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    Clinical Trial Results:
    An International, Randomised, Double-Blind, Two-Arm Study to Evaluate the Safety and Efficacy of Vandetanib 150 and 300 mg/day in Patients with Unresectable Locally Advanced or Metastatic Medullary Thyroid Carcinoma with Progressive or Symptomatic Disease

    Summary
    EudraCT number
    		 2011-004701-24
    Trial protocol
    		 CZ   NL   IT   PL   GB  
    Global end of trial date
    11 Jul 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Oct 2025
    First version publication date
    23 Oct 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    D4200C00097
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01496313
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Sanofi-Genzyme : LPS14809
    Sponsors
    Sponsor organisation name
    Genzyme Corporation
    Sponsor organisation address
    500 Kendall Street, Cambridge, Massachusetts, United States, 02142
    Public contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
    Scientific contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Mar 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Jul 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to assess the objective response rate for 2 starting doses of vandetanib, 150 milligrams (mg) and 300 mg, in participants with unresectable locally advanced or metastatic medullary thyroid carcinoma having progressive or symptomatic disease.
    Protection of trial subjects
    Participants were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the participant and considering the local culture. During the course of the trial, participants were provided with individual participant cards indicating the nature of the trial the participant is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Jun 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Czechia: 2
    Country: Number of subjects enrolled
    India: 2
    Country: Number of subjects enrolled
    Israel: 9
    Country: Number of subjects enrolled
    Italy: 33
    Country: Number of subjects enrolled
    Netherlands: 5
    Country: Number of subjects enrolled
    Poland: 17
    Country: Number of subjects enrolled
    Russian Federation: 1
    Country: Number of subjects enrolled
    United Kingdom: 9
    Country: Number of subjects enrolled
    United States: 3
    Worldwide total number of subjects
    81
    EEA total number of subjects
    57
    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)
    60
    From 65 to 84 years
    20
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 From 8 June 2012 to 2 April 2014, 93 participants were screened; 81 participants were randomized. The study consisted of a double-blind randomized period and an open-label period.

    Pre-assignment
    Screening details
    		 Participants with objective disease progression within 14 months on blinded treatment were given option to continue to receive vandetanib in open-label period for up to 2 years from time of study entry. They were followed for efficacy during randomized period only. No further efficacy data was collected in open-label period.

    Period 1
    Period 1 title
    Randomized Period: up to 14 Months
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Randomized Period: Vandetanib 150 mg
    Arm description
    		 Oral blinded tablet, taken once daily
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vandetanib
    Investigational medicinal product code
    ZD6474
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg, oral tablet

    Arm title
    		 Randomized Period: Vandetanib 300 mg
    Arm description
    		 Oral blinded tablet, taken once daily
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vandetanib
    Investigational medicinal product code
    ZD6474
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg, oral tablet

    Number of subjects in period 1
    		Randomized Period: Vandetanib 150 mg Randomized Period: Vandetanib 300 mg
    Started
    40
    41
    Completed
    35
    26
    Not completed
    5
    15
         Adverse event, serious fatal
    -
    2
         Participant decision
    1
    3
         Adverse event, non-fatal
    1
    3
         Condition under investigation worsened
    2
    3
         Unspecified
    1
    2
         Study-specific discontinuation criteria
    -
    2
    Period 2
    Period 2 title
    Open-Label Period (Month 14 to 2 Years)
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Open-Label Period: Vandetanib 100 mg
    Arm description
    		 Participants who received vandetanib 150 mg orally once daily but the dose was reduced to vandetanib 100 mg orally once daily for an adverse event (AE) or QT prolongation in randomized period continued receiving the reduced dose of vandetanib 100 mg orally once daily in open-label period as per the Investigator for a maximum of 2 years from study entry.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vandetanib
    Investigational medicinal product code
    ZD6474
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg, oral tablet

    Arm title
    		 Open-Label Period: Vandetanib 150 mg
    Arm description
    		 Participants who received vandetanib 150 mg orally once daily without any dose reduction for an AE or QT prolongation in randomized period were given an option to stay on vandetanib 150 mg orally once daily in open-label period for a maximum of 2 years from study entry.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vandetanib
    Investigational medicinal product code
    ZD6474
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg, oral tablet

    Arm title
    		 Open-Label Period: Vandetanib 200 mg
    Arm description
    		 Participants who received vandetanib 300 mg orally once daily but the dose was reduced to vandetanib 200 mg orally once daily for an AE or QT prolongation in randomized period continued receiving the reduced dose of vandetanib 200 mg orally once daily in open-label period as per the Investigator for a maximum of 2 years from study entry.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vandetanib
    Investigational medicinal product code
    ZD6474
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    200 mg, oral tablet

    Arm title
    		 Open-Label Period: Vandetanib 300 mg
    Arm description
    		 Participants who received vandetanib 150 mg or 300 mg orally once daily without any dose reduction for an AE or QT prolongation in randomized period were given an option to increase or continue vandetanib 300 mg orally once daily in open-label period respectively for a maximum of 2 years from study entry.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vandetanib
    Investigational medicinal product code
    ZD6474
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg, oral tablet

    Number of subjects in period 2
    		Open-Label Period: Vandetanib 100 mg Open-Label Period: Vandetanib 150 mg Open-Label Period: Vandetanib 200 mg Open-Label Period: Vandetanib 300 mg
    Started
    5
    9
    8
    39
    Completed
    3
    7
    7
    28
    Not completed
    2
    2
    1
    11
         Participant decision
    -
    -
    -
    3
         Unspecified
    2
    2
    1
    7
         Study-specific withdrawal criteria
    -
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Randomized Period: Vandetanib 150 mg
    Reporting group description
    		 Oral blinded tablet, taken once daily

    Reporting group title
    Randomized Period: Vandetanib 300 mg
    Reporting group description
    		 Oral blinded tablet, taken once daily

    Reporting group values
    		 Randomized Period: Vandetanib 150 mg Randomized Period: Vandetanib 300 mg Total
    Number of subjects
    		 40 41 81
    Age categorical
    Units: Subjects
    Age Continuous |
    Units: Years
        arithmetic mean (standard deviation)
    		 52.2 ( 15.24 ) 52.7 ( 15.42 ) -
    Gender, Male/Female
    Units: Participants
        Female
    		 15 12 27
        Male
    		 25 29 54
    Age, Customized
    Units: Subjects
        >=18 to <40 years
    		 9 9 18
        >=40 to <65 years
    		 22 20 42
        >=65 to <75 years
    		 7 10 17
        >=75 years
    		 2 2 4
    Race/Ethnicity, Customized
    Units: Subjects
        Asian
    		 1 2 3
        Black or African American
    		 0 1 1
        White
    		 39 37 76
        Other
    		 0 1 1

    End points

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    End points reporting groups
    Reporting group title
    Randomized Period: Vandetanib 150 mg
    Reporting group description
    		 Oral blinded tablet, taken once daily

    Reporting group title
    Randomized Period: Vandetanib 300 mg
    Reporting group description
    		 Oral blinded tablet, taken once daily
    Reporting group title
    Open-Label Period: Vandetanib 100 mg
    Reporting group description
    		 Participants who received vandetanib 150 mg orally once daily but the dose was reduced to vandetanib 100 mg orally once daily for an adverse event (AE) or QT prolongation in randomized period continued receiving the reduced dose of vandetanib 100 mg orally once daily in open-label period as per the Investigator for a maximum of 2 years from study entry.

    Reporting group title
    Open-Label Period: Vandetanib 150 mg
    Reporting group description
    		 Participants who received vandetanib 150 mg orally once daily without any dose reduction for an AE or QT prolongation in randomized period were given an option to stay on vandetanib 150 mg orally once daily in open-label period for a maximum of 2 years from study entry.

    Reporting group title
    Open-Label Period: Vandetanib 200 mg
    Reporting group description
    		 Participants who received vandetanib 300 mg orally once daily but the dose was reduced to vandetanib 200 mg orally once daily for an AE or QT prolongation in randomized period continued receiving the reduced dose of vandetanib 200 mg orally once daily in open-label period as per the Investigator for a maximum of 2 years from study entry.

    Reporting group title
    Open-Label Period: Vandetanib 300 mg
    Reporting group description
    		 Participants who received vandetanib 150 mg or 300 mg orally once daily without any dose reduction for an AE or QT prolongation in randomized period were given an option to increase or continue vandetanib 300 mg orally once daily in open-label period respectively for a maximum of 2 years from study entry.

