Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A multicenter, randomized, placebo-controlled, double-blind study on the efficacy, safety and tolerability of Certican® in preventing end-stage renal disease (ESRD) in patients with autosomal dominant polycystic kidney disease (ADPKD)

    Summary
    EudraCT number
    		 2006-001485-16
    Trial protocol
    		 AT   DE   FR  
    Global end of trial date
    11 Oct 2013

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Apr 2016
    First version publication date
    06 Apr 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CRAD001ADE12
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00414440
    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
    11 Oct 2013
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    11 Oct 2013
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Oct 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this trial was to demonstrate that everolimus has superior efficacy compared with placebo in reducing the mean total kidney volume from baseline to 24 months of treatment in patients with ADPKD.
    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 Dec 2006
    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
    Germany: 371
    Country: Number of subjects enrolled
    France: 35
    Country: Number of subjects enrolled
    Austria: 25
    Worldwide total number of subjects
    431
    EEA total number of subjects
    431
    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)
    423
    From 65 to 84 years
    8
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 431 patients were randomized to the two treatment groups in a 1:1 ratio

    Period 1
    Period 1 title
    Core period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Everolimus
    Arm description
    		 Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).
    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
    Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).

    Arm title
    		 Placebo
    Arm description
    		 Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Matching Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).

    Number of subjects in period 1
    		Everolimus Placebo
    Started
    214
    217
    Completed
    144
    185
    Not completed
    70
    32
         Consent withdrawn by subject
    70
    32
    Period 2
    Period 2 title
    Extension period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Everolimus
    Arm description
    		 Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).
    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
    Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).

    Arm title
    		 Placebo
    Arm description
    		 Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Matching Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).

    Number of subjects in period 2
    		Everolimus Placebo
    Started
    144
    185
    Completed
    73
    107
    Not completed
    71
    78
         Adverse event, serious fatal
    1
    2
         Consent withdrawn by subject
    9
    7
         Administrative
    16
    16
         Unknown
    1
    1
         Lost to follow-up
    44
    52

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Everolimus
    Reporting group description
    		 Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.

    Reporting group values
    		 Everolimus Placebo Total
    Number of subjects
    		 214 217 431
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 212 215 427
        From 65-84 years
    		 2 2 4
        85 years and over
    		 0 0 0
    Age Continuous |
    Units: years
        arithmetic mean (standard deviation)
    		 44.6 ± 10.1 44.5 ± 10.4 -
    Gender, Male/Female
    Units: participants
        Female
    		 105 117 222
        Male
    		 109 100 209
    Race/Ethnicity, Customized
    Units: Subjects
        Asian Oriental
    		 4 0 4
        Black or African American
    		 1 0 1
        White
    		 208 217 425
        Other, Unknown or Not Reported
    		 1 0 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Everolimus
    Reporting group description
    		 Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.
    Reporting group title
    Everolimus
    Reporting group description
    		 Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.

    Primary: Primary efficacy analysis of total kidney volume (mITT set, multiple imputation)

    		 Close Top of page
    End point title
    		 Primary efficacy analysis of total kidney volume (mITT set, multiple imputation)
    End point description
    Everolimus (RAD001) compared to placebo with respect to the change from baseline in total kidney volume at Month 24.
    End point type
    Primary
    End point timeframe
    Baseline, Month 24
    End point values
    		 Everolimus Placebo
    Number of subjects analysed
    214
    217
    Units: mL
        arithmetic mean (confidence interval)
    230.1 (172.4 to 287.9)
    300.8 (247.5 to 354.1)
    Statistical analysis title
    		 Analysis of Kidney Volume (mITT set)
    Comparison groups
    Everolimus v Placebo
    Number of subjects included in analysis
    431
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.062
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Course of calculated GFR (mL/min/1.73 m^2) from Month 24 to Month 60

