Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   38153   clinical trials with a EudraCT protocol, of which   6266   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    International Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of the Efficacy and Safety of KIACTA™ in Preventing Renal Function Decline in Patients With AA Amyloidosis

    Summary
    EudraCT number
    2010-022313-25
    Trial protocol
    LT   SE   GB   NL   CZ   FI   DE   ES   BE   PL   IT   BG   PT   LV   EE  
    Global end of trial date
    04 Mar 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    15 Oct 2017
    First version publication date
    15 Oct 2017
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    CL-503012
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01215747
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    A.T. Development Switzerland SARL
    Sponsor organisation address
    Route de la Corniche 3B, Epalinges, Switzerland,
    Public contact
    Monika Deme, AD Project Management, PPD , +31 .630037735., Monika.Deme@ppdi.com
    Scientific contact
    Monika Deme, AD Project Management, PPD , +31 .630037735., Monika.Deme@ppdi.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
    28 Sep 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    04 Mar 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Mar 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this double-blind, randomized, placebo-controlled, Phase 3 study was to assess the efficacy and safety of treatment with Kiacta in adult patients with AA amyloidosis. Efficacy was assessed by the time from Baseline to the primary endpoint. This primary efficacy endpoint was the time from Baseline to the earliest of a persistent decrease in creatinine clearance (CrCl) of 40% or more, a persistent increase in serum creatinine (SCr) of 80% or more, or progression to end-stage renal disease (ESRD). Safety was assessed by the incidence of non-serious adverse events (AEs) and serious AEs (SAEs). Neither progression to ESRD nor a clinically significant change in CrCl or SCr was considered an AE or SAE.
    Protection of trial subjects
    The study drug was to be taken a minimum of 1 hour before or 2 hours after morning and evening meals. Dose regimen of the subjects was adjusted according to CrCl levels (increases or decreases).
    Background therapy
    Subjects receiving cytotoxic agents, colchicine, antitumor necrosis factor agents, anti-interleukin-1 or anti-interleukin-6 agents, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, or a renin inhibitor had to be on stable doses for at least 3 months before the baseline visit. Patients were treated for worsening of hypertension or the underlying inflammatory condition as clinically indicated.
    Evidence for comparator
    No patient was maintained under exclusive placebo treatment during the study. The study drug (Kiacta or placebo) was administered in addition to the standard therapy currently available.
    Actual start date of recruitment
    04 Apr 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 10
    Country: Number of subjects enrolled
    Sweden: 1
    Country: Number of subjects enrolled
    Tunisia: 21
    Country: Number of subjects enrolled
    Turkey: 14
    Country: Number of subjects enrolled
    Ukraine: 18
    Country: Number of subjects enrolled
    United Kingdom: 9
    Country: Number of subjects enrolled
    United States: 10
    Country: Number of subjects enrolled
    Jordan: 1
    Country: Number of subjects enrolled
    Armenia: 10
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Bulgaria: 1
    Country: Number of subjects enrolled
    Czech Republic: 7
    Country: Number of subjects enrolled
    Egypt: 19
    Country: Number of subjects enrolled
    Estonia: 1
    Country: Number of subjects enrolled
    Finland: 1
    Country: Number of subjects enrolled
    France: 1
    Country: Number of subjects enrolled
    Georgia: 5
    Country: Number of subjects enrolled
    Germany: 4
    Country: Number of subjects enrolled
    India: 13
    Country: Number of subjects enrolled
    Israel: 8
    Country: Number of subjects enrolled
    Italy: 9
    Country: Number of subjects enrolled
    Latvia: 3
    Country: Number of subjects enrolled
    Lebanon: 3
    Country: Number of subjects enrolled
    Lithuania: 10
    Country: Number of subjects enrolled
    Mexico: 1
    Country: Number of subjects enrolled
    Netherlands: 2
    Country: Number of subjects enrolled
    Peru: 17
    Country: Number of subjects enrolled
    Poland: 22
    Country: Number of subjects enrolled
    Portugal: 5
    Country: Number of subjects enrolled
    Russian Federation: 32
    Worldwide total number of subjects
    260
    EEA total number of subjects
    88
    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)
    225
    From 65 to 84 years
    35
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    The study was designed to enroll adult patients with AA amyloidosis with persistent proteinuria ≥1 g/day and CrCl ≥25 mL/min/1.73 m2. Randomization was stratified by screening proteinuria (<3 or ≥3 g/day) and screening eGFR as calculated with the modification of diet in renal disease (MDRD) formula (<60 or ≥60 mL/min/1.73 m2).

    Pre-assignment
    Screening details
    Subjects were assessed at screening and baseline and then every 3 months until a primary endpoint was met or the end of study (EOS) was reached. Those subjects who met inclusion criteria and did not meet exclusion criteria were eligible to participate in the study and were randomized to treatment.

    Pre-assignment period milestones
    Number of subjects started
    462 [1]
    Number of subjects completed
    260

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    Consent withdrawn by subject: 1
    Reason: Number of subjects
    Screen failure: 201
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: A total of 462 patients were screened; 201 patients were screen failures. A total of 261 patients were enrolled to the study, of which 130 patients were randomized to the Kiacta group and 131 patients were randomized to the placebo group.
    Period 1
    Period 1 title
    Treatment period 1 (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor
    Blinding implementation details
    The study was double-blind. The patients, the investigators, the study site staff, the contract research organization (monitoring, central laboratory, and data management), and the sponsor remained blinded to study drug assignment during the entire study period. Kiacta and placebo were in the form of capsules, identical in external appearance.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Kiacta
    Arm description
    Subjects received 400 mg or 1200 mg (as 1 to 3 capsules of 400 mg) per dose of Kiacta, twice daily
    Arm type
    Experimental

    Investigational medicinal product name
    Kiacta
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    400 mg (1 to 3 capsules) twice daily

    Arm title
    Placebo
    Arm description
    1 to 3 capsules of Placebo, twice daily
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    1 to 3 capsules of Placebo, twice daily

    Number of subjects in period 1
    Kiacta Placebo
    Started
    129
    131
    Completed
    91
    94
    Not completed
    38
    37
         Protocol deviation
    1
    -
         Physician decision
    7
    5
         Adverse event, serious fatal
    15
    13
         Adverse event, non-fatal
    4
    5
         Consent withdrawn by subject
    9
    12
         Lost to follow-up
    2
    2

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Kiacta
    Reporting group description
    Subjects received 400 mg or 1200 mg (as 1 to 3 capsules of 400 mg) per dose of Kiacta, twice daily

    Reporting group title
    Placebo
    Reporting group description
    1 to 3 capsules of Placebo, twice daily

    Reporting group values
    Kiacta Placebo Total
    Number of subjects
    129 131 260
    Age categorical
    Male or nonpregnant, nonlactating females
    Units: Subjects
        Adults (18-64 years)
    115 110 225
        From 65-84 years
    14 21 35
    Gender categorical
    Units: Subjects
        Female
    57 63 120
        Male
    72 68 140
    Subject analysis sets

    Subject analysis set title
    ITT analysis set - TTE endpoints
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All patients who were randomized to a treatment group and took at least 1 dose of study drug.

    Subject analysis set title
    PP analysis set
    Subject analysis set type
    Per protocol
    Subject analysis set description
    All patients who had 80% to 120% (inclusive) compliance with the study drug (based on percentage of times study drug was taken), had no missing measurements on any relevant analyte (SCr, CrCl, or eGFR data) for 2 or more consecutive visits, had fulfilled all the study inclusion and exclusion criteria, and had no major protocol violations.

    Subject analysis set title
    ITT analysis set - non-TTE endpoints
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    For any endpoint, this analysis set included all patients who were randomized to a treatment group, took at least 1 dose of the study drug, and had at least 1 postbaseline assessment.

    Subject analysis sets values
    ITT analysis set - TTE endpoints PP analysis set ITT analysis set - non-TTE endpoints
    Number of subjects
    260
    216
    253
    Age categorical
    Male or nonpregnant, nonlactating females
    Units: Subjects
        Adults (18-64 years)
    225
        From 65-84 years
    35
    Age continuous
    Units:
        
    ±
    ±
    ±
    Gender categorical
    Units: Subjects
        Female
    120
        Male
    140

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Kiacta
    Reporting group description
    Subjects received 400 mg or 1200 mg (as 1 to 3 capsules of 400 mg) per dose of Kiacta, twice daily

    Reporting group title
    Placebo
    Reporting group description
    1 to 3 capsules of Placebo, twice daily

    Subject analysis set title
    ITT analysis set - TTE endpoints
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All patients who were randomized to a treatment group and took at least 1 dose of study drug.

    Subject analysis set title
    PP analysis set
    Subject analysis set type
    Per protocol
    Subject analysis set description
    All patients who had 80% to 120% (inclusive) compliance with the study drug (based on percentage of times study drug was taken), had no missing measurements on any relevant analyte (SCr, CrCl, or eGFR data) for 2 or more consecutive visits, had fulfilled all the study inclusion and exclusion criteria, and had no major protocol violations.

    Subject analysis set title
    ITT analysis set - non-TTE endpoints
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    For any endpoint, this analysis set included all patients who were randomized to a treatment group, took at least 1 dose of the study drug, and had at least 1 postbaseline assessment.

    Primary: Time from baseline to the earliest of a persistent decrease in CrCl of ≥40%, a persistent increase in SCr of ≥80%, or progression to ESRD

    Close Top of page
    End point title
    Time from baseline to the earliest of a persistent decrease in CrCl of ≥40%, a persistent increase in SCr of ≥80%, or progression to ESRD
    End point description
    End point type
    Primary
    End point timeframe
    The primary efficacy endpoint was to assess the effect of treatment with Kiacta on the time from baseline to the earliest of: a persistent decrease in CrCl ≥40%, a persistent increase in SCr ≥80%, or progression to ESRD.
    End point values
    Kiacta Placebo ITT analysis set - non-TTE endpoints
    Number of subjects analysed
    129
    131
    253
    Units: months
    median (confidence interval 95%)
        Time to persistent increase in SCr of ≥80%
    1.0667 (0.233 to 3.267)
    1.0333 (0.2 to 4.333)
    1.0333 (0.2 to 4.333)
        Time to persistent decrease in CrCl of ≥40%
    76.5 (28.3 to 270)
    67 (24.3 to 331)
    0.007 (-0.04 to 0.36)
        Time to progression to ESRD
    72 (22 to 525)
    61 (11 to 468)
    3.259 (-18.9 to 3.8)
    Statistical analysis title
    Statistical analysis plan dated 03 Jun 2016
    Comparison groups
    Kiacta v Placebo
    Number of subjects included in analysis
    260
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.882
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.7
         upper limit
    1.4
    Variability estimate
    Standard deviation

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were assessed from the time the subject signs the informed consent until 30 days after the last dose of the treatment.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Kiacta treatment group
    Reporting group description
    -

    Reporting group title
    Placebo treatment group
    Reporting group description
    -

