    Units: Months
        median (full range (min-max))
    19.9999 (19.4 to 53.8)
    37.9999 (37.6 to 41.9)
    ( to )
    25.0 (18.3 to 45.4)
    33.4 (0.9 to 51.3)
    17.9 (1.2 to 38.9)
    Notes
    [47] - No participant was analysed for the specified arm.
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part D

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    End point title
    		 Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part D [48]
    End point description
    An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. The safety population was analysed for this endpoint, which included all participants who received any treatment of MEDI-551.
    End point type
    Secondary
    End point timeframe
    Day 1 through 90-Day Post Last Dose (Approximately 9 years)
    Notes
    [48] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    14
    Units: Participants
        TEAEs
    14
        TESAEs
    5
    No statistical analyses for this end point

    Secondary: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part D

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    End point title
    		 Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part D [49]
    End point description
    Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine. The safety population was analysed for this endpoint, which included all participants who received any treatment of MEDI-551.
    End point type
    Secondary
    End point timeframe
    Day 1 through 90-Day Post Last Dose (Approximately 9 years)
    Notes
    [49] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    14
    Units: Participants
        Anemia
    2
        Febrile neutropenia
    1
        Lymphocyte count decreased
    3
        Neutropenia
    1
        Neutrophil count decreased
    4
        Platelet count decreased
    1
        Polycythemia
    1
        Thrombocytopenia
    2
        White blood cell count decreased
    3
        Blood ALP increased
    1
        Blood bilirubin increased
    1
        Blood LDH increased
    1
        Blood potassium decreased
    1
        Hypercalcemia
    1
        Hyperglycemia
    2
        Hyperuricemia
    2
        Hypocalcemia
    1
        Hypokalemia
    2
        Pollakiuria
    1
        Urinary incontinence
    1
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part D

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    End point title
    		 Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part D [50]
    End point description
    Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure, pulse rate, respiratory rate, and pulse oximetry). The safety population was analysed for this endpoint, which included all participants who received any treatment of MEDI-551.
    End point type
    Secondary
    End point timeframe
    Day 1 through 90-Day Post Last Dose (Approximately 9 years)
    Notes
    [50] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    14
    Units: Participants
        Chills
    2
        Dyspnea
    1
        Hypertension
    1
        Hypotension
    1
        Palpitations
    1
        Pyrexia
    2
        Tachycardia
    1
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part D

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    End point title
    		 Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part D [51]
    End point description
    Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, axis, and QT intervals from the primary lead of the digital 12-lead ECG. The safety population was analysed for this endpoint, which included all participants who received any treatment of MEDI-551.
    End point type
    Secondary
    End point timeframe
    Day 1 through 90-Day Post Last Dose (Approximately 9 years)
    Notes
    [51] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    14
    Units: Participants
        ECG QT prolonged
    1
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Complete Response for Part A

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    End point title
    		 Percentage of Participants With Complete Response for Part A [52]
    End point description
    The CR is defined as disappearance of all evidence of disease according to IWG criteria. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative .Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. Evaluable population for efficacy was analysed for this endpoint, which included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.
    End point type
    Secondary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [52] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg
    Number of subjects analysed
    3
    4
    3
    5
    3
    72
    Units: Percentage of Participants
        number (confidence interval 95%)
    33.3 (0.8 to 90.6)
    0 (0.0 to 60.2)
    0 (0.0 to 70.8)
    20.0 (0.5 to 71.6)
    0 (0.0 to 70.8)
    12.5 (5.9 to 22.4)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Partial Response for Part A

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    End point title
    		 Percentage of Participants With Partial Response for Part A [53]
    End point description
    The PR is defined as regression of measurable disease and no new sites according to IWG criteria. Nodal masses: >= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: >= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy. Evaluable population for efficacy included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.
    End point type
    Secondary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [53] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg
    Number of subjects analysed
    3
    4
    3
    5
    3
    72
    Units: Percentage of Participants
        number (not applicable)
    33.3
    0
    0
    0
    33.3
    15.3
    No statistical analyses for this end point

    Secondary: Duration of Complete Response for Part A

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    End point title
    		 Duration of Complete Response for Part A [54]
    End point description
    Duration of CR is from the first documentation of a CR to the time of progressive disease/relapse according to IWG criteria. The CR is disappearance of all evidence of disease. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. Kaplan-Meier method was used to evaluate duration of CR. Evaluable population for efficacy was analysed for this endpoint, which included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. Duration of CR is calculated for participants with CR.
    End point type
    Secondary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [54] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg
    Number of subjects analysed
    1
    0 [55]
    0 [56]
    1
    0 [57]
    9
    Units: Months
        median (full range (min-max))
    7.1 (7.1 to 7.1)
    ( to )
    ( to )
    14.9 (14.9 to 14.9)
    ( to )
    14.3 (1.9 to 31.8)
    Notes
    [55] - No participants were analysed, as no response was observed in this specified arm.
    [56] - No participants were analysed, as no response was observed in this specified arm.
    [57] - No participants were analysed, as no response was observed in this specified arm.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Objective Response Rate for Part A

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    End point title
    		 Percentage of Participants With Objective Response Rate for Part A [58]
    End point description
    The ORR is defined as proportion of participants with CR or PR according to IWG criteria. CR is disappearance of all evidence of disease. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if unknown by morphology, IHC was negative. PR is regression of measurable disease and no new sites. For nodal masses: >= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site b) FDG-avid or PET negative; regression on CT. For spleen and liver: >= 50% decrease in SPD of nodules; no increase in size of liver or spleen. For bone marrow: irrelevant if positive prior to therapy. Evaluable population for efficacy was analysed for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [58] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg
    Number of subjects analysed
    3
    4
    3
    5
    3
    72
    Units: Percentage of participants
        number (confidence interval 95%)
    66.7 (9.4 to 99.2)
    0 (0.0 to 60.2)
    0 (0.0 to 70.8)
    20.0 (0.5 to 71.6)
    33.3 (0.8 to 90.6)
    27.8 (17.9 to 39.6)
    No statistical analyses for this end point

    Secondary: Duration of Objective Response for Part A

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    End point title
    		 Duration of Objective Response for Part A [59]
    End point description
    The DOR is the first documentation of objective response to the first documented PD or relapse according to IWG criteria. PD is defined as any new lesion or increase by >=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) > 1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node > 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: > 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate DOR. Evaluable population for efficacy was analysed for this endpoint, which included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. The DOR were calculated for participants with objective response.
    End point type
    Secondary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [59] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg
    Number of subjects analysed
    2
    0 [60]
    0 [61]
    1
    1
    20
    Units: Months
        median (full range (min-max))
    8.8 (7.4 to 8.8)
    ( to )
    ( to )
    15.0 (15.0 to 15.0)
    3.0 (3.0 to 3.0)
    19.8 (0.0 to 41.9)
    Notes
    [60] - No participants were analysed, as no response was observed in this specified arm.
    [61] - No participants were analysed, as no response was observed in this specified arm.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Disease Control Rate for Part A

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    End point title
    		 Percentage of Participants With Disease Control Rate for Part A [62]
    End point description
    Disease control includes CR, PR, or SD for at least 8 weeks according to IWG criteria. The CR is disappearance of all evidence of disease. For nodal masses; FDG -avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. PR is regression of measurable disease and no new sites. For nodal masses: >= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site b) Variably FDG-avid or PET negative; regression on CT. For spleen and liver: >= 50% decrease in SPD of nodules. For bone marrow: irrelevant if positive prior to therapy. SD is failure to attain CR/PR or PD. Evaluable population for efficacy was analysed for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [62] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg
    Number of subjects analysed
    2
    2
    2
    4
    2
    53
    Units: Percentage of participants
        number (confidence interval 95%)
    66.7 (9.4 to 99.2)
    50.0 (6.8 to 93.2)
    66.7 (9.4 to 99.2)
    80.0 (28.4 to 99.5)
    66.7 (9.4 to 99.2)
    73.6 (61.9 to 83.3)
    No statistical analyses for this end point