    		 Close Top of page
    End point title
    		 Course of calculated GFR (mL/min/1.73 m^2) from Month 24 to Month 60
    End point description
    Course of calculated GFR (mL/min/1.73 m^2) at Months 24, 36, 48 and 60
    End point type
    Secondary
    End point timeframe
    Months 24, 36, 48 and 60
    End point values
    		 Everolimus Placebo
    Number of subjects analysed
    214
    217
    Units: mL/min/1.73 m^2
    arithmetic mean (standard deviation)
        Month 24
    43.9 ± 23.9
    48.8 ± 20.8
        Month 36
    42.6 ± 23.5
    44.9 ± 22.2
        Month 48
    39.6 ± 22.2
    42.7 ± 22.5
        Month 60
    37.7 ± 23.8
    37.6 ± 21.6
    No statistical analyses for this end point

    Secondary: Calculated GFR, change from baseline at Month 60 by baseline cGFR

    		 Close Top of page
    End point title
    		 Calculated GFR, change from baseline at Month 60 by baseline cGFR
    End point description
    Change in renal function was assessed by the estimated Glomerular Filtration Rate (eGFR) using the abbreviated (4 variables) Modification of Diet in Renal Disease (MDRD-4) formula which was developed by the MDRD Study Group and has been validated in patients with chronic kidney disease. The MDRD-4 formula used for the eGFR calculation is: eGFR (mL/min/1.73m^2) = 186.3*(C^-1.154)*(A^-0.203)*G*R, where C is the serum concentration of creatinine (mg/dL), A is age (years), G=0.742 when gender is female, otherwise G=1, R=1.21 when race is black, otherwise R=1. The changes in renal function were analyzed via analysis of covariance (ANCOVA) with treatment, pre-transplant hepatitis C virus status and randomization eGFR as covariates. Based on these ANCOVA analyses, the least-squares mean and standard errors of change were reported.
    End point type
    Secondary
    End point timeframe
    Months 24, 36, 48 and 60
    End point values
    		 Everolimus Placebo
    Number of subjects analysed
    64
    75
    Units: mL/min/1.73 m^2
    arithmetic mean (standard deviation)
        >70 mL/min/1.73 m^2 n=11, 18
    -14.8 ± 22.7
    -20.5 ± 11.1
        ≤70 mL/min/1.73 m^2 n=53, 57
    -16.1 ± 17.6
    -15.6 ± 15.2
        >60 mL/min/1.73 m^2 n=21.26
    -17 ± 17.3
    -20 ± 13.6
        ≤60 mL/min/1.73 m^2 n=43,49
    -15.3 ± 19
    -15.1 ± 14.7
        >50 mL/min/1.73 m^2 n=36,39
    -19 ± 17.3
    -19.4 ± 12.6
        ≤50 mL/min/1.73 m^2 n=28, 36
    -11.8 ± 19.2
    -14 ± 15.8
    No statistical analyses for this end point

    Secondary: Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP)

    		 Close Top of page
    End point title
    		 Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP)
    End point description
    Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), at baseline and then months 12 and 24
    End point type
    Secondary
    End point timeframe
    Baseline, Months 12 and 24
    End point values
    		 Everolimus Placebo
    Number of subjects analysed
    213
    216
    Units: mmHG
    arithmetic mean (standard deviation)
        Baseline SBP
    136 ± 16
    135 ± 17
        Month 12 SBP
    134 ± 15
    134 ± 16
        Month 24 SBP
    134 ± 17
    134 ± 15
        Baseline DBP
    88 ± 11
    88 ± 10
        Month 12 DBP
    86 ± 10
    86 ± 10
        Month 24 DBP
    85 ± 10
    85 ± 10
    No statistical analyses for this end point

    Secondary: Calculated GFR (mL/min/1.73 m^2), change from baseline by visit

    		 Close Top of page
    End point title
    		 Calculated GFR (mL/min/1.73 m^2), change from baseline by visit
    End point description
    Change in renal function was assessed by the Glomerular Filtration Rate (GFR) using the abbreviated (4 variables) Modification of Diet in Renal Disease (MDRD-4) formula which was developed by the MDRD Study Group and has been validated in patients with chronic kidney disease. The MDRD-4 formula used for the eGFR calculation is: eGFR (mL/min/1.73m^2) = 186.3*(C^-1.154)*(A^-0.203)*G*R, where C is the serum concentration of creatinine (mg/dL), A is age (years), G=0.742 when gender is female, otherwise G=1, R=1.21 when race is black, otherwise R=1. The changes in renal function were analyzed via analysis of covariance (ANCOVA) with treatment, pre-transplant hepatitis C virus status and randomization eGFR as covariates. Based on these ANCOVA analyses, the least-squares mean and standard errors of change were reported.
    End point type
    Secondary
    End point timeframe
    Months 3, 6, 9, 12, 18 and 24
    End point values
    		 Everolimus Placebo
    Number of subjects analysed
    213
    216
    Units: mL/min/1.73m^2
    arithmetic mean (standard deviation)
        Week 1
    2 ± 5.9
    -0.9 ± 6.1
        Week 2
    1.7 ± 5.9
    -0.9 ± 6.5
        Week 4
    0.6 ± 6.3
    -1.2 ± 6.7
        Month 3
    -0.5 ± 8.2
    -2.4 ± 6.7
        Month 6
    -2.3 ± 7.7
    -2.2 ± 6.7
        Month 9
    -4.6 ± 8.2
    -2.4 ± 6
        Month 12
    -5.4 ± 7.5
    -3.2 ± 6.9
        Month 18
    -7.7 ± 8.5
    -5.5 ± 6.7
        Month 24
    -8.9 ± 8.8
    -7.7 ± 6.6
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    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
    12.0
    Reporting groups
    Reporting group title
    Everolimus
    Reporting group description
    		 Everolimus

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo

    Serious adverse events
    		 Everolimus Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    80 / 214 (37.38%)
    51 / 217 (23.50%)
         number of deaths (all causes)
    1
    2
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma pancreas
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign ovarian tumour
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholesteatoma
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plasmacytoma
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroid neoplasm
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Angiodysplasia
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 214 (0.00%)
    2 / 217 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intermittent claudication
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iliac artery stenosis
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vasculitis
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicose vein
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Pregnancy
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 214 (0.93%)
    2 / 217 (0.92%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bloody discharge
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    4 / 214 (1.87%)
    2 / 217 (0.92%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug withdrawal syndrome
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic shock
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    House dust allergy
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Breast discharge
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast fibrosis
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast hyperplasia
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colpocele
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Menorrhagia
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysmenorrhoea
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Menstruation irregular
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fluid collection
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    7 / 214 (3.27%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    3 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polycystic ovaries
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    2 / 214 (0.93%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Painful respiration
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    2 / 214 (0.93%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Depressed mood
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute psychosis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paranoia
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    2 / 214 (0.93%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    3 / 214 (1.40%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    4 / 214 (1.87%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Arthropod sting
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Corneal abrasion
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conjunctival abrasion
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foreign body in eye
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    0 / 214 (0.00%)
    2 / 217 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament injury
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus lesion
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sternal fracture
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Polycystic liver disease
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    2 / 214 (0.93%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradyarrhythmia
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 214 (0.00%)
    3 / 217 (1.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myopericarditis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    2 / 214 (0.93%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral atrophy
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine with aura
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ruptured cerebral aneurysm
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 214 (0.00%)
    2 / 217 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 214 (0.93%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymph node pain
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute vestibular syndrome
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 214 (0.93%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    2 / 214 (0.93%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal tenderness
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aphthous stomatitis
         subjects affected / exposed
    2 / 214 (0.93%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colonic polyp
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    3 / 214 (1.40%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroduodenitis
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    2 / 214 (0.93%)
    4 / 217 (1.84%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    3 / 214 (1.40%)
    2 / 217 (0.92%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cyst
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatomegaly
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cyst ruptured
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Portal vein thrombosis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    8 / 214 (3.74%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    8 / 8
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoaesthesia facial
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Calculus ureteric
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    2 / 214 (0.93%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    2 / 214 (0.93%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cyst ruptured
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure acute
         subjects affected / exposed
    5 / 214 (2.34%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    2 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal haemorrhage
         subjects affected / exposed
    3 / 214 (1.40%)
    2 / 217 (0.92%)
         occurrences causally related to treatment / all
    3 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    2 / 214 (0.93%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Ankylosing spondylitis
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    2 / 214 (0.93%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis reactive
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    2 / 214 (0.93%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyarthritis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    4 / 214 (1.87%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    3 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Acute tonsillitis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anogenital warts
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    3 / 214 (1.40%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cyst infection
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes simplex
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster ophthalmic
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    2 / 214 (0.93%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    2 / 214 (0.93%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymph node tuberculosis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenitis bacterial
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media chronic
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papilloma viral infection
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    5 / 214 (2.34%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    5 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 214 (0.47%)
    2 / 217 (0.92%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cyst infection
         subjects affected / exposed
    2 / 214 (0.93%)
    4 / 217 (1.84%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 214 (0.00%)
    2 / 217 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    2 / 214 (0.93%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Everolimus Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    205 / 214 (95.79%)
    185 / 217 (85.25%)
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    38 / 214 (17.76%)
    13 / 217 (5.99%)
         occurrences all number
    39
    15
    Blood creatine phosphokinase increased
         subjects affected / exposed
    32 / 214 (14.95%)
    15 / 217 (6.91%)
         occurrences all number
    39
    16
    Vascular disorders
    Hypertension
         subjects affected / exposed
    33 / 214 (15.42%)
    29 / 217 (13.36%)
         occurrences all number
    35
    30
    Nervous system disorders
    Headache
         subjects affected / exposed
    37 / 214 (17.29%)
    27 / 217 (12.44%)
         occurrences all number
    49
    45
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    35 / 214 (16.36%)
    11 / 217 (5.07%)
         occurrences all number
    35
    11
    Thrombocytopenia
         subjects affected / exposed
    30 / 214 (14.02%)
    2 / 217 (0.92%)
         occurrences all number
    32
    2
    Leukopenia
         subjects affected / exposed
    38 / 214 (17.76%)
    6 / 217 (2.76%)
         occurrences all number
    42
    6
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    11 / 214 (5.14%)
    6 / 217 (2.76%)
         occurrences all number
    12
    7
    Oedema
         subjects affected / exposed
    25 / 214 (11.68%)
    12 / 217 (5.53%)
         occurrences all number
    27
    13
    Oedema peripheral
         subjects affected / exposed
    42 / 214 (19.63%)
    20 / 217 (9.22%)
         occurrences all number
    47
    23
    Pyrexia
         subjects affected / exposed
    12 / 214 (5.61%)
    9 / 217 (4.15%)
         occurrences all number
    13
    9
    Fatigue
         subjects affected / exposed
    20 / 214 (9.35%)
    19 / 217 (8.76%)
         occurrences all number
    21
    21
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    12 / 214 (5.61%)
    8 / 217 (3.69%)
         occurrences all number
    14
    8
    Abdominal pain
         subjects affected / exposed
    24 / 214 (11.21%)
    13 / 217 (5.99%)
         occurrences all number
    26
    13
    Abdominal pain upper
         subjects affected / exposed
    14 / 214 (6.54%)
    13 / 217 (5.99%)
         occurrences all number
    16
    14
    Aphthous stomatitis
         subjects affected / exposed
    83 / 214 (38.79%)
    12 / 217 (5.53%)
         occurrences all number
    121
    14
    Vomiting
         subjects affected / exposed
    11 / 214 (5.14%)
    14 / 217 (6.45%)
         occurrences all number
    11
    14
    Nausea
         subjects affected / exposed
    20 / 214 (9.35%)
    12 / 217 (5.53%)
         occurrences all number
    21
    13
    Diarrhoea
         subjects affected / exposed
    48 / 214 (22.43%)
    34 / 217 (15.67%)
         occurrences all number
    58
    35
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    24 / 214 (11.21%)
    19 / 217 (8.76%)
         occurrences all number
    31
    20
    Oropharyngeal pain
         subjects affected / exposed
    12 / 214 (5.61%)
    9 / 217 (4.15%)
         occurrences all number
    15
    11
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    30 / 214 (14.02%)
    6 / 217 (2.76%)
         occurrences all number
    34
    7
    Rash
         subjects affected / exposed
    18 / 214 (8.41%)
    8 / 217 (3.69%)
         occurrences all number
    18
    10
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    28 / 214 (13.08%)
    15 / 217 (6.91%)
         occurrences all number
    28
    15
    Haematuria
         subjects affected / exposed
    13 / 214 (6.07%)
    9 / 217 (4.15%)
         occurrences all number
    19
    11
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    13 / 214 (6.07%)
    5 / 217 (2.30%)
         occurrences all number
    17
    6
    Back pain
         subjects affected / exposed
    15 / 214 (7.01%)
    17 / 217 (7.83%)
         occurrences all number
    16
    21
    Flank pain
         subjects affected / exposed
    17 / 214 (7.94%)
    23 / 217 (10.60%)
         occurrences all number
    20
    25
    Muscle spasms
         subjects affected / exposed
    10 / 214 (4.67%)
    12 / 217 (5.53%)
         occurrences all number
    11
    13
    Myalgia
         subjects affected / exposed
    14 / 214 (6.54%)
    3 / 217 (1.38%)
         occurrences all number
    16
    3
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    21 / 214 (9.81%)
    23 / 217 (10.60%)
         occurrences all number
    23
    26
    Gastroenteritis
         subjects affected / exposed
    11 / 214 (5.14%)
    4 / 217 (1.84%)
         occurrences all number
    12
    4
    Nasopharyngitis
         subjects affected / exposed
    83 / 214 (38.79%)
    83 / 217 (38.25%)
         occurrences all number
    123
    124
    Oral herpes
         subjects affected / exposed
    15 / 214 (7.01%)
    4 / 217 (1.84%)
         occurrences all number
    16
    4
    Sinusitis
         subjects affected / exposed
    14 / 214 (6.54%)
    13 / 217 (5.99%)
         occurrences all number
    15
    14
    Urinary tract infection
         subjects affected / exposed
    22 / 214 (10.28%)
    19 / 217 (8.76%)
         occurrences all number
    27
    31
    Metabolism and nutrition disorders
    Hypercholesterolaemia
         subjects affected / exposed
    46 / 214 (21.50%)
    8 / 217 (3.69%)
         occurrences all number
    47
    9
    Hyperlipidaemia
         subjects affected / exposed
    28 / 214 (13.08%)
    5 / 217 (2.30%)
         occurrences all number
    28
    5
    Hypertriglyceridaemia
         subjects affected / exposed
    15 / 214 (7.01%)
    8 / 217 (3.69%)
         occurrences all number
    15
    8
    Hyperuricaemia
         subjects affected / exposed
    7 / 214 (3.27%)
    13 / 217 (5.99%)
         occurrences all number
    7
    14
    Iron deficiency
         subjects affected / exposed
    12 / 214 (5.61%)
    2 / 217 (0.92%)
         occurrences all number
    12
    2

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Apr 2007
    Issued approximately 9 months after study start / after randomization of 339 patients was to: -recalculate the required sample size (increase by 50 patients per group) to compensate for the drop-out rate which had been underestimated and to provide measures to maintain sufficient power in case of increased standard deviations - clarify the wording with respect to the primary variable, and to correct the alpha levels to be chosen for the statistical hypothesis, model, and method of analysis, which had been given erroneously in the study protocol from a draft version but not the final planning -introduce a multiple imputation procedure for dealing with missing values during analysis
    09 Mar 2012
    Issued approximately 36 months after completion of the core study was to: - extend the observation period of all patients for another 12 months to a total of 60 months - introduce an exploratory genome-wide analysis of each individual patient by applying e.g. Next-Generation Sequencing. The necessary DNA sample and informed consent were to be obtained during the additional visit at Month 60.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    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.

    European Medicines Agency © 1995-Fri Apr 26 22:38:27 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA