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    Clinical Trial Results:
    An Open-Label, Extension (Rollover) Study of Vemurafenib in Patients With BRAF V600 Mutation-Positive Malignancies Previously Enrolled in an Antecedent Vemurafenib Protocol

    Summary
    EudraCT number
    		 2012-003144-80
    Trial protocol
    		 GB   BE   HU   DE   GR   NL   ES   FI   PT   IT   HR   FR   CY  
    Global end of trial date
    17 Feb 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 Nov 2020
    First version publication date
    12 Nov 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    GO28399
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01739764
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH4070
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.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
    17 Feb 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Feb 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the long-term safety of Vemurafenib
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    19 Feb 2013
    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
    Bosnia and Herzegovina: 3
    Country: Number of subjects enrolled
    Belarus: 2
    Country: Number of subjects enrolled
    Brazil: 1
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    Cyprus: 3
    Country: Number of subjects enrolled
    Germany: 7
    Country: Number of subjects enrolled
    Egypt: 12
    Country: Number of subjects enrolled
    Spain: 22
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    Greece: 1
    Country: Number of subjects enrolled
    Croatia: 5
    Country: Number of subjects enrolled
    Hungary: 14
    Country: Number of subjects enrolled
    Israel: 9
    Country: Number of subjects enrolled
    Italy: 4
    Country: Number of subjects enrolled
    Korea, Republic of: 41
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    New Zealand: 2
    Country: Number of subjects enrolled
    Portugal: 2
    Country: Number of subjects enrolled
    Romania: 4
    Country: Number of subjects enrolled
    Russian Federation: 22
    Country: Number of subjects enrolled
    Serbia: 8
    Country: Number of subjects enrolled
    United States: 37
    Country: Number of subjects enrolled
    South Africa: 5
    Worldwide total number of subjects
    215
    EEA total number of subjects
    72
    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)
    162
    From 65 to 84 years
    51
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study was conducted at 82 centers in 24 countries.

    Pre-assignment
    Screening details
    		 215 subjects were enrolled into this OLE study and were included in the Safety population.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Vemurafenib 480mg BID
    Arm description
    		 Subjects received oral vemurafenib at 480 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the subject is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vemurafenib
    Investigational medicinal product code
    Other name
    Zelboraf
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Vemurafenib was administered orally twice daily (BID) at a dose of 480mg.

    Arm title
    		 Vemurafenib 720mg BID
    Arm description
    		 Subjects received oral vemurafenib at 720 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the subject is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vemurafenib
    Investigational medicinal product code
    Other name
    Zelboraf
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Vemurafenib was administered orally twice daily (BID) at a dose of 720mg.

    Arm title
    		 Vemurafenib 960mg BID
    Arm description
    		 Subjects received oral vemurafenib at 960 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the subject is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vemurafenib
    Investigational medicinal product code
    Other name
    Zelboraf
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Vemurafenib was administered orally twice daily (BID) at a dose of 960mg.

    Number of subjects in period 1
    		Vemurafenib 480mg BID Vemurafenib 720mg BID Vemurafenib 960mg BID
    Started
    29
    40
    146
    Completed
    3
    4
    20
    Not completed
    26
    36
    126
         Adverse event, serious fatal
    4
    6
    38
         Physician decision
    2
    2
    4
         Consent withdrawn by subject
    6
    5
    27
         Non-Compliance
    -
    -
    1
         Adverse event, non-fatal
    -
    3
    4
         Progressive Disease
    3
    5
    16
         Multiple Reasons
    3
    2
    3
         Study Terminated by Sponsor
    8
    13
    26
         Lost to follow-up
    -
    -
    5
         Protocol deviation
    -
    -
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Vemurafenib 480mg BID
    Reporting group description
    		 Subjects received oral vemurafenib at 480 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the subject is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.

    Reporting group title
    Vemurafenib 720mg BID
    Reporting group description
    		 Subjects received oral vemurafenib at 720 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the subject is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.

    Reporting group title
    Vemurafenib 960mg BID
    Reporting group description
    		 Subjects received oral vemurafenib at 960 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the subject is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.

