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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:
    A Randomized, Actively Controlled, Open-label, Multicenter Study of Efficacy and Safety of Evolocumab Compared With Low Density Lipoprotein Cholesterol (LDL-C) Apheresis, Followed by Single-Arm Evolocumab Administration in Subjects Receiving LDL-C Apheresis Prior to Study Enrollment

    Summary
    EudraCT number
    		 2015-001343-37
    Trial protocol
    		 DE   ES   CZ   IT  
    Global end of trial date
    20 Jan 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Jan 2018
    First version publication date
    19 Jan 2018
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    20140316
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02585895
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Amgen Inc.
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
    Public contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
    Scientific contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.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
    20 Jan 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Jan 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective was to evaluate the efficacy of subcutaneous evolocumab, compared with regularly scheduled low-density lipoprotein cholesterol (LDL-C) apheresis, on reducing the need for future apheresis.
    Protection of trial subjects
    This study was conducted in accordance with International Council on Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines. The study was reviewed by an independent ethics committee (IEC) or institutional review board (IRB). All subjects provided written informed consent before undergoing any study-related procedures, including screening procedures.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 Dec 2015
    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
    Australia: 1
    Country: Number of subjects enrolled
    Czech Republic: 2
    Country: Number of subjects enrolled
    France: 1
    Country: Number of subjects enrolled
    Germany: 7
    Country: Number of subjects enrolled
    Italy: 12
    Country: Number of subjects enrolled
    Spain: 3
    Country: Number of subjects enrolled
    United Kingdom: 5
    Country: Number of subjects enrolled
    United States: 8
    Worldwide total number of subjects
    39
    EEA total number of subjects
    30
    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
    18
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This study was conducted at 15 centers in the following 8 countries: Australia, Czech Republic, France, Germany, Italy, Spain, the United Kingdom, and the United States. Participants were enrolled from 21 December 2015 to 21 July 2016.

    Pre-assignment
    Screening details
    		 Participants were randomized in a 1:1 ratio to continue apheresis on the same schedule as before study entry, or to stop apheresis and receive evolocumab. Randomization was stratified by screening low-density lipoprotein cholesterol (LDL-C) (< 160 mg/dL [4.1 mmol/L] vs ≥ 160 mg/dL).

    Period 1
    Period 1 title
    Primary Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Apheresis
    Arm description
    		 Participants continued apheresis at the same schedule, every week (QW) or every two weeks (Q2W), as prior to study entry, for 6 weeks during the primary period of the study.
    Arm type
    		 Comparator procedure

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Evolocumab
    Arm description
    		 Participants received 140 mg evolocumab every 2 weeks (Q2W) administered by subcutaneous injection for 6 weeks during the primary period of the study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Evolocumab
    Investigational medicinal product code
    AMG 145
    Other name
    Repatha
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once every 2 weeks

    Number of subjects in period 1
    		Apheresis Evolocumab
    Started
    20
    19
    Completed
    20
    19
    Period 2
    Period 2 title
    Post-primary Period
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Apheresis/Evolocumab
    Arm description
    		 Participants who received apheresis for 6 weeks during the primary period of the study then received 140 mg evolocumab Q2W from week 6 to week 24 in the post-primary period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Evolocumab
    Investigational medicinal product code
    AMG 145
    Other name
    Repatha
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once every 2 weeks

    Arm title
    		 Evolocumab/Evolocumab
    Arm description
    		 Participants who received 140 mg evolocumab Q2W for 6 weeks during the primary period of the study continued receiving 140 mg evolocumab Q2W from week 6 to week 24 in the post-primary period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Evolocumab
    Investigational medicinal product code
    AMG 145
    Other name
    Repatha
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once every 2 weeks

    Number of subjects in period 2
    		Apheresis/Evolocumab Evolocumab/Evolocumab
    Started
    20
    19
    Completed
    20
    19

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Apheresis
    Reporting group description
    		 Participants continued apheresis at the same schedule, every week (QW) or every two weeks (Q2W), as prior to study entry, for 6 weeks during the primary period of the study.

    Reporting group title
    Evolocumab
    Reporting group description
    		 Participants received 140 mg evolocumab every 2 weeks (Q2W) administered by subcutaneous injection for 6 weeks during the primary period of the study.

