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    Clinical Trial Results:
    A PHASE II RANDOMIZED STUDY OF DOCETAXEL WITH OR WITHOUT NINTEDANIB (BIBF-1120) IN PATIENT RECEIVING A SECOND-LINE OF CHEMOTHERAPY FOR HER NEGATIVE, METASTATIC OR LOCALLY RECURRENT BREAST CANCER

    Summary
    EudraCT number
    		 2012-002214-38
    Trial protocol
    		 FR  
    Global end of trial date
    15 Sep 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Nov 2025
    First version publication date
    19 Nov 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    VAROCE-1206
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01658462
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Centre Oscar Lambret
    Sponsor organisation address
    rue Frederic Combemale, Lille, France, 59000
    Public contact
    Project Manager, Centre Oscar Lambret, 33 320295918, promotion@o-lambret.fr
    Scientific contact
    Project Manager, Centre Oscar Lambret, 33 320295918, promotion@o-lambret.fr
    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
    24 Aug 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Sep 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Sep 2016
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate progression-free survival in patients receiving Docetaxel + Nintedanib treatment (Arm A) compared to Docetaxel alone (Arm B)
    Protection of trial subjects
    This clinical trial will be conducted in accordance with the protocol, the ethical principles laid down by the 18th World Medical Assembly (Helsinki, 1964) and all applicable amendments laid down by the World Medical Assemblies, the International Conference on Harmonization (ICH) consolidated Guideline E6 for Good Clinical Practice (CPMP/ICH/135/95), and all applicable laws and regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 May 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
    France: 51
    Worldwide total number of subjects
    51
    EEA total number of subjects
    51
    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)
    37
    From 65 to 84 years
    14
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 51 patients were included between 23/05/2013 and 23/02/2016 in 6 french centers : 26 in Arm A (docetaxel + nintedanib) and 25 in Arm B (docetaxel alone)

    Pre-assignment
    Screening details
    		 The planned sample size was to randomize 252 patients (126 per arm) during an accrual period of 24 months and a study duration of 36 months. However, this sample size was not reached because of low accrual and 51 patients were included on the accrual period.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm A : Docetaxel + Nintedanib
    Arm description
    		 Docetaxel 75 mg/m² IV D1 / 3 weeks + Nintedanib 200 mg x 2 per os daily from D2 Patients will be stratified at randomization according to first-line chemotherapy / Second-line chemotherapy for metastatic or locally recurrent breast cancer Treatment until progression or unacceptable toxicity Visits are planned every 3 weeks during treatment and every 3 months after end of treatment or patient’s withdrawal
    Arm type
    		 Experimental

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Docetaxel 75 mg/m² IV D1 / 3 weeks

    Investigational medicinal product name
    Nintedanib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Nintedanib 200 mg x 2 per os daily from D2

    Arm title
    		 Arm B : Docetaxel
    Arm description
    		 Docetaxel 75 mg/m² IV D1 / 3 weeks Dose can be increased to 100 mg/m² secondarily at cycle 2 on the initiative of the investigator Patients will be stratified at randomization according to first-line chemotherapy / Second-line chemotherapy for metastatic or locally recurrent breast cancer Treatment until progression or unacceptable toxicity Visits are planned every 3 weeks during treatment and every 3 months after end of treatment or patient’s withdrawal
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Docetaxel 75 mg/m² IV D1 / 3 weeks Dose can be increased to 100 mg/m² secondarily at cycle 2 on the initiative of the investigator

    Number of subjects in period 1
    		Arm A : Docetaxel + Nintedanib Arm B : Docetaxel
    Started
    26
    25
    Completed
    26
    24
    Not completed
    0
    1
         Patient decision
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm A : Docetaxel + Nintedanib
    Reporting group description
    		 Docetaxel 75 mg/m² IV D1 / 3 weeks + Nintedanib 200 mg x 2 per os daily from D2 Patients will be stratified at randomization according to first-line chemotherapy / Second-line chemotherapy for metastatic or locally recurrent breast cancer Treatment until progression or unacceptable toxicity Visits are planned every 3 weeks during treatment and every 3 months after end of treatment or patient’s withdrawal

    Reporting group title
    Arm B : Docetaxel
    Reporting group description
    		 Docetaxel 75 mg/m² IV D1 / 3 weeks Dose can be increased to 100 mg/m² secondarily at cycle 2 on the initiative of the investigator Patients will be stratified at randomization according to first-line chemotherapy / Second-line chemotherapy for metastatic or locally recurrent breast cancer Treatment until progression or unacceptable toxicity Visits are planned every 3 weeks during treatment and every 3 months after end of treatment or patient’s withdrawal

    Reporting group values
    		 Arm A : Docetaxel + Nintedanib Arm B : Docetaxel Total
    Number of subjects
    		 26 25 51
    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)
    		 18 19 37
        From 65-84 years
    		 8 6 14
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 57.5 (37 to 75) 53 (35 to 78) -
    Gender categorical
    Units: Subjects
        Female
    		 26 25 51
        Male
    		 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Arm A : Docetaxel + Nintedanib
    Reporting group description
    		 Docetaxel 75 mg/m² IV D1 / 3 weeks + Nintedanib 200 mg x 2 per os daily from D2 Patients will be stratified at randomization according to first-line chemotherapy / Second-line chemotherapy for metastatic or locally recurrent breast cancer Treatment until progression or unacceptable toxicity Visits are planned every 3 weeks during treatment and every 3 months after end of treatment or patient’s withdrawal

    Reporting group title
    Arm B : Docetaxel
    Reporting group description
    		 Docetaxel 75 mg/m² IV D1 / 3 weeks Dose can be increased to 100 mg/m² secondarily at cycle 2 on the initiative of the investigator Patients will be stratified at randomization according to first-line chemotherapy / Second-line chemotherapy for metastatic or locally recurrent breast cancer Treatment until progression or unacceptable toxicity Visits are planned every 3 weeks during treatment and every 3 months after end of treatment or patient’s withdrawal

    Primary: Progression-free survival

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    End point title
    		 Progression-free survival
    End point description
    Progression Free Survival (PFS) is estimated using the Kaplan-Meier method and defined as the time from randomization to first occurrence of disease progression (evaluation of tumor assessments using RECIST version 1.1) or death from any cause; patients alive without progression are censored at the last followup.
    End point type
    Primary
    End point timeframe
    Median PFS - overall trial
    End point values
    		 Arm A : Docetaxel + Nintedanib Arm B : Docetaxel
    Number of subjects analysed
    26
    25
    Units: month
        number (confidence interval 95%)
    9.3 (6.9 to 10.3)
    8.6 (5.9 to 15.7)
    Statistical analysis title
    		 Comparison of PFS between arms
    Statistical analysis description
    PFS was compared between the two arms using Logrank test and the Hazard Ratio was estimated with its 95% confidence interval using a Cox regression model.
    Comparison groups
    Arm B : Docetaxel v Arm A : Docetaxel + Nintedanib
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.52
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 1.5

    Secondary: Overall survival

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    End point title
    		 Overall survival
    End point description
    Overall survival was estimated using the Kaplan-Meier method and defined as the time from randomization to death. Patients alive were censored at the last follow-up date.
    End point type
    Secondary
    End point timeframe
    18-month and 24-month overall survival rate
    End point values
    		 Arm A : Docetaxel + Nintedanib Arm B : Docetaxel
    Number of subjects analysed
    26
    25
    Units: percent
    number (confidence interval 95%)
        18-month OS rate
    66.8 (41.9 to 82.9)
    65.6 (39.8 to 82.4)
        24-month OS rate
    55.7 (26.9 to 77.0)
    57.4 (30.6 to 77.1)
    Statistical analysis title
    		 Comparison of OS between arms
    Statistical analysis description
    Overall survival was compared between the two arms using Logrank test and the Hazard Ratio was estimated with its 95% confidence interval using a Cox regression model.
    Comparison groups
    Arm A : Docetaxel + Nintedanib v Arm B : Docetaxel
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.75
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.33
         upper limit
    		 2.24

    Secondary: Objective response rate

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    End point title
    		 Objective response rate
    End point description
    Responses were evaluated using RECIST version 1.1 and had to be confirmed at least 28 days after initial documentation of response. Objective response rate (OR rate) was defined as the number of complete or partial response / all included patients in the intent to treat (ITT) principle.
    End point type
    Secondary
    End point timeframe
    3-month objective response rate
    End point values
    		 Arm A : Docetaxel + Nintedanib Arm B : Docetaxel
    Number of subjects analysed
    26
    25
    Units: percent
        number (confidence interval 95%)
    42.3 (23.4 to 63.1)
    32.0 (14.9 to 53.5)
    Statistical analysis title
    		 Comparison of overall response rate between arms
    Statistical analysis description
    Response rates were compared between the two arms using the Khi-2 test.
    Comparison groups
    Arm A : Docetaxel + Nintedanib v Arm B : Docetaxel
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.45
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Disease control rate

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    End point title
    		 Disease control rate
    End point description
    Responses were evaluated using RECIST version 1.1 and had to be confirmed at least 28 days after initial documentation of response. Disease control rate (DC rate) was defined as the number of complete response, partial response or stable disease / all included patients in the intent to treat (ITT) principle.
    End point type
    Secondary
    End point timeframe
    3-month disease control rate
    End point values
    		 Arm A : Docetaxel + Nintedanib Arm B : Docetaxel
    Number of subjects analysed
    26
    25
    Units: percent
        number (confidence interval 95%)
    73.1 (52.2 to 88.4)
    68.0 (46.5 to 85.1)
    Statistical analysis title
    		 Comparison of disease control rates between arms
    Statistical analysis description
    Response rates were compared between the two arms using the Khi-2 test.
    Comparison groups
    Arm B : Docetaxel v Arm A : Docetaxel + Nintedanib
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.69
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Quality of life

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    End point title
    		 Quality of life
    End point description
    Quality of life was evaluated using EORTC QLQ C30 and module BR23 questionnary and scores were calculated according to EORTC method. For each scale of QLQC30 (or BR23), a definitive deterioration was defined by a decrease of the score (for functional scales and increase for symptom scales) by more than 10 points as compared with the score at randomization time, without later improvement (for functional scales and deterioration for symptom scales) superior to 10 points as compared with randomization time. Time until definitive deterioration (TUDD) of quality of life were defined as the time from randomization to the first observation of a definitive deterioration of QLQ-C30 (or BR23) score or death. Patients without any quality of life questionnaires were censored at baseline (J+1). Patients alive without definitive deterioration were censored at their date of last news. Results are given here for global health status and in attached document for functionnal and symptom scales.
    End point type
    Secondary
    End point timeframe
    Mediane Time Until Definitive Deterioration (TUDD) of quality of life - Global health status
    End point values
    		 Arm A : Docetaxel + Nintedanib Arm B : Docetaxel
    Number of subjects analysed
    26 [1]
    25 [2]
    Units: month
    number (confidence interval 95%)
        Global health status
    4.6 (2.5 to 1000)
    6.5 (2.3 to 1000)
    Attachments
    		 Quality_of_life_analysis
    Notes
    [1] - Arm A : Upper limit of 95% CI was not reached (noted "1000")
    [2] - Arm B: Upper limit of 95% CI was not reached (noted "1000")
    Statistical analysis title
    		 Comparison of TUDD for QLQ-C30global health status
    Statistical analysis description
    TUDD were compared between the two arms and Hazard Ratio were estimated with their 95% confidence intervals using Cox regression models.
    Comparison groups
    Arm A : Docetaxel + Nintedanib v Arm B : Docetaxel
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.68
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.39
         upper limit
    		 1.84

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    The AE reporting period begins upon signature of the informed consent form by the study subject and ends 30 days after last study treatment dose.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Arm A : Docetaxel + Nintedanib
    Reporting group description
    		 -

    Reporting group title
    Arm B : Docetaxel
    Reporting group description
    		 -

    Serious adverse events
    		 Arm A : Docetaxel + Nintedanib Arm B : Docetaxel
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 26 (30.77%)
    6 / 24 (25.00%)
         number of deaths (all causes)
    9
    8
         number of deaths resulting from adverse events
    0
    0
    Vascular disorders
    THROMBOSIS
    Additional description: THROMBOSIS
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    PERICARDIAL EFFUSION
    Additional description: PERICARDIAL EFFUSION
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    FEBRILE BONE MARROW APLASIA
    Additional description: FEBRILE BONE MARROW APLASIA
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FEBRILE NEUTROPENIA
    Additional description: FEBRILE NEUTROPENIA
         subjects affected / exposed
    3 / 26 (11.54%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    HYPERTHERMIA
    Additional description: HYPERTHERMIA
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MALAISE
    Additional description: MALAISE
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PYREXIA
    Additional description: PYREXIA
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    CATARACT
    Additional description: CATARACT
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN
    Additional description: ABDOMINAL PAIN
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    CHOLECYSTITIS
    Additional description: CHOLECYSTITIS
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (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
    Additional description: DYSPNOEA
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    GROIN PAIN
    Additional description: GROIN PAIN
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MUSCULOSKELETAL CHEST PAIN
    Additional description: MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    PNEUMONIA
    Additional description: PNEUMONIA
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    DEHYDRATION
    Additional description: DEHYDRATION
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (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: 0%
    Non-serious adverse events
    		 Arm A : Docetaxel + Nintedanib Arm B : Docetaxel
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    26 / 26 (100.00%)
    24 / 24 (100.00%)
    Vascular disorders
    BEHCET'S SYNDROME
    Additional description: BEHCET'S SYNDROME
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    2
    FLUSHING
    Additional description: FLUSHING
         subjects affected / exposed
    6 / 26 (23.08%)
    4 / 24 (16.67%)
         occurrences all number
    7
    6
    HOT FLUSH
    Additional description: HOT FLUSH
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    HYPERTENSION
    Additional description: HYPERTENSION
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    HYPOTENSION
    Additional description: HYPOTENSION
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 24 (0.00%)
         occurrences all number
    3
    0
    LYMPHOEDEMA
    Additional description: LYMPHOEDEMA
         subjects affected / exposed
    1 / 26 (3.85%)
    3 / 24 (12.50%)
         occurrences all number
    1
    4
    PHLEBITIS
    Additional description: PHLEBITIS
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    SYSTOLIC HYPERTENSION
    Additional description: SYSTOLIC HYPERTENSION
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    ASTHENIA
    Additional description: ASTHENIA
         subjects affected / exposed
    22 / 26 (84.62%)
    23 / 24 (95.83%)
         occurrences all number
    69
    121
    AXILLARY PAIN
    Additional description: AXILLARY PAIN
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    CHILLS
    Additional description: CHILLS
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    CHEST PAIN
    Additional description: CHEST PAIN
         subjects affected / exposed
    3 / 26 (11.54%)
    5 / 24 (20.83%)
         occurrences all number
    3
    5
    FACE OEDEMA
    Additional description: FACE OEDEMA
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 24 (0.00%)
         occurrences all number
    4
    0
    FATIGUE
    Additional description: FATIGUE
         subjects affected / exposed
    6 / 26 (23.08%)
    2 / 24 (8.33%)
         occurrences all number
    12
    3
    FEELING ABNORMAL
    Additional description: FEELING ABNORMAL
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    FEELING HOT
    Additional description: FEELING HOT
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    HYPERTHERMIA
    Additional description: HYPERTHERMIA
         subjects affected / exposed
    4 / 26 (15.38%)
    3 / 24 (12.50%)
         occurrences all number
    4
    3
    INFLAMMATION
    Additional description: INFLAMMATION
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    INFLUENZA LIKE ILLNESS
    Additional description: INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 24 (4.17%)
         occurrences all number
    2
    1
    LOCAL SWELLING
    Additional description: LOCAL SWELLING
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    MALAISE
    Additional description: MALAISE
         subjects affected / exposed
    1 / 26 (3.85%)
    3 / 24 (12.50%)
         occurrences all number
    1
    3
    MUCOSAL INFLAMMATION
    Additional description: MUCOSAL INFLAMMATION
         subjects affected / exposed
    9 / 26 (34.62%)
    15 / 24 (62.50%)
         occurrences all number
    12
    28
    OEDEMA
    Additional description: OEDEMA
         subjects affected / exposed
    2 / 26 (7.69%)
    3 / 24 (12.50%)
         occurrences all number
    2
    3
    OEDEMA PERIPHERAL
    Additional description: OEDEMA PERIPHERAL
         subjects affected / exposed
    8 / 26 (30.77%)
    12 / 24 (50.00%)
         occurrences all number
    10
    17
    PYREXIA
    Additional description: PYREXIA
         subjects affected / exposed
    5 / 26 (19.23%)
    5 / 24 (20.83%)
         occurrences all number
    11
    6
    PAIN
    Additional description: PAIN
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 24 (8.33%)
         occurrences all number
    1
    3
    XEROSIS
    Additional description: XEROSIS
         subjects affected / exposed
    2 / 26 (7.69%)
    3 / 24 (12.50%)
         occurrences all number
    2
    3
    Immune system disorders
    ANAPHYLACTIC REACTION
    Additional description: ANAPHYLACTIC REACTION
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    BREAST PAIN
    Additional description: BREAST PAIN
         subjects affected / exposed
    1 / 26 (3.85%)
    4 / 24 (16.67%)
         occurrences all number
    1
    5
    PRURITUS GENITAL
    Additional description: PRURITUS GENITAL
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    VAGINAL DISCHARGE
    Additional description: VAGINAL DISCHARGE
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    VULVOVAGINAL DRYNESS
    Additional description: VULVOVAGINAL DRYNESS
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    COUGH
    Additional description: COUGH
         subjects affected / exposed
    2 / 26 (7.69%)
    7 / 24 (29.17%)
         occurrences all number
    4
    9
    EPISTAXIS
    Additional description: EPISTAXIS
         subjects affected / exposed
    10 / 26 (38.46%)
    4 / 24 (16.67%)
         occurrences all number
    21
    5
    DYSPNOEA EXERTIONAL
    Additional description: DYSPNOEA EXERTIONAL
         subjects affected / exposed
    3 / 26 (11.54%)
    0 / 24 (0.00%)
         occurrences all number
    3
    0
    DYSPNOEA
    Additional description: DYSPNOEA
         subjects affected / exposed
    6 / 26 (23.08%)
    11 / 24 (45.83%)
         occurrences all number
    7
    13
    DYSPHONIA
    Additional description: DYSPHONIA
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    OROPHARYNGEAL PAIN
    Additional description: OROPHARYNGEAL PAIN
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    NASAL DRYNESS
    Additional description: NASAL DRYNESS
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    NASAL CONGESTION
    Additional description: NASAL CONGESTION
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    RHINORRHOEA
    Additional description: RHINORRHOEA
         subjects affected / exposed
    3 / 26 (11.54%)
    0 / 24 (0.00%)
         occurrences all number
    3
    0
    PLEURAL EFFUSION
    Additional description: PLEURAL EFFUSION
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    PRODUCTIVE COUGH
    Additional description: PRODUCTIVE COUGH
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    1
    2
    Psychiatric disorders
    AGITATION
    Additional description: AGITATION
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    ANXIETY
    Additional description: ANXIETY
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 24 (4.17%)
         occurrences all number
    3
    1
    DEPRESSED MOOD
    Additional description: DEPRESSED MOOD
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    DEPRESSION
    Additional description: DEPRESSION
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    EATING DISORDER
    Additional description: EATING DISORDER
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    HYPOMANIA
    Additional description: HYPOMANIA
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    INSOMNIA
    Additional description: INSOMNIA
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    SLEEP DISORDER
    Additional description: SLEEP DISORDER
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
    Additional description: ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    20 / 26 (76.92%)
    8 / 24 (33.33%)
         occurrences all number
    45
    11
    ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED
    Additional description: ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED
         subjects affected / exposed
    4 / 26 (15.38%)
    0 / 24 (0.00%)
         occurrences all number
    4
    0
    ASPARTATE AMINOTRANSFERASE INCREASED
    Additional description: ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    20 / 26 (76.92%)
    7 / 24 (29.17%)
         occurrences all number
    25
    8
    BLOOD UREA INCREASED
    Additional description: BLOOD UREA INCREASED
         subjects affected / exposed
    4 / 26 (15.38%)
    1 / 24 (4.17%)
         occurrences all number
    4
    1
    BLOOD PROTIDS INCREASED
    Additional description: BLOOD PROTIDS INCREASED
         subjects affected / exposed
    12 / 26 (46.15%)
    12 / 24 (50.00%)
         occurrences all number
    12
    12
    BLOOD CREATININE INCREASED
    Additional description: BLOOD CREATININE INCREASED
         subjects affected / exposed
    9 / 26 (34.62%)
    2 / 24 (8.33%)
         occurrences all number
    9
    2
    BLOOD BILIRUBIN INCREASED
    Additional description: BLOOD BILIRUBIN INCREASED
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 24 (4.17%)
         occurrences all number
    3
    1
    BLOOD ALKALINE PHOSPHATASE INCREASED
    Additional description: BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    19 / 26 (73.08%)
    8 / 24 (33.33%)
         occurrences all number
    22
    8
    CREATININE CLEARANCE INCREASED
    Additional description: CREATININE CLEARANCE INCREASED
         subjects affected / exposed
    6 / 26 (23.08%)
    5 / 24 (20.83%)
         occurrences all number
    6
    5
    GAMMA-GLUTAMYLTRANSFERASE INCREASED
    Additional description: GAMMA-GLUTAMYLTRANSFERASE INCREASED
         subjects affected / exposed
    8 / 26 (30.77%)
    2 / 24 (8.33%)
         occurrences all number
    15
    4
    INR INCREASED
    Additional description: INR INCREASED
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 24 (4.17%)
         occurrences all number
    2
    1
    WEIGHT DECREASED
    Additional description: WEIGHT DECREASED
         subjects affected / exposed
    5 / 26 (19.23%)
    1 / 24 (4.17%)
         occurrences all number
    5
    1
    WEIGHT INCREASED
    Additional description: WEIGHT INCREASED
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    3
    Injury, poisoning and procedural complications
    ARTHROPOD STING
    Additional description: ARTHROPOD STING
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    CHILLBLAINS
    Additional description: CHILLBLAINS
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Cardiac disorders
    PALPITATIONS
    Additional description: PALPITATIONS
         subjects affected / exposed
    3 / 26 (11.54%)
    0 / 24 (0.00%)
         occurrences all number
    4
    0
    TACHYCARDIA
    Additional description: TACHYCARDIA
         subjects affected / exposed
    3 / 26 (11.54%)
    0 / 24 (0.00%)
         occurrences all number
    3
    0
    Nervous system disorders
    AGEUSIA
    Additional description: AGEUSIA
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    DISTURBANCE IN ATTENTION
    Additional description: DISTURBANCE IN ATTENTION
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    DIZZINESS
    Additional description: DIZZINESS
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    DYSGEUSIA
    Additional description: DYSGEUSIA
         subjects affected / exposed
    16 / 26 (61.54%)
    11 / 24 (45.83%)
         occurrences all number
    38
    31
    DYSAESTHESIA
    Additional description: DYSAESTHESIA
         subjects affected / exposed
    8 / 26 (30.77%)
    6 / 24 (25.00%)
         occurrences all number
    19
    8
    FORMICATION
    Additional description: FORMICATION
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    HEADACHE
    Additional description: HEADACHE
         subjects affected / exposed
    9 / 26 (34.62%)
    6 / 24 (25.00%)
         occurrences all number
    15
    14
    HYPERAESTHESIA
    Additional description: HYPERAESTHESIA
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 24 (4.17%)
         occurrences all number
    9
    1
    HYPOAESTHESIA
    Additional description: HYPOAESTHESIA
         subjects affected / exposed
    5 / 26 (19.23%)
    3 / 24 (12.50%)
         occurrences all number
    5
    3
    MIGRAINE
    Additional description: MIGRAINE
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    MUSCLE CONTRACTIONS INVOLUNTARY
    Additional description: MUSCLE CONTRACTIONS INVOLUNTARY
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    NEUROPATHY PERIPHERAL
    Additional description: NEUROPATHY PERIPHERAL
         subjects affected / exposed
    10 / 26 (38.46%)
    18 / 24 (75.00%)
         occurrences all number
    16
    41
    PARAESTHESIA
    Additional description: PARAESTHESIA
         subjects affected / exposed
    5 / 26 (19.23%)
    10 / 24 (41.67%)
         occurrences all number
    7
    18
    RESTLESS LEGS SYNDROME
    Additional description: RESTLESS LEGS SYNDROME
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    SCIATICA
    Additional description: SCIATICA
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 24 (8.33%)
         occurrences all number
    1
    2
    TREMOR
    Additional description: TREMOR
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    Blood and lymphatic system disorders
    ANAEMIA
    Additional description: ANAEMIA
         subjects affected / exposed
    17 / 26 (65.38%)
    17 / 24 (70.83%)
         occurrences all number
    24
    19
    FEBRILE BONE MARROW APLASIA
    Additional description: FEBRILE BONE MARROW APLASIA
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    FEBRILE NEUTROPENIA
    Additional description: FEBRILE NEUTROPENIA
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    LEUKOPENIA
    Additional description: LEUKOPENIA
         subjects affected / exposed
    14 / 26 (53.85%)
    9 / 24 (37.50%)
         occurrences all number
    37
    15
    LYMPHOPENIA
    Additional description: LYMPHOPENIA
         subjects affected / exposed
    5 / 26 (19.23%)
    8 / 24 (33.33%)
         occurrences all number
    11
    13
    NEUTROPENIA
    Additional description: NEUTROPENIA
         subjects affected / exposed
    10 / 26 (38.46%)
    8 / 24 (33.33%)
         occurrences all number
    29
    11
    NEUTROPHILIA
    Additional description: NEUTROPHILIA
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    THROMBOPENIA
    Additional description: THROMBOPENIA
         subjects affected / exposed
    2 / 26 (7.69%)
    2 / 24 (8.33%)
         occurrences all number
    2
    2
    Ear and labyrinth disorders
    HYPOACUSIS
    Additional description: HYPOACUSIS
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    TINNITUS
    Additional description: TINNITUS
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 24 (4.17%)
         occurrences all number
    3
    1
    VERTIGO
    Additional description: VERTIGO
         subjects affected / exposed
    2 / 26 (7.69%)
    2 / 24 (8.33%)
         occurrences all number
    2
    3
    Eye disorders
    DRY EYE
    Additional description: DRY EYE
         subjects affected / exposed
    0 / 26 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    4
    EYE DISORDER
    Additional description: EYE DISORDER
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    EYE IRRITATION
    Additional description: EYE IRRITATION
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    EYE PAIN
    Additional description: EYE PAIN
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    EYELID DISORDER
    Additional description: EYELID DISORDER
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 24 (0.00%)
         occurrences all number
    3
    0
    EYELID OEDEMA
    Additional description: EYELID OEDEMA
         subjects affected / exposed
    1 / 26 (3.85%)
    3 / 24 (12.50%)
         occurrences all number
    1
    3
    LACRIMATION INCREASED
    Additional description: LACRIMATION INCREASED
         subjects affected / exposed
    15 / 26 (57.69%)
    15 / 24 (62.50%)
         occurrences all number
    29
    21
    PERIORBITAL OEDEMA
    Additional description: PERIORBITAL OEDEMA
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    VISION BLURRED
    Additional description: VISION BLURRED
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    VISUAL ACUITY REDUCED
    Additional description: VISUAL ACUITY REDUCED
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    AEROPHAGIA
    Additional description: AEROPHAGIA
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    ABDOMINAL RIGIDITY
    Additional description: ABDOMINAL RIGIDITY
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 24 (0.00%)
         occurrences all number
    8
    0
    ABDOMINAL PAIN UPPER
    Additional description: ABDOMINAL PAIN UPPER
         subjects affected / exposed
    3 / 26 (11.54%)
    6 / 24 (25.00%)
         occurrences all number
    3
    11
    ABDOMINAL PAIN
    Additional description: ABDOMINAL PAIN
         subjects affected / exposed
    13 / 26 (50.00%)
    5 / 24 (20.83%)
         occurrences all number
    37
    7
    ABDOMINAL DISTENSION
    Additional description: ABDOMINAL DISTENSION
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    APHTHOUS ULCER
    Additional description: APHTHOUS ULCER
         subjects affected / exposed
    3 / 26 (11.54%)
    1 / 24 (4.17%)
         occurrences all number
    3
    1
    ASCITES
    Additional description: ASCITES
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    CONSTIPATION
    Additional description: CONSTIPATION
         subjects affected / exposed
    3 / 26 (11.54%)
    6 / 24 (25.00%)
         occurrences all number
    5
    12
    COLITIS
    Additional description: COLITIS
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    DIARRHOEA
    Additional description: DIARRHOEA
         subjects affected / exposed
    24 / 26 (92.31%)
    14 / 24 (58.33%)
         occurrences all number
    118
    29
    DRY MOUTH
    Additional description: DRY MOUTH
         subjects affected / exposed
    4 / 26 (15.38%)
    5 / 24 (20.83%)
         occurrences all number
    6
    6
    DYSPEPSIA
    Additional description: DYSPEPSIA
         subjects affected / exposed
    0 / 26 (0.00%)
    5 / 24 (20.83%)
         occurrences all number
    0
    5
    FLATULENCE
    Additional description: FLATULENCE
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    GASTROINTESTINAL MOTILITY DISORDER
    Additional description: GASTROINTESTINAL MOTILITY DISORDER
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    GASTROOESOPHAGEAL REFLUX DISEASE
    Additional description: GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    2 / 26 (7.69%)
    2 / 24 (8.33%)
         occurrences all number
    3
    2
    GINGIVAL BLEEDING
    Additional description: GINGIVAL BLEEDING
         subjects affected / exposed
    3 / 26 (11.54%)
    0 / 24 (0.00%)
         occurrences all number
    4
    0
    GINGIVAL PAIN
    Additional description: GINGIVAL PAIN
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    GLOSSITIS
    Additional description: GLOSSITIS
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    2
    1
    MOUTH ULCERATION
    Additional description: MOUTH ULCERATION
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    NAUSEA
    Additional description: NAUSEA
         subjects affected / exposed
    17 / 26 (65.38%)
    14 / 24 (58.33%)
         occurrences all number
    51
    44
    NONINFECTIVE SIALOADENITIS
    Additional description: NONINFECTIVE SIALOADENITIS
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    ODYNOPHAGIA
    Additional description: ODYNOPHAGIA
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    OESOPHAGEAL ULCER
    Additional description: OESOPHAGEAL ULCER
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    STOMATITIS
    Additional description: STOMATITIS
         subjects affected / exposed
    4 / 26 (15.38%)
    5 / 24 (20.83%)
         occurrences all number
    11
    6
    TONGUE COATED
    Additional description: TONGUE COATED
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    TOOTHACHE
    Additional description: TOOTHACHE
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    VOMITING
    Additional description: VOMITING
         subjects affected / exposed
    14 / 26 (53.85%)
    4 / 24 (16.67%)
         occurrences all number
    33
    8
    Hepatobiliary disorders
    HEPATIC PAIN
    Additional description: HEPATIC PAIN
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    HEPATOMEGALY
    Additional description: HEPATOMEGALY
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Skin and subcutaneous tissue disorders
    ALOPECIA
    Additional description: ALOPECIA
         subjects affected / exposed
    13 / 26 (50.00%)
    16 / 24 (66.67%)
         occurrences all number
    14
    21
    BEHCET'S SYNDROME
    Additional description: BEHCET'S SYNDROME
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    9
    DERMATITIS EXFOLIATIVE
    Additional description: DERMATITIS EXFOLIATIVE
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    3
    DRY SKIN
    Additional description: DRY SKIN
         subjects affected / exposed
    5 / 26 (19.23%)
    1 / 24 (4.17%)
         occurrences all number
    5
    1
    ECZEMA
    Additional description: ECZEMA
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 24 (4.17%)
         occurrences all number
    2
    1
    ECCHYMOSIS
    Additional description: ECCHYMOSIS
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    ERYTHROSIS
    Additional description: ERYTHROSIS
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    ERYTHEMA
    Additional description: ERYTHEMA
         subjects affected / exposed
    6 / 26 (23.08%)
    3 / 24 (12.50%)
         occurrences all number
    6
    3
    NAIL BED TENDERNESS
    Additional description: NAIL BED TENDERNESS
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    NAIL DISCOLOURATION
    Additional description: NAIL DISCOLOURATION
         subjects affected / exposed
    3 / 26 (11.54%)
    1 / 24 (4.17%)
         occurrences all number
    3
    1
    NAIL DISCOMFORT
    Additional description: NAIL DISCOMFORT
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    NAIL DISORDER
    Additional description: NAIL DISORDER
         subjects affected / exposed
    4 / 26 (15.38%)
    9 / 24 (37.50%)
         occurrences all number
    7
    14
    NAIL DYSTROPHY
    Additional description: NAIL DYSTROPHY
         subjects affected / exposed
    1 / 26 (3.85%)
    4 / 24 (16.67%)
         occurrences all number
    2
    6
    NAIL RIDGING
    Additional description: NAIL RIDGING
         subjects affected / exposed
    0 / 26 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    4
    ONYCHALGIA
    Additional description: ONYCHALGIA
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    ONYCHOCLASIS
    Additional description: ONYCHOCLASIS
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    ONYCHOLYSIS
    Additional description: ONYCHOLYSIS
         subjects affected / exposed
    10 / 26 (38.46%)
    7 / 24 (29.17%)
         occurrences all number
    18
    11
    ONYCHOMADESIS
    Additional description: ONYCHOMADESIS
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME
    Additional description: PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME
         subjects affected / exposed
    4 / 26 (15.38%)
    8 / 24 (33.33%)
         occurrences all number
    4
    14
    PHOTOSENSITIVITY REACTION
    Additional description: PHOTOSENSITIVITY REACTION
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    PRURITUS
    Additional description: PRURITUS
         subjects affected / exposed
    4 / 26 (15.38%)
    3 / 24 (12.50%)
         occurrences all number
    5
    3
    PSORIASIS
    Additional description: PSORIASIS
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    RASH
    Additional description: RASH
         subjects affected / exposed
    4 / 26 (15.38%)
    2 / 24 (8.33%)
         occurrences all number
    4
    2
    SKIN EXFOLIATION
    Additional description: SKIN EXFOLIATION
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    SKIN FISSURES
    Additional description: SKIN FISSURES
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    2
    SKIN STRIAE
    Additional description: SKIN STRIAE
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    SKIN TOXICITY
    Additional description: SKIN TOXICITY
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 24 (8.33%)
         occurrences all number
    1
    2
    Renal and urinary disorders
    URINARY TRACT DISORDER
    Additional description: URINARY TRACT DISORDER
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Endocrine disorders
    CUSHINGOID
    Additional description: CUSHINGOID
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
    Additional description: ARTHRALGIA
         subjects affected / exposed
    6 / 26 (23.08%)
    9 / 24 (37.50%)
         occurrences all number
    20
    15
    BONE PAIN
    Additional description: BONE PAIN
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 24 (4.17%)
         occurrences all number
    3
    1
    BACK PAIN
    Additional description: BACK PAIN
         subjects affected / exposed
    6 / 26 (23.08%)
    8 / 24 (33.33%)
         occurrences all number
    8
    13
    JOINT STIFFNESS
    Additional description: JOINT STIFFNESS
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    LIMB DISCOMFORT
    Additional description: LIMB DISCOMFORT
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    MUSCLE FATIGUE
    Additional description: MUSCLE FATIGUE
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    MUSCLE SPASMS
    Additional description: MUSCLE SPASMS
         subjects affected / exposed
    3 / 26 (11.54%)
    2 / 24 (8.33%)
         occurrences all number
    3
    2
    MUSCULAR WEAKNESS
    Additional description: MUSCULAR WEAKNESS
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    MUSCULOSKELETAL CHEST PAIN
    Additional description: MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    3 / 26 (11.54%)
    3 / 24 (12.50%)
         occurrences all number
    4
    3
    MUSCULOSKELETAL DISCOMFORT
    Additional description: MUSCULOSKELETAL DISCOMFORT
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    MUSCULOSKELETAL PAIN
    Additional description: MUSCULOSKELETAL PAIN
         subjects affected / exposed
    5 / 26 (19.23%)
    13 / 24 (54.17%)
         occurrences all number
    9
    29
    MYALGIA
    Additional description: MYALGIA
         subjects affected / exposed
    9 / 26 (34.62%)
    17 / 24 (70.83%)
         occurrences all number
    14
    44
    NECK PAIN
    Additional description: NECK PAIN
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    OSTEOARTHRITIS
    Additional description: OSTEOARTHRITIS
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    PAIN IN EXTREMITY
    Additional description: PAIN IN EXTREMITY
         subjects affected / exposed
    2 / 26 (7.69%)
    3 / 24 (12.50%)
         occurrences all number
    2
    3
    SPINAL PAIN
    Additional description: SPINAL PAIN
         subjects affected / exposed
    2 / 26 (7.69%)
    2 / 24 (8.33%)
         occurrences all number
    2
    2
    Infections and infestations
    ANAL ABSCESS
    Additional description: ANAL ABSCESS
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    BRONCHITIS
    Additional description: BRONCHITIS
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 24 (8.33%)
         occurrences all number
    1
    4
    CONJUNCTIVITIS
    Additional description: CONJUNCTIVITIS
         subjects affected / exposed
    2 / 26 (7.69%)
    3 / 24 (12.50%)
         occurrences all number
    2
    6
    CYSTITIS
    Additional description: CYSTITIS
         subjects affected / exposed
    1 / 26 (3.85%)
    4 / 24 (16.67%)
         occurrences all number
    1
    6
    DERMATOPHYTOSIS OF NAIL
    Additional description: DERMATOPHYTOSIS OF NAIL
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    FUNGAL INFECTION
    Additional description: FUNGAL INFECTION
         subjects affected / exposed