    Secondary: Duration of Disease Control for Part A

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    End point title
    		 Duration of Disease Control for Part A [63]
    End point description
    Duration of disease control is defined as time period from start of MEDI-551 administration to event of PD/relapse according to IWG criteria. PD is defined as new lesion or increase by >=50% of previously involved sites from nadir. Nodal masses:appearance of a new lesion >1.5 cm in any axis, >= 50% increase in SPD of more than one node, or >= 50% increase in longest diameter of a previously identified node >1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. Spleen: >50% increase from nadir in the SPD of any previous lesions. Bone marrow:New or recurrent involvement. Kaplan-Meier method was used to evaluate duration of disease control. Evaluable population for efficacy was analysed for this endpoint. Duration of disease control is calculated for the participants with objective response or stable disease response. Arbitrary numbers "9.9999 and 3.9999" signifies median was not estimable because insufficient number of participants had events.
    End point type
    Secondary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [63] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg
    Number of subjects analysed
    2
    2
    2
    4
    2
    53
    Units: Months
        median (full range (min-max))
    12.6 (1.4 to 12.6)
    9.9999 (9.4 to 21.0)
    3.9999 (3.5 to 7.4)
    10.9 (3.9 to 94.9)
    6.6 (2.8 to 6.6)
    18.0 (0.9 to 49.7)
    No statistical analyses for this end point

    Secondary: Time to Response for Part A

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    End point title
    		 Time to Response for Part A [64]
    End point description
    The TTR is measured from the start of MEDI-551 administration to the first documentation of response (CR or PR) and assessed in participants who have achieved objective response. Kaplan-Meier method was used to evaluate TTR. Evaluable population for efficacy was analysed for this endpoint, which included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. TTR were calculated for the participants with objective response.
    End point type
    Secondary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [64] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg
    Number of subjects analysed
    2
    0 [65]
    0 [66]
    1
    1
    20
    Units: Months
        median (full range (min-max))
    3.7 (3.5 to 3.9)
    ( to )
    ( to )
    1.9 (1.9 to 1.9)
    3.6 (3.6 to 3.6)
    3.2 (0.3 to 22.6)
    Notes
    [65] - No participants were analysed, as no response was observed in this specified arm.
    [66] - No participants were analysed, as no response was observed in this specified arm.
    No statistical analyses for this end point

    Secondary: Progression Free Survival for Part A

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    End point title
    		 Progression Free Survival for Part A [67]
    End point description
    The PFS is measured from the start of MEDI-551 treatment until the first documentation of disease progression, relapse or death, whichever occurs first. Kaplan-Meier method was used to evaluate PFS. The PFS was censored on the date of last disease assessment for participants who have no documented PD/relapse or death prior to data cutoff, dropout, or the initiation of alternative anticancer therapy. Evaluable population for efficacy was analysed for this endpoint, which included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment.
    End point type
    Secondary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [67] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg
    Number of subjects analysed
    3
    4
    3
    5
    3
    72
    Units: Months
        median (full range (min-max))
    12.6 (1.4 to 12.6)
    5.9 (0.6 to 21.0)
    3.5 (1.6 to 9.9)
    4.9 (1.1 to 94.9)
    6.6 (2.1 to 6.6)
    11.3 (0.0 to 49.7)
    No statistical analyses for this end point

    Secondary: Overall Survival for Part A

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    End point title
    		 Overall Survival for Part A [68]
    End point description
    The OS is measured from the start of MEDI-551 treatment until death. For participants who are alive at the end of study or lost to follow-up, OS will be censored on the last date when participants were known to be alive. Kaplan-Meier method was used to evaluate OS. Evaluable population for efficacy was analysed for this endpoint, which included all participants who received any treatment of MEDI-551 and completed at least one post-baseline disease assessment. Here, the arbitrary number "1.9999" signifies that median was not estimable because insufficient number of participants had events.
    End point type
    Secondary
    End point timeframe
    Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)
    Notes
    [68] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg
    Number of subjects analysed
    3
    4
    3
    5
    3
    72
    Units: Months
        median (full range (min-max))
    1.9999 (1.4 to 21.5)
    44.6 (0.8 to 91.5)
    9.9 (2.8 to 9.9)
    1.9999 (1.7 to 94.9)
    8.1 (2.8 to 12.5)
    45.3 (0.7 to 83.5)
    No statistical analyses for this end point

    Secondary: Trough Serum Concentration of MEDI-551 by Treatment Cycle

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    End point title
    		 Trough Serum Concentration of MEDI-551 by Treatment Cycle
    End point description
    Trough serum concentration (Ctrough) is defined as lowest concentration reached by a drug before the next dose is administered. The PK population was analysed for this endpoint, which included all participants who received at least one dose of MEDI-551 and had at least one measurable serum concentration of MEDI-551. Here, the arbitrary numbers "999", "9999", "99999", and "999999" signifies that the sample was below limit of quantification, analysis is not applicable, standard deviation is not reported as only one participant was evaluable, and no participants were analysed for the specified arms respectively.
    End point type
    Secondary
    End point timeframe
    For Part A: C1D1 of each cycles; For Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; For Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10;For Part D: C1D1, C1D8, then Day 1 of each cycle until Cycle 10
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg Part A-MEDI-551 12 mg/kg (expansion)
    Number of subjects analysed
    3
    4
    3
    6
    3
    6
    3
    3
    1
    3
    17
    14
    67
    Units: μg/mL
    arithmetic mean (standard deviation)
        C1D1(n= 3, 4, 3, 6, 3, 6, 3, 3, 1, 3, 17, 14, 66)
    999 ( 999 )
    0.333 ( 0.665 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    9999 ( 9999 )
    9999 ( 9999 )
    999 ( 999 )
    2.97 ( 24.1 )
        C1D2(n= 3, 4, 3, 6, 3, 6, 3, 3, 1, 3, 17, 14, 67)
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    999 ( 999 )
    999 ( 999 )
    9999 ( 9999 )
    9999 ( 9999 )
        C1D8(n= 3, 4, 3,6,3,6,3,3,1,3,16,14,67)
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    46.5 ( 20.9 )
    102 ( 25.0 )
    125 ( 99999 )
    58.0 ( 14.3 )
    115 ( 38.0 )
    109 ( 58.5 )
    9999 ( 9999 )
        C1D15(n= 3,4,3, 6, 3, 6,3, 3, 1,3 17,14,67)
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    81.8 ( 38.3 )
    197 ( 51.2 )
    329 ( 99999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
        C1D22(n= 3,4,3,6,3,6,3,3,0,3,17,14,67)
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    116 ( 47.4 )
    281 ( 29.5 )
    999999 ( 999999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
        C2D1(n= 3,3,3,4,3,6,3,3,0,3,12,11,56)
    15.6 ( 0.823 )
    25.9 ( 10.9 )
    12.9 ( 4.55 )
    59.4 ( 11.0 )
    89.8 ( 64.9 )
    166 ( 54.0 )
    122 ( 37.2 )
    326 ( 68.0 )
    999999 ( 999999 )
    52.4 ( 17.7 )
    106 ( 28.8 )
    114 ( 40.1 )
    124 ( 64.8 )
        C3D1(n= 2,3,2, 4,2,6,3,3,0,3,11,6,46)
    19.3 ( 3.33 )
    26.9 ( 12.2 )
    6.78 ( 2.01 )
    43.0 ( 8.40 )
    97.0 ( 94.5 )
    149 ( 46.2 )
    57.6 ( 43.1 )
    187 ( 80.6 )
    999999 ( 999999 )
    44.7 ( 14.2 )
    92.1 ( 30.7 )
    93.9 ( 35.6 )
    113 ( 70.3 )
        C4D1(n=2,2,2,4,1,5,3,3,0,3,10,6,43)
    20.9 ( 6.69 )
    36.5 ( 0.550 )
    5.59 ( 0.146 )
    37.9 ( 13.8 )
    33.4 ( 99999 )
    146 ( 55.5 )
    36.0 ( 31.6 )
    134 ( 67.7 )
    999999 ( 999999 )
    48.2 ( 20.8 )
    113 ( 70.0 )
    102 ( 61.5 )
    113 ( 57.1 )
        C5D1(n= 2,2,0,3,1,3,3,3,0,2,7, 2, 34)
    26.6 ( 7.17 )
    46.8 ( 8.03 )
    999999 ( 999999 )
    56.9 ( 19.6 )
    31.8 ( 99999 )
    136 ( 19.3 )
    35.7 ( 32.0 )
    121 ( 78.1 )
    999999 ( 999999 )
    51.6 ( 2.64 )
    102 ( 26.3 )
    147 ( 105 )
    117 ( 60.9 )
        C6D1 (n= 2,2,1,1,1,3,3,3,0,1,7,2, 35)
    29.1 ( 6.17 )
    29.1 ( 17.3 )
    11.7 ( 99999 )
    32.0 ( 99999 )
    33.7 ( 99999 )
    138 ( 27.2 )
    37.3 ( 33.5 )
    106 ( 54.6 )
    999999 ( 999999 )
    45.9 ( 99999 )
    100 ( 22.9 )
    150 ( 116 )
    123 ( 67.9 )
        C7D1(n= 2,2,1,1,1,3,3,3,0,1 5,1, 28)
    31.4 ( 7.08 )
    25.1 ( 27.8 )
    9.93 ( 99999 )
    38.2 ( 99999 )
    27.9 ( 99999 )
    144 ( 42.4 )
    28.1 ( 21.2 )
    95.1 ( 54.4 )
    999999 ( 999999 )
    45.3 ( 99999 )
    108 ( 20.2 )
    248 ( 99999 )
    109 ( 64.2 )
        C8D1 (n= 2,2,1,1,0,1,3,3,0,0,5,1, 27)
    27.1 ( 14.9 )
    28.0 ( 1.86 )
    8.80 ( 99999 )
    33.3 ( 99999 )
    999999 ( 999999 )
    109 ( 99999 )
    30.8 ( 30.4 )
    86.8 ( 54.4 )
    999999 ( 999999 )
    999999 ( 999999 )
    147 ( 82.2 )
    177 ( 99999 )
    114 ( 63.8 )
        C9D1(n= 1,2, 1, 1, 0, 2, 3, 3, 0, 0, 5, 2, 22)
    21.6 ( 99999 )
    31.6 ( 1.23 )
    10.7 ( 99999 )
    33.6 ( 99999 )
    999999 ( 999999 )
    124 ( 23.2 )
    27.3 ( 27.1 )
    94.8 ( 69.4 )
    999999 ( 999999 )
    999999 ( 999999 )
    95.0 ( 7.59 )
    192 ( 25.9 )
    121 ( 77.5 )
        C10D1(n= 1, 1, 1, 1, 0, 2, 3, 3, 0, 0, 4, 1, 23)
    17.6 ( 99999 )
    25.1 ( 99999 )
    10.6 ( 99999 )
    32.9 ( 99999 )
    999999 ( 999999 )
    98.3 ( 5.05 )
    33.4 ( 34.8 )
    84.2 ( 57.4 )
    999999 ( 999999 )
    999999 ( 999999 )
    113 ( 27.6 )
    215 ( 99999 )
    139 ( 80.4 )
    No statistical analyses for this end point

    Secondary: Peak Serum Concentration of MEDI-551 by Treatment Cycle

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    End point title
    		 Peak Serum Concentration of MEDI-551 by Treatment Cycle
    End point description
    Peak serum concentration is concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and before the administration of a second dose. The PK population was analysed for this endpoint, which included all participants who received at least one dose of MEDI-551 and had at least one measurable serum concentration of MEDI-551. Here, the arbitrary numbers "999", "9999", and "99999", signifies that no participants were analysed, standard deviation is not reported as only one participant was evaluable, and analysis is not applicable, for the specified arms respectively.
    End point type
    Secondary
    End point timeframe
    For Part A: C1D1 of each cycles; For Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; For Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10;For Part D: C1D1, C1D8, then Day 1 of each cycle until Cycle 10
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg Part A-MEDI-551 12 mg/kg (expansion)
    Number of subjects analysed
    3
    4
    3
    6
    3
    6
    3
    3
    1
    3
    17
    14
    67
    Units: μg/mL
    arithmetic mean (standard deviation)
        C1 D1 (n= 3,4,3,4,3,6,3,3,1,3,17, 13, 62)
    12.3 ( 1.20 )
    22.8 ( 1.24 )
    46.0 ( 22.2 )
    100 ( 11.0 )
    166 ( 59.5 )
    280 ( 99.1 )
    122 ( 24.2 )
    335 ( 79.1 )
    199 ( 9999 )
    99999 ( 99999 )
    99999 ( 99999 )
    260 ( 87.3 )
    240 ( 90.0 )
        C1D2 (n= 3,4,3,6,3,6,3,3,1,3 17, 14, 67)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    160 ( 23.5 )
    214 ( 79.9 )
    99999 ( 99999 )
    99999 ( 99999 )
        C1D8 (n= 3,4,3,6,3,6,3,3,1,3,16, 13, 67)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    162 ( 17.3 )
    393 ( 80.8 )
    470 ( 9999 )
    246 ( 76.1 )
    115 ( 38.0 )
    303 ( 97.4 )
    99999 ( 99999 )
        C1D15(n= 3,4 3,6 3,6,3,3,1,3 17, 14, 67)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    182 ( 31.1 )
    517 ( 135 )
    619 ( 9999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        C1D22(n= 3,4,3,6,3,6,3,3 0,3 17, 14, 67)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    208 ( 46.7 )
    533 ( 223 )
    999 ( 999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        C2D1(n= 3,3,3,4 3,6 3,3 0,3,12, 10, 53 )
    27.5 ( 0.752 )
    43.9 ( 13.2 )
    48.8 ( 21.7 )
    149 ( 29.7 )
    238 ( 106 )
    467 ( 114 )
    186 ( 116 )
    749 ( 133 )
    999 ( 999 )
    205 ( 33.5 )
    304 ( 108 )
    333 ( 72.7 )
    350 ( 130 )
        C3D1(n= 2,3,2,4,2,6,3,3 0,3,11,6, 46)
    26.3 ( 2.20 )
    46.4 ( 16.6 )
    58.7 ( 0.783 )
    145 ( 31.2 )
    260 ( 89.6 )
    374 ( 116 )
    155 ( 38.2 )
    374 ( 125 )
    999 ( 999 )
    192 ( 78.1 )
    311 ( 74.0 )
    277 ( 95.7 )
    326 ( 110 )
        C4D1 (n= 2,2,2,4 1,5 3,3 0,3 10, 6, 41)
    30.3 ( 5.46 )
    48.3 ( 12.7 )
    63.7 ( 35.1 )
    161 ( 85.6 )
    201 ( 9999 )
    359 ( 115 )
    156 ( 81.7 )
    384 ( 169 )
    999 ( 999 )
    212 ( 84.1 )
    261 ( 99.4 )
    295 ( 116 )
    342 ( 119 )
        C5D1(n= 2,2 0,2 1,3 3,3 0,2 7,2, 32)
    39.4 ( 6.85 )
    70.8 ( 5.43 )
    999 ( 999 )
    151 ( 58.1 )
    203 ( 9999 )
    372 ( 113 )
    153 ( 71.6 )
    363 ( 261 )
    999 ( 999 )
    250 ( 82.3 )
    290 ( 66.0 )
    338 ( 245 )
    347 ( 98.1 )
        C6D1 (n= 2,2 1,1,1,3, 3, 3, 0, 1, 6, 2, 35 )
    40.4 ( 3.87 )
    34.4 ( 4.21 )
    43.2 ( 9999 )
    123 ( 9999 )
    198 ( 9999 )
    345 ( 101 )
    130 ( 45.7 )
    349 ( 140 )
    999 ( 999 )
    209 ( 9999 )
    332 ( 102 )
    303 ( 237 )
    337 ( 82.1 )
        C7D1(n= 2,2 1,1, 1, 3,3 3,0,1,5, 1, 27)
    41.3 ( 4.72 )
    39.5 ( 30.8 )
    41.0 ( 9999 )
    123 ( 9999 )
    182 ( 9999 )
    383 ( 54.6 )
    174 ( 60.4 )
    333 ( 133 )
    999 ( 999 )
    235 ( 9999 )
    392 ( 93.0 )
    502 ( 9999 )
    355 ( 95.7 )
        C8D1 (n= 2,2 1,1 0,1, 3, 3, 0, 0, 5, 1, 26)
    29.9 ( 12.3 )
    58.2 ( 16.9 )
    32.2 ( 9999 )
    130 ( 9999 )
    999 ( 999 )
    409 ( 9999 )
    164 ( 52.0 )
    342 ( 173 )
    999 ( 999 )
    999 ( 999 )
    317 ( 150 )
    511 ( 9999 )
    367 ( 102 )
        C9D1 (n= 1,2 1,1 0,2, 3, 3, 0, 0, 5, 2, 22)
    32.2 ( 9999 )
    46.8 ( 5.58 )
    37.8 ( 9999 )
    127 ( 999 )
    999 ( 999 )
    391 ( 79.6 )
    159 ( 64.7 )
    299 ( 69.8 )
    999 ( 999 )
    999 ( 999 )
    363 ( 90.3 )
    593 ( 200 )
    394 ( 125 )
        C10D1 (n= 1,1,1,1,0,2, 3, 3, 0, 0, 4, 1, 21)
    43.3 ( 9999 )
    33.5 ( 9999 )
    42.3 ( 9999 )
    133 ( 9999 )
    999 ( 999 )
    307 ( 49.8 )
    166 ( 64.1 )
    316 ( 189 )
    999 ( 999 )
    999 ( 999 )
    349 ( 70.4 )
    484 ( 9999 )
    394 ( 157 )
    No statistical analyses for this end point