    Primary: Overall Response Rate (ORR) for Vandetanib 150 and 300 mg With Responses Determined by the Investigator

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    End point title
    		 Overall Response Rate (ORR) for Vandetanib 150 and 300 mg With Responses Determined by the Investigator [1]
    End point description
    ORR=proportion of patients with a best response of complete or partial response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial response (PR), at least a 30% decrease in the sum of diameters of target lesions; ORR = CR + PR.
    End point type
    Primary
    End point timeframe
    Randomisation to week 60 (maximum)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
    End point values
    		 Randomized Period: Vandetanib 150 mg Randomized Period: Vandetanib 300 mg
    Number of subjects analysed
    40
    41
    Units: Proportion of participants
        number (confidence interval 95%)
    0.2 (0.105 to 0.348)
    0.29 (0.176 to 0.445)
    No statistical analyses for this end point

    Secondary: Best Objective Response

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    End point title
    		 Best Objective Response
    End point description
    Per RECIST v1.1 for target lesions: CR, disappearance of all target lesions; PR, at least a 30% decrease in the sum of diameters of target lesions; Progressive disease (PD), at least 20% increase in the sum of diameters of target lesions; Stable disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
    End point type
    Secondary
    End point timeframe
    Randomisation to week 60 (maximum)
    End point values
    		 Randomized Period: Vandetanib 150 mg Randomized Period: Vandetanib 300 mg
    Number of subjects analysed
    40
    41
    Units: Participants
        Complete response
    0
    1
        Partial response
    8
    11
        Stable disease
    21
    23
        Progressive disease
    9
    2
        Non-evaluable
    2
    4
    No statistical analyses for this end point

    Secondary: Duration of Objective Response (RECIST 1.1) by Treatment arm

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    End point title
    		 Duration of Objective Response (RECIST 1.1) by Treatment arm
    End point description
    Per RECIST v1.1 for target lesions: CR, disappearance of all target lesions; PR, at least a 30% decrease in the sum of diameters of target lesions; Progressive disease (PD), at least 20% increase in the sum of diameters of target lesions; Stable disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
    End point type
    Secondary
    End point timeframe
    Randomization to Week 60 (maximum)
    End point values
    		 Randomized Period: Vandetanib 150 mg Randomized Period: Vandetanib 300 mg
    Number of subjects analysed
    8
    12
    Units: Months
        median (confidence interval 95%)
    9.8 (2.8 to 11.2)
    8.4 (3 to 11.2)
    No statistical analyses for this end point

    Secondary: Time to Objective Response (RECIST 1.1) by Treatment arm

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    End point title
    		 Time to Objective Response (RECIST 1.1) by Treatment arm
    End point description
    Per RECIST v1.1 for target lesions: CR, disappearance of all target lesions; PR, at least a 30% decrease in the sum of diameters of target lesions; Progressive disease (PD), at least 20% increase in the sum of diameters of target lesions; Stable disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
    End point type
    Secondary
    End point timeframe
    Randomization to Week 60 (maximum)
    End point values
    		 Randomized Period: Vandetanib 150 mg Randomized Period: Vandetanib 300 mg
    Number of subjects analysed
    8
    12
    Units: Months
        median (confidence interval 95%)
    4.2 (2.8 to 11.2)
    4.4 (2.8 to 11.1)
    No statistical analyses for this end point

    Secondary: Percentage Change From Baseline in Target Lesion Size (RECIST 1.1) by Treatment arm

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    End point title
    		 Percentage Change From Baseline in Target Lesion Size (RECIST 1.1) by Treatment arm
    End point description
    Per RECIST v1.1 for target lesions: CR, disappearance of all target lesions; PR, at least a 30% decrease in the sum of diameters of target lesions; Progressive disease (PD), at least 20% increase in the sum of diameters of target lesions; Stable disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
    End point type
    Secondary
    End point timeframe
    Randomization to Week 60 (maximum)
    End point values
    		 Randomized Period: Vandetanib 150 mg Randomized Period: Vandetanib 300 mg
    Number of subjects analysed
    40
    41
    Units: % change
    arithmetic mean (standard deviation)
        Week 12
    -3.8 ( 29.24 )
    -17.5 ( 18.24 )
        Week 24
    -13 ( 19.51 )
    -24.9 ( 22.11 )
        Week 36
    -16.7 ( 24.33 )
    -29.1 ( 22.96 )
        Week 48
    -20.7 ( 23.56 )
    -30.6 ( 25.31 )
        Follow-up RECIST assessment
    -51 ( 0 )
    -11.4 ( 67.05 )
        Disc. of blinded vandetanib
    -11.9 ( 27.98 )
    -27.3 ( 29.58 )
    No statistical analyses for this end point

    Secondary: Plasma Concentration of Vandetanib in the Bloodstream (Cmax) for Patients by Treatment arm

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    End point title
    		 Plasma Concentration of Vandetanib in the Bloodstream (Cmax) for Patients by Treatment arm
    End point description
    All patients who received at least 1 dose of vandetanib and for whom quantifiable plasma concentration data were available.
    End point type
    Secondary
    End point timeframe
    Week 3 to week 60 (maximum)
    End point values
    		 Randomized Period: Vandetanib 150 mg Randomized Period: Vandetanib 300 mg
    Number of subjects analysed
    40
    41
    Units: ng/ml
    arithmetic mean (standard deviation)
        Week 3 (Day 21)
    428.6 ( 140.71 )
    786.2 ( 243.15 )
        Week 8 (Day 56)
    510.5 ( 206.50 )
    941.0 ( 249.4 )
        Week 12 (Day 84)
    561.4 ( 215.66 )
    969.9 ( 396.18 )
        Week 24 (Day 168)
    549.7 ( 189.62 )
    1017.7 ( 330.89 )
        Discontinuation of blinded vandetanib
    536.8 ( 225.34 )
    964.0 ( 357.30 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Serious adverse events (SAEs) and all-cause mortality (deaths) were collected from randomization (Day 1) up to end of follow-up, approximately 12 years. Other (non-serious) AEs were reported from randomization (Day 1) up to Week 108 (final analysis visit)
    Adverse event reporting additional description
    Analysis was performed on the safety population which included all participants who received at least 1 dose of randomized study drug (vandetanib) and for whom any post-dose data were available.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    12.0-25.1
    Reporting groups
    Reporting group title
    Randomized Period: Vandetanib 150 mg
    Reporting group description
    		 Oral blinded tablet, taken once daily

    Reporting group title
    Randomized Period: Vandetanib 300 mg
    Reporting group description
    		 Oral blinded tablet, taken once daily

    Reporting group title
    Open-label Period: Vandetanib 100 mg
    Reporting group description
    		 Participants who received vandetanib 150 mg orally once daily but the dose was reduced to vandetanib 100 mg orally once daily for an AE or QT prolongation in randomized period continued receiving the reduced dose of vandetanib 100 mg orally once daily in open-label period as per the Investigator for a maximum of 2 years from study entry.

    Reporting group title
    Open-label Period: Vandetanib 150 mg
    Reporting group description
    		 Participants who received vandetanib 150 mg orally once daily without any dose reduction for an AE or QT prolongation in randomized period were given an option to stay on vandetanib 150 mg orally once daily in open-label period for a maximum of 2 years from study entry.

    Reporting group title
    Open-label Period: Vandetanib 200 mg
    Reporting group description
    		 Participants who received vandetanib 300 mg orally once daily but the dose was reduced to vandetanib 200 mg orally once daily for an AE or QT prolongation in randomized period continued receiving the reduced dose of vandetanib 200 mg orally once daily in open-label period as per the Investigator for a maximum of 2 years from study entry.

    Reporting group title
    Open-label Period: Vandetanib 300 mg
    Reporting group description
    		 Participants who received vandetanib 150 mg or 300 mg orally once daily without any dose reduction for an AE or QT prolongation in randomized period were given an option to increase or continue vandetanib 300 mg orally once daily in open-label period respectively for a maximum of 2 years from study entry.

    Serious adverse events
    		 Randomized Period: Vandetanib 150 mg Randomized Period: Vandetanib 300 mg Open-label Period: Vandetanib 100 mg Open-label Period: Vandetanib 150 mg Open-label Period: Vandetanib 200 mg Open-label Period: Vandetanib 300 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 40 (22.50%)
    9 / 41 (21.95%)
    0 / 5 (0.00%)
    4 / 9 (44.44%)
    2 / 8 (25.00%)
    11 / 39 (28.21%)
         number of deaths (all causes)
    1
    6
    0
    0
    1
    10
         number of deaths resulting from adverse events
    0
    2
    0
    0
    1
    4
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast Cancer
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign Laryngeal Neoplasm
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma Pancreas
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep Vein Thrombosis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Drug Interaction
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden Death
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Malaise
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General Physical Health Deterioration
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngeal Haemorrhage
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Laryngeal Obstruction
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngeal Oedema
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Embolism
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Post Procedural Fistula
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post Procedural Haemorrhage
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Post Procedural Haematoma
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute Myocardial Infarction
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac Failure Acute
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Angina Pectoris
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial Infarction
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Miller Fisher Syndrome
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular Accident
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral Motor Neuropathy
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal Cord Compression
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastritis Erosive
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal Obstruction
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal Ulcer Perforation
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis Acute
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bile Duct Stone
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin Ulcer
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary Retention
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Calculus Ureteric
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Soft Tissue Necrosis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back Pain
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neurocysticercosis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia Aspiration
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral Infection
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypocalcaemia
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Randomized Period: Vandetanib 150 mg Randomized Period: Vandetanib 300 mg Open-label Period: Vandetanib 100 mg Open-label Period: Vandetanib 150 mg Open-label Period: Vandetanib 200 mg Open-label Period: Vandetanib 300 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    38 / 40 (95.00%)
    40 / 41 (97.56%)
    5 / 5 (100.00%)
    7 / 9 (77.78%)
    7 / 8 (87.50%)
    31 / 39 (79.49%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases To Bone
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    1 / 39 (2.56%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    8 / 40 (20.00%)
    11 / 41 (26.83%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    6 / 39 (15.38%)
         occurrences all number
    10
    14
    1
    1
    0
    7
    Surgical and medical procedures
    Cataract Operation
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Oedema Peripheral
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Non-Cardiac Chest Pain
         subjects affected / exposed
    0 / 40 (0.00%)
    4 / 41 (9.76%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    0
    4
    0
    0
    0
    1
    Fatigue
         subjects affected / exposed
    8 / 40 (20.00%)
    7 / 41 (17.07%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 8 (25.00%)
    3 / 39 (7.69%)
         occurrences all number
    8
    7
    0
    0
    2
    3
    Asthenia
         subjects affected / exposed
    5 / 40 (12.50%)
    7 / 41 (17.07%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    8 / 39 (20.51%)
         occurrences all number
    6
    7
    1
    1
    0
    10
    Respiratory, thoracic and mediastinal disorders
    Lower Respiratory Tract Inflammation
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Dyspnoea
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    3 / 39 (7.69%)
         occurrences all number
    2
    0
    0
    0
    0
    3
    Dysphonia
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    Dysaesthesia Pharynx
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Pulmonary Hypertension
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Cough
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    3 / 39 (7.69%)
         occurrences all number
    2
    0
    0
    0
    1
    3
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    2 / 40 (5.00%)
    6 / 41 (14.63%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    2
    6
    0
    0
    0
    1
    Depression
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    0
    Depressed Mood
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Anxiety
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    1 / 39 (2.56%)
         occurrences all number
    0
    1
    0
    0
    1
    1
    Investigations
    Blood Alkaline Phosphatase Increased
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    1
    1
    0
    0
    0
    2
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    3 / 40 (7.50%)
    6 / 41 (14.63%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    6 / 39 (15.38%)
         occurrences all number
    3
    6
    1
    0
    0
    7
    Alanine Aminotransferase Increased
         subjects affected / exposed
    5 / 40 (12.50%)
    7 / 41 (17.07%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    6 / 39 (15.38%)
         occurrences all number
    5
    7
    0
    1
    0
    7
    Electrocardiogram Qt Prolonged
         subjects affected / exposed
    5 / 40 (12.50%)
    14 / 41 (34.15%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    7 / 39 (17.95%)
         occurrences all number
    5
    15
    1
    0
    1
    8
    Blood Thyroid Stimulating Hormone Increased
         subjects affected / exposed
    12 / 40 (30.00%)
    9 / 41 (21.95%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    5 / 39 (12.82%)
         occurrences all number
    12
    11
    0
    0
    1
    8
    Blood Creatinine Increased
         subjects affected / exposed
    5 / 40 (12.50%)
    2 / 41 (4.88%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    3 / 39 (7.69%)
         occurrences all number
    6
    2
    0
    0
    0
    4
    Blood Glucose Increased
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Blood Thyroid Stimulating Hormone Decreased
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Blood Bilirubin Increased
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    Blood Creatine Phosphokinase Increased
         subjects affected / exposed
    2 / 40 (5.00%)
    2 / 41 (4.88%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    3
    2
    0
    0
    0
    2
    Ejection Fraction Decreased
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    1
    0
    0
    0
    0
    2
    White Blood Cell Count Decreased
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Weight Decreased
         subjects affected / exposed
    2 / 40 (5.00%)
    5 / 41 (12.20%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    4 / 39 (10.26%)
         occurrences all number
    2
    6
    0
    0
    0
    4
    Platelet Count Decreased
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 41 (4.88%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    1
    2
    1
    0
    0
    1
    Gamma-Glutamyltransferase Increased
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    1
    1
    0
    0
    0
    2
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Arthropod Bite
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Corneal Abrasion
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Cardiac disorders
    Sinus Tachycardia
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    2
    0
    0
    1
    0
    Nervous system disorders
    Head Titubation
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Dysgeusia
         subjects affected / exposed
    1 / 40 (2.50%)
    3 / 41 (7.32%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    2
    3
    0
    0
    0
    2
    Disturbance In Attention
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Headache
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 41 (4.88%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    3 / 39 (7.69%)
         occurrences all number
    1
    2
    1
    0
    0
    4
    Transient Ischaemic Attack
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Neuropathy Peripheral
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Tremor
         subjects affected / exposed
    0 / 40 (0.00%)
    3 / 41 (7.32%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    4
    1
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 40 (0.00%)
    2 / 41 (4.88%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    2
    0
    0
    1
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Eye disorders
    Corneal Opacity
         subjects affected / exposed
    2 / 40 (5.00%)
    4 / 41 (9.76%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    2
    5
    0
    0
    0
    1
    Keratopathy
         subjects affected / exposed
    6 / 40 (15.00%)
    14 / 41 (34.15%)
    2 / 5 (40.00%)
    2 / 9 (22.22%)
    0 / 8 (0.00%)
    6 / 39 (15.38%)
         occurrences all number
    6
    17
    3
    2
    0
    7
    Keratitis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Eye Pain
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Gastrointestinal disorders
    Dry Mouth
         subjects affected / exposed
    4 / 40 (10.00%)
    2 / 41 (4.88%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    4
    2
    0
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    15 / 40 (37.50%)
    18 / 41 (43.90%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    2 / 8 (25.00%)
    7 / 39 (17.95%)
         occurrences all number
    17
    21
    0
    1
    3
    7
    Constipation
         subjects affected / exposed
    2 / 40 (5.00%)
    3 / 41 (7.32%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    2
    3
    0
    0
    0
    0
    Anal Fissure
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Abdominal Pain Upper
         subjects affected / exposed
    1 / 40 (2.50%)
    3 / 41 (7.32%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    1
    4
    0
    0
    0
    2
    Vomiting
         subjects affected / exposed
    0 / 40 (0.00%)
    2 / 41 (4.88%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    3 / 39 (7.69%)
         occurrences all number
    0
    2
    0
    0
    0
    3
    Nausea
         subjects affected / exposed
    4 / 40 (10.00%)
    5 / 41 (12.20%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    5 / 39 (12.82%)
         occurrences all number
    5
    6
    0
    0
    0
    5
    Dysphagia
         subjects affected / exposed
    2 / 40 (5.00%)
    4 / 41 (9.76%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    2
    4
    1
    0
    0
    0
    Dyspepsia
         subjects affected / exposed
    0 / 40 (0.00%)
    2 / 41 (4.88%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    0
    3
    0
    0
    0
    2
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    2 / 40 (5.00%)
    3 / 41 (7.32%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    2
    3
    0
    0
    0
    0
    Alopecia
         subjects affected / exposed
    3 / 40 (7.50%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    3
    1
    0
    0
    0
    2
    Dermatitis Acneiform
         subjects affected / exposed
    6 / 40 (15.00%)
    6 / 41 (14.63%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    7
    8
    1
    0
    0
    1
    Dry Skin
         subjects affected / exposed
    5 / 40 (12.50%)
    5 / 41 (12.20%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    3 / 39 (7.69%)
         occurrences all number
    5
    5
    0
    0
    0
    3
    Erythema
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 41 (4.88%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    1
    2
    0
    0
    1
    0
    Onychoclasis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Palmar-Plantar Erythrodysaesthesia Syndrome
         subjects affected / exposed
    1 / 40 (2.50%)
    4 / 41 (9.76%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    5
    0
    1
    0
    0
    Photosensitivity Reaction
         subjects affected / exposed
    2 / 40 (5.00%)
    3 / 41 (7.32%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    2
    4
    0
    2
    0
    2
    Pruritus
         subjects affected / exposed
    2 / 40 (5.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    3 / 39 (7.69%)
         occurrences all number
    2
    1
    0
    0
    0
    3
    Psoriasis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Rash
         subjects affected / exposed
    8 / 40 (20.00%)
    13 / 41 (31.71%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    5 / 39 (12.82%)
         occurrences all number
    9
    19
    0
    0
    2
    5
    Rash Erythematous
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    1
    1
    0
    0
    2
    0
    Renal and urinary disorders
    Pollakiuria
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Proteinuria
         subjects affected / exposed
    6 / 40 (15.00%)
    2 / 41 (4.88%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    7
    4
    0
    0
    0
    2
    Nephrolithiasis
         subjects affected / exposed
    3 / 40 (7.50%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    3
    1
    0
    0
    0
    0
    Micturition Urgency
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Renal Pain
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Haematuria
         subjects affected / exposed
    4 / 40 (10.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    6
    1
    0
    1
    0
    1
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    3 / 40 (7.50%)
    5 / 41 (12.20%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 8 (12.50%)
    2 / 39 (5.13%)
         occurrences all number
    3
    6
    0
    1
    1
    2
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    1
    0
    0
    0
    0
    2
    Muscular Weakness
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    Muscle Spasms
         subjects affected / exposed
    3 / 40 (7.50%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    5
    0
    0
    0
    0
    1
    Back Pain
         subjects affected / exposed
    1 / 40 (2.50%)
    3 / 41 (7.32%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    2 / 39 (5.13%)
         occurrences all number
    1
    3
    0
    0
    1
    2
    Pain In Extremity
         subjects affected / exposed
    3 / 40 (7.50%)
    2 / 41 (4.88%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    3
    2
    0
    0
    0
    1
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Paronychia
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Lower Respiratory Tract Infection Bacterial
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Influenza
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    Conjunctivitis
         subjects affected / exposed
    2 / 40 (5.00%)
    2 / 41 (4.88%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    2
    3
    0
    0
    1
    0
    Pneumonia Staphylococcal
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Rash Pustular
         subjects affected / exposed
    2 / 40 (5.00%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    2 / 9 (22.22%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    2
    1
    0
    2
    0
    1
    Urinary Tract Infection
         subjects affected / exposed
    0 / 40 (0.00%)
    2 / 41 (4.88%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    0
    2
    0
    1
    0
    1
    Vulval Abscess
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Metabolism and nutrition disorders
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 41 (2.44%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    1
    1
    0
    0
    2
    0
    Hypercalcaemia
         subjects affected / exposed
    0 / 40 (0.00%)
    2 / 41 (4.88%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    0
    2
    0
    0
    0
    2
    Dehydration
         subjects affected / exposed
    0 / 40 (0.00%)
    2 / 41 (4.88%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    0
    Decreased Appetite
         subjects affected / exposed
    2 / 40 (5.00%)
    7 / 41 (17.07%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    2
    8
    1
    1
    0
    1
    Hypocalcaemia
         subjects affected / exposed
    7 / 40 (17.50%)
    10 / 41 (24.39%)
    2 / 5 (40.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    8 / 39 (20.51%)
         occurrences all number
    8
    11
    3
    0
    0
    9
    Iron Deficiency
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Hypophosphataemia
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 8 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    0
    0
    1
    1
    0
    1
    Hyponatraemia
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 8 (0.00%)
    3 / 39 (7.69%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    Hypomagnesaemia
         subjects affected / exposed
    4 / 40 (10.00%)
    6 / 41 (14.63%)
    2 / 5 (40.00%)
    0 / 9 (0.00%)
    1 / 8 (12.50%)
    5 / 39 (12.82%)
         occurrences all number
    5
    9
    2
    0
    2
    6
    Hypokalaemia
         subjects affected / exposed
    2 / 40 (5.00%)
    7 / 41 (17.07%)
    2 / 5 (40.00%)
    1 / 9 (11.11%)
    1 / 8 (12.50%)
    6 / 39 (15.38%)
         occurrences all number
    3
    8
    3
    1
    1
    8

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Aug 2012
    Updates made due to new safety information, adding consistency with current label claims and clarification of wording where previously there was the potential for misinterpretation.

    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.

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