    3 / 26 (11.54%)
    1 / 24 (4.17%)
         occurrences all number
    3
    2
    FUNGAL SKIN INFECTION
    Additional description: FUNGAL SKIN INFECTION
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    FURUNCLE
    Additional description: FURUNCLE
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    GASTROENTERITIS
    Additional description: GASTROENTERITIS
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    2
    HERPES ZOSTER
    Additional description: HERPES ZOSTER
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    GASTROINTESTINAL INFECTION
    Additional description: GASTROINTESTINAL INFECTION
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    LARYNGITIS
    Additional description: LARYNGITIS
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    LOCALISED INFECTION
    Additional description: LOCALISED INFECTION
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    LUNG INFECTION
    Additional description: LUNG INFECTION
         subjects affected / exposed
    3 / 26 (11.54%)
    1 / 24 (4.17%)
         occurrences all number
    3
    1
    LYMPHANGITIS
    Additional description: LYMPHANGITIS
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    NAIL INFECTION
    Additional description: NAIL INFECTION
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    NAIL BED INFECTION
    Additional description: NAIL BED INFECTION
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    1
    2
    NASOPHARYNGITIS
    Additional description: NASOPHARYNGITIS
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    3
    OESOPHAGEAL CANDIDIASIS
    Additional description: OESOPHAGEAL CANDIDIASIS
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    ORAL FUNGAL INFECTION
    Additional description: ORAL FUNGAL INFECTION
         subjects affected / exposed
    0 / 26 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    4
    PHARYNGITIS
    Additional description: PHARYNGITIS
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    3
    RHINITIS
    Additional description: RHINITIS
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 24 (8.33%)
         occurrences all number
    1
    2
    SKIN INFECTION
    Additional description: SKIN INFECTION
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    SUPERINFECTION
    Additional description: SUPERINFECTION
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    URINARY TRACT INFECTION
    Additional description: URINARY TRACT INFECTION
         subjects affected / exposed
    3 / 26 (11.54%)
    2 / 24 (8.33%)
         occurrences all number
    4
    2
    SEPSIS
    Additional description: SEPSIS
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    VIRAL INFECTION
    Additional description: VIRAL INFECTION
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    DECREASED APPETITE
    Additional description: DECREASED APPETITE
         subjects affected / exposed
    8 / 26 (30.77%)
    9 / 24 (37.50%)
         occurrences all number
    11
    11
    FLUID RETENTION
    Additional description: FLUID RETENTION
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    GOUT
    Additional description: GOUT
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    HYPERCALCAEMIA
    Additional description: HYPERCALCAEMIA
         subjects affected / exposed
    3 / 26 (11.54%)
    2 / 24 (8.33%)
         occurrences all number
    3
    2
    HYPERCHLORAEMIA
    Additional description: HYPERCHLORAEMIA
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    HYPERGLYCAEMIA
    Additional description: HYPERGLYCAEMIA
         subjects affected / exposed
    8 / 26 (30.77%)
    11 / 24 (45.83%)
         occurrences all number
    8
    15
    HYPERKALAEMIA
    Additional description: HYPERKALAEMIA
         subjects affected / exposed
    7 / 26 (26.92%)
    4 / 24 (16.67%)
         occurrences all number
    7
    4
    HYPERNATRAEMIA
    Additional description: HYPERNATRAEMIA
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    HYPERURICAEMIA
    Additional description: HYPERURICAEMIA
         subjects affected / exposed
    8 / 26 (30.77%)
    5 / 24 (20.83%)
         occurrences all number
    9
    7
    HYPOCALCAEMIA
    Additional description: HYPOCALCAEMIA
         subjects affected / exposed
    9 / 26 (34.62%)
    7 / 24 (29.17%)
         occurrences all number
    13
    8
    HYPOGLYCAEMIA
    Additional description: HYPOGLYCAEMIA
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    HYPOKALAEMIA
    Additional description: HYPOKALAEMIA
         subjects affected / exposed
    3 / 26 (11.54%)
    2 / 24 (8.33%)
         occurrences all number
    3
    2
    HYPONATRAEMIA
    Additional description: HYPONATRAEMIA
         subjects affected / exposed
    3 / 26 (11.54%)
    2 / 24 (8.33%)
         occurrences all number
    3
    2
    HYPOPHOSPHATEMIA
    Additional description: HYPOPHOSPHATEMIA
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    MALNUTRITION
    Additional description: MALNUTRITION
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Nov 2013
    Substantial change n°1 : - Change in selection criteria - Addition of a blood sample - Addition and removal of participating centers - Change of principal investigator of a participating center
    05 Jun 2014
    Substantial change n°2 : - Update of the Summary of Product Characteristics of docetaxel - Addition of participating centers
    04 Nov 2014
    Substantial change n°3 : - Inclusion criteria : patient receiving a first or second line chemotherapy for HER negative, metastatic or locally recurrent breast cancer (previously only patients with second line chemotherapy were included) - Randomization with stratification according to first or second-line chemotherapy - Bevacizumab in 1st line allowed with a wash-out of 4 weeks, with recovery to NCI-CTCAE v3.0 toxicity
    20 Nov 2015
    Substantial change n°4 : - Update of participating centers - Change in some principal investigators, addition of co-investigator

    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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