    Secondary: Area Under the Concentration Curve at Steady State (AUCss) of MEDI-551

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    End point title
    		 Area Under the Concentration Curve at Steady State (AUCss) of MEDI-551
    End point description
    Area under the concentration-time curve at steady state (Css, AUC) of MEDI-551 is reported. Pharmacokinetic (PK) population was analysed for this endpoint, which included all participants who received at least one dose of MEDI-551 and had at least one measurable serum concentration of MEDI-551. Here, the arbitrary number "999" signifies that data not reported due to limited PK data up to Cycle 1 Day 15.
    End point type
    Secondary
    End point timeframe
    Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg Part A-MEDI-551 12 mg/kg (expansion)
    Number of subjects analysed
    3
    4
    3
    6
    3
    6
    3
    3
    1
    3
    17
    14
    67
    Units: μg⋅day/mL
        arithmetic mean (standard deviation)
    212 ( 28.1 )
    287 ( 110 )
    479 ( 57.7 )
    1660 ( 778 )
    2880 ( 2190 )
    5720 ( 1620 )
    1730 ( 1030 )
    4920 ( 1440 )
    999 ( 999 )
    2240 ( 338 )
    4260 ( 1340 )
    4250 ( 2000 )
    4850 ( 1720 )
    No statistical analyses for this end point

    Secondary: Apparent Clearance of MEDI-551

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    End point title
    		 Apparent Clearance of MEDI-551
    End point description
    Apparent clearance of MEDI-551 is reported. The PK population was analysed for this endpoint, which included all participants who received at least one dose of MEDI-551 and had at least one measurable serum concentration of MEDI-551. Here, the arbitrary number "999" signifies that standard deviation is not reported as only one participant was evaluable for the specified arm.
    End point type
    Secondary
    End point timeframe
    Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg Part A-MEDI-551 12 mg/kg (expansion)
    Number of subjects analysed
    3
    4
    3
    6
    3
    6
    3
    3
    1
    3
    17
    14
    67
    Units: mL/day
        arithmetic mean (standard deviation)
    206 ( 101 )
    302 ( 173 )
    373 ( 70.9 )
    210 ( 28.9 )
    268 ( 126 )
    198 ( 44.3 )
    303 ( 108 )
    243 ( 81.6 )
    279 ( 999 )
    288 ( 43.0 )
    235 ( 87.5 )
    237 ( 72.5 )
    235 ( 110 )
    No statistical analyses for this end point

    Secondary: Volume of Distribution of MEDI-551

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    End point title
    		 Volume of Distribution of MEDI-551
    End point description
    Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Central volume of distribution (Vd1) is defined as hypothetical volume into which a drug initially distributes upon administration and peripheral volume of distribution (Vd2) is defined as the sum of all tissue spaces outside the central compartment. The PK population was analysed for this endpoint, which included all participants who received at least one dose of MEDI-551 and had at least one measurable serum concentration of MEDI-551. Here, the arbitrary number "999" signifies that standard deviation is not reported as only one participant was evaluable for the specified arm.
    End point type
    Secondary
    End point timeframe
    Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg Part A-MEDI-551 12 mg/kg (expansion)
    Number of subjects analysed
    3
    4
    3
    6
    3
    6
    3
    3
    1
    3
    17
    14
    67
    Units: mL
    arithmetic mean (standard deviation)
        Vd1
    3970 ( 851 )
    3920 ( 491 )
    4350 ( 948 )
    4070 ( 464 )
    4210 ( 510 )
    4230 ( 234 )
    3560 ( 286 )
    4490 ( 947 )
    5690 ( 999 )
    4520 ( 126 )
    4350 ( 851 )
    4510 ( 647 )
    4450 ( 889 )
        Vd2
    2670 ( 351 )
    2010 ( 1080 )
    1980 ( 888 )
    2290 ( 767 )
    2620 ( 1240 )
    2920 ( 1070 )
    3290 ( 1440 )
    2640 ( 1840 )
    3670 ( 999 )
    4590 ( 847 )
    2640 ( 1200 )
    3200 ( 1440 )
    3430 ( 2250 )
    No statistical analyses for this end point

    Secondary: Terminal Half-life (t1/2) of MEDI-551

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    End point title
    		 Terminal Half-life (t1/2) of MEDI-551
    End point description
    Terminal half-life is the time required for the plasma concentration of MEDI-551 to fall by 50% during the terminal phase. The PK population was analysed for this endpoint, which included all participants who received at least one dose of MEDI-551 and had at least one measurable serum concentration of MEDI-551. Here, the arbitrary number "999" signifies that standard deviation is not reported as only one participant was evaluable for the specified arm.
    End point type
    Secondary
    End point timeframe
    Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg Part A-MEDI-551 12 mg/kg (expansion)
    Number of subjects analysed
    3
    4
    3
    6
    3
    6
    3
    3
    1
    3
    17
    14
    67
    Units: Days
        arithmetic mean (standard deviation)
    26.0 ( 6.88 )
    17.3 ( 7.65 )
    13.3 ( 6.41 )
    22.1 ( 3.26 )
    21.7 ( 8.65 )
    27.9 ( 9.08 )
    19.9 ( 9.34 )
    23.8 ( 10.9 )
    25.1 ( 999 )
    25.3 ( 4.40 )
    23.6 ( 9.38 )
    25.6 ( 7.96 )
    28.9 ( 15.0 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Positive Anti-drug Antibodies (ADA) Titer to MEDI-551

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    End point title
    		 Number of Participants With Positive Anti-drug Antibodies (ADA) Titer to MEDI-551 [69]
    End point description
    Number of participants with positive Anti-drug antibodies (ADA) titer to MEDI-551 is reported. The safety population was analysed for this endpoint, which included all participants who received any treatment of MEDI-551. Participants only with positive ADA is reported.
    End point type
    Secondary
    End point timeframe
    Part A:C1D1; Part B: C1D1; Part C: C1D1; Part D: C1D1; End of treatment (EOT); 90 Days post last dose (approximately 9 years)
    Notes
    [69] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    3
    4
    3
    6
    3
    76
    3
    3
    3
    17
    14
    Units: Participants
        C1D1
    0
    1
    0
    0
    0
    2
    0
    0
    0
    0
    2
        EOT
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        90 Day Post Dose0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: B-cell Concentration in Serum

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    End point title
    		 B-cell Concentration in Serum
    End point description
    B-cell concentration in serum is reported. The safety population was analysed for this endpoint, which included all participants who received any treatment of MEDI-551.Safety population included all participants who received any treatment of MEDI-551. It was pre-specified that B-cell analysis was not required, due to limited data availability.
    End point type
    Secondary
    End point timeframe
    Part A:C1D1 of each cycles; Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10; Part D: C1D1, C1D8, Day 1 of each cycle until Cycle 10; EOT;90 Days post last dose (approximately 9 years)
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 6 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part C-MEDI-551 12 mg/kg + rituximab Part D-MEDI-551 12 mg/kg
    Number of subjects analysed
    0 [70]
    0 [71]
    0 [72]
    0 [73]
    0 [74]
    0 [75]
    0 [76]
    0 [77]
    0 [78]
    0 [79]
    0 [80]
    0 [81]
    Units: mg/dL
    Notes
    [70] - It was pre-specified that B-cell analysis was not required, due to limited data availability
    [71] - It was pre-specified that B-cell analysis was not required, due to limited data availability
    [72] - It was pre-specified that B-cell analysis was not required, due to limited data availability
    [73] - It was pre-specified that B-cell analysis was not required, due to limited data availability
    [74] - It was pre-specified that B-cell analysis was not required, due to limited data availability
    [75] - It was pre-specified that B-cell analysis was not required, due to limited data availability
    [76] - It was pre-specified that B-cell analysis was not required, due to limited data availability
    [77] - It was pre-specified that B-cell analysis was not required, due to limited data availability
    [78] - It was pre-specified that B-cell analysis was not required, due to limited data availability
    [79] - It was pre-specified that B-cell analysis was not required, due to limited data availability
    [80] - It was pre-specified that B-cell analysis was not required, due to limited data availability
    [81] - It was pre-specified that B-cell analysis was not required, due to limited data availability
    No statistical analyses for this end point

    Secondary: Immunoglobulin (Ig) Concentration in Serum

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    End point title
    		 Immunoglobulin (Ig) Concentration in Serum [82]
    End point description
    Immunoglobin (Ig) concentration in serum is reported. The safety population was analysed for this endpoint, which included all participants who received any treatment of MEDI-551. Here, the arbitrary numbers "9999 and 999"signifies that no participants were analysed for the specified arm and standard deviation is not reported as only one participant was evaluable for the specified arm respectively.
    End point type
    Secondary
    End point timeframe
    Part A:C1D1 of each cycles; EOT;90 Days post last dose (approximately 9 years)
    Notes
    [82] - 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: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 8 mg/kg Part A-MEDI-551 12 mg/kg
    Number of subjects analysed
    3
    4
    3
    6
    3
    76
    Units: mg/dL
    arithmetic mean (standard deviation)
        C1D1 (n= 3, 4, 3, 6, 3, 68)
    120.00 ( 46.36 )
    110.00 ( 76.25 )
    81.00 ( 66.36 )
    61.67 ( 54.52 )
    93.33 ( 46.11 )
    93.01 ( 88.56 )
        C2D1 (n= 2, 33, 4, 2, 59)
    67.50 ( 7.78 )
    113.67 ( 92.81 )
    67.67 ( 58.05 )
    57.00 ( 47.05 )
    74.50 ( 47.38 )
    88.90 ( 92.05 )
        C3D1 (n= 2, 3, 2, 4, 2, 50)
    62.50 ( 6.36 )
    106.00 ( 87.93 )
    31.00 ( 29.70 )
    57.25 ( 48.29 )
    76.50 ( 50.20 )
    67.90 ( 66.59 )
        C4D1 (n= 2, 2, 2, 3, 1, 50)
    64.00 ( 9.90 )
    152.50 ( 13.44 )
    31.00 ( 33.94 )
    63.67 ( 56.52 )
    98.00 ( 999 )
    66.84 ( 61.83 )
        C5D1 (2, 2, 1, 3, 1, 38)
    69.00 ( 11.31 )
    145.50 ( 38.89 )
    50.00 ( 999 )
    58.67 ( 45.17 )
    77.00 ( 999 )
    69.24 ( 70.45 )
        C6D1 (2, 2, 0, 1, 1, 36)
    63.50 ( 13.44 )
    156.00 ( 48.08 )
    9999 ( 9999 )
    41.00 ( 999 )
    71.00 ( 999 )
    62.86 ( 65.04 )
        C7D1 (n= 2, 1, 1, 1, 1, 31)
    56.00 ( 1.41 )
    127.00 ( 999 )
    47.00 ( 999 )
    41.00 ( 999 )
    61.00 ( 999 )
    67.26 ( 69.36 )
        C8D1 (n= 2, 2, 1, 1, 0, 29)
    47.00 ( 7.07 )
    147.00 ( 28.28 )
    45.00 ( 999 )
    41.00 ( 999 )
    9999 ( 9999 )
    73.76 ( 66.87 )
        C9D1 (n= 1, 2, 1, 1, 0, 26)
    51.00 ( 999 )
    137.50 ( 30.41 )
    46.00 ( 999 )
    41.00 ( 999 )
    9999 ( 9999 )
    62.35 ( 61.90 )
        C10D1 (1, 1, 1, 1, 0, 24)
    47.00 ( 999 )
    155.00 ( 999 )
    46.00 ( 999 )
    41.00 ( 999 )
    9999 ( 9999 )
    73.17 ( 66.34 )
        EOT (n= 2, 3, 3, 5, 3, 48)
    43.50 ( 12.02 )
    96.00 ( 80.58 )
    7.00 ( 999 )
    54.40 ( 46.55 )
    65.33 ( 19.76 )
    217.25 ( 1003.38 )
        90 Days Post Dose (n= 1, 2, 0, 3, 0, 15)
    49.00 ( 999 )
    84.50 ( 60.10 )
    9999 ( 9999 )
    93.33 ( 42.06 )
    9999 ( 9999 )
    45.20 ( 38.72 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 through 90-Day Post Last Dose (Approximately 9 years)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Part A-MEDI-551 0.5 mg/kg
    Reporting group description
    		 Participants received intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part A-MEDI-551 1 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part A-MEDI-551 4 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part A-MEDI-551 2 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part A-MEDI-551 8 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part B-MEDI-551 6 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part A-MEDI-551 12 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part B-MEDI-551 12 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part B-MEDI-551 24 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation was observed.

    Reporting group title
    Part C-MEDI-551 8 mg/kg + rituximab
    Reporting group description
    		 Participants received IV infusion of 8 mg/kg on days 2 and 8 during Cycle 1 and day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m2 on days 1, 8, 15, and 22. From Cycle 3 only MEDI-551 8 mg/kg was administered on day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdraws consent.

    Reporting group title
    Part D-MEDI-551 12 mg/kg
    Reporting group description
    		 Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment was continued until the participants experiences unacceptable toxicity, disease progression, reached CR or consent withdrawal.

    Reporting group title
    Part C-MEDI-551 12 mg/kg + rituximab
    Reporting group description
    		 Participants received IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg was administered on Day 1 of each 28-day cycle. The treatment was continued until the participants experienced unacceptable toxicity, disease progression, reached complete response or withdraws consent.

    Serious adverse events
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 8 mg/kg Part B-MEDI-551 6 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part D-MEDI-551 12 mg/kg Part C-MEDI-551 12 mg/kg + rituximab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    2 / 3 (66.67%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    23 / 76 (30.26%)
    2 / 3 (66.67%)
    1 / 1 (100.00%)
    1 / 3 (33.33%)
    5 / 14 (35.71%)
    9 / 17 (52.94%)
         number of deaths (all causes)
    0
    2
    1
    2
    2
    1
    30
    0
    1
    2
    8
    9
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (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
    Diffuse large b-cell lymphoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    Malignant melanoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 14 (0.00%)
    0 / 17 (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 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-hodgkin's lymphoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (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 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Polycythaemia vera
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    Deep vein thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (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
    Haematoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    Shock haemorrhagic
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    General physical health deterioration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchiectasis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (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 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    6 / 6
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (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
    Procedural pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Sinus bradycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (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
    Nervous system disorders
    Cauda equina syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    Syncope
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (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
    Toxic encephalopathy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (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 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    Abdominal pain upper
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Acute hepatic failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    Pemphigoid
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    Lumbar spinal stenosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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 chest pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (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 / 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
    Osteolysis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (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 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess limb
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    Bacteraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         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 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    Lung infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (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 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 3
    1 / 1
    0 / 0
    0 / 0
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Sepsis syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    Sinusitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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 sepsis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Varicella
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    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
    Dehydration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Part A-MEDI-551 0.5 mg/kg Part A-MEDI-551 1 mg/kg Part A-MEDI-551 4 mg/kg Part A-MEDI-551 2 mg/kg Part A-MEDI-551 8 mg/kg Part B-MEDI-551 6 mg/kg Part A-MEDI-551 12 mg/kg Part B-MEDI-551 12 mg/kg Part B-MEDI-551 24 mg/kg Part C-MEDI-551 8 mg/kg + rituximab Part D-MEDI-551 12 mg/kg Part C-MEDI-551 12 mg/kg + rituximab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    4 / 4 (100.00%)
    6 / 6 (100.00%)
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    75 / 76 (98.68%)
    3 / 3 (100.00%)
    1 / 1 (100.00%)
    3 / 3 (100.00%)
    14 / 14 (100.00%)
    17 / 17 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    1
    0
    0
    0
    0
    Benign neoplasm of thyroid gland
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Bowen's disease
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    0
    0
    0
    0
    0
    Haemangioma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Melanocytic naevus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Metastatic lymphoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Seborrhoeic keratosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    2
    Skin papilloma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    1
    0
    0
    0
    2
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 76 (1.32%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    1
    0
    0
    0
    0
    Tumour pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Flushing
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    1
    Haematoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    4 / 76 (5.26%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    5
    0
    0
    0
    1
    1
    Hot flush
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    2
    0
    Hypertension
         subjects affected / exposed
    2 / 3 (66.67%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    8 / 76 (10.53%)
    2 / 3 (66.67%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    2 / 17 (11.76%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    8
    5
    0
    0
    2
    4
    Hypotension
         subjects affected / exposed
    1 / 3 (33.33%)
    3 / 4 (75.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    2 / 17 (11.76%)
         occurrences all number
    1
    3
    0
    1
    0
    0
    3
    0
    1
    0
    1
    2
    Orthostatic hypotension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Phlebitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Systolic hypertension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    0
    0
    0
    0
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    5 / 76 (6.58%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    6
    0
    0
    0
    0
    4
    Breakthrough pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Chills
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    5 / 76 (6.58%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    6
    4
    0
    0
    3
    1
    Cyst
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    Early satiety
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Fatigue
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    2 / 6 (33.33%)
    1 / 3 (33.33%)
    3 / 3 (100.00%)
    2 / 3 (66.67%)
    28 / 76 (36.84%)
    3 / 3 (100.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    5 / 14 (35.71%)
    9 / 17 (52.94%)
         occurrences all number
    1
    5
    2
    1
    3
    2
    33
    6
    0
    2
    6
    20
    Gait disturbance
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    3 / 17 (17.65%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    3
    Gravitational oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Ill-defined disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Influenza like illness
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Infusion site pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Localised oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Malaise
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    0
    0
    1
    0
    Mass
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    Medical device site bruise
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Medical device site pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Mucosal inflammation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    2
    Necrosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    0
    1
    0
    0
    Oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    8 / 76 (10.53%)
    2 / 3 (66.67%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    5 / 17 (29.41%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    9
    5
    2
    0
    2
    9
    Pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    4 / 76 (5.26%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    4
    0
    0
    0
    0
    0
    Performance status decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Peripheral swelling
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    5 / 76 (6.58%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    9
    0
    0
    0
    0
    2
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    13 / 76 (17.11%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    2
    1
    0
    1
    18
    4
    0
    0
    2
    3
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Immune system disorders
    Hypogammaglobulinaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    2
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Immune system disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Seasonal allergy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    Social circumstances
    Ex-tobacco user
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Reproductive system and breast disorders
    Breast swelling
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Erectile dysfunction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Haematospermia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Nipple disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    26 / 76 (34.21%)
    3 / 3 (100.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    3 / 17 (17.65%)
         occurrences all number
    1
    3
    0
    0
    0
    1
    31
    7
    0
    0
    5
    3
    Dry throat
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Dyspnoea
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    9 / 76 (11.84%)
    2 / 3 (66.67%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    4 / 17 (23.53%)
         occurrences all number
    0
    1
    1
    1
    0
    0
    10
    6
    1
    0
    1
    5
    Dyspnoea exertional
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    3
    0
    0
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    4
    0
    0
    0
    1
    2
    Increased bronchial secretion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Nasal congestion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    1
    0
    0
    0
    3
    Nasal polyps
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Obstructive airways disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    3 / 76 (3.95%)
    2 / 3 (66.67%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    3
    4
    0
    0
    0
    0
    Paranasal sinus hypersecretion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    0
    0
    0
    2
    0
    Pleural effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    1
    Pleuritic pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Pneumothorax
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Productive cough
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    1
    5
    Pulmonary alveolar haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    2
    2
    0
    0
    1
    1
    Sinus congestion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    4 / 76 (5.26%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    4
    0
    0
    0
    0
    1
    Sneezing
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Sputum discoloured
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Throat tightness
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    2
    4
    Wheezing
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    6
    0
    0
    0
    2
    Psychiatric disorders
    Aggression
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Agitation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    1
    Anxiety
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    8 / 76 (10.53%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    1 / 14 (7.14%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    8
    1
    0
    1
    1
    4
    Confusional state
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    2 / 17 (11.76%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    2
    0
    0
    0
    2
    2
    Depressed mood
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Depression
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    1 / 14 (7.14%)
    3 / 17 (17.65%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    3
    0
    0
    1
    1
    3
    Hallucination
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Hallucinations, mixed
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Insomnia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    8 / 76 (10.53%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    4 / 14 (28.57%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    8
    0
    0
    0
    4
    5
    Mental status changes
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Sleep disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Product issues
    Device dislocation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    3
    0
    2
    0
    0
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    4 / 76 (5.26%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    4
    0
    3
    0
    0
    1
    Blood albumin decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    2
    0
    1
    4
    Blood bilirubin increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Blood chloride decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood cholesterol increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    1 / 3 (33.33%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    1
    1
    0
    0
    2
    Blood fibrinogen decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Blood fibrinogen increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    2
    0
    0
    0
