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    Clinical Trial Results:
    Neurotoxicity characterization phase II randomized study of nab-paclitaxel versus conventional paclitaxel as first-line therapy of metastatic HER2-negative breast cancer.

    Summary
    EudraCT number
    		 2012-002361-36
    Trial protocol
    		 ES  
    Global end of trial date
    29 Mar 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    20 Feb 2022
    First version publication date
    20 Feb 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ONCOSUR-2012-01
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01763710
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    ONCOSUR
    Sponsor organisation address
    Avda. de Cordoba s.n. Hospital 12 de Octubre, Servicio de Oncología Médica, Madrid, Spain,
    Public contact
    Operaciones clínicas, ONCOSUR, ana.moreno@apices.es
    Scientific contact
    Operaciones Clínicas, ONCOSUR, ana.moreno@apices.es
    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
    29 Mar 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Mar 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To characterize neurotoxicity according to Total Neuropathy Score
    Protection of trial subjects
    Not applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Oct 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 60
    Worldwide total number of subjects
    60
    EEA total number of subjects
    60
    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)
    45
    From 65 to 84 years
    15
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Patients were included in the study between 17th January 2013 and 24th July 2014

    Pre-assignment
    Screening details
    		 65 patients were recruited initially in the study which were analyzed 60. 5 patients were screening failures

    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
    Arm description
    		 Patients received conventional Paclitaxel 80mg/m2 at days 1, 8 and 15 in cycles of 28 days
    Arm type
    		 Standard

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    80 mg/m2 at days 1, 8 and 15 in cycles of 28 days

    Arm title
    		 Arm B
    Arm description
    		 Patients received nab-paclitaxel 100mg/m2 at days 1, 8 and 15 in cycles of 28 days
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100mg/m2 at days 1, 8 and 15 in cycles of 28 days

    Arm title
    		 Arm C
    Arm description
    		 Patientes received Nab-paclitaxel 150mg/m2 at days 1, 8 and 15 in cycles of 28 days
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    150 mg/m2 at days 1, 8 and 15 in cycles of 28 days

    Arm title
    		 Arm D
    Arm description
    		 Patients received Nab-paclitaxel 150 mg/m2 at days 1 and 15 in cycles of 28 days
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nab-paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    150 mg/m2 at days 1 and 15 in cycles of 28 days

    Number of subjects in period 1
    		Arm A Arm B Arm C Arm D
    Started
    14
    16
    14
    16
    Completed
    14
    16
    14
    16

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm A
    Reporting group description
    		 Patients received conventional Paclitaxel 80mg/m2 at days 1, 8 and 15 in cycles of 28 days

    Reporting group title
    Arm B
    Reporting group description
    		 Patients received nab-paclitaxel 100mg/m2 at days 1, 8 and 15 in cycles of 28 days

    Reporting group title
    Arm C
    Reporting group description
    		 Patientes received Nab-paclitaxel 150mg/m2 at days 1, 8 and 15 in cycles of 28 days

    Reporting group title
    Arm D
    Reporting group description
    		 Patients received Nab-paclitaxel 150 mg/m2 at days 1 and 15 in cycles of 28 days

    Reporting group values
    		 Arm A Arm B Arm C Arm D Total
    Number of subjects
    		 14 16 14 16 60
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 9 11 10 10 40
        From 65-84 years
    		 5 5 4 6 20
        85 years and over
    		 0 0 0 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 56.8 (37.4 to 80.6) 59.8 (40.8 to 84.6) 57.3 (38.8 to 78.5) 62.1 (37.8 to 79.6) -
    Gender categorical
    Units: Subjects
        Female
    		 14 16 14 16 60
        Male
    		 0 0 0 0 0
    ECOG-PS
    Units: Subjects
        (0)
    		 10 7 12 10 39
        (1)
    		 3 7 2 6 18
        Unknown
    		 1 2 0 0 3
    Raze
    Units: Subjects
        Caucasian
    		 14 14 12 15 55
        Latin/hispanic
    		 0 1 2 0 3
        Arabic
    		 0 1 0 1 2
    Diagnostic stage
    Units: Subjects
        (I)
    		 4 1 2 2 9
        (II)
    		 3 8 6 5 22
        (III)
    		 2 2 2 4 10
        (IV)
    		 4 5 4 3 16
        ND
    		 1 0 0 2 3
    Previous radiotherapy
    Units: Subjects
        No
    		 6 9 6 6 27
        Yes
    		 8 7 8 10 33
    Previous surgery
    Units: Subjects
        No
    		 3 4 4 3 14
        Si
    		 11 12 10 13 46
    Type of surgery
    Units: Subjects
        mastectomy
    		 1 2 3 0 6
        modified radical mastectomy
    		 4 4 4 7 19
        radical mastectomy
    		 3 1 1 0 5
        lumpectomy
    		 3 4 2 6 15
        not available
    		 3 5 4 3 15
    Previous chemotherapy
    Units: Subjects
        No
    		 7 6 5 5 23
        Yes
    		 7 10 9 11 37
    weight
    Units: kilograms
        median (full range (min-max))
    		 63.9 (46.8 to 92.8) 64.6 (51.6 to 100.6) 62.5 (51.4 to 99) 63.3 (47.4 to 85.4) -
    Height
    Units: centimeter
        median (full range (min-max))
    		 156 (148 to 169) 158.5 (146 to 169) 159.5 (144 to 174) 156 (148 to 176) -
    Corporal surface
    Units: square meter
        median (full range (min-max))
    		 1.6 (1.4 to 2) 1.7 (1.5 to 1.9) 1.7 (1.5 to 2.0) 1.6 (1.4 to 2.0) -
    Time since first diagnosis
    Units: month
        median (full range (min-max))
    		 44.5 (0.3 to 312.3) 50.4 (0.0 to 239.2) 65.3 (0.5 to 408.7) 68.5 (0.4 to 212.8) -
    Number of cycles administered
    Units: cycles
        median (full range (min-max))
    		 6.0 (3 to 11) 7.0 (1 to 14) 8.0 (2 to 15) 4.5 (3 to 12) -
    Relative dose Intensity
    Units: mg/m2/week
        median (full range (min-max))
    		 0.93 (0.57 to 1.00) 0.92 (0.33 to 1.00) 0.77 (0.48 to 0.89) 0.90 (0.66 to 1.00) -

    End points

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    End points reporting groups
    Reporting group title
    Arm A
    Reporting group description
    		 Patients received conventional Paclitaxel 80mg/m2 at days 1, 8 and 15 in cycles of 28 days

    Reporting group title
    Arm B
    Reporting group description
    		 Patients received nab-paclitaxel 100mg/m2 at days 1, 8 and 15 in cycles of 28 days

    Reporting group title
    Arm C
    Reporting group description
    		 Patientes received Nab-paclitaxel 150mg/m2 at days 1, 8 and 15 in cycles of 28 days

    Reporting group title
    Arm D
    Reporting group description
    		 Patients received Nab-paclitaxel 150 mg/m2 at days 1 and 15 in cycles of 28 days

    Primary: Total Neuropathy Score

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    End point title
    		 Total Neuropathy Score [1]
    End point description
    Change from baseline in TNS score.
    End point type
    Primary
    End point timeframe
    Every 12 weeks
    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: Not statistical significant differences were found (ANOVA p-value: 0.587).
    End point values
    		 Arm A Arm B Arm C Arm D
    Number of subjects analysed
    14
    16
    14
    16
    Units: percent
        median (full range (min-max))
    3.8 (-2 to 12.0)
    3.5 (-1.0 to 12.0)
    3.8 (0.0 to 11.0)
    2.4 (0.0 to 4.0)
    No statistical analyses for this end point

    Secondary: Incidence of neuropathy

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    End point title
    		 Incidence of neuropathy
    End point description
    Proportion of patients that present neuropathy (any grade) according to NCI-CTCAE.
    End point type
    Secondary
    End point timeframe
    Every week
    End point values
    		 Arm A Arm B Arm C Arm D
    Number of subjects analysed
    14
    16
    14
    16
    Units: percent
        number (not applicable)
    50.0
    81.3
    78.6
    62.6
    No statistical analyses for this end point

    Secondary: Progression free survival

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    End point title
    		 Progression free survival
    End point description
    Progression free survival is the time elapsed since the start of study treatment until the criteria for progression of the illness or the patient dies.
    End point type
    Secondary
    End point timeframe
    Every week
    End point values
    		 Arm A Arm B Arm C Arm D
    Number of subjects analysed
    14
    16
    14
    16
    Units: months
        median (full range (min-max))
    7.401 (3.468 to 11.334)
    5.954 (0.000 to 12.588)
    11.579 (11.037 to 12.121)
    15.691 (12.229 to 19.153)
    No statistical analyses for this end point

    Secondary: Time until appearance of neurotoxicity

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    End point title
    		 Time until appearance of neurotoxicity
    End point description
    Time elapsed from patient entry into the study until first neurotoxicity event grade ≥ 2 Median time until appearance of neurotoxicity not reached in arms A, B and D.
    End point type
    Secondary
    End point timeframe
    Weekly
    End point values
    		 Arm A Arm B Arm C Arm D
    Number of subjects analysed
    14
    16
    14
    16
    Units: month
        median (confidence interval 95%)
    0 (0 to 0)
    0 (0 to 0)
    3.717 (2.571 to 4.863)
    0 (0 to 0)
    No statistical analyses for this end point

    Secondary: Time until neurotoxicity recovery

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    End point title
    		 Time until neurotoxicity recovery
    End point description
    Time that elapses from the patient's appearance of grade 2 neurotoxicity to recovery.
    End point type
    Secondary
    End point timeframe
    Weekly
    End point values
    		 Arm A Arm B Arm C Arm D
    Number of subjects analysed
    14
    16
    14
    16
    Units: months
        median (confidence interval 95%)
    8.783 (0.000 to 23.262)
    6.908 (5.566 to 8.250)
    14.605 (9.412 to 19.798)
    12.599 (0.000 to 37.742)
    No statistical analyses for this end point

    Secondary: Time to progression

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    End point title
    		 Time to progression
    End point description
    Time to progression is the time from the start of study treatment until disease progression criteria are met or the patient dies due to disease progression.
    End point type
    Secondary
    End point timeframe
    every week
    End point values
    		 Arm A Arm B Arm C Arm D
    Number of subjects analysed
    14
    16
    14
    16
    Units: months
        median (confidence interval 95%)
    5.954 (0.000 to 12.588)
    11.579 (11.037 to 12.121)
    15.691 (12.229 to 19.153)
    7.401 (3.468 to 11.334)
    No statistical analyses for this end point

    Secondary: Quality of Life through the EORTC QLQC30 and EORTC QLQ-CIPN20 questionnaires.

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    End point title
    		 Quality of Life through the EORTC QLQC30 and EORTC QLQ-CIPN20 questionnaires.
    End point description
    Mean change in the Global Health Status EORTC QLQ-CIPN20 and in the Global Health Status EORTC QLQ-C30 scores from baseline.
    End point type
    Secondary
    End point timeframe
    Initial visit
    End point values
    		 Arm A Arm B Arm C Arm D
    Number of subjects analysed
    14
    16
    14
    16
    Units: percent
    least squares mean (confidence interval 95%)
        EORTC QLQ-CPIN20
    14.4 (14.4 to 14.4)
    28.4 (-4.8 to 32.9)
    33.4 (1.1 to 37.0)
    14.0 (-17.8 to 17.1)
        EORTC QLQ-C30
    -12.7 (-12.7 to -12.7)
    -6.6 (-21.7 to 33.9)
    -24.7 (-38.1 to 14.1)
    -8.9 (-21.6 to 29.1)
    No statistical analyses for this end point

    Secondary: Objective response rate

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    End point title
    		 Objective response rate
    End point description
    Proportion of patients with complete response or partial response according to RECIST 1.1 criteria.
    End point type
    Secondary
    End point timeframe
    Every week
    End point values
    		 Arm A Arm B Arm C Arm D
    Number of subjects analysed
    14
    16
    14
    16
    Units: percent
        median (confidence interval 95%)
    12.5 (0 to 28.7)
    21.4 (0 to 42.9)
    37.5 (13.8 to 61.2)
    42.9 (16.9 to 68.8)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Every 15 days
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Total
    Reporting group description
    		 -

    Reporting group title
    Arm a
    Reporting group description
    		 Patients received conventional Paclitaxel 80 mg/m2 at days 1, 8 and 15 in cycles of 28 days

    Reporting group title
    Arm b
    Reporting group description
    		 Patients received nab-paclitaxel 100 mg/m2 at days 1, 8 and 15 in cycles of 28 days

    Reporting group title
    Arm c
    Reporting group description
    		 Patients received nab-paclitaxel 150 mg/m2 at days 1, 8 and 15 in cycles of 28 days

    Reporting group title
    Arm d
    Reporting group description
    		 Patients received nab-paclitaxel 150 mg/m2 at days 1 and 15 in cycles of 28 days

    Serious adverse events
    		 Total Arm a Arm b Arm c Arm d
    Total subjects affected by serious adverse events
         subjects affected / exposed
    24 / 60 (40.00%)
    2 / 14 (14.29%)
    9 / 16 (56.25%)
    9 / 14 (64.29%)
    4 / 16 (25.00%)
         number of deaths (all causes)
    17
    8
    1
    3
    5
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Investigations
    liver biopsy
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Salpingo-oophorectomy
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Salpingo-oophorectomy bilateral
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    mastectomy
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    pyrexia
         subjects affected / exposed
    4 / 60 (6.67%)
    1 / 14 (7.14%)
    1 / 16 (6.25%)
    2 / 14 (14.29%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
    0 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    diarrhea
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Abnormal liver function
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pneumothorax
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism pulmonary
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Bone pain
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacterial peritonitis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Total Arm a Arm b Arm c Arm d
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    60 / 60 (100.00%)
    14 / 14 (100.00%)
    16 / 16 (100.00%)
    14 / 14 (100.00%)
    16 / 16 (100.00%)
    Vascular disorders
    Lymphoedema
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Overheating
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Hypotension
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    General disorders and administration site conditions
    Gait disturbance
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    1 / 16 (6.25%)
         occurrences all number
    3
    1
    0
    1
    1
    Asthenia
         subjects affected / exposed
    38 / 60 (63.33%)
    8 / 14 (57.14%)
    7 / 16 (43.75%)
    9 / 14 (64.29%)
    14 / 16 (87.50%)
         occurrences all number
    38
    8
    7
    9
    14
    Chest discomfort
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    2 / 16 (12.50%)
         occurrences all number
    3
    1
    0
    0
    2
    Mucous dryness
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    2
    1
    0
    1
    0
    Peripheral edema
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    1
    1
    0
    Pyrexia
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    2
    0
    1
    0
    1
    Oedema
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Fatigue
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    1 / 16 (6.25%)
         occurrences all number
    2
    0
    0
    1
    1
    Mucosal inflammation
         subjects affected / exposed
    4 / 60 (6.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    2 / 14 (14.29%)
    2 / 16 (12.50%)
         occurrences all number
    4
    0
    0
    2
    2
    General discomfort
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Generalised oedema
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    0
    0
    0
    1
    Reproductive system and breast disorders
    Amenorrhoea
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    4 / 60 (6.67%)
    1 / 14 (7.14%)
    2 / 16 (12.50%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    4
    1
    2
    0
    1
    Nasal dryness
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Cold
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 14 (0.00%)
    2 / 16 (12.50%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    2
    0
    0
    Cough
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    2 / 16 (12.50%)
         occurrences all number
    3
    0
    1
    0
    2
    Epistaxis
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    2 / 14 (14.29%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    0
    2
    0
    Pharyngeal inflammation
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Depression
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Investigations
    decreased weight
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 60 (6.67%)
    0 / 14 (0.00%)
    3 / 16 (18.75%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    4
    0
    3
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 14 (0.00%)
    2 / 16 (12.50%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    3
    0
    2
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    1
    1
    0
    blood lactatodehydrogenase increased
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    1
    1
    0
    Blood albumin decreased
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    1 / 16 (6.25%)
         occurrences all number
    2
    0
    0
    1
    1
    Blood calcium decreased
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Blood alkaline phosphatase
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    2 / 14 (14.29%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    0
    2
    0
    Blood glucose decreased
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Total proteins decreased
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Monocyte count elevated
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Blood urea decreased
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    0
    0
    0
    1
    Nervous system disorders
    Aphonia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Polyneuropathy
         subjects affected / exposed
    41 / 60 (68.33%)
    7 / 14 (50.00%)
    13 / 16 (81.25%)
    11 / 14 (78.57%)
    10 / 16 (62.50%)
         occurrences all number
    41
    7
    13
    11
    10
    Dysgeusia
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    2
    1
    0
    1
    0
    Psychomotor hyperactivity
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    tingling
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Neurotoxicity
         subjects affected / exposed
    10 / 60 (16.67%)
    3 / 14 (21.43%)
    1 / 16 (6.25%)
    5 / 14 (35.71%)
    1 / 16 (6.25%)
         occurrences all number
    10
    3
    1
    5
    1
    Paresthesia
         subjects affected / exposed
    8 / 60 (13.33%)
    2 / 14 (14.29%)
    0 / 16 (0.00%)
    3 / 14 (21.43%)
    3 / 16 (18.75%)
         occurrences all number
    8
    2
    0
    3
    3
    Syncope
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Balance disorder
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Dizziness
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Hypoesthesia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    0
    0
    0
    1
    Neuralgia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    29 / 60 (48.33%)
    3 / 14 (21.43%)
    8 / 16 (50.00%)
    9 / 14 (64.29%)
    9 / 16 (56.25%)
         occurrences all number
    29
    3
    8
    9
    9
    Leukopenia
         subjects affected / exposed
    27 / 60 (45.00%)
    8 / 14 (57.14%)
    8 / 16 (50.00%)
    7 / 14 (50.00%)
    4 / 16 (25.00%)
         occurrences all number
    27
    8
    8
    7
    4
    Lymphopenia
         subjects affected / exposed
    6 / 60 (10.00%)
    1 / 14 (7.14%)
    2 / 16 (12.50%)
    1 / 14 (7.14%)
    2 / 16 (12.50%)
         occurrences all number
    6
    1
    2
    1
    2
    Monocytopenia
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    2
    1
    0
    1
    0
    Febrile neutropenia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    4 / 60 (6.67%)
    1 / 14 (7.14%)
    1 / 16 (6.25%)
    1 / 14 (7.14%)
    1 / 16 (6.25%)
         occurrences all number
    4
    1
    1
    1
    1
    Lymphocyte count elevated
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Eye disorders
    Blindness
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Gastrointestinal disorders
    Diarrhea
         subjects affected / exposed
    9 / 60 (15.00%)
    2 / 14 (14.29%)
    2 / 16 (12.50%)
    3 / 14 (21.43%)
    2 / 16 (12.50%)
         occurrences all number
    9
    2
    2
    3
    2
    Dyspepsia
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 14 (7.14%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    3
    1
    1
    0
    1
    Mouth discomfort
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Vomiting
         subjects affected / exposed
    6 / 60 (10.00%)
    1 / 14 (7.14%)
    2 / 16 (12.50%)
    1 / 14 (7.14%)
    2 / 16 (12.50%)
         occurrences all number
    6
    1
    2
    1
    2
    Constipation
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Nausea
         subjects affected / exposed
    9 / 60 (15.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    3 / 14 (21.43%)
    5 / 16 (31.25%)
         occurrences all number
    9
    0
    1
    3
    5
    Abdominal pain
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    1 / 16 (6.25%)
         occurrences all number
    2
    0
    0
    1
    1
    Esophagitis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    0
    0
    0
    1
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Hepatotoxicity
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    19 / 60 (31.67%)
    6 / 14 (42.86%)
    6 / 16 (37.50%)
    5 / 14 (35.71%)
    2 / 16 (12.50%)
         occurrences all number
    19
    6
    6
    5
    2
    Rash
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Onycholysis
         subjects affected / exposed
    13 / 60 (21.67%)
    4 / 14 (28.57%)
    5 / 16 (31.25%)
    2 / 14 (14.29%)
    2 / 16 (12.50%)
         occurrences all number
    13
    4
    5
    2
    2
    Dry skin
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    2
    1
    0
    1
    0
    Nail toxicity
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    2
    1
    0
    1
    0
    Nail dystrophy
         subjects affected / exposed
    4 / 60 (6.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    2 / 14 (14.29%)
    1 / 16 (6.25%)
         occurrences all number
    4
    0
    1
    2
    1
    Onychoclasia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Skin toxicity
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Skin hyperpigmentation
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    0
    0
    0
    1
    Renal and urinary disorders
    Urinary incontinence
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Pain in an extremity
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    2 / 14 (14.29%)
    0 / 16 (0.00%)
         occurrences all number
    3
    1
    0
    2
    0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Muscle spasms
         subjects affected / exposed
    4 / 60 (6.67%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    2 / 14 (14.29%)
    1 / 16 (6.25%)
         occurrences all number
    4
    1
    0
    2
    1
    Myalgia
         subjects affected / exposed
    4 / 60 (6.67%)
    1 / 14 (7.14%)
    1 / 16 (6.25%)
    2 / 14 (14.29%)
    0 / 16 (0.00%)
         occurrences all number
    4
    1
    1
    2
    0
    Limb discomfort
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    1 / 16 (6.25%)
         occurrences all number
    2
    0
    0
    1
    1
    Arthralgia
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    2 / 16 (12.50%)
         occurrences all number
    2
    0
    0
    0
    2
    Muscle strength loss
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    0
    0
    0
    1
    Infections and infestations
    Respiratory tract infection
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Dental infection
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Cellulite
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    2 / 14 (14.29%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    0
    2
    0
    Folliculitis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    0
    0
    0
    1
    Herpes zoster
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    6 / 60 (10.00%)
    2 / 14 (14.29%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    3 / 16 (18.75%)
         occurrences all number
    6
    2
    0
    1
    3
    Hyperphosphatemia
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Hypoproteinaemia
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Fluid retention
         subjects affected / exposed
    11 / 60 (18.33%)
    1 / 14 (7.14%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Hyperglycemia
         subjects affected / exposed
    4 / 60 (6.67%)
    0 / 14 (0.00%)
    2 / 16 (12.50%)
    0 / 14 (0.00%)
    2 / 16 (12.50%)
         occurrences all number
    4
    0
    2
    0
    2
    Hypoalbuminemia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Hypocalcemia
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    2 / 16 (12.50%)
         occurrences all number
    3
    0
    1
    0
    2
    Hypophosphataemia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Hypoglycemia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Hypernatremia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    0
    0
    0
    1
    Hypokalemia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    0
    0
    0
    1
    Stomatitis
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
    1 / 16 (6.25%)
         occurrences all number
    2
    0
    0
    1
    1
    Emesis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 14 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    0
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Sep 2012
    Amendment 1: Protocol version 2.0
    09 Sep 2015
    Amendment 2: Protcol version 4.0

    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.
    The main limitations of this study are the small sample size and lack of blinding
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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