    Reporting group values
    		 Vemurafenib 480mg BID Vemurafenib 720mg BID Vemurafenib 960mg BID Total
    Number of subjects
    		 29 40 146 215
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 18 22 122 162
        From 65-84 years
    		 10 17 24 51
        85 years and over
    		 1 1 0 2
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 60.4 ( 11.7 ) 60.6 ( 12.4 ) 52.3 ( 13.5 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 18 20 57 95
        Male
    		 11 20 89 120
    Race/Ethnicity, Customized
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 2 2 3 7
        Not Hispanic or Latino
    		 24 37 137 198
        Not Stated
    		 3 1 6 10
    Race/Ethnicity, Customized
    Race
    Units: Subjects
        Asian
    		 2 2 39 43
        Black or African American
    		 1 0 0 1
        White
    		 23 37 101 161
        Other
    		 0 1 2 3
        Unknown
    		 3 0 4 7

    End points

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    End points reporting groups
    Reporting group title
    Vemurafenib 480mg BID
    Reporting group description
    		 Subjects received oral vemurafenib at 480 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the subject is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.

    Reporting group title
    Vemurafenib 720mg BID
    Reporting group description
    		 Subjects received oral vemurafenib at 720 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the subject is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.

    Reporting group title
    Vemurafenib 960mg BID
    Reporting group description
    		 Subjects received oral vemurafenib at 960 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the subject is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.

    Primary: Dose Intensity of Vemurafenib

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    End point title
    		 Dose Intensity of Vemurafenib [1]
    End point description
    Dose Intensity was defined as (total actual doses taken/total planned doses) *100, where total planned doses = prescribed doses * planned days on treatment, where planned days on treatment were defined as the interval between date of first dose and date of last dose. Please note that for this Outcome Measure, one subject who received 960 mg BID of Vemurafenib had no treatment end date indicated and was excluded from the calculation of study treatment exposure summaries.
    End point type
    Primary
    End point timeframe
    Baseline up to a maximum of 7 years.
    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: No statistical analyses were performed, as no efficacy analysis was conducted and only safety data was collected.
    End point values
    		 Vemurafenib 480mg BID Vemurafenib 720mg BID Vemurafenib 960mg BID
    Number of subjects analysed
    29
    40
    145
    Units: Percentage of Planned Dose
        arithmetic mean (standard deviation)
    95.3 ( 8.1 )
    92.9 ( 12.1 )
    94.5 ( 11.0 )
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Adverse Events (AEs) or Serious Adverse Events (SAEs)

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    End point title
    		 Percentage of Subjects With Adverse Events (AEs) or Serious Adverse Events (SAEs)
    End point description
    An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as Adverse Events. Reported are the Percentage of Subjects with AEs and Serious Adverse Events (SAEs).
    End point type
    Secondary
    End point timeframe
    Baseline up to 28 days after the last dose of study drug (up to a maximum of 7 years).
    End point values
    		 Vemurafenib 480mg BID Vemurafenib 720mg BID Vemurafenib 960mg BID
    Number of subjects analysed
    29
    40
    146
    Units: Percentage of Subjects
    number (not applicable)
        AEs
    93.1
    92.5
    93.2
        SAEs
    48.3
    37.5
    19.9
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to 28 days after the last dose of study drug (up to a maximum of 7 years).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Vemurafenib 480mg BID
    Reporting group description
    		 Subjects received oral vemurafenib at 480 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the subject is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.

    Reporting group title
    Vemurafenib 960mg BID
    Reporting group description
    		 Subjects received oral vemurafenib at 960 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the subject is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.

    Reporting group title
    Vemurafenib 720mg BID
    Reporting group description
    		 Subjects received oral vemurafenib at 720 mg BID, depending on the last dose in the antecedent protocol until progression of disease or as long as the subject is deriving clinical benefit, as judged by the investigator, death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the sponsor to terminate the study, whichever occurs first.

    Serious adverse events
    		 Vemurafenib 480mg BID Vemurafenib 960mg BID Vemurafenib 720mg BID
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 29 (48.28%)
    29 / 146 (19.86%)
    15 / 40 (37.50%)
         number of deaths (all causes)
    4
    38
    6
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BRAIN NEOPLASM BENIGN
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BREAST CANCER
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBRAL HAEMANGIOMA
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATIC CANCER
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INVASIVE DUCTAL BREAST CARCINOMA
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MALIGNANT MELANOMA
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    METASTASES TO LUNG
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    METASTATIC MALIGNANT MELANOMA
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SQUAMOUS CELL CARCINOMA
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SQUAMOUS CELL CARCINOMA OF SKIN
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    TRACHEAL RESECTION
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEATH
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    FATIGUE
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    BRONCHOSPASM
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    1 / 29 (3.45%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EPISTAXIS
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMOPTYSIS
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    ANXIETY DISORDER
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BIPOLAR DISORDER
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COMPLETED SUICIDE
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLOOD BILIRUBIN INCREASED
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLOOD LACTATE DEHYDROGENASE INCREASED
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ELECTROCARDIOGRAM QT PROLONGED
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    FEMUR FRACTURE
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ROAD TRAFFIC ACCIDENT
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TRACHEAL HAEMORRHAGE
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    ACUTE CORONARY SYNDROME
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ARTERIOSCLEROSIS CORONARY ARTERY
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATRIAL FIBRILLATION
         subjects affected / exposed
    1 / 29 (3.45%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CARDIAC FAILURE
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    0 / 29 (0.00%)
    3 / 146 (2.05%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Nervous system disorders
    CEREBRAL INFARCTION
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBROVASCULAR ACCIDENT
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EPILEPSY
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FACIAL PARALYSIS
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEADACHE
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYDROCEPHALUS
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SEIZURE
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    CATARACT NUCLEAR
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PAROPHTHALMIA
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    COLITIS ULCERATIVE
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    0 / 29 (0.00%)
    3 / 146 (2.05%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIVERTICULAR PERFORATION
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    GASTRIC ULCER
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMATOCHEZIA
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMOPERITONEUM
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMORRHOIDS
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL OBSTRUCTION
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OESOPHAGEAL STENOSIS
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS ACUTE
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RECTAL HAEMORRHAGE
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    JAUNDICE
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    RENAL COLIC
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL FAILURE
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MYOPATHY TOXIC
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NECK PAIN
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PATHOLOGICAL FRACTURE
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ROTATOR CUFF SYNDROME
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    CELLULITIS
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CLOSTRIDIUM DIFFICILE COLITIS
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ERYSIPELAS
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROENTERITIS
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MENINGITIS
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POSTOPERATIVE WOUND INFECTION
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SINUSITIS BACTERIAL
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VIRAL UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    DIABETES MELLITUS
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Vemurafenib 480mg BID Vemurafenib 960mg BID Vemurafenib 720mg BID
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    21 / 29 (72.41%)
    119 / 146 (81.51%)
    29 / 40 (72.50%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BASAL CELL CARCINOMA
         subjects affected / exposed
    0 / 29 (0.00%)
    3 / 146 (2.05%)
    2 / 40 (5.00%)
         occurrences all number
    0
    3
    4
    MELANOCYTIC NAEVUS
         subjects affected / exposed
    2 / 29 (6.90%)
    4 / 146 (2.74%)
    1 / 40 (2.50%)
         occurrences all number
    4
    5
    2
    SQUAMOUS CELL CARCINOMA OF SKIN
         subjects affected / exposed
    0 / 29 (0.00%)
    7 / 146 (4.79%)
    2 / 40 (5.00%)
         occurrences all number
    0
    13
    3
    SKIN PAPILLOMA
         subjects affected / exposed
    1 / 29 (3.45%)
    16 / 146 (10.96%)
    0 / 40 (0.00%)
         occurrences all number
    1
    24
    0
    Vascular disorders
    HYPERTENSION
         subjects affected / exposed
    2 / 29 (6.90%)
    8 / 146 (5.48%)
    3 / 40 (7.50%)
         occurrences all number
    2
    8
    3
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    3 / 29 (10.34%)
    3 / 146 (2.05%)
    5 / 40 (12.50%)
         occurrences all number
    4
    3
    5
    FATIGUE
         subjects affected / exposed
    2 / 29 (6.90%)
    28 / 146 (19.18%)
    5 / 40 (12.50%)
         occurrences all number
    2
    33
    5
    OEDEMA PERIPHERAL
         subjects affected / exposed
    0 / 29 (0.00%)
    5 / 146 (3.42%)
    2 / 40 (5.00%)
         occurrences all number
    0
    6
    2
    PYREXIA
         subjects affected / exposed
    1 / 29 (3.45%)
    9 / 146 (6.16%)
    1 / 40 (2.50%)
         occurrences all number
    1
    11
    2
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    2 / 29 (6.90%)
    10 / 146 (6.85%)
    1 / 40 (2.50%)
         occurrences all number
    2
    10
    1
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 29 (0.00%)
    3 / 146 (2.05%)
    2 / 40 (5.00%)
         occurrences all number
    0
    4
    3
    BLOOD BILIRUBIN INCREASED
         subjects affected / exposed
    2 / 29 (6.90%)
    8 / 146 (5.48%)
    4 / 40 (10.00%)
         occurrences all number
    2
    8
    9
    BLOOD CHOLESTEROL INCREASED
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    2 / 40 (5.00%)
         occurrences all number
    0
    2
    2
    ELECTROCARDIOGRAM QT PROLONGED
         subjects affected / exposed
    0 / 29 (0.00%)
    7 / 146 (4.79%)
    2 / 40 (5.00%)
         occurrences all number
    0
    11
    2
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    1 / 29 (3.45%)
    8 / 146 (5.48%)
    3 / 40 (7.50%)
         occurrences all number
    3
    10
    3
    PLATELET COUNT DECREASED
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    2
    WEIGHT DECREASED
         subjects affected / exposed
    1 / 29 (3.45%)
    10 / 146 (6.85%)
    1 / 40 (2.50%)
         occurrences all number
    1
    10
    1
    Injury, poisoning and procedural complications
    SUNBURN
         subjects affected / exposed
    0 / 29 (0.00%)
    6 / 146 (4.11%)
    2 / 40 (5.00%)
         occurrences all number
    0
    8
    2
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 146 (1.37%)
    3 / 40 (7.50%)
         occurrences all number
    2
    2
    3
    HEADACHE
         subjects affected / exposed
    0 / 29 (0.00%)
    15 / 146 (10.27%)
    4 / 40 (10.00%)
         occurrences all number
    0
    15
    4
    NEUROPATHY PERIPHERAL
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 146 (1.37%)
    0 / 40 (0.00%)
         occurrences all number
    2
    2
    0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    1 / 29 (3.45%)
    13 / 146 (8.90%)
    5 / 40 (12.50%)
         occurrences all number
    1
    18
    6
    Ear and labyrinth disorders
    VERTIGO
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    3 / 40 (7.50%)
         occurrences all number
    0
    1
    3
    Eye disorders
    GLAUCOMA
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 146 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    2
    UVEITIS
         subjects affected / exposed
    2 / 29 (6.90%)
    3 / 146 (2.05%)
    2 / 40 (5.00%)
         occurrences all number
    2
    4
    5
    VISION BLURRED
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 146 (0.68%)
    2 / 40 (5.00%)
         occurrences all number
    2
    1
    2
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    3 / 29 (10.34%)
    4 / 146 (2.74%)
    4 / 40 (10.00%)
         occurrences all number
    6
    4
    4
    CONSTIPATION
         subjects affected / exposed
    2 / 29 (6.90%)
    6 / 146 (4.11%)
    2 / 40 (5.00%)
         occurrences all number
    2
    7
    2
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 146 (1.37%)
    1 / 40 (2.50%)
         occurrences all number
    2
    2
    1
    DIARRHOEA
         subjects affected / exposed
    3 / 29 (10.34%)
    16 / 146 (10.96%)
    3 / 40 (7.50%)
         occurrences all number
    6
    18
    5
    DYSPEPSIA
         subjects affected / exposed
    1 / 29 (3.45%)
    8 / 146 (5.48%)
    3 / 40 (7.50%)
         occurrences all number
    1
    8
    3
    DYSPHAGIA
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 146 (1.37%)
    1 / 40 (2.50%)
         occurrences all number
    2
    2
    1
    NAUSEA
         subjects affected / exposed
    4 / 29 (13.79%)
    16 / 146 (10.96%)
    8 / 40 (20.00%)
         occurrences all number
    4
    22
    8
    VOMITING
         subjects affected / exposed
    2 / 29 (6.90%)
    12 / 146 (8.22%)
    4 / 40 (10.00%)
         occurrences all number
    2
    13
    5
    Skin and subcutaneous tissue disorders
    ACTINIC KERATOSIS
         subjects affected / exposed
    2 / 29 (6.90%)
    7 / 146 (4.79%)
    3 / 40 (7.50%)
         occurrences all number
    2
    12
    3
    ALOPECIA
         subjects affected / exposed
    0 / 29 (0.00%)
    21 / 146 (14.38%)
    2 / 40 (5.00%)
         occurrences all number
    0
    21
    2
    DERMAL CYST
         subjects affected / exposed
    1 / 29 (3.45%)
    5 / 146 (3.42%)
    2 / 40 (5.00%)
         occurrences all number
    1
    5
    2
    DERMATITIS
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 146 (1.37%)
    2 / 40 (5.00%)
         occurrences all number
    0
    2
    2
    DRY SKIN
         subjects affected / exposed
    0 / 29 (0.00%)
    9 / 146 (6.16%)
    5 / 40 (12.50%)
         occurrences all number
    0
    10
    5
    ERYTHEMA
         subjects affected / exposed
    3 / 29 (10.34%)
    7 / 146 (4.79%)
    2 / 40 (5.00%)
         occurrences all number
    5
    13
    2
    HYPERKERATOSIS
         subjects affected / exposed
    1 / 29 (3.45%)
    20 / 146 (13.70%)
    3 / 40 (7.50%)
         occurrences all number
    1
    21
    4
    PANNICULITIS
         subjects affected / exposed
    2 / 29 (6.90%)
    3 / 146 (2.05%)
    1 / 40 (2.50%)
         occurrences all number
    2
    10
    1
    PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME
         subjects affected / exposed
    2 / 29 (6.90%)
    12 / 146 (8.22%)
    4 / 40 (10.00%)
         occurrences all number
    2
    13
    4
    PHOTOSENSITIVITY REACTION
         subjects affected / exposed
    1 / 29 (3.45%)
    22 / 146 (15.07%)
    2 / 40 (5.00%)
         occurrences all number
    1
    32
    4
    PRURITUS
         subjects affected / exposed
    1 / 29 (3.45%)
    13 / 146 (8.90%)
    3 / 40 (7.50%)
         occurrences all number
    1
    15
    3
    RASH
         subjects affected / exposed
    2 / 29 (6.90%)
    14 / 146 (9.59%)
    1 / 40 (2.50%)
         occurrences all number
    2
    16
    1
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    4 / 29 (13.79%)
    30 / 146 (20.55%)
    10 / 40 (25.00%)
         occurrences all number
    4
    41
    15
    BACK PAIN
         subjects affected / exposed
    1 / 29 (3.45%)
    9 / 146 (6.16%)
    1 / 40 (2.50%)
         occurrences all number
    2
    9
    1
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 146 (1.37%)
    0 / 40 (0.00%)
         occurrences all number
    2
    2
    0
    MYALGIA
         subjects affected / exposed
    0 / 29 (0.00%)
    6 / 146 (4.11%)
    2 / 40 (5.00%)
         occurrences all number
    0
    6
    3
    PAIN IN EXTREMITY
         subjects affected / exposed
    2 / 29 (6.90%)
    7 / 146 (4.79%)
    2 / 40 (5.00%)
         occurrences all number
    2
    12
    2
    Infections and infestations
    CHORIORETINITIS
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 146 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    2
    0
    1
    NASOPHARYNGITIS
         subjects affected / exposed
    2 / 29 (6.90%)
    10 / 146 (6.85%)
    1 / 40 (2.50%)
         occurrences all number
    2
    10
    1
    GASTROENTERITIS
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 146 (0.68%)
    2 / 40 (5.00%)
         occurrences all number
    0
    1
    2
    PNEUMONIA
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 146 (1.37%)
    3 / 40 (7.50%)
         occurrences all number
    2
    2
    3
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    2 / 29 (6.90%)
    6 / 146 (4.11%)
    1 / 40 (2.50%)
         occurrences all number
    3
    7
    1
    URINARY TRACT INFECTION
         subjects affected / exposed
    3 / 29 (10.34%)
    1 / 146 (0.68%)
    4 / 40 (10.00%)
         occurrences all number
    3
    1
    5
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    2 / 29 (6.90%)
    19 / 146 (13.01%)
    3 / 40 (7.50%)
         occurrences all number
    2
    24
    5
    DEHYDRATION
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 146 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    2
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    25 Sep 2013
    Following updates were made: [1] Safety Information for Vemurafenib updated to include three newly identified adverse drug reactions in subjects treated with Vemurafenib; [2] Updates to Study Title, Medical Monitor contact information, references to Urinalysis removed; [3] Clarification of timing for prohibited therapy prior to study entry; [4] Clarification to personnel who can perform dermatological examinations and [5] Updating of language around serious adverse events and adverse events of special interest.
    21 Mar 2014
    Following updates were made: [1] Updating of Safety Information for Vemurafenib; [2] Modification of oral Vemurafenib dose to include 960 mg, 720 mg and 480 mg twice daily; [3] Deletion of anticoagulation therapy and antiplatelet agents from the list of prohibited medications; [4] Addition of instructions on the collection of electrocardiograms; [5] Changes to the permitted windows of time for the screening assessments; [6] Modification to the Schedule of Assessments and [7] Change to allow for a one-year safety follow-up visit for subjects with papillary thyroid cancer.
    13 Mar 2015
    Following update was made: [1] New safety information for subjects being treated with Vemurafenib for pancreatitis and for potentiation of radiation treatment toxicity and the reporting of a second case of progression of a preexisting RAS-mutated malignancy (pancreatic adenocarcinoma with KRAS mutation).
    28 Aug 2018
    Following updates were made: [1] Removal of Safety follow-up visits at 3 and 6 months; [2] Updating of End of study safety follow up and dermatological evaluations; [3] Updating of Follow-up for new primary malignancies; [4] Addition of new Safety information; [5] Clarification to Adverse Event reporting and [6] Clarification to language on partner pregnancies.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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