    0
    Blood immunoglobulin m decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Blood iron decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    1
    0
    1
    1
    Blood phosphorus decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Blood potassium decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    2
    0
    Blood triglycerides increased
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    5
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Blood urea increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    2
    5
    0
    0
    0
    0
    Electrocardiogram qt prolonged
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    1
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    0
    0
    0
    0
    0
    Glucose urine present
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Haematocrit decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Karnofsky scale worsened
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Low density lipoprotein increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    3 / 14 (21.43%)
    2 / 17 (11.76%)
         occurrences all number
    0
    4
    0
    0
    0
    0
    0
    0
    11
    0
    3
    7
    Mean cell volume increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Neutrophil count abnormal
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    5 / 76 (6.58%)
    1 / 3 (33.33%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    4 / 14 (28.57%)
    2 / 17 (11.76%)
         occurrences all number
    2
    5
    4
    0
    0
    0
    7
    3
    1
    0
    4
    2
    Occult blood positive
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    1 / 3 (33.33%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    1
    1
    0
    1
    1
    Prostatic specific antigen increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Protein total decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    2
    0
    0
    0
    0
    Red blood cell count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Serum ferritin decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Vitamin d decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    3
    1
    0
    0
    1
    1
    Weight increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    5
    White blood cell count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    2 / 3 (66.67%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    3 / 14 (21.43%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    4
    4
    8
    0
    4
    4
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    2
    1
    0
    0
    2
    0
    1
    0
    0
    3
    Fall
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    1
    1
    Infusion related reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    34 / 76 (44.74%)
    2 / 3 (66.67%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    4 / 14 (28.57%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    2
    0
    0
    6
    108
    8
    1
    0
    12
    1
    Laceration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    0
    0
    0
    0
    Limb injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Post-traumatic pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Procedural complication
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Procedural pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    0
    0
    0
    0
    Rib fracture
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Skin abrasion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Vascular access complication
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Wrong drug administered
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Atrial fibrillation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    2
    0
    0
    0
    0
    Atrial flutter
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    Atrial tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    0
    0
    0
    0
    Bradycardia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Cardiac failure chronic
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Mitral valve incompetence
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    2
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    6 / 76 (7.89%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    7
    0
    0
    0
    1
    2
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    1
    0
    0
    0
    0
    Anosmia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    10 / 76 (13.16%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    3 / 14 (21.43%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    12
    0
    1
    0
    4
    2
    Dysgeusia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Headache
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    15 / 76 (19.74%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    3 / 17 (17.65%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    20
    7
    0
    0
    0
    3
    Hypersomnia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    4 / 76 (5.26%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    0
    0
    0
    0
    1
    Memory impairment
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Neuropathy peripheral
         subjects affected / exposed
    2 / 3 (66.67%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    1
    0
    0
    1
    0
    1
    Paraesthesia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    0
    0
    0
    0
    2
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    1
    0
    0
    0
    1
    Presyncope
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Sciatica
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    3
    Seizure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Sinus headache
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Somnolence
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Syncope
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    3
    0
    0
    0
    1
    0
    Tremor
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    6 / 76 (7.89%)
    1 / 3 (33.33%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    4 / 17 (23.53%)
         occurrences all number
    0
    2
    0
    0
    1
    0
    8
    1
    2
    0
    3
    18
    Febrile neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Hypergammaglobulinaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Increased tendency to bruise
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Leukocytosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Leukopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    5
    0
    0
    0
    0
    Lymph node pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    2
    Lymphopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    1
    0
    0
    0
    0
    Neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    13 / 76 (17.11%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    1 / 14 (7.14%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    19
    13
    0
    1
    2
    7
    Polycythaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Splenomegaly
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    3 / 6 (50.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    6 / 76 (7.89%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    2 / 17 (11.76%)
         occurrences all number
    0
    1
    7
    0
    0
    0
    7
    2
    0
    0
    4
    19
    Ear and labyrinth disorders
    Cerumen impaction
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Deafness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Ear pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    3
    0
    0
    0
    0
    2
    Ear swelling
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Excessive cerumen production
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypoacusis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Otorrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    2
    0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Dry eye
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Exophthalmos
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Eye pruritus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Glaucoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Ocular hyperaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Vision blurred
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    1
    0
    0
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    0
    0
    0
    0
    Abdominal distension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    4
    0
    0
    1
    0
    Abdominal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    6 / 76 (7.89%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    2 / 17 (11.76%)
         occurrences all number
    0
    3
    0
    0
    1
    0
    7
    2
    0
    0
    1
    3
    Abdominal pain lower
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    1
    0
    0
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    4 / 76 (5.26%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    0
    0
    0
    0
    0
    Anal incontinence
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Constipation
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    10 / 76 (13.16%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    2 / 14 (14.29%)
    6 / 17 (35.29%)
         occurrences all number
    0
    5
    0
    0
    0
    1
    12
    3
    0
    1
    2
    7
    Dental caries
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Diarrhoea
         subjects affected / exposed
    3 / 3 (100.00%)
    2 / 4 (50.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    18 / 76 (23.68%)
    2 / 3 (66.67%)
    1 / 1 (100.00%)
    1 / 3 (33.33%)
    3 / 14 (21.43%)
    5 / 17 (29.41%)
         occurrences all number
    10
    4
    0
    1
    0
    1
    21
    3
    2
    1
    4
    15
    Dry mouth
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    1
    0
    1
    2
    Dyspepsia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    1
    0
    0
    0
    0
    Dysphagia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    1 / 76 (1.32%)
    2 / 3 (66.67%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    1
    3
    0
    0
    3
    2
    Gingival pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    1
    0
    0
    0
    0
    Impaired gastric emptying
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Inguinal hernia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Intestinal ischaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Lip dry
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Nausea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    13 / 76 (17.11%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    3 / 14 (21.43%)
    5 / 17 (29.41%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    16
    1
    0
    2
    3
    9
    Oesophageal stenosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Oral pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    1
    Salivary hypersecretion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Stomatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    2
    0
    0
    0
    0
    2
    Tongue coated
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Toothache
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    7 / 76 (9.21%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 14 (0.00%)
    4 / 17 (23.53%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    8
    1
    0
    1
    0
    6
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Skin and subcutaneous tissue disorders
    Actinic keratosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    1
    0
    0
    0
    1
    Alopecia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    1
    Blister
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    2
    Dermatitis allergic
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Dry skin
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    1
    1
    Ecchymosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Eczema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Erythema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    1
    0
    0
    0
    1
    Erythema annulare
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    5 / 76 (6.58%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    5
    0
    0
    0
    0
    0
    Ingrowing nail
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Macule
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Miliaria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Night sweats
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    6 / 76 (7.89%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    7
    1
    0
    0
    1
    0
    Petechiae
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Pruritus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    7 / 76 (9.21%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    11
    1
    0
    0
    0
    2
    Purpura
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    1
    0
    0
    0
    0
    Rash
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    11 / 76 (14.47%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    3 / 17 (17.65%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    19
    1
    0
    0
    0
    4
    Rash erythematous
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Rash macular
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    3
    0
    Rash pruritic
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Scab
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Skin exfoliation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Skin irritation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Skin lesion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    0
    0
    0
    0
    0
    Solar lentigo
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Swelling face
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    Urticaria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Renal and urinary disorders
    Bladder spasm
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Dysuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Haematuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    2
    Haemoglobinuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    0
    0
    0
    0
    Hydronephrosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Micturition urgency
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Pollakiuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    1
    0
    Urinary incontinence
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    1
    Urinary retention
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Urine flow decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    6 / 76 (7.89%)
    2 / 3 (66.67%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 14 (0.00%)
    3 / 17 (17.65%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    9
    5
    0
    1
    0
    6
    Arthritis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    1
    0
    0
    0
    0
    Back pain
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    11 / 76 (14.47%)
    2 / 3 (66.67%)
    0 / 1 (0.00%)
    2 / 3 (66.67%)
    2 / 14 (14.29%)
    4 / 17 (23.53%)
         occurrences all number
    2
    2
    0
    0
    2
    0
    12
    4
    0
    2
    6
    5
    Bone pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    5
    0
    0
    0
    0
    2
    Bursitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Groin pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    2 / 76 (2.63%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    3
    1
    0
    0
    0
    0
    Inguinal mass
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Joint swelling
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Muscle spasms
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    9 / 76 (11.84%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    11
    0
    0
    0
    3
    1
    Muscular weakness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    1
    0
    0
    2
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    1 / 3 (33.33%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    2
    2
    1
    0
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    1
    0
    0
    2
    5
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Myalgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    4 / 76 (5.26%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    1
    0
    0
    0
    3
    Osteoarthritis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Osteonecrosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Pain in extremity
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    6 / 76 (7.89%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    5 / 17 (29.41%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    9
    2
    0
    0
    0
    6
    Pain in jaw
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    2
    0
    0
    0
    0
    Sarcopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Spondylitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Infections and infestations
    Abscess limb
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Bacterial vaginosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Bronchitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    4 / 76 (5.26%)
    2 / 3 (66.67%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    1
    0
    2
    6
    3
    0
    0
    3
    1
    Candida infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Cellulitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    3
    Chronic sinusitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    0
    0
    0
    0
    Diverticulitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    0
    0
    0
    0
    Ear infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    1 / 14 (7.14%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    0
    1
    1
    7
    Furuncle
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    1
    0
    0
    0
    0
    Herpes zoster
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    0
    0
    0
    0
    1
    Influenza
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    Laryngitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    4 / 76 (5.26%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    5
    2
    0
    0
    0
    1
    Oral herpes
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    1
    0
    0
    0
    0
    4
    Pharyngitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    1
    0
    3
    1
    0
    0
    0
    2
    2
    Pyelonephritis acute
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Rash pustular
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    1
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    1
    0
    0
    0
    0
    Rhinitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    1
    2
    0
    0
    1
    0
    Sinusitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    4 / 76 (5.26%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    4 / 17 (23.53%)
         occurrences all number
    0
    0
    0
    0
    0
    6
    4
    2
    0
    0
    2
    8
    Tonsillitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Tooth infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    9 / 76 (11.84%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    3 / 17 (17.65%)
         occurrences all number
    0
    1
    0
    0
    0
    6
    11
    10
    0
    0
    2
    4
    Urinary tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    8 / 76 (10.53%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    9
    1
    0
    0
    0
    3
    Viral infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    7 / 76 (9.21%)
    1 / 3 (33.33%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    5 / 14 (35.71%)
    2 / 17 (11.76%)
         occurrences all number
    0
    2
    1
    1
    0
    0
    7
    1
    1
    0
    6
    2
    Dehydration
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Hypercalcaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 76 (3.95%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    0
    0
    1
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    7
    0
    0
    0
    2
    4
    Hyperkalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    6
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypernatraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    3
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    4 / 76 (5.26%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    5
    0
    0
    0
    0
    0
    Hyperuricaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    1 / 17 (5.88%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    4
    0
    2
    0
    2
    1
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    3
    0
    0
    6
    Hypocalcaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    1 / 3 (33.33%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    1 / 14 (7.14%)
    2 / 17 (11.76%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    1
    2
    0
    1
    2
    Hypoglycaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Hypokalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 76 (1.32%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 14 (14.29%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    2
    5
    Hypomagnesaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 76 (2.63%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    2
    0
    0
    0
    5
    Hyponatraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    6
    2
    0
    0
    0
    0
    0
    0
    0
    0
    6
    Hypophosphataemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    3
    Vitamin d deficiency
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 76 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 14 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 May 2009
    Inclusion criterion number 11 amended. Exclusion criterion 1 added to exclude participants who were eligible for a life-prolonging or life-saving standard line of therapy.
    06 Nov 2009
    Text was added to indicate that an interim safety analysis was to be conducted when the MTD or OBD had been established. Inclusion criterion number 3 was edited to specify that the chronic lymphocytic leukemia (CLL) population was to include participants with SLL. Inclusion criterion number 10 was edited to specify platelet count >= 75,000/mm^3 (except for CLL participants with evidence of bone marrow disease, who must have had a platelet count >= 50,000/mm^3. Inclusion criterion number 12 was edited to clarify the recommended methods of contraception and to state that participants must use adequate contraception methods through 90 days after the last dose of MEDI-551. Inclusion criterion number 13 was edited to specify that for participants with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) only, disease was to be evaluable by the International Working Group criteria (formerly RECIST criteria). An additional analysis population, the Per-protocol population (defined as all participants who completed 2 cycles of treatment or who discontinued treatment for toxicity due to MEDI-551, disease progression, or death due to disease) was added.
    27 Jan 2010
    Exclusion criterion number 12 was edited to clarify that participants with active hepatitis B or C infection as defined by seropositivity for hepatitis are not eligible to participate in the study.
    23 Sep 2010
    The study design and treatment sections of the protocol were updated to specify that dose escalation began in participants with FL or multiple myeloma (MM) per Protocol Version 4.0 through Cohort 2, and that Cohorts 3 to 6 would enroll participants with FL, MM, CLL or DLBCL with a modified dosing schedule. Participants in Cohorts 1 and 2 would continue to follow the Protocol Version 4.0 dose schedule of 0.5 mg/kg (Cohort 1) or 1 mg/kg (Cohort 2) MEDI-551 IV infusion QW in 4-week cycles. Participants enrolled on Cohorts 3 and higher were to receive 2, 4, 8, or 12 mg/kg MEDI-551 (Cohorts 3 to 6, respectively) IV once per week on Days 1 and 8 in the first cycle (loading doses) and then Q4W at the start of each subsequent cycle on Days 1 and 8 in the first cycle (loading doses) and then Q4W at the start of each subsequent cycle.
    18 Jul 2011
    The text was updated to specify that all participants (US and non-US) who achieved a CR may receive an additional 2 cycles of MEDI-551 at the same dose level. The FDA were to be consulted concerning the possibility of additional treatment with MEDI-551 for participants within the US who achieved a CR and subsequently relapse; however, non-US participants were not to be re-treated on subsequent relapse. The objective response rate was revised from 12 weeks to 8 weeks.
    04 Oct 2011
    Sections throughout the protocol were amended to state that the maximum dose-escalation phase dose of 12 mg/kg was selected for the expansion phase of the study. An additional safety follow-up visit at 60 days after the last dose was added (subsequent Protocol Versions increased doses of MEDI-551 above 12 mg/kg).
    02 May 2012
    Sections throughout the protocol were modified to note discontinuation of enrollment of MM participants. The expansion phase was to enrol approximately 60 participants: 20 participants each with FL, CLL (including small lymphocytic lymphoma [SLL]), or DLBCL. All eligibility criteria and evaluations pertaining to participants with MM were removed. Inclusion criterion number 3 was modified to state that participants with a diagnosis of CLL (including SLL), DLBCL, or FL are included and that SLL, DLBCL, and FL must be histologically confirmed. Inclusion criterion number 7 was revised to specify that permitted prior radiation therapy must have occurred at least 6 weeks before the first dose of MEDI-551. Inclusion criteria number 10 was changed to provide different hematological criteria for CLL participants with BM involvement. Inclusion criterion number 11 was changed to modify the definition of adequate organ function. IgE testing was removed.
    15 Jul 2013
    Text was added to specify that study completion would be after the deaths of 50% of all planned participants or the date the sponsor stops the study. Inclusion criterion number 5 had the term SLL removed.
    07 Oct 2013
    Primary, secondary, and exploratory objectives and endpoints were added for Arms B and C. Inclusion criteria numbers 3 to 6, and 10 were revised to reflect the participants to be included in Arms B and C. Exclusion criterion number 10 was modified to indicate that it only applied to Arm A. A sentence was added to indicate that the schedule of study procedures for Arms A, B, and C are presented in separate subsections. The schedule of study procedures and by-visit descriptions of procedures were added for Arm B and Arm C. The Per-protocol population was removed, and the statistical analysis for efficacy, safety and sample size were all updated to include the assessments for Arms A, B and C.
    21 Mar 2014
    Primary, secondary, and exploratory objectives and endpoints were added for Arm D. Inclusion criteria numbers 3, 5, 6 and 10 were revised. Inclusion criterion number 4 was revised indicating fresh tumor biopsy was optional and applicable to Arm D. Exclusion criteria numbers 4 and 5 were revised to reflect a washout period of 28 days or 5 half-lives instead of 6 weeks. Exclusion criteria number 7 was revised indicating “live or attenuated” vaccines. Exclusion criterion number 9 was removed. Exclusion criteria numbers 18 and 20 were revised for clarification. Schedule of study procedures and by-visit descriptions of procedures were added for Arm D. In addition, schedule of study procedures and by-visit descriptions of procedures for Arms B and C were updated to include Karnofsky performance status assessment and BM biopsy with minimal residual disease analysis. Statistical analysis for efficacy, safety and sample size were all updated to include assessments for Arm D.
    27 Jan 2015
    Language was added where relevant to describe the dosing schedule for participnats in Arm B receiving 24 or 48 mg/kg dose levels of MEDI-551. The initial doses were to be administered over 2 days on Day 1 and Day 2 in Cycle 1. Exclusion criterion number 12 was modified. Exclusion criterion number 22 was added.
    01 Jun 2017
    Key safety assessments relevant to MEDI-551 were retained. Vital signs were to be evaluated pre-dose and at end of infusion only. Exploratory evaluations were removed. Disease evaluations were to be performed at regular intervals to determine whether MEDI-551 was continuing to provide clinical benefit. Study completion was updated to be defined as the date of the last protocol-specified visit for the last participants in the study.

    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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