    Reporting group values
    		 Apheresis Evolocumab Total
    Number of subjects
    		 20 19 39
    Age, Customized
    Units: Subjects
        < 65 years
    		 14 7 21
        ≥ 65 years
    		 6 12 18
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 59.6 ± 10.0 65.4 ± 8.1 -
    Gender, Male/Female
    Units: Subjects
        Female
    		 7 9 16
        Male
    		 13 10 23
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 0 0 0
        Black or African American
    		 0 1 1
        Native Hawaiian or Other Pacific Islander|
    		 0 0 0
        White
    		 20 18 38
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 2 2
        Not Hispanic or Latino
    		 20 17 37
        Unknown or Not Reported
    		 0 0 0
    Stratification Factor: Screening LDL-C Level
    Units: Subjects
        < 160 mg/dL
    		 11 11 22
        ≥ 160 mg/dL
    		 9 8 17
    LDL-C Concentration
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 150.6 ± 25.6 152.4 ± 21.2 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Apheresis
    Reporting group description
    		 Participants continued apheresis at the same schedule, every week (QW) or every two weeks (Q2W), as prior to study entry, for 6 weeks during the primary period of the study.

    Reporting group title
    Evolocumab
    Reporting group description
    		 Participants received 140 mg evolocumab every 2 weeks (Q2W) administered by subcutaneous injection for 6 weeks during the primary period of the study.
    Reporting group title
    Apheresis/Evolocumab
    Reporting group description
    		 Participants who received apheresis for 6 weeks during the primary period of the study then received 140 mg evolocumab Q2W from week 6 to week 24 in the post-primary period.

    Reporting group title
    Evolocumab/Evolocumab
    Reporting group description
    		 Participants who received 140 mg evolocumab Q2W for 6 weeks during the primary period of the study continued receiving 140 mg evolocumab Q2W from week 6 to week 24 in the post-primary period.

    Primary: Percentage of participants with Apheresis Avoidance at the End of Randomized Therapy

    		 Close Top of page
    End point title
    		 Percentage of participants with Apheresis Avoidance at the End of Randomized Therapy
    End point description
    Avoidance of apheresis at end of randomized therapy was defined as no apheresis at week 5 and week 6. Aperesis at weeks 5 or 6 was based on LDL-C level at week 4: participants with LDL-C ≥ 100 mg/dL at week 4 received apheresis at week 5 (participants who received apheresis QW before study entry) or week 6 (participants who received apheresis Q2W prior to study entry). If LDL-C was < 100 mg/dL at week 4, no apheresis was performed at week 5 or week 6, irrespective of assigned treatment group. Participants who ended the study prior to week 6 were considered as not achieving apheresis avoidance.
    End point type
    Primary
    End point timeframe
    Week 5 and week 6
    End point values
    		 Apheresis Evolocumab
    Number of subjects analysed
    20
    19
    Units: percentage of participants
        number (confidence interval 95%)
    10.0 (2.8 to 30.1)
    84.2 (62.4 to 94.5)
    Statistical analysis title
    		 Primary Analysis of Apheresis Avoidance
    Comparison groups
    Apheresis v Evolocumab
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [1]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Treatment Difference
    Point estimate
    74.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 44.6
         upper limit
    		 86.8
    Notes
    [1] - Based on Cochran-Mantel-Haenszel (CMH) test stratified by screening LDL-C level

    Secondary: Percent Change from Baseline in Low-density Lipoprotein Cholesterol

    		 Close Top of page
    End point title
    		 Percent Change from Baseline in Low-density Lipoprotein Cholesterol
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline and week 4
    End point values
    		 Apheresis Evolocumab
    Number of subjects analysed
    19
    19
    Units: percent change
        least squares mean (standard error)
    2.61 ± 3.97
    -50.13 ± 4.03
    Statistical analysis title
    		 Analysis of Percent Change From Baseline in LDL-C
    Comparison groups
    Apheresis v Evolocumab
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [2]
    Method
    		 Repeated measures linear effects model
    Parameter type
    		 Treatment Difference
    Point estimate
    -52.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -64.18
         upper limit
    		 -41.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.64
    Notes
    [2] - Model included treatment group, screening LDL-C level, scheduled visit, and the interaction of treatment group with scheduled visit as covariates.

    Secondary: Percent Change from Baseline in Non-high-density Lipoprotein-Cholesterol

    		 Close Top of page
    End point title
    		 Percent Change from Baseline in Non-high-density Lipoprotein-Cholesterol
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline and Week 4
    End point values
    		 Apheresis Evolocumab
    Number of subjects analysed
    19
    19
    Units: percent change
        least squares mean (standard error)
    1.80 ± 3.29
    -44.58 ± 3.34
    Statistical analysis title
    		 Analysis of Change from Baseline in Non-HDL-C
    Comparison groups
    Apheresis v Evolocumab
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [3]
    Method
    		 Repeated measures linear effects model
    Parameter type
    		 Treatment Difference
    Point estimate
    -46.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -55.85
         upper limit
    		 -36.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.67
    Notes
    [3] - Model included treatment group, screening LDL-C level, scheduled visit, and the interaction of treatment group with scheduled visit as covariates.

