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    Clinical Trial Results:
    A 12-month randomized, multiple dose, open-label, study evaluating safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD) and efficacy of an anti-CD40 monoclonal antibody, CFZ533, in combination with mycophenolate mofetil (MMF) and corticosteroids (CS), with and without tacrolimus (Tac), in de novo renal transplant recipients

    Summary
    EudraCT number
    		 2015-000925-36
    Trial protocol
    		 DE   NL   ES  
    Global end of trial date
    29 Nov 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 Dec 2018
    First version publication date
    12 Dec 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CCFZ533X2201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02217410
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.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
    29 Nov 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Nov 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the safety, tolerability and PK of multiple IV and SC doses of CFZ533 in combination with MMF, CS, and Tac (standard exposure) in de novo renal transplant patients over the treatment and follow-up period.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Feb 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 19
    Country: Number of subjects enrolled
    Netherlands: 11
    Country: Number of subjects enrolled
    Germany: 22
    Country: Number of subjects enrolled
    Brazil: 7
    Worldwide total number of subjects
    59
    EEA total number of subjects
    33
    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)
    47
    From 65 to 84 years
    12
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 In Part 1, patients were enrolled into Arm 1. In Part 2, patients were randomized (2:1) to Arms 2A and 2B.

    Pre-assignment
    Screening details
    		 Study Part 1 focused on measuring the multiple-dose safety, tolerability, PK, and PD of both IV and SC CFZ533 when administered with the SoC treatment regimen. Study Part 2 investigated efficacy, safety, tolerability, PK and PD of CFZ533 in the absence of Tac.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 CFZ533 + TAC + MMF (part 1)
    Arm description
    		 CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).
    Arm type
    		 Experimental

    Investigational medicinal product name
    CFZ533
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for cutaneous solution, Concentrate for solution for injection/infusion
    Routes of administration
    Intravascular use , Intravenous use
    Dosage and administration details
    CFZ533 was supplied as 150 mg/mL lyophilized open-label bulk medication requiring reconstitution. 3 mg/kg CFZ533 was administered IV pre-transplant or intra-operatively on Day 1 and subsequently CFZ533 SC was administered for a period of 3 months. MMF (CellCept® or Generics) was taken as 2 tablets of 500 mg or 4 capsules of 250 mg BID (2 g/day) or as per local practice. For patients who remained intubated >24 hours posttransplant and/or whom were otherwise unable to swallow oral medication, IV MMF was substituted until oral conversion was possible. The first dose of MMF was administered within 24 hours after graft reperfusion of the allograft or according to local practice.

    Arm title
    		 CFZ533 + MMF (part 2)
    Arm description
    		 CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction
    Arm type
    		 Experimental

    Investigational medicinal product name
    CFZ533
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for cutaneous solution, Concentrate for solution for injection/infusion
    Routes of administration
    Intravascular use , Intravenous use
    Dosage and administration details
    CFZ533 was supplied as 150 mg/mL lyophilized open-label bulk medication requiring reconstitution. CFZ533 150 mg/mL concentrate for solution for infusion/ solution for injection (liquid in vial) was introduced in Part 2. 10 mg/kg CFZ533 was administered IV pre-transplant or intra-operatively on Day 1 and subsequently CFZ533 IV was administered for 12 months. MMF (CellCept® or Generics) was taken as 2 tablets of 500 mg or 4 capsules of 250 mg BID (2 g/day) or as per local practice. For patients who remained intubated >24 hours post-transplant and/or whom were otherwise unable to swallow oral medication, IV MMF was substituted until oral conversion was possible. The first dose of MMF was administered within 24 hours after graft reperfusion of the allograft or according to local practice.

    Arm title
    		 Tac + MMF (part 2)
    Arm description
    		 Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction]
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Either Prograf® or Generics
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Tac was administered as taken by mouth (PO) capsules twice a day (BID) and adjusted to maintain within the target ranges of 4-11 ng/mL. Tac was initiated within 24 hours after reperfusion of the graft. MMF (CellCept® or Generics) was taken as 2 tablets of 500 mg or 4 capsules of 250 mg BID (2 g/day) or as per local practice. For patients who remained intubated >24 hours post-transplant and/or whom were otherwise unable to swallow oral medication, IV MMF was substituted until oral conversion was possible. The first dose of MMF was administered within 24 hours after graft reperfusion of the allograft or according to local practice.

    Number of subjects in period 1
    		CFZ533 + TAC + MMF (part 1) CFZ533 + MMF (part 2) Tac + MMF (part 2)
    Started
    7
    34
    18
    Completed
    6
    30
    13
    Not completed
    1
    4
    5
         Physician decision
    1
    3
    -
         Graft Loss
    -
    -
    2
         Consent withdrawn by subject
    -
    -
    2
         Lost to follow-up
    -
    -
    1
         Lack of efficacy
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    CFZ533 + TAC + MMF (part 1)
    Reporting group description
    		 CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).

    Reporting group title
    CFZ533 + MMF (part 2)
    Reporting group description
    		 CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction

    Reporting group title
    Tac + MMF (part 2)
    Reporting group description
    		 Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction]

    Reporting group values
    		 CFZ533 + TAC + MMF (part 1) CFZ533 + MMF (part 2) Tac + MMF (part 2) Total
    Number of subjects
    		 7 34 18 59
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 6 30 11 47
        From 65-84 years
    		 1 4 7 12
        85 years and over
    		 0 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 48.1 ( 9.30 ) 49.0 ( 15.79 ) 53.4 ( 18.01 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 3 8 6 17
        Male
    		 4 26 12 42
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 1 0 1
        Not Hispanic or Latino
    		 2 20 9 31
        Unknown or Not Reported
    		 5 13 9 27

    End points

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    End points reporting groups
    Reporting group title
    CFZ533 + TAC + MMF (part 1)
    Reporting group description
    		 CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).

    Reporting group title
    CFZ533 + MMF (part 2)
    Reporting group description
    		 CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction

    Reporting group title
    Tac + MMF (part 2)
    Reporting group description
    		 Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction]

    Subject analysis set title
    sCD40 (part I)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).

    Subject analysis set title
    sCD154
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).

    Subject analysis set title
    Free CD40 on whole blood B ceels
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction

    Subject analysis set title
    Total CD40 on whole blood B cells
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction

    Primary: Mean Cmax Pharmacokinetic Parameter- Part I

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    End point title
    		 Mean Cmax Pharmacokinetic Parameter- Part I [1] [2]
    End point description
    Pharmacokinetics as defined by the systemic concentrations and Cmax of certain immunosuppressant medications used in Part I
    End point type
    Primary
    End point timeframe
    Day 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: descriptive statistics
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: descriptive statistics
    End point values
    		 CFZ533 + TAC + MMF (part 1)
    Number of subjects analysed
    7
    Units: ug/mL
        arithmetic mean (standard deviation)
    66.3 ( 12.3 )
    No statistical analyses for this end point

    Primary: Mean Tmax Pharmacokinetic Parameter - Part I

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    End point title
    		 Mean Tmax Pharmacokinetic Parameter - Part I [3] [4]
    End point description
    Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.
    End point type
    Primary
    End point timeframe
    Day 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: descriptive statistics
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: descriptive statistics
    End point values
    		 CFZ533 + TAC + MMF (part 1)
    Number of subjects analysed
    7
    Units: day
        median (full range (min-max))
    0.237 (0 to 1.02)
    No statistical analyses for this end point

    Primary: Mean AUClast Pharmacokinetic Parameter - Part I

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    End point title
    		 Mean AUClast Pharmacokinetic Parameter - Part I [5] [6]
    End point description
    Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.
    End point type
    Primary
    End point timeframe
    Day 1
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: descriptive statistics
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: descriptive statistics
    End point values
    		 CFZ533 + TAC + MMF (part 1)
    Number of subjects analysed
    7
    Units: day*ug/mL
        arithmetic mean (standard deviation)
    367 ( 52.0 )
    No statistical analyses for this end point

    Primary: Efficacy as defined by the frequency and severity (Banff classification) of treated biopsy proven acute rejection (tBPAR) adjudicated data - Part II

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    End point title
    		 Efficacy as defined by the frequency and severity (Banff classification) of treated biopsy proven acute rejection (tBPAR) adjudicated data - Part II [7]
    End point description
    To assess the activity of the investigational arm as compared to the standard of care control arm in de novo renal transplant patients as measured by the frequency and severity of tBPAR as measured on the Banff classification scale. An adjudication was performed on all on cause renal biopsies by an independent expert committee blinded to therapy.
    End point type
    Primary
    End point timeframe
    3, 6, 9, and 12 months
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: descriptive statistics
    End point values
    		 CFZ533 + MMF (part 2) Tac + MMF (part 2)
    Number of subjects analysed
    33
    18
    Units: events
        Month 3|
    6
    2
        Month 6|
    7
    3
        Month 9|
    7
    3
        Month 12|
    7
    3
    Statistical analysis title
    		 Frequency and severity of tBPAR-adjudicated data
    Statistical analysis description
    Banff classification
    Comparison groups
    CFZ533 + MMF (part 2) v Tac + MMF (part 2)
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8976
    Method
    		 Bayesian posterior probability
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.095
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.067
         upper limit
    		 0.263
    Statistical analysis title
    		 Frequency and severity of tBPAR-adjudicated data
    Statistical analysis description
    Banff classification
    Comparison groups
    CFZ533 + MMF (part 2) v Tac + MMF (part 2)
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8836
    Method
    		 Bayesian posterior probability
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.093
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.084
         upper limit
    		 0.271
    Statistical analysis title
    		 Frequency and severity of tBPAR-adjudicated data
    Statistical analysis description
    Banff classification
    Comparison groups
    CFZ533 + MMF (part 2) v Tac + MMF (part 2)
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8822
    Method
    		 Bayesian posterior probability
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.093
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.085
         upper limit
    		 0.272
    Statistical analysis title
    		 Frequency and severity of tBPAR-adjudicated data
    Statistical analysis description
    Banff classification
    Comparison groups
    CFZ533 + MMF (part 2) v Tac + MMF (part 2)
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8821
    Method
    		 Bayesian posterior probability
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.093
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.087
         upper limit
    		 0.273

    Secondary: Total soluble CD40 and total soluble CD154 concentrations in plasma - Part 1

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    End point title
    		 Total soluble CD40 and total soluble CD154 concentrations in plasma - Part 1
    End point description
    To quantify the change from baseline and recovery of peripheral blood total soluble CD40 and total soluble CD154
    End point type
    Secondary
    End point timeframe
    Baseline to end of study (Day 1, Day 29, Day 337)
    End point values
    		 sCD40 (part I) sCD154
    Number of subjects analysed
    7
    7
    Units: ng/ml
    arithmetic mean (standard deviation)
        Baseline|
    4.03 ( 4.08 )
    0.125 ( 0.007 )
        Day 1|
    8.86 ( 0.0585 )
    0.0585 ( 0.0711 )
        Day 2|
    16.7 ( 4.51 )
    0.139 ( 0.193 )
        Day 3|
    24.8 ( 4.47 )
    0.157 ( 0.235 )
        Day 4|
    31.3 ( 6.34 )
    0.241 ( 0.418 )
        Day 8|
    54.0 ( 11.2 )
    0.399 ( 0.636 )
        Day 15|
    84.1 ( 13.8 )
    0.0879 ( 0.139 )
        Day 22|
    102 ( 13.9 )
    0.0500 ( 0.132 )
        Day 29|
    120 ( 15.7 )
    0.225 ( 0.504 )
        Day 36|
    128 ( 19.2 )
    0.116 ( 0.2 )
        Day 43|
    145 ( 25.6 )
    0.0193 ( 0.0474 )
        Day 50|
    156 ( 6.35 )
    0.0478 ( 0.0687 )
        Day 57|
    161 ( 21.2 )
    0 ( 0 )
        Day 64|
    163 ( 24.2 )
    0.0316 ( 0.0492 )
        Day 71|
    156 ( 19.2 )
    0.0148 ( 0.0363 )
        Day 85|
    168 ( 21.4 )
    0.0139 ( 0.0340 )
        Day 99|
    155 ( 23.3 )
    0 ( 0 )
        Day 113|
    85.7 ( 47.9 )
    0.0668 ( 0.164 )
        Day 127|
    12.2 ( 15.7 )
    0.0488 ( 0.0697 )
        EoS|
    0.918 ( 0.330 )
    0.0184 ( 0.0411 )
    No statistical analyses for this end point

    Secondary: Free CD40 and total CD40 on B cells - Part II

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    End point title
    		 Free CD40 and total CD40 on B cells - Part II
    End point description
    The magnitude and duration of peripheral blood CD40 occupancy. MESF: molecules of equivalent soluble fluorochrome
    End point type
    Secondary
    End point timeframe
    Baseline to end of study (Day 1/predose)
    End point values
    		 Free CD40 on whole blood B ceels Total CD40 on whole blood B cells
    Number of subjects analysed
    26
    29
    Units: MESF
    arithmetic mean (standard deviation)
        CFZ553 + MMF (Baseline)|
    30836.00 ( 13648.69 )
    12778.80 ( 7873.76 )
        CFZ553 + MMF (D1 - 6h post dose)|
    1623.81 ( 1359.85 )
    13806.90 ( 7185.66 )
        CFZ553 + MMF (D15)|
    799.62 ( 762.38 )
    15160.38 ( 7398.57 )
        CFZ553 + MMF (D 29)|
    817.63 ( 1540.16 )
    13299.60 ( 6330.89 )
        CFZ553 + MMF (D 57)|
    597.13 ( 523.55 )
    12234.38 ( 6943.13 )
        CFZ553 + MMF (D 85)|
    635.47 ( 614.68 )
    9330.86 ( 8484.46 )
        CFZ553 + MMF (D 197)|
    3699.0 ( 7298.98 )
    2820.72 ( 2347.11 )
        CFZ553 + MMF (253)|
    2667.38 ( 6146.86 )
    1427.14 ( 740.48 )
        CFZ553 + MMF (EoS)|
    176.17 ( 266.82 )
    1069.67 ( 809.12 )
        Tac + MMF (Baseline)|
    31508.33 ( 12759.49 )
    14581.43 ( 9342.79 )
        Tac + MMF (D1 - 6h post dose)|
    26437.65 ( 11930.50 )
    13715.00 ( 8293.33 )
        Tac + MMF (D15)|
    24441.67 ( 9125.93 )
    13707.14 ( 6770.14 )
        Tac + MMF (D29)|
    27840.00 ( 12106.72 )
    12698.75 ( 6002.96 )
        Tac + MMF (D57)|
    27994.29 ( 12004.57 )
    12583.85 ( 6210.07 )
        Tac + MMF (D85)|
    25044.00 ( 10896.65 )
    8701.54 ( 4183.00 )
        Tac + MMF (D197)|
    21360.00 ( 3155.67 )
    2067.60 ( 1617.28 )
        Tac + MMF (D253)|
    15752.75 ( 7145.32 )
    1750.50 ( 1005.84 )
        Tac + MMF (EoS)|
    21200.00 ( 4407.95 )
    6276.17 ( 11271.20 )
    No statistical analyses for this end point

    Secondary: Anti-CFZ533 antibodies - Part I

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    End point title
    		 Anti-CFZ533 antibodies - Part I [8]
    End point description
    To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies
    End point type
    Secondary
    End point timeframe
    Baseline to end of study
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: descriptive statistics
    End point values
    		 CFZ533 + TAC + MMF (part 1)
    Number of subjects analysed
    7
    Units: anti-CFZ533 antibodies
    0
    No statistical analyses for this end point

    Secondary: Anti-CFZ533 antibodies - Part II

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    End point title
    		 Anti-CFZ533 antibodies - Part II [9]
    End point description
    To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies
    End point type
    Secondary
    End point timeframe
    Baseline to end of study (screening, baseline, Day 141, Day 225, Day 309, Study Completion)
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: descriptive statistics
    End point values
    		 CFZ533 + MMF (part 2) Tac + MMF (part 2)
    Number of subjects analysed
    34
    18
    Units: anti-CFZ533 antibodies
        Screening|
    0
    0
        Baseline|
    0
    0
        Day 141|
    0
    0
        Day 225|
    0
    0
        Day 309|
    0
    0
        Study Completion|
    0
    0
    No statistical analyses for this end point

    Secondary: eGFR - Part II

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    End point title
    		 eGFR - Part II [10]
    End point description
    Renal function as assessed by MDRD (Modification of Diet in Renal Disease) formula. eGFR: Estimated glomerular filtration rate
    End point type
    Secondary
    End point timeframe
    Day 1, Day 29, Day 337,
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: descriptive statistics
    End point values
    		 CFZ533 + MMF (part 2) Tac + MMF (part 2)
    Number of subjects analysed
    32
    18
    Units: ml/min
    arithmetic mean (confidence interval 90%)
        Day 1|
    9.8 (8.3 to 11.3)
    9.7 (7.7 to 11.8)
        Day 29|
    55.6 (50.4 to 60.7)
    44.3 (37.2 to 51.4)
        Day 337|
    58.2 (52.2 to 64.2)
    44.2 (36.1 to 52.3)
    No statistical analyses for this end point

    Secondary: CFZ533 plasma PK concentrations - Part II

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    End point title
    		 CFZ533 plasma PK concentrations - Part II [11]
    End point description
    Quantify the systemic concentrations of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods. A full pharmacokinetic analysis can be performed on the concentration-time data to evaluate the impact of renal transplantation on the various medications used in the treatment regimen.
    End point type
    Secondary
    End point timeframe
    throughout study period (day 1 to day 336)
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: descriptive statistics
    End point values
    		 CFZ533 + MMF (part 2)
    Number of subjects analysed
    32
    Units: ug/mL
    arithmetic mean (standard deviation)
        Day 1|
    150 ( 42.8 )
        Day 2|
    148 ( 77.5 )
        Day 3|
    277 ( 91.3 )
        Day 14|
    262 ( 59.8 )
        Day 28|
    258 ( 52.8 )
        Day 56|
    306 ( 61.0 )
        Day 84|
    247 ( 58.2 )
        Day 112|
    211 ( 51.8 )
        Day 140|
    178 ( 54.9 )
        Day 168|
    157 ( 57.4 )
        Day 196|
    148 ( 53.1 )
        Day 224|
    147 ( 53.8 )
        Day 252|
    151 ( 35.2 )
        Day 280|
    160 ( 87.7 )
        Day 308|
    132 ( 42.5 )
        Day 336|
    156 ( 85.2 )
        End of study|
    133 ( 57.8 )
    No statistical analyses for this end point

    Secondary: Total sCD40 plasma concentrations - Part II

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    End point title
    		 Total sCD40 plasma concentrations - Part II [12]
    End point description
    To quantify the change from baseline and recovery of peripheral blood total soluble CD40
    End point type
    Secondary
    End point timeframe
    12 months
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: descriptive statistics
    End point values
    		 CFZ533 + MMF (part 2) Tac + MMF (part 2)
    Number of subjects analysed
    32
    17
    Units: ng/mL
    arithmetic mean (standard deviation)
        Baseline|
    3.02 ( 2.44 )
    3.67 ( 2.15 )
        Day 1|
    6.95 ( 4.29 )
    1.16 ( 1.15 )
        Day 4|
    24.6 ( 11.0 )
    1.16 ( 1.15 )
        Day 15|
    69.6 ( 21.5 )
    0.869 ( 1.55 )
        Day 29|
    101 ( 18.9 )
    0.362 ( 0.0746 )
        Day 57|
    140 ( 17.4 )
    0.438 ( 0.316 )
        Day 85|
    189 ( 76.4 )
    0.429 ( 0.324 )
        Day 113|
    215 ( 75.5 )
    0.391 ( 0.129 )
        Day 141|
    237 ( 93.1 )
    0.453 ( 0.271 )
        Day 169|
    238 ( 80.3 )
    0.537 ( 0.215 )
        Day 197|
    253 ( 81.3 )
    0.423 ( 0.0908 )
        Day 225|
    258 ( 77.7 )
    0.452 ( 0.119 )
        Day 253|
    236 ( 36.5 )
    0.457 ( 0.0800 )
        Day 281|
    273 ( 71.3 )
    0.455 ( 0.0789 )
        Day 309|
    286 ( 66.0 )
    0.454 ( 0.0957 )
        Day 337|
    298 ( 57.4 )
    0.411 ( 0.0581 )
        End of Study|
    303 ( 59.7 )
    0.959 ( 1.88 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    CFZ533 + TAC + MMF (part 1)
    Reporting group description
    		 CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentrationcontrolled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS)

    Reporting group title
    CFZ533 + MMF (part 2)
    Reporting group description
    		 CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction

    Reporting group title
    Tac + MMF (part 2)
    Reporting group description
    		 Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction]

    Reporting group title
    Total
    Reporting group description
    		 Total

    Serious adverse events
    		 CFZ533 + TAC + MMF (part 1) CFZ533 + MMF (part 2) Tac + MMF (part 2) Total
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 7 (57.14%)
    21 / 34 (61.76%)
    12 / 18 (66.67%)
    37 / 59 (62.71%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basosquamous carcinoma
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphocele
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic venous thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Kidney transplant rejection
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 34 (14.71%)
    1 / 18 (5.56%)
    6 / 59 (10.17%)
         occurrences causally related to treatment / all
    0 / 0
    5 / 6
    0 / 1
    5 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transplant rejection
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Amylase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Arteriovenous fistula aneurysm
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Complications of transplanted kidney
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 34 (2.94%)
    2 / 18 (11.11%)
    4 / 59 (6.78%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delayed graft function
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Graft loss
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    2 / 18 (11.11%)
    2 / 59 (3.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incarcerated incisional hernia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transplant dysfunction
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transplant failure
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tricuspid valve incompetence
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Photophobia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vision blurred
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    3 / 59 (5.08%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    1 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea haemorrhagic
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mouth ulceration
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    3 / 59 (5.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal tubular necrosis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 34 (8.82%)
    2 / 18 (11.11%)
    5 / 59 (8.47%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    1 / 2
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterobacter bacteraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis C
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Polyomavirus-associated nephropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 34 (11.76%)
    1 / 18 (5.56%)
    5 / 59 (8.47%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 4
    0 / 1
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    3 / 18 (16.67%)
    5 / 59 (8.47%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    3 / 4
    4 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cyst infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    2 / 18 (11.11%)
    2 / 59 (3.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 CFZ533 + TAC + MMF (part 1) CFZ533 + MMF (part 2) Tac + MMF (part 2) Total
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 7 (100.00%)
    33 / 34 (97.06%)
    18 / 18 (100.00%)
    58 / 59 (98.31%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Haematoma
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    0
    2
    0
    2
    Hot flush
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    0
    2
    0
    2
    Hypertension
         subjects affected / exposed
    1 / 7 (14.29%)
    13 / 34 (38.24%)
    6 / 18 (33.33%)
    20 / 59 (33.90%)
         occurrences all number
    1
    13
    7
    21
    Hypotension
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    3 / 18 (16.67%)
    5 / 59 (8.47%)
         occurrences all number
    0
    2
    3
    5
    Lymphocele
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    1
    2
    Orthostatic hypotension
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    1
    Poor venous access
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    0
    2
    0
    2
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Catheter site pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    2 / 18 (11.11%)
    2 / 59 (3.39%)
         occurrences all number
    0
    0
    2
    2
    Chills
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 34 (8.82%)
    0 / 18 (0.00%)
    3 / 59 (5.08%)
         occurrences all number
    0
    3
    0
    3
    Cyst
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Fatigue
         subjects affected / exposed
    1 / 7 (14.29%)
    5 / 34 (14.71%)
    5 / 18 (27.78%)
    11 / 59 (18.64%)
         occurrences all number
    1
    5
    5
    11
    Generalised oedema
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    1
    Impaired healing
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    1 / 18 (5.56%)
    3 / 59 (5.08%)
         occurrences all number
    0
    2
    1
    3
    Influenza like illness
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    1
    Infusion site swelling
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Malaise
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Oedema peripheral
         subjects affected / exposed
    2 / 7 (28.57%)
    7 / 34 (20.59%)
    6 / 18 (33.33%)
    15 / 59 (25.42%)
         occurrences all number
    3
    11
    8
    22
    Pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    1
    Peripheral swelling
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Pyrexia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    2
    3
    Secretion discharge
         subjects affected / exposed
    3 / 7 (42.86%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    3 / 59 (5.08%)
         occurrences all number
    3
    0
    0
    3
    Swelling
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Kidney transplant rejection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Dysmenorrhoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    2 / 18 (11.11%)
    2 / 59 (3.39%)
         occurrences all number
    0
    0
    2
    2
    Erectile dysfunction
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Menorrhagia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Penile oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Penile pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Prostatomegaly
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Scrotal swelling
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Vulvovaginal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 7 (0.00%)
    10 / 34 (29.41%)
    2 / 18 (11.11%)
    12 / 59 (20.34%)
         occurrences all number
    0
    13
    2
    15
    Dyspnoea
         subjects affected / exposed
    3 / 7 (42.86%)
    2 / 34 (5.88%)
    3 / 18 (16.67%)
    8 / 59 (13.56%)
         occurrences all number
    3
    3
    3
    9
    Dyspnoea exertional
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Lung infiltration
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Nasal congestion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 34 (8.82%)
    0 / 18 (0.00%)
    3 / 59 (5.08%)
         occurrences all number
    0
    3
    0
    3
    Pleural effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Productive cough
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    1
    1
    0
    2
    Respiratory distress
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Wheezing
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    1
    1
    0
    2
    Delirium
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Insomnia
         subjects affected / exposed
    1 / 7 (14.29%)
    11 / 34 (32.35%)
    5 / 18 (27.78%)
    17 / 59 (28.81%)
         occurrences all number
    1
    12
    5
    18
    Mood swings
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Phonophobia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    1
    Restlessness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Amylase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 34 (8.82%)
    1 / 18 (5.56%)
    4 / 59 (6.78%)
         occurrences all number
    0
    3
    1
    4
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    1
    2
    Blood creatinine increased
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 34 (8.82%)
    1 / 18 (5.56%)
    4 / 59 (6.78%)
         occurrences all number
    0
    3
    1
    4
    Blood glucose increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Blood phosphorus decreased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    1
    Blood phosphorus increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    C-reactive protein increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Cardiac murmur
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    1
    Cytomegalovirus test positive
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Drug level decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Electrocardiogram ST segment abnormal
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    1
    Electrocardiogram T wave abnormal
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    1 / 18 (5.56%)
    3 / 59 (5.08%)
         occurrences all number
    0
    2
    1
    3
    Haemoglobin decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Heart rate irregular
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Lipase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    0
    2
    0
    2
    Polyomavirus test positive
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Vitamin D decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Weight decreased
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    1
    1
    0
    2
    Weight increased
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    1 / 18 (5.56%)
    3 / 59 (5.08%)
         occurrences all number
    0
    2
    1
    3
    White blood cell count decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    White blood cell count increased
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 34 (8.82%)
    0 / 18 (0.00%)
    3 / 59 (5.08%)
         occurrences all number
    0
    3
    0
    3
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Arterial injury
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Arteriovenous fistula site complication
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Arthropod bite
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Complications of transplant surgery
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    1
    Complications of transplanted kidney
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 34 (8.82%)
    2 / 18 (11.11%)
    5 / 59 (8.47%)
         occurrences all number
    0
    6
    2
    8
    Delayed graft function
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 34 (8.82%)
    3 / 18 (16.67%)
    6 / 59 (10.17%)
         occurrences all number
    0
    3
    3
    6
    Fall
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Graft complication
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    1
    2
    Incision site complication
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    1
    2
    Incision site erythema
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    1
    Incision site haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Incision site pain
         subjects affected / exposed
    3 / 7 (42.86%)
    6 / 34 (17.65%)
    2 / 18 (11.11%)
    11 / 59 (18.64%)
         occurrences all number
    3
    6
    2
    11
    Incisional hernia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Joint injury
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Ligament sprain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Lip injury
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    2
    0
    2
    Post procedural complication
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Post procedural swelling
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Postoperative wound complication
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 34 (14.71%)
    1 / 18 (5.56%)
    6 / 59 (10.17%)
         occurrences all number
    0
    6
    1
    7
    Procedural pain
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 34 (8.82%)
    6 / 18 (33.33%)
    9 / 59 (15.25%)
         occurrences all number
    0
    3
    8
    11
    Radius fracture
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    1
    Seroma
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Transplant dysfunction
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    3 / 18 (16.67%)
    5 / 59 (8.47%)
         occurrences all number
    0
    2
    3
    5
    Wound complication
         subjects affected / exposed
    0 / 7 (0.00%)
    11 / 34 (32.35%)
    8 / 18 (44.44%)
    19 / 59 (32.20%)
         occurrences all number
    0
    11
    8
    19
    Wound dehiscence
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Wound haematoma
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    1
    2
    Congenital, familial and genetic disorders
    Hydrocele
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    1
    2
    Arrhythmia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    1 / 18 (5.56%)
    3 / 59 (5.08%)
         occurrences all number
    0
    2
    1
    3
    Atrial fibrillation
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    1 / 18 (5.56%)
    3 / 59 (5.08%)
         occurrences all number
    0
    2
    2
    4
    Bradycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Extrasystoles
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Myocardial infarction
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Palpitations
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Sinus tachycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    2
    0
    2
    Tachycardia
         subjects affected / exposed
    2 / 7 (28.57%)
    4 / 34 (11.76%)
    1 / 18 (5.56%)
    7 / 59 (11.86%)
         occurrences all number
    2
    4
    1
    7
    Tricuspid valve incompetence
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Burning sensation
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Dizziness
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 34 (5.88%)
    3 / 18 (16.67%)
    6 / 59 (10.17%)
         occurrences all number
    1
    2
    3
    6
    Dizziness postural
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    1
    0
    1
    2
    Headache
         subjects affected / exposed
    1 / 7 (14.29%)
    6 / 34 (17.65%)
    4 / 18 (22.22%)
    11 / 59 (18.64%)
         occurrences all number
    1
    7
    4
    12
    Hypoaesthesia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Migraine
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Paraesthesia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    1
    0
    1
    2
    Peroneal nerve palsy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Polyneuropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Tremor
         subjects affected / exposed
    2 / 7 (28.57%)
    3 / 34 (8.82%)
    6 / 18 (33.33%)
    11 / 59 (18.64%)
         occurrences all number
    2
    3
    8
    13
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 34 (8.82%)
    4 / 18 (22.22%)
    8 / 59 (13.56%)
         occurrences all number
    1
    3
    4
    8
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    1
    2
    Leukocytosis
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 34 (8.82%)
    2 / 18 (11.11%)
    6 / 59 (10.17%)
         occurrences all number
    1
    4
    2
    7
    Leukopenia
         subjects affected / exposed
    1 / 7 (14.29%)
    13 / 34 (38.24%)
    3 / 18 (16.67%)
    17 / 59 (28.81%)
         occurrences all number
    1
    18
    3
    22
    Lymphopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    0
    2
    0
    2
    Microcytic anaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Nephrogenic anaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Neutropenia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    2 / 18 (11.11%)
    3 / 59 (5.08%)
         occurrences all number
    0
    1
    2
    3
    Normocytic anaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Pancytopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Polycythaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Thrombocytopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Thrombocytosis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Ear and labyrinth disorders
    Ear discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Vertigo
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Eye disorders
    Chalazion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Dry eye
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Eye movement disorder
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    2
    0
    0
    2
    Ocular hyperaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Retinal vein occlusion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    1
    2
    Abdominal distension
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    1
    Abdominal pain
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 34 (8.82%)
    3 / 18 (16.67%)
    7 / 59 (11.86%)
         occurrences all number
    1
    3
    3
    7
    Abdominal pain lower
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    1
    2
    Abdominal pain upper
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 34 (14.71%)
    0 / 18 (0.00%)
    5 / 59 (8.47%)
         occurrences all number
    0
    6
    0
    6
    Anal fissure
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Aphthous ulcer
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    1
    1
    0
    2
    Colitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Constipation
         subjects affected / exposed
    1 / 7 (14.29%)
    14 / 34 (41.18%)
    8 / 18 (44.44%)
    23 / 59 (38.98%)
         occurrences all number
    1
    17
    8
    26
    Diarrhoea
         subjects affected / exposed
    2 / 7 (28.57%)
    8 / 34 (23.53%)
    10 / 18 (55.56%)
    20 / 59 (33.90%)
         occurrences all number
    2
    9
    15
    26
    Duodenogastric reflux
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Dyspepsia
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    4 / 59 (6.78%)
         occurrences all number
    3
    1
    1
    5
    Dysphagia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Flatulence
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    2 / 18 (11.11%)
    3 / 59 (5.08%)
         occurrences all number
    0
    1
    2
    3
    Gastric polyps
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Gastritis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Gastritis haemorrhagic
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Gingival pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Gingival recession
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Gingival swelling
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    2 / 18 (11.11%)
    2 / 59 (3.39%)
         occurrences all number
    0
    0
    2
    2
    Haemorrhoids
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    2 / 18 (11.11%)
    3 / 59 (5.08%)
         occurrences all number
    0
    1
    2
    3
    Ileus
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Inguinal hernia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    2
    0
    2
    Mouth ulceration
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    2
    0
    2
    Nausea
         subjects affected / exposed
    4 / 7 (57.14%)
    10 / 34 (29.41%)
    9 / 18 (50.00%)
    23 / 59 (38.98%)
         occurrences all number
    4
    10
    13
    27
    Odynophagia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Oesophagitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Paraesthesia oral
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    1
    1
    0
    2
    Stomatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    2 / 18 (11.11%)
    2 / 59 (3.39%)
         occurrences all number
    0
    0
    3
    3
    Tongue discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Vomiting
         subjects affected / exposed
    3 / 7 (42.86%)
    8 / 34 (23.53%)
    4 / 18 (22.22%)
    15 / 59 (25.42%)
         occurrences all number
    3
    8
    5
    16
    Hepatobiliary disorders
    Hepatic function abnormal
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Hepatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Hepatomegaly
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    1
    Alopecia
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 34 (5.88%)
    2 / 18 (11.11%)
    5 / 59 (8.47%)
         occurrences all number
    1
    2
    2
    5
    Decubitus ulcer
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Dermatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    0
    2
    0
    2
    Hyperhidrosis
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 34 (8.82%)
    0 / 18 (0.00%)
    3 / 59 (5.08%)
         occurrences all number
    0
    3
    0
    3
    Lipohypertrophy
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Night sweats
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    1 / 18 (5.56%)
    3 / 59 (5.08%)
         occurrences all number
    0
    2
    1
    3
    Pityriasis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Pruritus
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    2 / 18 (11.11%)
    3 / 59 (5.08%)
         occurrences all number
    0
    1
    2
    3
    Rash
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    3 / 18 (16.67%)
    3 / 59 (5.08%)
         occurrences all number
    0
    0
    3
    3
    Skin lesion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Urticaria
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Renal and urinary disorders
    Bladder pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Bladder spasm
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 34 (8.82%)
    0 / 18 (0.00%)
    3 / 59 (5.08%)
         occurrences all number
    0
    3
    0
    3
    Chronic kidney disease
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Dysuria
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    1
    1
    0
    2
    Haematuria
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    2 / 18 (11.11%)
    3 / 59 (5.08%)
         occurrences all number
    0
    1
    2
    3
    Leukocyturia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    1
    2
    Micturition urgency
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 34 (0.00%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    1
    Nocturia
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    1
    1
    0
    2
    Perinephric collection
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    0
    2
    0
    2
    Perinephric oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Polyuria
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 34 (14.71%)
    0 / 18 (0.00%)
    5 / 59 (8.47%)
         occurrences all number
    0
    5
    0
    5
    Proteinuria
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    1 / 18 (5.56%)
    3 / 59 (5.08%)
         occurrences all number
    0
    3
    2
    5
    Renal impairment
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    2 / 18 (11.11%)
    2 / 59 (3.39%)
         occurrences all number
    0
    0
    3
    3
    Renal tubular acidosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Renal tubular injury
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Renal tubular necrosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    2 / 18 (11.11%)
    2 / 59 (3.39%)
         occurrences all number
    0
    0
    2
    2
    Sterile pyuria
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Tubulointerstitial nephritis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Urethral pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Urinary incontinence
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    2 / 18 (11.11%)
    3 / 59 (5.08%)
         occurrences all number
    0
    1
    2
    3
    Urinary retention
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Urinary tract disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Urinary tract obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Endocrine disorders
    Hyperparathyroidism
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Hyperparathyroidism secondary
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    3 / 59 (5.08%)
         occurrences all number
    2
    0
    1
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    0
    2
    0
    2
    Back pain
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 34 (14.71%)
    1 / 18 (5.56%)
    6 / 59 (10.17%)
         occurrences all number
    0
    5
    1
    6
    Bursitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Flank pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Groin pain
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 34 (8.82%)
    1 / 18 (5.56%)
    5 / 59 (8.47%)
         occurrences all number
    1
    5
    2
    8
    Hypercreatinaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Joint effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Muscle spasms
         subjects affected / exposed
    1 / 7 (14.29%)
    6 / 34 (17.65%)
    1 / 18 (5.56%)
    8 / 59 (13.56%)
         occurrences all number
    1
    8
    1
    10
    Muscle twitching
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Muscular weakness
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Musculoskeletal discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Myalgia
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 34 (11.76%)
    0 / 18 (0.00%)
    4 / 59 (6.78%)
         occurrences all number
    0
    4
    0
    4
    Neck pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Osteochondrosis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    2 / 18 (11.11%)
    4 / 59 (6.78%)
         occurrences all number
    0
    3
    4
    7
    Pain in jaw
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    BK virus infection
         subjects affected / exposed
    3 / 7 (42.86%)
    10 / 34 (29.41%)
    6 / 18 (33.33%)
    19 / 59 (32.20%)
         occurrences all number
    3
    14
    7
    24
    Bronchitis
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 34 (11.76%)
    0 / 18 (0.00%)
    4 / 59 (6.78%)
         occurrences all number
    0
    4
    0
    4
    Conjunctivitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 7 (0.00%)
    6 / 34 (17.65%)
    2 / 18 (11.11%)
    8 / 59 (13.56%)
         occurrences all number
    0
    7
    2
    9
    Cytomegalovirus viraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Diarrhoea infectious
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    2
    0
    2
    Epstein-Barr virus infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Folliculitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Fungal skin infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    2 / 18 (11.11%)
    2 / 59 (3.39%)
         occurrences all number
    0
    0
    2
    2
    Gastroenteritis
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    0
    3
    0
    3
    Gastroenteritis Escherichia coli
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Gastroenteritis norovirus
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Gastroenteritis viral
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Gastrointestinal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    1
    2
    Herpes zoster
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    0
    3
    0
    3
    Human polyomavirus infection
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    0
    3
    0
    3
    Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    1
    2
    Influenza
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    1 / 18 (5.56%)
    3 / 59 (5.08%)
         occurrences all number
    0
    2
    1
    3
    Laryngitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Latent tuberculosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Lung infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Mucocutaneous candidiasis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Nasopharyngitis
         subjects affected / exposed
    1 / 7 (14.29%)
    10 / 34 (29.41%)
    4 / 18 (22.22%)
    15 / 59 (25.42%)
         occurrences all number
    1
    13
    5
    19
    Oral candidiasis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Oral herpes
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Oral infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Otitis media
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    2
    0
    2
    Pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    0
    2
    0
    2
    Polyomavirus-associated nephropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 34 (8.82%)
    1 / 18 (5.56%)
    4 / 59 (6.78%)
         occurrences all number
    0
    3
    2
    5
    Pyelonephritis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    1
    2
    Pyuria
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    1
    2
    Respiratory tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    0
    2
    0
    2
    Rhinitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Sinusitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Skin infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    2
    3
    Soft tissue infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Subcutaneous abscess
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Tinea versicolour
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Tooth infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Tracheobronchitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    0 / 18 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    0
    2
    0
    2
    Urinary tract infection
         subjects affected / exposed
    1 / 7 (14.29%)
    8 / 34 (23.53%)
    7 / 18 (38.89%)
    16 / 59 (27.12%)
         occurrences all number
    1
    9
    9
    19
    Urinary tract infection viral
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Viral infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Wound infection bacterial
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 34 (11.76%)
    1 / 18 (5.56%)
    5 / 59 (8.47%)
         occurrences all number
    0
    4
    1
    5
    Diabetes mellitus
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 34 (8.82%)
    3 / 18 (16.67%)
    6 / 59 (10.17%)
         occurrences all number
    0
    3
    3
    6
    Dyslipidaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Fluid overload
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    1 / 18 (5.56%)
    2 / 59 (3.39%)
         occurrences all number
    0
    1
    1
    2
    Folate deficiency
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Hypercalcaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 34 (5.88%)
    1 / 18 (5.56%)
    3 / 59 (5.08%)
         occurrences all number
    0
    2
    1
    3
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    2 / 18 (11.11%)
    3 / 59 (5.08%)
         occurrences all number
    0
    1
    2
    3
    Hyperglycaemia
         subjects affected / exposed
    3 / 7 (42.86%)
    4 / 34 (11.76%)
    4 / 18 (22.22%)
    11 / 59 (18.64%)
         occurrences all number
    3
    4
    4
    11
    Hyperkalaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    9 / 34 (26.47%)
    5 / 18 (27.78%)
    15 / 59 (25.42%)
         occurrences all number
    1
    14
    6
    21
    Hyperlipidaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 34 (5.88%)
    1 / 18 (5.56%)
    4 / 59 (6.78%)
         occurrences all number
    1
    2
    1
    4
    Hyperphosphataemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    1 / 18 (5.56%)
    1 / 59 (1.69%)
         occurrences all number
    0
    0
    1
    1
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Hyperuricaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 34 (11.76%)
    1 / 18 (5.56%)
    5 / 59 (8.47%)
         occurrences all number
    0
    4
    1
    5
    Hypervolaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 34 (0.00%)
    2 / 18 (11.11%)
    2 / 59 (3.39%)
         occurrences all number
    0
    0
    2
    2
    Hypocalcaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 34 (11.76%)
    1 / 18 (5.56%)
    5 / 59 (8.47%)
         occurrences all number
    0
    4
    1
    5
    Hypokalaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    6 / 34 (17.65%)
    5 / 18 (27.78%)
    12 / 59 (20.34%)
         occurrences all number
    1
    8
    5
    14
    Hypomagnesaemia
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 34 (0.00%)
    3 / 18 (16.67%)
    5 / 59 (8.47%)
         occurrences all number
    2
    0
    3
    5
    Hyponatraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 34 (8.82%)
    1 / 18 (5.56%)
    4 / 59 (6.78%)
         occurrences all number
    0
    3
    1
    4
    Hypophosphataemia
         subjects affected / exposed
    5 / 7 (71.43%)
    11 / 34 (32.35%)
    5 / 18 (27.78%)
    21 / 59 (35.59%)
         occurrences all number
    5
    12
    5
    22
    Increased appetite
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Magnesium deficiency
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    0 / 18 (0.00%)
    1 / 59 (1.69%)
         occurrences all number
    0
    1
    0
    1
    Metabolic acidosis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 34 (2.94%)
    2 / 18 (11.11%)
    3 / 59 (5.08%)
         occurrences all number
    0
    1
    2
    3
    Vitamin D deficiency
         subjects affected / exposed
    2 / 7 (28.57%)
    2 / 34 (5.88%)
    1 / 18 (5.56%)
    5 / 59 (8.47%)
         occurrences all number
    2
    2
    1
    5

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Jul 2015
    Removal of the 3 mg/kg CFZ533 SC arm (former treatment arm 2A) and introduction of a more frequent dosing regimen during the first 2 months in the 10 mg/kg CFZ533 intravenous (IV) arm in Part 2
    11 Apr 2016
    Introduction of a new CFZ533 presentation, a concentrate for solution for infusion/solution for injection (also referred to as liquid in vial in the protocol). Initially, CFZ533 was developed as a lyophilized powder for solution for infusion/injection requiring reconstitution with water for injection prior to infusion or injection.
    20 Sep 2017
    Introduced by the open-label design in Part 2, to centrally evaluate all biopsies taken for suspected rejection reactions and other kidney disease related events in an unbiased, standardized and blinded manner. The decision was taken not to pursue CFZ533 exposure-response profiling (Part 3) in the scope of the present study, but to open a separate study. Therefore, Part 3 is being removed from this study protocol and the protocol is adapted accordingly including adaptation of the statistical analysis section.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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