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    Clinical Trial Results:
    A Phase III, International, Randomised, Double-Blind, Parallel-Group, Multi-Centre Study to Assess the Efficacy of ZD6474(ZACTIMA™) Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in Patients With Locally Advanced or Metastatic (Stage IIIB – IV) Non-Small Cell Lung Cancer (NSCLC) after Prior Therapy with an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI)

    Summary
    EudraCT number
    		 2006-002384-12
    Trial protocol
    		 BE   DE   FR   AT   NL   GB   IT   ES  
    Global end of trial date
    30 Nov 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Jun 2016
    First version publication date
    09 Jun 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D4200C00044
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00404924
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca
    Sponsor organisation address
    151 85, Södertälje, Sweden,
    Public contact
    Gabriella Mariani, AstraZeneca, aztrial_results_posting@astrazeneca.com
    Scientific contact
    Gabriella Mariani, AstraZeneca, aztrial_results_posting@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    30 Mar 2010
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    19 Oct 2009
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Nov 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to demonstrate an improvement in overall survival for ZD6474 plus best supportive care (BSC) compared with placebo plus BSC in patients with locally advanced or metastatic NSCLC after prior therapy with an EGFR TKI.
    Protection of trial subjects
    The study will be performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and are consistent with ICH/Good Clinical Practice, applicable regulatory requirements and the AstraZeneca policy on Bioethics.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Nov 2006
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy
    Long term follow-up duration
    		 15 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 26
    Country: Number of subjects enrolled
    Australia: 19
    Country: Number of subjects enrolled
    Austria: 17
    Country: Number of subjects enrolled
    Belgium: 44
    Country: Number of subjects enrolled
    Canada: 73
    Country: Number of subjects enrolled
    China: 170
    Country: Number of subjects enrolled
    France: 61
    Country: Number of subjects enrolled
    Germany: 112
    Country: Number of subjects enrolled
    Hong Kong: 44
    Country: Number of subjects enrolled
    Israel: 17
    Country: Number of subjects enrolled
    Italy: 62
    Country: Number of subjects enrolled
    Korea, Republic of: 220
    Country: Number of subjects enrolled
    Mexico: 23
    Country: Number of subjects enrolled
    Netherlands: 3
    Country: Number of subjects enrolled
    Peru: 13
    Country: Number of subjects enrolled
    Philippines: 9
    Country: Number of subjects enrolled
    Singapore: 16
    Country: Number of subjects enrolled
    Spain: 18
    Country: Number of subjects enrolled
    Taiwan: 135
    Country: Number of subjects enrolled
    Thailand: 33
    Country: Number of subjects enrolled
    United Kingdom: 24
    Country: Number of subjects enrolled
    United States: 1
    Worldwide total number of subjects
    1140
    EEA total number of subjects
    341
    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)
    700
    From 65 to 84 years
    434
    85 years and over
    6

    Subject disposition

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    Recruitment
    Recruitment details
    		 First patient enrolled 08 November 2006, last patient enrolled 09 October 2008, cut off date 19 October 2009. 1140 patients were screened in the study.

    Pre-assignment
    Screening details
    		 1140 patients signed inform consent and 924 randomised

    Pre-assignment period milestones
    Number of subjects started
    		 1140
    Number of subjects completed
    		 924

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Adverse event, serious fatal: 4
    Reason: Number of subjects
    		 Consent withdrawn by subject: 12
    Reason: Number of subjects
    		 Protocol deviation: 200
    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Monitor, Carer, Data analyst, Subject, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Vandetanib 300 mg
    Arm description
    		 vandetanib (300 mg daily) plus best supportive care
    Arm type
    		 Experimental

    Investigational medicinal product name
    ZACTIMA
    Investigational medicinal product code
    ZD6474
    Other name
    Caprelsa
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Single oral dose 300mg daily

    Arm title
    		 Placebo
    Arm description
    		 Placebo plus best supportive care
    Arm type
    		 Placebo

    Investigational medicinal product name
    placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Single oral dose 300mg daily

    Number of subjects in period 1 [1]
    		Vandetanib 300 mg Placebo
    Started
    617
    307
    Completed
    14
    1
    Not completed
    603
    306
         Consent withdrawn by subject
    26
    13
         Adverse event, non-fatal
    75
    16
         Condition under investigation worsened
    475
    264
         Not Specified
    25
    11
         Lost to follow-up
    1
    1
         Randomised but not received treatment
    1
    1
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: I have an error stating that the number for the worldwide enrolled is not equal to the number of patients who started the overall study at baseline - if the number enrolled is the number screened then this won't equal the number at baseline as this is the number randomised

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Vandetanib 300 mg
    Reporting group description
    		 vandetanib (300 mg daily) plus best supportive care

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo plus best supportive care

    Reporting group values
    		 Vandetanib 300 mg Placebo Total
    Number of subjects
    		 617 307 924
    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)
    		 396 180 576
        From 65-74 years
    		 157 92 249
        75 years and over
    		 64 35 99
    Age Continuous |
    Units: years
        arithmetic mean (full range (min-max))
    		 59.8 (20 to 85) 60.6 (21 to 84) -
    Gender, Male/Female
    Units: Participants
        Female
    		 329 160 489
        Male
    		 288 147 435

    End points

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    End points reporting groups
    Reporting group title
    Vandetanib 300 mg
    Reporting group description
    		 vandetanib (300 mg daily) plus best supportive care

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo plus best supportive care

    Primary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    Overall Survival (OS) is defined as the time from date of randomization until death. Any blinded/unknown patient which have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie, their status must be known at the censored date and should not be lost to follow up or unknown).
    End point type
    Primary
    End point timeframe
    Time to death in months
    End point values
    		 Vandetanib 300 mg Placebo
    Number of subjects analysed
    617
    307
    Units: Months
        median (confidence interval)
    8.5 (7.81 to 9.76)
    7.8 (6.08 to 9.17)
    Statistical analysis title
    		 Summary of Primary Analysis of Overall Survival
    Comparison groups
    Vandetanib 300 mg v Placebo
    Number of subjects included in analysis
    924
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5273
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.95
    Confidence interval
         level
    		 95.2%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 1.11

    Secondary: Progression-Free Survival (PFS)

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    End point title
    		 Progression-Free Survival (PFS)
    End point description
    Median time (in months) from randomisation until objective disease progression (determined by RECIST assessments) or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment
    End point type
    Secondary
    End point timeframe
    RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression
    End point values
    		 Vandetanib 300 mg Placebo
    Number of subjects analysed
    617
    307
    Units: month
        median (confidence interval)
    1.9 (1.84 to 2.23)
    1.8 (1.74 to 1.84)
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR)

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    End point title
    		 Objective Response Rate (ORR)
    End point description
    The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as defined by RECIST criteria. The categories for best objective response are CR, PR, stable disease (SD)>= 8 weeks, progressive disease (PD) or NE.
    End point type
    Secondary
    End point timeframe
    Each patient was assessed for objective response from the sequence of RECIST scan data up to data cut off. RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression.
    End point values
    		 Vandetanib 300 mg Placebo
    Number of subjects analysed
    617
    307
    Units: Participants
    16
    2
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR)

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    End point title
    		 Disease Control Rate (DCR)
    End point description
    Disease control rate is defined as the number of patients who achieved disease control at 8 weeks following randomisation. Disease control at 8 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 8 weeks
    End point type
    Secondary
    End point timeframe
    RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression
    End point values
    		 Vandetanib 300 mg Placebo
    Number of subjects analysed
    617
    307
    Units: Participants
    189
    48
    No statistical analyses for this end point

    Secondary: Duration of Response (DoR)

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    End point title
    		 Duration of Response (DoR)
    End point description
    Response is defined as a confirmed best objective response of CR or PR. Duration of response is defined as time from the date of first documented response until date of documented progression or death in the absence of disease progression (provided death is within 3 months of last RECIST assessment)
    End point type
    Secondary
    End point timeframe
    RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression
    End point values
    		 Vandetanib 300 mg Placebo
    Number of subjects analysed
    16
    2
    Units: Weeks
        median (confidence interval)
    23.9 (16.57 to 27)
    24.3 (16 to 32.57)
    No statistical analyses for this end point

    Secondary: Time to deterioration of disease-related symptoms (TDS) by questionnaire - the lung cancer subscale (LCS) a selection of the FACT-L focusing on symptoms of lung cancer plus pain and fatigue (LCS-PF)

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    End point title
    		 Time to deterioration of disease-related symptoms (TDS) by questionnaire - the lung cancer subscale (LCS) a selection of the FACT-L focusing on symptoms of lung cancer plus pain and fatigue (LCS-PF)
    End point description
    Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of ‘worsened’ with no visit assessment of ‘improved’ within the next 28 days. Where assessment is by a selection of questions from the Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) questionnaire.
    End point type
    Secondary
    End point timeframe
    Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication) and every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit
    End point values
    		 Vandetanib 300 mg Placebo
    Number of subjects analysed
    617
    307
    Units: weeks
        median (inter-quartile range (Q1-Q3))
    6.1 (5.14 to 8.14)
    7.1 (5.86 to 8.43)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs were collected up to 60days after discontinuation of study treatment.
    Adverse event reporting additional description
    The Safety Analysis Set included 922 patients (619 vandetanib & 303 placebo), which represents more than 99% of all randomized pts. 2 (1 in each arm) were excluded from the SAS as they were not dosed. Additionally 3 pts randomized to receive placebo received at least one dose of vandetanib, these 3 pts are included in the vandetanib arm in the SAS
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    12.1
    Reporting groups
    Reporting group title
    Vandetanib
    Reporting group description
    		 Vandetanib 300 mg

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo

    Serious adverse events
    		 Vandetanib Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    160 / 619 (25.85%)
    63 / 303 (20.79%)
         number of deaths (all causes)
    474
    230
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer Pain
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    7 / 619 (1.13%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    5 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep Vein Thrombosis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial Thrombosis Limb
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jugular Vein Thrombosis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis Superficial
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visceral Arterial Ischaemia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    5 / 619 (0.81%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 619 (0.48%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    Fatigue
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 619 (0.48%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 619 (0.48%)
    3 / 303 (0.99%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest Pain
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General Physical Health Deterioration
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Drug Hypersensitivity
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic Reaction
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    12 / 619 (1.94%)
    5 / 303 (1.65%)
         occurrences causally related to treatment / all
    1 / 14
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural Effusion
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    5 / 619 (0.81%)
    5 / 303 (1.65%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary Embolism
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 619 (0.48%)
    5 / 303 (1.65%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Haemoptysis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 619 (0.48%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    2 / 2
    0 / 0
    Cough
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia Aspiration
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonitis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute Respiratory Distress Syndrome
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Bronchial Haemorrhage
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Bronchospasm
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Idiopathic Pulmonary Fibrosis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary Artery Thrombosis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary Haemorrhage
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Respiratory Failure
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Respiratory Tract Haemorrhage
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional State
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Electrocardiogram T Wave Inversion
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lipase Increased
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil Count Decreased
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur Fracture
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral Neck Fracture
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint Dislocation
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple Injuries
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumothorax Traumatic
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist Fracture
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial Fibrillation
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac Failure
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    Myocardial Infarction
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 1
    1 / 1
    Angina Pectoris
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac Arrest
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac Valve Disease
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial Effusion
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsion
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    5 / 619 (0.81%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral Infarction
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    3 / 303 (0.99%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral Ischaemia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 619 (0.48%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular Accident
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 619 (0.48%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Cerebral Haemorrhage
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cognitive Disorder
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss Of Consciousness
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial Seizures
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Somnolence
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid Haemorrhage
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient Ischaemic Attack
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tremor
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile Neutropenia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 619 (0.48%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deafness
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Diplopia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vision Blurred
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visual Acuity Reduced
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    8 / 619 (1.29%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    5 / 8
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    4 / 619 (0.65%)
    3 / 303 (0.99%)
         occurrences causally related to treatment / all
    2 / 5
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal Distension
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal Pain
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal Ulcer
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal Perforation
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Gastrooesophageal Reflux Disease
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gingival Pain
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus Paralytic
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal Haemorrhage
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Intestinal Perforation
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Neutropenic Colitis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia Oral
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumatosis Intestinalis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proctalgia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subileus
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile Duct Stenosis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytolytic Hepatitis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    4 / 619 (0.65%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stevens-Johnson Syndrome
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 619 (0.48%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Photosensitivity Reaction
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermatitis Allergic
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dry Skin
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erythema
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erythema Multiforme
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash Pruritic
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary Retention
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus Urinary
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal Failure
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (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
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary Incontinence
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperthyroidism
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back Pain
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal Pain
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthralgia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone Pain
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle Twitching
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal Chest Pain
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck Pain
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain In Extremity
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    21 / 619 (3.39%)
    6 / 303 (1.98%)
         occurrences causally related to treatment / all
    0 / 26
    0 / 7
         deaths causally related to treatment / all
    0 / 3
    0 / 3
    Sepsis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 619 (0.48%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung Infection
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Urinary Tract Infection
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis Bacterial
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial Sepsis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bronchitis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter Site Infection
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridial Infection
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Empyema
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injection Site Abscess
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lobar Pneumonia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lower Respiratory Tract Infection
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pharyngitis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal Sepsis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous Abscess
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheitis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper Respiratory Tract Infection
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    4 / 619 (0.65%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased Appetite
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 619 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 619 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 619 (0.16%)
    0 / 303 (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
    		 Vandetanib Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    557 / 619 (89.98%)
    234 / 303 (77.23%)
    Investigations
    Weight Decreased
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    47 / 619 (7.59%)
    18 / 303 (5.94%)
         occurrences all number
    49
    18
    Electrocardiogram Qt Prolonged
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    37 / 619 (5.98%)
    1 / 303 (0.33%)
         occurrences all number
    48
    1
    Vascular disorders
    Hypertension
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    160 / 619 (25.85%)
    9 / 303 (2.97%)
         occurrences all number
    182
    9
    Nervous system disorders
    Dizziness
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    68 / 619 (10.99%)
    27 / 303 (8.91%)
         occurrences all number
    79
    28
    Headache
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    61 / 619 (9.85%)
    24 / 303 (7.92%)
         occurrences all number
    70
    25
    Blood and lymphatic system disorders
    Anaemia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    19 / 619 (3.07%)
    19 / 303 (6.27%)
         occurrences all number
    22
    22
    General disorders and administration site conditions
    Fatigue
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    109 / 619 (17.61%)
    50 / 303 (16.50%)
         occurrences all number
    122
    53
    Asthenia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    62 / 619 (10.02%)
    30 / 303 (9.90%)
         occurrences all number
    72
    34
    Pyrexia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    44 / 619 (7.11%)
    29 / 303 (9.57%)
         occurrences all number
    52
    34
    Oedema Peripheral
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    33 / 619 (5.33%)
    29 / 303 (9.57%)
         occurrences all number
    33
    31
    Gastrointestinal disorders
    Diarrhoea
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    284 / 619 (45.88%)
    34 / 303 (11.22%)
         occurrences all number
    407
    38
    Nausea
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    138 / 619 (22.29%)
    51 / 303 (16.83%)
         occurrences all number
    170
    63
    Constipation
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    88 / 619 (14.22%)
    63 / 303 (20.79%)
         occurrences all number
    99
    69
    Vomiting
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    82 / 619 (13.25%)
    36 / 303 (11.88%)
         occurrences all number
    106
    50
    Stomatitis
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    34 / 619 (5.49%)
    13 / 303 (4.29%)
         occurrences all number
    37
    14
    Abdominal Pain
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    26 / 619 (4.20%)
    19 / 303 (6.27%)
         occurrences all number
    28
    19
    Respiratory, thoracic and mediastinal disorders
    Cough
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    108 / 619 (17.45%)
    54 / 303 (17.82%)
         occurrences all number
    122
    59
    Dyspnoea
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    98 / 619 (15.83%)
    52 / 303 (17.16%)
         occurrences all number
    102
    56
    Skin and subcutaneous tissue disorders
    Rash
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    258 / 619 (41.68%)
    33 / 303 (10.89%)
         occurrences all number
    295
    35
    Pruritus
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    70 / 619 (11.31%)
    16 / 303 (5.28%)
         occurrences all number
    83
    16
    Dry Skin
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    49 / 619 (7.92%)
    8 / 303 (2.64%)
         occurrences all number
    55
    8
    Psychiatric disorders
    Insomnia
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    63 / 619 (10.18%)
    24 / 303 (7.92%)
         occurrences all number
    68
    24
    Renal and urinary disorders
    Proteinuria
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    56 / 619 (9.05%)
    10 / 303 (3.30%)
         occurrences all number
    66
    13
    Musculoskeletal and connective tissue disorders
    Back Pain
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    54 / 619 (8.72%)
    19 / 303 (6.27%)
         occurrences all number
    59
    22
    Musculoskeletal Pain
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    22 / 619 (3.55%)
    20 / 303 (6.60%)
         occurrences all number
    22
    21
    Metabolism and nutrition disorders
    Decreased Appetite
    alternative dictionary used: MedDRA 12.1
    alternative assessment type: Systematic
         subjects affected / exposed
    143 / 619 (23.10%)
    63 / 303 (20.79%)
         occurrences all number
    158
    67

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 May 2007
    Procedural clarifications for ECG, archival tumour samples and patients taking contraindicated concomitant medications. Schedule of assessments clarification for RECIST assessments, collection of AE/SAEs. Clarification on statistical analyses, DMC requirements
    16 Apr 2009
    Procedural clarifications. Clarification of secondary endpoints for PRO analysis. Remove co-primary analysis and adjust significance levels and testing procedures accordingly.
    08 Jan 2010
    Update to prodecures for patients still receiving treatment after final planned data analysis.

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

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