    Serious adverse events
    Kiacta treatment group Placebo treatment group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    58 / 129 (44.96%)
    64 / 131 (48.85%)
         number of deaths (all causes)
    15
    13
         number of deaths resulting from adverse events
    0
    0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superior mesenteric artery syndrome
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal cancer
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to spine
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Prostate cancer
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Diarrhoea
         subjects affected / exposed
    1 / 129 (0.78%)
    6 / 131 (4.58%)
         occurrences causally related to treatment / all
    0 / 115
    1 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Fatigue
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Generalised oedema
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inflammation
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multi-organ disorder
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Reproductive system and breast disorders
    Gynaecomastia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scrotal swelling
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Testicular mass
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foreign body in eye
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Open fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematuria
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic fracture
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac amyloidosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ischaemic cardiomyopathy
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Familial mediterranean fever
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystic fibrosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertrophic cardiomyopathy
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 129 (3.88%)
    3 / 131 (2.29%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia of chronic disease
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone marrow failure
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Bronchopneumopathy
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthmatic crisis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nervous system disorders
    Autonomic neuropathy
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Amaurosis fugax
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angle closure glaucoma
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulcerative keratitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vitreous haemorrhage
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    0 / 129 (0.00%)
    3 / 131 (2.29%)
         occurrences causally related to treatment / all
    0 / 115
    1 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    2 / 129 (1.55%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aphthous stomatitis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal stenosis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis acute
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hepatocellular injury
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure acute
         subjects affected / exposed
    4 / 129 (3.10%)
    5 / 131 (3.82%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nephrotic syndrome
         subjects affected / exposed
    4 / 129 (3.10%)
    4 / 131 (3.05%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Calculus ureteric
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis haemorrhagic
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prerenal failure
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary bladder haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Henoch-Schonlein purpura
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Rheumatoid arthritis
         subjects affected / exposed
    4 / 129 (3.10%)
    5 / 131 (3.82%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankylosing spondylitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle atrophy
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteochondrosis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psoriatic arthropathy
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rheumatic disorder
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hypoglycaemia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    4 / 129 (3.10%)
    7 / 131 (5.34%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 1
    0 / 4
    Gastroenteritis
         subjects affected / exposed
    2 / 129 (1.55%)
    3 / 131 (2.29%)
         occurrences causally related to treatment / all
    1 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of bronchiectasis
         subjects affected / exposed
    3 / 129 (2.33%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 129 (1.55%)
    3 / 131 (2.29%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 129 (1.55%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 129 (1.55%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bronchitis
         subjects affected / exposed
    2 / 129 (1.55%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute tonsillitis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alpha haemolytic streptococcal infection
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis infective
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis viral
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atypical mycobacterial pneumonia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis of male external genital organ
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Genitourinary tract infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Haematoma infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella bacteraemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leishmaniasis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 165
    0 / 115
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ophthalmic herpes simplex
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retroperitoneal abscess
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal urinary tract infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 115
    0 / 165
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Kiacta treatment group Placebo treatment group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    110 / 129 (85.27%)
    114 / 131 (87.02%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    16 / 129 (12.40%)
    17 / 131 (12.98%)
         occurrences all number
    33
    33
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    22 / 129 (17.05%)
    17 / 131 (12.98%)
         occurrences all number
    39
    39
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    13 / 129 (10.08%)
    20 / 131 (15.27%)
         occurrences all number
    33
    33
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    26 / 129 (20.16%)
    24 / 131 (18.32%)
         occurrences all number
    50
    50
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    15 / 129 (11.63%)
    23 / 131 (17.56%)
         occurrences all number
    38
    38
    Bronchitis
         subjects affected / exposed
    16 / 129 (12.40%)
    11 / 131 (8.40%)
         occurrences all number
    27
    27

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Feb 2013
    Protocol CL-503012 Version 5.0 states that details for the analysis of samples taken for assessment of urinary glycosaminoglycans (GAGs), urinary creatinine, and urine proteomics was provided in a separate protocol (Protocol CL-503014). However, Auven Therapeutics (formerly Celtic Therapeutics) subsequently decided not to develop Protocol CL-503014. Samples for urinary GAGs, urinary creatinine, and urine proteomics were collected, stored, and analyzed as planned in Protocol CL-503012 Version 5.0 but the development plan for a diagnostic has not yet been determined. The affected sections of the protocol are as follows: Section 7.5.3.1 Safety Measures – Clinical Laboratory Parameters Section 8.3.1 Safety Evaluations – Clinical Laboratory Parameters

    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
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA