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    Clinical Trial Results:
    Phase II study of the histone-deacetylase inhibitor GIVINOSTAT (ITF2357) in combination with hydroxyurea in patients with JAK2V617F positive Polycythemia Vera non-responder to hydroxyurea monotherapy.

    Summary
    EudraCT number
    		 2009-010982-22
    Trial protocol
    		 IT  
    Global end of trial date
    07 Jul 2011

    Results information
    Results version number
    		 v2(current)
    This version publication date
    31 Jul 2019
    First version publication date
    25 May 2019
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Friendly description should be changed.

    Trial information

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    Trial identification
    Sponsor protocol code
    DSC/08/2357/38
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00928707
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Italfarmaco S.p.A.
    Sponsor organisation address
    Via dei Lavoratori 54 , Milano, Italy, 20092
    Public contact
    Clinical Trial Transparency Manager, Italfarmaco S.p.A., Italfarmaco S.p.A., +39 02 66041503, info@italfarmaco.com
    Scientific contact
    Clinical Trial Transparency Manager, Italfarmaco S.p.A., Italfarmaco S.p.A., +39 02 66041503, info@italfarmaco.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    07 Jul 2011
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    07 Jul 2011
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Jul 2011
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of GIVINOSTAT (ITF2357) in combination with hydroxyurea in patients with JAK2V617F positive Polycythemia Vera non-responders to the maximum tolerated dose of hydroxyurea monotherapy
    Protection of trial subjects
    The study was conducted under the provisions of the Declaration of Helsinki and in accordance with the International Conference on Harmonisation (ICH) Consolidated Guideline on Good Clinical Practice (GCP).
    Background therapy
    		 Hydroxyurea (HU) monotherapy was already in use before admission to the study and was continued at the maximum tolerated dose (MTD) throughout the study
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 Jul 2009
    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
    Italy: 45
    Worldwide total number of subjects
    45
    EEA total number of subjects
    45
    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)
    21
    From 65 to 84 years
    24
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total number of 45 patients were randomised to receive: 23 Givinostat 50 mg o.d. and 22 Givinostat 50 mg b.i.d. One subject in the o.d. group was discontinued due to ineligibility/protocol violation and did not receive the assigned treatment. Therefore, 22 patients in either group received treatment.

    Pre-assignment
    Screening details
    		 Pre-enrolment screening tests and evaluations were used to determine eligibility of each candidate for study inclusion. All evaluations had to be performed within 2 weeks prior to starting treatment with Givinostat. If all eligibility criteria were met at screening visit, the treatment with Givinostat could start.

    Period 1
    Period 1 title
    Overall study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    No blinding procedures are applicable as the study was open-label.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Group A (50 mg od)
    Arm description
    		 Group A: 50 mg o.d. of oral Givinostat in combination with the maximum tolerated dose of hydroxyurea monotherapy (already in use before admission to the study) were administered for 12 weeks. In case of no response at week 12, dose was increased to 50 mg b.i.d. in weeks 13-24.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Givinostat
    Investigational medicinal product code
    Other name
    ITF2357
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Givinostat 50 mg hard gelatine capsules for oral administration, in combination with hydroxyurea monotherapy at the maximum tolerated dose.

    Investigational medicinal product name
    Hydroxyurea
    Investigational medicinal product code
    Other name
    Onco Carbide, hydroxycarbamide
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Hydroxyurea 500 mg capsules – already in use before admission to the study – at the maximum tolerated dose, in combination with Givinostat.

    Arm title
    		 Group B (50 mg bid)
    Arm description
    		 Group B: 50 mg b.i.d. of oral Givinostat in combination with the maximum tolerated dose of hydroxyurea monotherapy (already in use before admission to the study) were administered for 12 weeks. In case of no response at week 12, dose was increased to 50 mg t.i.d. in weeks 13-24.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Givinostat
    Investigational medicinal product code
    Other name
    ITF2357
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Givinostat 50 mg hard gelatine capsules for oral administration, in combination with hydroxyurea monotherapy at the maximum tolerated dose.

    Investigational medicinal product name
    Hydroxyurea
    Investigational medicinal product code
    Other name
    Onco Carbide, hydroxycarbamide
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Hydroxyurea 500 mg capsules – already in use before admission to the study – at the maximum tolerated dose, in combination with Givinostat.

    Number of subjects in period 1
    		Group A (50 mg od) Group B (50 mg bid)
    Started
    23
    22
    Completed
    22
    22
    Not completed
    1
    0
         ineligibility/protocol violation
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Group A (50 mg od)
    Reporting group description
    		 Group A: 50 mg o.d. of oral Givinostat in combination with the maximum tolerated dose of hydroxyurea monotherapy (already in use before admission to the study) were administered for 12 weeks. In case of no response at week 12, dose was increased to 50 mg b.i.d. in weeks 13-24.

    Reporting group title
    Group B (50 mg bid)
    Reporting group description
    		 Group B: 50 mg b.i.d. of oral Givinostat in combination with the maximum tolerated dose of hydroxyurea monotherapy (already in use before admission to the study) were administered for 12 weeks. In case of no response at week 12, dose was increased to 50 mg t.i.d. in weeks 13-24.

    Reporting group values
    		 Group A (50 mg od) Group B (50 mg bid) Total
    Number of subjects
    		 23 22 45
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 10 11 21
        From 65-84 years
    		 13 11 24
    Gender categorical
    Units: Subjects
        Female
    		 9 7 16
        Male
    		 14 15 29
    Subject analysis sets

    Subject analysis set title
    Group A - Safety/ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Safety/Intention-to-treat (ITT) population, which included all randomized subjects who received at least one dose of study medication.

    Subject analysis set title
    Group B - Safety/ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Safety/Intention-to-treat (ITT) population, which included all randomized subjects who received at least one dose of study medication.

    Subject analysis sets values
    		 Group A - Safety/ITT Group B - Safety/ITT
    Number of subjects
    22
    22
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    9
    11
        From 65-84 years
    13
    11
    Age continuous
    Units:
        
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
    9
    7
        Male
    13
    15

    End points

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    End points reporting groups
    Reporting group title
    Group A (50 mg od)
    Reporting group description
    		 Group A: 50 mg o.d. of oral Givinostat in combination with the maximum tolerated dose of hydroxyurea monotherapy (already in use before admission to the study) were administered for 12 weeks. In case of no response at week 12, dose was increased to 50 mg b.i.d. in weeks 13-24.

    Reporting group title
    Group B (50 mg bid)
    Reporting group description
    		 Group B: 50 mg b.i.d. of oral Givinostat in combination with the maximum tolerated dose of hydroxyurea monotherapy (already in use before admission to the study) were administered for 12 weeks. In case of no response at week 12, dose was increased to 50 mg t.i.d. in weeks 13-24.

    Subject analysis set title
    Group A - Safety/ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Safety/Intention-to-treat (ITT) population, which included all randomized subjects who received at least one dose of study medication.

    Subject analysis set title
    Group B - Safety/ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Safety/Intention-to-treat (ITT) population, which included all randomized subjects who received at least one dose of study medication.

    Primary: Overall hematological response rate at week 12

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    End point title
    		 Overall hematological response rate at week 12 [1]
    End point description
    The number and rate of patients with overall (complete or partial) response at week 12 were assessed. · Complete response: 1. HCT< 45% without phlebotomy, and 2. platelets ≤ 400 x109/L, and 3. WBC ≤ 10 x 109/L, and 4. no splenomegaly, and 5. no disease related systemic symptoms (microvascular disturbances, pruritus, headache); · Partial response: 1. HCT < 45% without phlebotomy, or 2. fulfilment of at least 3 of the other above mentioned criteria; · No response: any response that did not satisfy the criteria set for partial response.
    End point type
    Primary
    End point timeframe
    At week 12
    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: Sample size has been computed and data will be evaluated based upon a Simon's phase II dose-selection design where the objective involves selecting a promising dose among a set of candidates. For each dose group, a sample size of 22 patients is estimated using exact method (binomial) and assuming: 1. two treatment dosages; 2. 0 = 0.20 as the smallest response rate; 3. 1 = 0.40 as the best dose response rate; 4. a probability greater than 90% of correctly selecting the best dosa
    End point values
    		 Group A - Safety/ITT Group B - Safety/ITT
    Number of subjects analysed
    22
    22
    Units: percentage of patients
    number (confidence interval 95%)
        Responder
    54.5 (33.7 to 75.4)
    50.0 (29.1 to 70.9)
        Non responder
    45.5 (24.6 to 66.3)
    50.0 (29.1 to 70.9)
    No statistical analyses for this end point

    Secondary: Hematological response rate at week 24 by dose escalation after week 12

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    End point title
    		 Hematological response rate at week 24 by dose escalation after week 12
    End point description
    Rate of haematological response after a 50 mg increase of the initial Givinostat dose in non-responder patients at the time when the primary endpoint was assessed (week 12). · Complete response: 1. HCT< 45% without phlebotomy, and 2. platelets ≤ 400 x109/L, and 3. WBC ≤ 10 x 109/L, and 4. no splenomegaly, and 5. no disease related systemic symptoms (microvascular disturbances, pruritus, headache); · Partial response: 1. HCT < 45% without phlebotomy, or 2. fulfilment of at least 3 of the other above mentioned criteria; · No response: any response that did not satisfy the criteria set for partial response.
    End point type
    Secondary
    End point timeframe
    At week 24.
    End point values
    		 Group A - Safety/ITT Group B - Safety/ITT
    Number of subjects analysed
    22
    22
    Units: percentage of patients
    number (confidence interval 95%)
        Responder
    63.6 (43.5 to 83.7)
    40.9 (20.4 to 61.5)
        Non responder
    36.4 (16.3 to 56.5)
    59.1 (38.5 to 79.6)
    No statistical analyses for this end point

    Secondary: Reduction of the JAK2V617F allele burden by quantitative RT-PCR

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    End point title
    		 Reduction of the JAK2V617F allele burden by quantitative RT-PCR
    End point description
    Quantitative RT-PCR for JAK2V617F mutational status on peripheral blood (PB) granulocyte and haematopoietic colonies (with and without HGFs).
    End point type
    Secondary
    End point timeframe
    At weeks 12, 24, at "drop out visit" and at "End of Study" (EOS). EOS stays for 7 days after last drug intake if patient is withdrawn from the study before week 24.
    End point values
    		 Group A - Safety/ITT Group B - Safety/ITT
    Number of subjects analysed
    22
    21
    Units: percentage
    arithmetic mean (standard deviation)
        Week 12
    -2.6 ( 8.2 )
    0.0 ( 6.0 )
        Week 24
    -3.8 ( 11.5 )
    4.6 ( 5.7 )
        Drop-out
    -4.0 ( 000 )
    -9.5 ( 20.5 )
        EOS
    -3.8 ( 11.1 )
    3.0 ( 8.6 )
    No statistical analyses for this end point

    Secondary: Reduction of the fraction of JAK2V617F positive clonogenic progenitor

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    End point title
    		 Reduction of the fraction of JAK2V617F positive clonogenic progenitor
    End point description
    JAK2V617F genotyping and quantification were performed on gradient-separated mononuclear cells during the pre-treatment evaluations, halfway through the study (12th weeks) and at the end of the study period (24th weeks). Only data at baseline are reported. No significant reduction of the mean fraction of JAK2V617F positive clonogenic progenitor from baseline to both week 12 and week 24 in both groups was observed.
    End point type
    Secondary
    End point timeframe
    At week 12 and at week 24
    End point values
    		 Group A - Safety/ITT Group B - Safety/ITT
    Number of subjects analysed
    22
    22
    Units: number of subject
        Heterozygous
    6
    5
        Homozygous
    16
    16
        Not done
    0
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AE were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    13.0
    Reporting groups
    Reporting group title
    Group B - 50 mg bid - Safety/ITT
    Reporting group description
    		 Safety/Intention-to-treat (ITT) population included all randomized subjects who received at least one dose of study medication.

    Reporting group title
    Group A - 50 mg o.d. - Safety/ITT
    Reporting group description
    		 Safety/Intention-to-treat (ITT) population included all randomized subjects who received at least one dose of study medication.

    Serious adverse events
    		 Group B - 50 mg bid - Safety/ITT Group A - 50 mg o.d. - Safety/ITT
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 22 (9.09%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Surgical and medical procedures
    Appendicectomy
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Social circumstances
    Pregnancy of partner
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (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
    Embolism
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 4%
    Non-serious adverse events
    		 Group B - 50 mg bid - Safety/ITT Group A - 50 mg o.d. - Safety/ITT
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    21 / 22 (95.45%)
    21 / 22 (95.45%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Hypertension
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    Phlebitis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    2
    Surgical and medical procedures
    Curetting of chalazion
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 22 (9.09%)
         occurrences all number
    2
    2
    Fatigue
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 22 (9.09%)
         occurrences all number
    1
    2
    Oedema
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    Pyrexia
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 22 (9.09%)
         occurrences all number
    1
    3
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
         occurrences all number
    1
    1
    Dyspnoea
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Epistaxis
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
         occurrences all number
    1
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    Panic attack
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
         occurrences all number
    1
    2
    BBlood creatine phosphokinase increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    2 / 22 (9.09%)
    3 / 22 (13.64%)
         occurrences all number
    6
    3
    Blood magnesium increased
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    2
    Blood triglycerides increased
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    4
    0
    Blood urea increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Electrocardiogram QT prolonged
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    Platelet count increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    White blood cell count increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Injury
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Cardiac disorders
    Arrhythmia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Atrial fibrillation
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    Tachycardia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    2
    Headache
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 22 (9.09%)
         occurrences all number
    1
    2
    Paraesthesia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 22 (4.55%)
         occurrences all number
    3
    1
    Leukopenia
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 22 (0.00%)
         occurrences all number
    3
    0
    Lymphadenitis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Lymphopenia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    3
    0
    Thrombocytopenia
         subjects affected / exposed
    7 / 22 (31.82%)
    5 / 22 (22.73%)
         occurrences all number
    8
    5
    Thrombocytosis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 22 (4.55%)
    3 / 22 (13.64%)
         occurrences all number
    1
    3
    Abdominal pain upper
         subjects affected / exposed
    3 / 22 (13.64%)
    2 / 22 (9.09%)
         occurrences all number
    3
    2
    Constipation
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 22 (9.09%)
         occurrences all number
    1
    2
    Diarrhoea
         subjects affected / exposed
    7 / 22 (31.82%)
    10 / 22 (45.45%)
         occurrences all number
    10
    12
    Dyspepsia
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    Gastritis
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
         occurrences all number
    1
    1
    Haematochezia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    0 / 22 (0.00%)
    3 / 22 (13.64%)
         occurrences all number
    0
    3
    Stomatitis
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 22 (9.09%)
         occurrences all number
    1
    3
    Tongue haemorrhage
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
         occurrences all number
    1
    1
    Skin and subcutaneous tissue disorders
    Actinic keratosis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Eczema
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Renal colic
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Back pain
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    Myalgia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Infections and infestations
    Genitourinary tract infection
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    Influenza
         subjects affected / exposed
    1 / 22 (4.55%)
    3 / 22 (13.64%)
         occurrences all number
    1
    3
    Pharyngitis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    Rhinitis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    Tooth abscess
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    Urogenital infection fungal
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 22 (4.55%)
         occurrences all number
    1
    1
    Hyperkalaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 22 (9.09%)
         occurrences all number
    1
    3
    Hyperuricaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 22 (9.09%)
         occurrences all number
    2
    3
    Hypokalaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Sep 2009
    The key features of the present amendment are: a) the variation of one exclusion criteria, b) the collection of a whole blood sample both at Baseline and at the middle of the study (at Week 12), c) the increase of study Centers number.

    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.
    No limitations and caveats are applicable to this summary of results.
    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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