    Secondary: Percent Change from Baseline in Total cholesterol/High-density Lipoprotein Cholesterol Ratio

    		 Close Top of page
    End point title
    		 Percent Change from Baseline in Total cholesterol/High-density Lipoprotein Cholesterol Ratio
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline and Week 4
    End point values
    		 Apheresis Evolocumab
    Number of subjects analysed
    19
    19
    Units: percent change
        least squares mean (standard error)
    0.15 ± 2.65
    -35.65 ± 2.67
    Statistical analysis title
    		 Analysis of Change from Baseline in TC/HDL-C Ratio
    Comparison groups
    Apheresis v Evolocumab
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [4]
    Method
    		 Repeated measures linear effects model
    Parameter type
    		 Treatment Difference
    Point estimate
    -35.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -43.39
         upper limit
    		 -28.21
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.74
    Notes
    [4] - Model included treatment group, screening LDL-C level, scheduled visit, and the interaction of treatment group with scheduled visit as covariates.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    6 Weeks for the primary period, and 20 Weeks for post-primary period
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Primary Period: Apheresis QW
    Reporting group description
    		 Participants received apheresis every week (QW) for 6 weeks during the primary period of the study.

    Reporting group title
    Primary Period: Apheresis Q2W
    Reporting group description
    		 Participants received apheresis every 2 weeks (Q2W) for 6 weeks during the primary period of the study.

    Reporting group title
    Primary Period: Evolocumab
    Reporting group description
    		 Participants received 140 mg evolocumab every 2 weeks (Q2W) administered by subcutaneous injection for 6 weeks during the primary period of the study.

    Reporting group title
    Post-primary Period: Apheresis/Evolocumab
    Reporting group description
    		 Starting at week 6 participants received 140 mg evolocumab Q2W up to week 24.

    Reporting group title
    Post-primary Period: Evolocumab/Evolocumab
    Reporting group description
    		 Participants received 140 mg evolocumab Q2W from week 6 to week 24.

    Serious adverse events
    		 Primary Period: Apheresis QW Primary Period: Apheresis Q2W Primary Period: Evolocumab Post-primary Period: Apheresis/Evolocumab Post-primary Period: Evolocumab/Evolocumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 16 (12.50%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    2 / 19 (10.53%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Cardiac disorders
    Myocardial ischaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal vein occlusion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 19 (5.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 19 (5.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    		 Primary Period: Apheresis QW Primary Period: Apheresis Q2W Primary Period: Evolocumab Post-primary Period: Apheresis/Evolocumab Post-primary Period: Evolocumab/Evolocumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 4 (50.00%)
    5 / 16 (31.25%)
    10 / 19 (52.63%)
    6 / 20 (30.00%)
    8 / 19 (42.11%)
    Vascular disorders
    Phlebitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    1
    1
    Chest pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Fatigue
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 19 (5.26%)
    2 / 20 (10.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    Influenza like illness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    2 / 20 (10.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Injection site erythema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Injection site pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Social circumstances
    Menopause
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Dyspnoea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Psychiatric disorders
    Mood swings
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Arteriovenous fistula site complication
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    1
    Ligament sprain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Cardiac disorders
    Myocardial ischaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    2
    0
    2
    0
    Nervous system disorders
    Cervicobrachial syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Dizziness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Headache
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    2 / 19 (10.53%)
    2 / 20 (10.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    4
    2
    6
    Restless legs syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    2
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Eye disorders
    Visual acuity reduced
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    6
    0
    Diarrhoea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    2 / 20 (10.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    6
    1
    Gastric disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Nausea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    2 / 20 (10.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Vomiting
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    1
    Rash
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    2 / 19 (10.53%)
    0 / 20 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    2
    0
    1
    Skin lesion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    1
    Back pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Gouty arthritis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Myalgia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    2 / 19 (10.53%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    2
    2
    0
    Pain in extremity
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Infections and infestations
    Ear infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    1
    Mastitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 19 (5.26%)
         occurrences all number
    0
    0
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Otitis externa
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Tooth abscess
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 16 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Metabolism and nutrition disorders
    Gout
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Hyperuricaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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
    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.

    European Medicines Agency © 1995-Fri Apr 19 23:21:34 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA