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    Clinical Trial Results:
    Multicenter, prospective, open-label, controlled, randomized, parallel groups study to evaluate the renal function of adult liver transplant recipients treated with two everolimus-based immunosuppressive regimens (tacrolimus withdrawal vs. minimization) until 12 months post-transplant, with a 6-months follow-up

    Summary
    EudraCT number
    		 2013-004325-91
    Trial protocol
    		 IT  
    Global end of trial date
    30 Sep 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Oct 2017
    First version publication date
    14 Oct 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CRAD001HIT34
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02115113
    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,
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
    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
    30 Sep 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Sep 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to compare, at Month 12 post-transplantation, renal function measured by estimated GFR (MDRD-4) between a tacrolimus withdrawal regimen and an early tacrolimus minimization regimen, both facilitated by everolimus introduction 4 weeks after liver transplantation.
    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
    28 Mar 2014
    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
    Italy: 78
    Worldwide total number of subjects
    78
    EEA total number of subjects
    78
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    69
    From 65 to 84 years
    9
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 This study included a run-in period and a randomization period. Run-in started 4 weeks post-transplant and ended at 5 months post randomization. After run-in, eligible participants were randomized in a 1:1 ratio to tacrolimus elimination or tacrolimus minimization.

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

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Group A (Tacrolimus Elimination Arm)
    Arm description
    		 At study start, participants received an Everolimus starting dose of 1.0 mg twice daily in combination with Tacrolimus. Tacrolimus was administered as per center practice. Thereafter, Everolimus doses were adjusted to achieve Everolimus C-0h blood trough levels between 3-8 ng/mL by week 1 after drug initiation until 5 months after transplant. At 5 months after transplant, Everolimus doses were adjusted to achieve C-0h blood trough level target ranges 6-10 ng/mL. Tacrolimus withdrawal was completed by 6 months after transplant.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Everolimus
    Investigational medicinal product code
    RAD001
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    At study start, participants received an Everolimus starting dose of 1.0 mg twice daily in combination with Tacrolimus. Thereafter, Everolimus doses were adjusted to achieve Everolimus C-0h blood trough levels between 3-8 ng/mL by week 1 after drug initiation until 5 months after transplant. At 5 months after transplant, Everolimus doses were adjusted to achieve C-0h blood trough level target ranges 6-10 ng/mL.

    Investigational medicinal product name
    Tacrolimus
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    At study start, participants received an Everolimus starting dose of 1.0 mg twice daily in combination with Tacrolimus. Tacrolimus was administered as per center practice. Tacrolimus withdrawal was completed by 6 months after transplant.

    Arm title
    		 Group B (Tacrolimus Minimization Arm)
    Arm description
    		 At study start, participants received an Everolimus starting dose of 1.0 mg twice daily in combination with Tacrolimus. Tacrolimus was administered as per center practice. Thereafter, Everolimus doses were adjusted to achieve Everolimus C-0h blood trough levels between 3-8 ng/mL by week 1 after drug initiation until 5 months after transplant. At 5 months after transplant, Everolimus doses continued to be adjusted to achieve C-0h blood trough level target ranges 3-8 ng/mL and Tacrolimus doses were adjusted to achieve C-0h blood trough level target ranges 3-5 ng/mL.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Everolimus
    Investigational medicinal product code
    RAD001
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    At study start, participants received an Everolimus starting dose of 1.0 mg twice daily in combination with Tacrolimus. Thereafter, Everolimus doses were adjusted to achieve Everolimus C-0h blood trough levels between 3-8 ng/mL by week 1 after drug initiation until 5 months after transplant. At 5 months after transplant, Everolimus doses continued to be adjusted to achieve C-0h blood trough level target ranges 3-8 ng/mL.

    Investigational medicinal product name
    Tacrolimus
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    At study start, participants received an Everolimus starting dose of 1.0 mg twice daily in combination with Tacrolimus. Tacrolimus was administered as per center practice. At 5 months after transplant, Tacorlimus doses were adjusted to achieve C-0h blood trough level target ranges 3-5 ng/mL.

    Arm title
    		 Total enrolled at run-in
    Arm description
    		 Participants, who had a successful liver transplantation and who had initiated a tacrolimus-based regimen and possible induction therapy or intravenous (i.v.) steroids according to local practice, were enrolled into the study 4 weeks (+/- 7 days) after transplantation and started on a everolimus-based regimen with tacrolimus minimization up until 5 months post transplantation.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tacrolimus
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    At study start, participants received an Everolimus starting dose of 1.0 mg twice daily in combination with Tacrolimus. Tacrolimus was administered as per center practice.

    Investigational medicinal product name
    Everolimus
    Investigational medicinal product code
    RAD001
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    At study start, participants received an Everolimus starting dose of 1.0 mg twice daily in combination with Tacrolimus. Thereafter, Everolimus doses were adjusted to achieve Everolimus C-0h blood trough levels between 3-8 ng/mL by week 1 after drug initiation until 5 months after transplant.

    Number of subjects in period 1
    		Group A (Tacrolimus Elimination Arm) Group B (Tacrolimus Minimization Arm) Total enrolled at run-in
    Started
    24
    26
    78
    Completed
    22
    26
    68
    Not completed
    2
    0
    10
         Consent withdrawn by subject
    -
    -
    3
         Death
    1
    -
    1
         Administrative problems
    -
    -
    1
         Lost to follow-up
    1
    -
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall period
    Reporting group description
    		 -

    Reporting group values
    		 Overall period Total
    Number of subjects
    		 78 78
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 69 69
        From 65-84 years
    		 9 9
        85 years and over
    		 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 53.73 ( 9.69 ) -
    Gender, Male/Female
    Units: Subjects
        Female
    		 19 19
        Male
    		 59 59

    End points

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    End points reporting groups
    Reporting group title
    Group A (Tacrolimus Elimination Arm)
    Reporting group description
    		 At study start, participants received an Everolimus starting dose of 1.0 mg twice daily in combination with Tacrolimus. Tacrolimus was administered as per center practice. Thereafter, Everolimus doses were adjusted to achieve Everolimus C-0h blood trough levels between 3-8 ng/mL by week 1 after drug initiation until 5 months after transplant. At 5 months after transplant, Everolimus doses were adjusted to achieve C-0h blood trough level target ranges 6-10 ng/mL. Tacrolimus withdrawal was completed by 6 months after transplant.

    Reporting group title
    Group B (Tacrolimus Minimization Arm)
    Reporting group description
    		 At study start, participants received an Everolimus starting dose of 1.0 mg twice daily in combination with Tacrolimus. Tacrolimus was administered as per center practice. Thereafter, Everolimus doses were adjusted to achieve Everolimus C-0h blood trough levels between 3-8 ng/mL by week 1 after drug initiation until 5 months after transplant. At 5 months after transplant, Everolimus doses continued to be adjusted to achieve C-0h blood trough level target ranges 3-8 ng/mL and Tacrolimus doses were adjusted to achieve C-0h blood trough level target ranges 3-5 ng/mL.

    Reporting group title
    Total enrolled at run-in
    Reporting group description
    		 Participants, who had a successful liver transplantation and who had initiated a tacrolimus-based regimen and possible induction therapy or intravenous (i.v.) steroids according to local practice, were enrolled into the study 4 weeks (+/- 7 days) after transplantation and started on a everolimus-based regimen with tacrolimus minimization up until 5 months post transplantation.

    Primary: Renal function assessed by estimated glomerular filtartion rate (eGFR)

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    End point title
    		 Renal function assessed by estimated glomerular filtartion rate (eGFR) [1]
    End point description
    Renal function was assessed by eGFR using the MDRD-4 formula at 12 months after transplant: eGFR = 186.3 * (serum creatinine)-1.154 * age-0.203 * (0.742 for women) * (1.21 if African American) where serum creatinine was in mg/dL and age in years.
    End point type
    Primary
    End point timeframe
    At 12 months post-transplant
    Notes
    [1] - 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: All arms do not apply to the statistical analysis.
    End point values
    		 Group A (Tacrolimus Elimination Arm) Group B (Tacrolimus Minimization Arm)
    Number of subjects analysed
    24
    26
    Units: mL/min/1.73m^2
        least squares mean (standard error)
    85.5 ( 3.97 )
    80.26 ( 3.87 )
    Statistical analysis title
    		 Renal function assessed by eGFR
    Comparison groups
    Group A (Tacrolimus Elimination Arm) v Group B (Tacrolimus Minimization Arm)
    Number of subjects included in analysis
    50
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3013
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    5.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.86
         upper limit
    		 15.34
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.01

    Secondary: Percentage of participants with treated biopsy proven acute rejection (tBPAR) acute rejection (AR), Graft Loss (GL) or Death (D)

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    End point title
    		 Percentage of participants with treated biopsy proven acute rejection (tBPAR) acute rejection (AR), Graft Loss (GL) or Death (D) [2]
    End point description
    Participants were assessed for tBPAR, AR, GL or death. For all suspected rejection episodes, regardless of initiation of anti-rejection treatment, a liver biopsy was to be performed preferably within 24 hours, latest within 48 hours whenever clinically possible. A treated biopsy proven acute rejection was considered an episode of acute rejection when demonstrated by local pathology reading with a rejection activity index of at least 3 or greater of acute rejection index and when treated with anti-rejection therapy. The allograft was considered lost on the day the subject was re-transplanted or died due to liver failure.
    End point type
    Secondary
    End point timeframe
    At 12 and 18 months post-transplant
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical analysis does not apply to this end point.
    End point values
    		 Group A (Tacrolimus Elimination Arm) Group B (Tacrolimus Minimization Arm)
    Number of subjects analysed
    24
    26
    Units: Number of participants
        tBPAR, 12 months
    2
    1
        AR, 12 months
    2
    1
        GL, 12 months
    0
    0
        Death, 12 months
    1
    0
        tBPAR, 18 months
    2
    1
        AR, 18 months
    2
    1
        GL, 18 months
    0
    0
        Death, 18 months
    1
    1
    No statistical analyses for this end point

    Secondary: Change from baseline (randomization) in serum creatinine at 12 months post-transplant

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    End point title
    		 Change from baseline (randomization) in serum creatinine at 12 months post-transplant [3]
    End point description
    Blood samples were collected to assess serum creatinine.
    End point type
    Secondary
    End point timeframe
    baseline, 12 months post-transplant
    Notes
    [3] - 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: Statistical analysis does not apply to this end point.
    End point values
    		 Group A (Tacrolimus Elimination Arm) Group B (Tacrolimus Minimization Arm)
    Number of subjects analysed
    24
    26
    Units: mg/dL
        least squares mean (standard error)
    -0.11 ( 0.04 )
    -0.05 ( 0.03 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Run-in population Total
    Reporting group description
    		 Run-in population Total

    Reporting group title
    Run-in population Tacrolimus Elimination
    Reporting group description
    		 Run-in population Tacrolimus Elimination

    Reporting group title
    Run-in population Tacrolimus Minimization
    Reporting group description
    		 Run-in population Tacrolimus Minimization

    Reporting group title
    Randomization treatment period Tacrolimus Elimination
    Reporting group description
    		 Randomization treatment period Tacrolimus Elimination

    Reporting group title
    Randomization treatment period Tacrolimus Minimization
    Reporting group description
    		 Randomization treatment period Tacrolimus Minimization

    Serious adverse events
    		 Run-in population Total Run-in population Tacrolimus Elimination Run-in population Tacrolimus Minimization Randomization treatment period Tacrolimus Elimination Randomization treatment period Tacrolimus Minimization
    Total subjects affected by serious adverse events
         subjects affected / exposed
    25 / 78 (32.05%)
    4 / 24 (16.67%)
    9 / 26 (34.62%)
    4 / 24 (16.67%)
    9 / 26 (34.62%)
         number of deaths (all causes)
    1
    0
    0
    1
    0
         number of deaths resulting from adverse events
    0
    0
    0
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Metastases to bone
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Metastases to lung
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Schwannoma
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Lymphocele
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Biliary anastomosis
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Multi-organ failure
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    5 / 78 (6.41%)
    0 / 24 (0.00%)
    2 / 26 (7.69%)
    1 / 24 (4.17%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    2 / 5
    0 / 0
    0 / 2
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Transplant rejection
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Adnexa uteri mass
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    5 / 78 (6.41%)
    1 / 24 (4.17%)
    1 / 26 (3.85%)
    1 / 24 (4.17%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    7 / 78 (8.97%)
    2 / 24 (8.33%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 78 (2.56%)
    1 / 24 (4.17%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    6 / 78 (7.69%)
    1 / 24 (4.17%)
    2 / 26 (7.69%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Weight increased
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    White blood cell count increased
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Biliary anastomosis complication
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Pericarditis
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cranial nerve disorder
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    2 / 26 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Diplopia
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stenosis
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    3 / 78 (3.85%)
    2 / 24 (8.33%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic artery stenosis
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertransaminasaemia
         subjects affected / exposed
    3 / 78 (3.85%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver disorder
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia infection
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis C
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    1 / 24 (4.17%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes virus infection
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 78 (3.85%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Run-in population Total Run-in population Tacrolimus Elimination Run-in population Tacrolimus Minimization Randomization treatment period Tacrolimus Elimination Randomization treatment period Tacrolimus Minimization
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    57 / 78 (73.08%)
    20 / 24 (83.33%)
    21 / 26 (80.77%)
    16 / 24 (66.67%)
    15 / 26 (57.69%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    6 / 78 (7.69%)
    1 / 24 (4.17%)
    1 / 26 (3.85%)
    3 / 24 (12.50%)
    1 / 26 (3.85%)
         occurrences all number
    6
    1
    1
    3
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    3 / 78 (3.85%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    4 / 24 (16.67%)
    0 / 26 (0.00%)
         occurrences all number
    3
    0
    1
    4
    0
    Blood bilirubin increased
         subjects affected / exposed
    6 / 78 (7.69%)
    2 / 24 (8.33%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    10
    2
    2
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    4 / 78 (5.13%)
    1 / 24 (4.17%)
    2 / 26 (7.69%)
    4 / 24 (16.67%)
    2 / 26 (7.69%)
         occurrences all number
    4
    1
    2
    4
    2
    Transaminases increased
         subjects affected / exposed
    9 / 78 (11.54%)
    4 / 24 (16.67%)
    4 / 26 (15.38%)
    2 / 24 (8.33%)
    2 / 26 (7.69%)
         occurrences all number
    9
    4
    4
    2
    2
    Weight increased
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    2 / 24 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    1
    2
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    6 / 78 (7.69%)
    3 / 24 (12.50%)
    2 / 26 (7.69%)
    0 / 24 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    6
    3
    2
    0
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    8 / 78 (10.26%)
    3 / 24 (12.50%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    8
    3
    1
    0
    0
    Tremor
         subjects affected / exposed
    5 / 78 (6.41%)
    2 / 24 (8.33%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    5
    2
    1
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 78 (6.41%)
    0 / 24 (0.00%)
    3 / 26 (11.54%)
    0 / 24 (0.00%)
    5 / 26 (19.23%)
         occurrences all number
    6
    0
    4
    0
    5
    Leukopenia
         subjects affected / exposed
    6 / 78 (7.69%)
    0 / 24 (0.00%)
    4 / 26 (15.38%)
    1 / 24 (4.17%)
    2 / 26 (7.69%)
         occurrences all number
    6
    0
    4
    1
    2
    Thrombocytopenia
         subjects affected / exposed
    5 / 78 (6.41%)
    1 / 24 (4.17%)
    3 / 26 (11.54%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    5
    1
    3
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    7 / 78 (8.97%)
    4 / 24 (16.67%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    8
    5
    1
    0
    0
    Oedema peripheral
         subjects affected / exposed
    3 / 78 (3.85%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    5 / 24 (20.83%)
    1 / 26 (3.85%)
         occurrences all number
    3
    0
    1
    6
    2
    Pyrexia
         subjects affected / exposed
    14 / 78 (17.95%)
    4 / 24 (16.67%)
    4 / 26 (15.38%)
    3 / 24 (12.50%)
    4 / 26 (15.38%)
         occurrences all number
    17
    5
    5
    3
    7
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    6 / 78 (7.69%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    6
    0
    1
    0
    1
    Gastritis
         subjects affected / exposed
    2 / 78 (2.56%)
    2 / 24 (8.33%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
    0 / 26 (0.00%)
         occurrences all number
    2
    2
    0
    1
    0
    Mouth ulceration
         subjects affected / exposed
    4 / 78 (5.13%)
    1 / 24 (4.17%)
    2 / 26 (7.69%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    4
    1
    2
    0
    0
    Nausea
         subjects affected / exposed
    8 / 78 (10.26%)
    3 / 24 (12.50%)
    2 / 26 (7.69%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    8
    3
    2
    0
    1
    Stomatitis
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    0
    0
    3
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    3 / 78 (3.85%)
    0 / 24 (0.00%)
    2 / 26 (7.69%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    3
    0
    2
    0
    0
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    2 / 24 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    3 / 78 (3.85%)
    2 / 24 (8.33%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    3
    2
    0
    0
    0
    Myalgia
         subjects affected / exposed
    3 / 78 (3.85%)
    2 / 24 (8.33%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    3
    2
    1
    0
    0
    Infections and infestations
    Cytomegalovirus infection
         subjects affected / exposed
    4 / 78 (5.13%)
    1 / 24 (4.17%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    4
    1
    1
    0
    1
    Dermo-hypodermitis
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    2 / 26 (7.69%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    2
    0
    0
    Epstein-Barr virus infection
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    2 / 26 (7.69%)
    1 / 24 (4.17%)
    1 / 26 (3.85%)
         occurrences all number
    2
    0
    2
    1
    1
    Hepatitis C
         subjects affected / exposed
    3 / 78 (3.85%)
    1 / 24 (4.17%)
    0 / 26 (0.00%)
    2 / 24 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    3
    1
    0
    2
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
    2 / 24 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    Pharyngitis
         subjects affected / exposed
    2 / 78 (2.56%)
    2 / 24 (8.33%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    2
    2
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    5 / 78 (6.41%)
    1 / 24 (4.17%)
    2 / 26 (7.69%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    5
    1
    2
    0
    0
    Diabetes mellitus
         subjects affected / exposed
    6 / 78 (7.69%)
    1 / 24 (4.17%)
    4 / 26 (15.38%)
    1 / 24 (4.17%)
    1 / 26 (3.85%)
         occurrences all number
    6
    1
    4
    1
    1
    Dyslipidaemia
         subjects affected / exposed
    3 / 78 (3.85%)
    2 / 24 (8.33%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    3
    2
    0
    0
    0
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
    1 / 24 (4.17%)
    3 / 26 (11.54%)
         occurrences all number
    1
    0
    1
    1
    3
    Hypercreatininaemia
         subjects affected / exposed
    4 / 78 (5.13%)
    1 / 24 (4.17%)
    3 / 26 (11.54%)
    0 / 24 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    4
    1
    3
    0
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    5 / 78 (6.41%)
    2 / 24 (8.33%)
    3 / 26 (11.54%)
    0 / 24 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    5
    2
    3
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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