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   43874   clinical trials with a EudraCT protocol, of which   7293   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 Phase 2b Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose‑Ranging Study to Assess the Efficacy, Safety, and Tolerability of Vupanorsen (PF‑07285557) in Statin-Treated Subjects with Dyslipidemia

    Summary
    EudraCT number
    		 2020-002796-35
    Trial protocol
    		 PL  
    Global end of trial date
    06 Dec 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Dec 2022
    First version publication date
    15 Dec 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    C4491011
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.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 Jun 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Dec 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To estimate the effects of multiple dose levels and regimens of vupanorsen compared to placebo on non-high-density lipoprotein cholesterol (non-HDL-C).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Sep 2020
    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
    Canada: 126
    Country: Number of subjects enrolled
    Poland: 33
    Country: Number of subjects enrolled
    United States: 127
    Worldwide total number of subjects
    286
    EEA total number of subjects
    33
    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)
    151
    From 65 to 84 years
    134
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Adult subjects aged greater than equal to (>=) 40 years with dyslipidemia on a stable dose of statin (with or without ezetimibe) were included in the study. The study was conducted across 3 countries.

    Pre-assignment
    Screening details
    		 727 subjects signed the informed consent form (ICF). 391 subjects were screen failures who did not meet criteria and were not enrolled. 336 subjects were enrolled into the study of which 50 subjects were not randomised and 286 subjects were assigned to a study treatment.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Subjects were randomised to receive vupanorsen (PF-07285557) matched placebo subcutaneous (SC) injection. Single or double administration was given at every 2 or 4 weeks (Q2W or Q4W) to match active treatment groups. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received vupanorsen matched placebo SC injection administered Q2W or Q4W up to 24 weeks.

    Arm title
    		 Vupanorsen: 80 mg Q4W
    Arm description
    		 Subjects were randomised to receive vupanorsen 80 mg single SC injection at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vupanorsen
    Investigational medicinal product code
    PF-07285557
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received vupanorsen 80 mg single SC injection administered Q4W for 24 weeks.

    Arm title
    		 Vupanorsen: 60 mg Q2W
    Arm description
    		 Subjects were randomised to receive vupanorsen 60 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vupanorsen
    Investigational medicinal product code
    PF-07285557
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received vupanorsen 60 mg single SC injection administered Q2W for 24 weeks.

    Arm title
    		 Vupanorsen: 120 mg Q4W
    Arm description
    		 Subjects were randomised to receive vupanorsen 60 mg double SC injection (120 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vupanorsen
    Investigational medicinal product code
    PF-07285557
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received vupanorsen 60 mg double SC injection (120 mg in total) administered Q4W for 24 weeks.

    Arm title
    		 Vupanorsen: 80 mg Q2W
    Arm description
    		 Subjects were randomised to receive vupanorsen 80 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vupanorsen
    Investigational medicinal product code
    PF-07285557
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received vupanorsen 80 mg single SC injection administered Q2W for 24 weeks.

    Arm title
    		 Vupanorsen: 160 mg Q4W
    Arm description
    		 Subjects were randomised to receive vupanorsen 80 mg double SC injection (160 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vupanorsen
    Investigational medicinal product code
    PF-07285557
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received vupanorsen 80 mg double SC injection (160 mg in total) administered Q4W for 24 weeks.

    Arm title
    		 Vupanorsen: 120 mg Q2W
    Arm description
    		 Subjects were randomised to receive vupanorsen 60 mg double SC injection (120 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vupanorsen
    Investigational medicinal product code
    PF-07285557
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received vupanorsen 60 mg double SC injection (120 mg in total) administered Q2W for 24 weeks.

    Arm title
    		 Vupanorsen: 160 mg Q2W
    Arm description
    		 Subjects were randomised to receive vupanorsen 80 mg double SC injection (160 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vupanorsen
    Investigational medicinal product code
    PF-07285557
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received vupanorsen 80 mg double SC injection (160 mg in total) administered Q2W for 24 weeks.

    Number of subjects in period 1
    		Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
    Started
    44
    23
    24
    23
    45
    45
    46
    36
    Completed
    44
    22
    23
    21
    43
    45
    46
    36
    Not completed
    0
    1
    1
    2
    2
    0
    0
    0
         Consent withdrawn by subject
    -
    -
    -
    -
    1
    -
    -
    -
         Adverse event, non-fatal
    -
    -
    1
    -
    1
    -
    -
    -
         Unspecified
    -
    1
    -
    2
    -
    -
    -
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects were randomised to receive vupanorsen (PF-07285557) matched placebo subcutaneous (SC) injection. Single or double administration was given at every 2 or 4 weeks (Q2W or Q4W) to match active treatment groups. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 80 mg Q4W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 80 mg single SC injection at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 60 mg Q2W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 60 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 120 mg Q4W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 60 mg double SC injection (120 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 80 mg Q2W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 80 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 160 mg Q4W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 80 mg double SC injection (160 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 120 mg Q2W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 60 mg double SC injection (120 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 160 mg Q2W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 80 mg double SC injection (160 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group values
    		 Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W Total
    Number of subjects
    		 44 23 24 23 45 45 46 36 286
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 23 11 11 13 23 23 30 17 151
        From 65-84 years
    		 21 12 12 10 22 22 16 19 134
        85 years and over
    		 0 0 1 0 0 0 0 0 1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 64.23 ± 8.09 65.78 ± 7.27 64.21 ± 9.92 61.04 ± 9.31 63.38 ± 8.41 63.09 ± 8.80 62.74 ± 8.64 64.47 ± 7.74 -
    Sex: Female, Male
    Units: Subjects
        Female
    		 17 13 7 9 24 17 20 19 126
        Male
    		 27 10 17 14 21 28 26 17 160
    Race
    Units: Subjects
        Asian
    		 4 2 2 1 3 0 4 4 20
        Black or African American
    		 0 1 1 0 4 1 4 1 12
        White
    		 38 20 21 21 38 44 37 31 250
        Unknown or Not Reported
    		 2 0 0 1 0 0 1 0 4
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 5 2 1 6 4 6 2 1 27
        Not Hispanic or Latino
    		 39 21 23 17 41 39 44 35 259

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects were randomised to receive vupanorsen (PF-07285557) matched placebo subcutaneous (SC) injection. Single or double administration was given at every 2 or 4 weeks (Q2W or Q4W) to match active treatment groups. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 80 mg Q4W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 80 mg single SC injection at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 60 mg Q2W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 60 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 120 mg Q4W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 60 mg double SC injection (120 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 80 mg Q2W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 80 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 160 mg Q4W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 80 mg double SC injection (160 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 120 mg Q2W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 60 mg double SC injection (120 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 160 mg Q2W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 80 mg double SC injection (160 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Primary: Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (non-HDL-C) at Week 24

    		 Close Top of page
    End point title
    		 Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (non-HDL-C) at Week 24
    End point description
    Fasting was required at least 10 hours before blood sample collection. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing. Full analysis set primary (FAS_primary) included all subjects randomised to study intervention and who took at least 1 dose of study intervention, had a baseline measurement and at least one post-baseline measurement with all observations that occurred after discontinuation of treatment or after initiation of severe hypertriglyceridaemia excluded.
    End point type
    Primary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
    Number of subjects analysed
    44
    23
    23
    23
    42
    45
    46
    35
    Units: Percent change
        least squares mean (standard error)
    -1.1 ± 2.76
    -23.5 ± 4.08
    -23.2 ± 4.02
    -25.3 ± 4.23
    -28.8 ± 3.02
    -27.8 ± 2.88
    -25.8 ± 2.84
    -27.6 ± 3.57
    Statistical analysis title
    		 Placebo versus Vupanorsen: 80 mg Q4W
    Statistical analysis description
    Mixed Model Analysis (MMRM) with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 80 mg Q4W
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Square (LS) Mean difference
    Point estimate
    -22.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -32.1
         upper limit
    		 -12.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.93
    Statistical analysis title
    		 Placebo versus Vupanorsen: 60 mg Q2W
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 60 mg Q2W
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -31.7
         upper limit
    		 -12.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.88
    Statistical analysis title
    		 Placebo versus Vupanorsen: 120 mg Q4W
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 120 mg Q4W
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -24.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -34.1
         upper limit
    		 -14.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.05
    Statistical analysis title
    		 Placebo versus Vupanorsen: 80 mg Q2W
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 80 mg Q2W
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -27.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -35.7
         upper limit
    		 -19.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.09
    Statistical analysis title
    		 Placebo versus Vupanorsen: 160 mg Q4W
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 160 mg Q4W
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -26.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -34.5
         upper limit
    		 -18.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.98
    Statistical analysis title
    		 Placebo versus Vupanorsen: 120 mg Q2W
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 120 mg Q2W
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -24.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -32.5
         upper limit
    		 -16.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.96
    Statistical analysis title
    		 Placebo versus Vupanorsen: 160 mg Q2W
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 160 mg Q2W
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -26.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -35.4
         upper limit
    		 -17.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.51

    Secondary: Percent Change From Baseline in Triglyceride (TG), Apolipoprotein B (ApoB), Low-Density Lipoprotein-Cholesterol (LDL-C), and non-HDL-C at Week 16

    		 Close Top of page
    End point title
    		 Percent Change From Baseline in Triglyceride (TG), Apolipoprotein B (ApoB), Low-Density Lipoprotein-Cholesterol (LDL-C), and non-HDL-C at Week 16
    End point description
    Blood samples were collected from subjects in a fasted state for the measurement of TG, ApoB, HDL-C and LDL-C. Fasting was required at least 10 hours before blood sample collection. Non-HDL-C was calculated as total cholesterol minus HDL cholesterol. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing. FAS included all subjects randomised to study intervention and who took at least 1 dose of study intervention and had a baseline measurement and at least one post-baseline measurement. Here, "n" signifies subjects evaluable for specific rows.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    End point values
    		 Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
    Number of subjects analysed
    44
    23
    24
    23
    43
    45
    46
    36
    Units: Percent change
    arithmetic mean (standard deviation)
        TG (n=43,22,23,21,40,43,44,35)
    -2.53 ± 31.247
    -42.17 ± 28.081
    -44.71 ± 22.725
    -39.57 ± 32.546
    -49.21 ± 21.049
    -40.33 ± 21.311
    -50.55 ± 20.234
    -55.76 ± 14.625
        ApoB (n=41,21,22,22,40,44,43,34)
    0.66 ± 20.372
    -12.12 ± 15.839
    -12.30 ± 12.604
    -10.41 ± 17.067
    -10.40 ± 14.690
    -10.42 ± 19.332
    -11.74 ± 15.560
    -6.76 ± 18.890
        LDL-C (n=41,22,22,20,40,42,44,35)
    -1.42 ± 24.092
    -10.40 ± 31.199
    -12.61 ± 21.904
    -2.09 ± 26.921
    -11.38 ± 22.001
    -10.88 ± 26.640
    -13.78 ± 19.861
    -6.30 ± 29.825
        Non-HDL-C (n=43,22,23,21,40,43,44,35)
    -3.25 ± 21.631
    -21.65 ± 24.347
    -24.71 ± 16.678
    -20.06 ± 16.698
    -24.79 ± 18.266
    -21.68 ± 23.898
    -27.23 ± 12.799
    -22.44 ± 24.145
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in TG, ApoB, and LDL-C at Week 24

    		 Close Top of page
    End point title
    		 Percent Change From Baseline in TG, ApoB, and LDL-C at Week 24
    End point description
    Fasting was required for all lipid measures at least 10 hours before blood sample collection. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing. FAS_primary included all subjects randomised to study intervention and who took at least 1 dose of study intervention, had a baseline measurement and at least one post-baseline measurement with all observations that occurred after discontinuation of treatment or after initiation of severe hypertriglyceridaemia excluded. Here, "n" signifies subjects evaluable for specific rows.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
    Number of subjects analysed
    44
    23
    23
    23
    42
    45
    46
    35
    Units: Percent change
    least squares mean (standard error)
        TG (n=44,23,23,23,42,45,46,35)
    -1.8 ± 3.71
    -45.8 ± 5.53
    -45.6 ± 5.50
    -43.1 ± 5.76
    -52.3 ± 4.10
    -47.7 ± 3.90
    -52.5 ± 3.85
    -58.6 ± 4.90
        ApoB (n=42,22,22,23,41,45,44,35)
    0.3 ± 2.46
    -14.8 ± 3.60
    -10.3 ± 3.57
    -11.2 ± 3.76
    -12.2 ± 2.68
    -12.2 ± 2.55
    -5.6 ± 2.57
    -8.1 ± 3.17
        LDL-C (n=43,23,22,22,42,43,46,35)
    -1.2 ± 3.69
    -11.2 ± 5.41
    -9.1 ± 5.52
    -12.7 ± 5.63
    -17.3 ± 4.00
    -15.7 ± 3.92
    -9.1 ± 3.77
    -10.2 ± 4.74
    Statistical analysis title
    		 Placebo versus Vupanorsen: 80 mg Q4W - TG
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 80 mg Q4W
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -57.1
         upper limit
    		 -30.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.66
    Statistical analysis title
    		 Placebo versus Vupanorsen: 60 mg Q2W - TG
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 60 mg Q2W
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -43.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -56.9
         upper limit
    		 -30.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.64
    Statistical analysis title
    		 Placebo versus Vupanorsen: 120 mg Q4W - TG
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 120 mg Q4W
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -41.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -54.8
         upper limit
    		 -27.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.85
    Statistical analysis title
    		 Placebo versus Vupanorsen: 80 mg Q2W - TG
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 80 mg Q2W
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -50.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -61.4
         upper limit
    		 -39.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.54
    Statistical analysis title
    		 Placebo versus Vupanorsen: 160 mg Q4W - TG
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 160 mg Q4W
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -45.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -56.5
         upper limit
    		 -35.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.38
    Statistical analysis title
    		 Placebo versus Vupanorsen: 120 mg Q2W - TG
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 120 mg Q2W
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -50.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -61.2
         upper limit
    		 -40.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.35
    Statistical analysis title
    		 Placebo versus Vupanorsen: 160 mg Q2W - TG
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 160 mg Q2W
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -56.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -68.9
         upper limit
    		 -44.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.14
    Statistical analysis title
    		 Placebo versus Vupanorsen: 80 mg Q4W - ApoB
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 80 mg Q4W
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -15.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.7
         upper limit
    		 -6.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.36
    Statistical analysis title
    		 Placebo versus Vupanorsen: 60 mg Q2W - ApoB
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 60 mg Q2W
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.015
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -10.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.2
         upper limit
    		 -2.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.34
    Statistical analysis title
    		 Placebo versus Vupanorsen: 120 mg Q4W - ApoB
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 120 mg Q4W
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.011
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -11.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.3
         upper limit
    		 -2.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.49
    Statistical analysis title
    		 Placebo versus Vupanorsen: 80 mg Q2W - ApoB
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 80 mg Q2W
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -12.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.7
         upper limit
    		 -5.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.64
    Statistical analysis title
    		 Placebo versus Vupanorsen: 160 mg Q4W - ApoB
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 160 mg Q4W
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -12.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.5
         upper limit
    		 -5.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.54
    Statistical analysis title
    		 Placebo versus Vupanorsen: 120 mg Q2W - ApoB
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 120 mg Q2W
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.095
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13
         upper limit
    		 1
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.56
    Statistical analysis title
    		 Placebo versus Vupanorsen: 160 mg Q2W - ApoB
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 160 mg Q2W
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.036
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -8.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.4
         upper limit
    		 -0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.01
    Statistical analysis title
    		 Placebo versus Vupanorsen: 80 mg Q4W - LDL-C
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 80 mg Q4W
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.129
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -10
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.9
         upper limit
    		 2.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.55
    Statistical analysis title
    		 Placebo versus Vupanorsen: 60 mg Q2W - LDL-C
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 60 mg Q2W
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.238
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -7.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21
         upper limit
    		 5.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.65
    Statistical analysis title
    		 Placebo versus Vupanorsen: 120 mg Q4W - LDL-C
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 120 mg Q4W
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.09
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -11.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.7
         upper limit
    		 1.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.73
    Statistical analysis title
    		 Placebo versus Vupanorsen: 160 mg Q4W - LDL-C
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 160 mg Q4W
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.008
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -14.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.1
         upper limit
    		 -3.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.38
    Statistical analysis title
    		 Placebo versus Vupanorsen: 80 mg Q2W - LDL-C
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 80 mg Q2W
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.004
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.7
         upper limit
    		 -5.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.44
    Statistical analysis title
    		 Placebo versus Vupanorsen: 120 mg Q2W - LDL-C
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 120 mg Q2W
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.136
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -7.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.3
         upper limit
    		 2.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.28
    Statistical analysis title
    		 Placebo versus Vupanorsen: 160 mg Q2W - LDL-C
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 160 mg Q2W
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.138
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.8
         upper limit
    		 2.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.01

    Secondary: Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 16

    		 Close Top of page
    End point title
    		 Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 16
    End point description
    ANGPTL3 is a protein primarily synthesized and secreted by the liver and is a member of the angiopoietin-like family of proteins. Blood samples were collected from subjects in a fasted state for the measurement of ANGPTL3. Fasting was required at least 10 hours before blood sample collection. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing. FAS included all subjects randomised to study intervention and who took at least 1 dose of study intervention and had a baseline measurement and at least one post-baseline measurement. Here, "Number of Subjects Analyzed" signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    End point values
    		 Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
    Number of subjects analysed
    41
    21
    21
    21
    39
    44
    41
    32
    Units: Percent change
        arithmetic mean (standard deviation)
    9.14 ± 36.729
    -51.12 ± 30.444
    -63.61 ± 16.934
    -58.19 ± 22.175
    -65.56 ± 21.908
    -60.35 ± 21.040
    -77.55 ± 15.469
    -75.14 ± 23.549
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in ANGPTL3 at Week 24

    		 Close Top of page
    End point title
    		 Percent Change From Baseline in ANGPTL3 at Week 24
    End point description
    ANGPTL3 is a protein primarily synthesized and secreted by the liver and is a member of the angiopoietin-like family of proteins. Blood samples were collected from subjects in a fasted state for the measurement of ANGPTL3. Fasting was required at least 10 hours before blood sample collection. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing. FAS_primary included all subjects randomised to study intervention and who took at least 1 dose of study intervention, had a baseline measurement and at least one post-baseline measurement with all observations that occurred after discontinuation of treatment or after initiation of severe hypertriglyceridaemia excluded. Here, "Number of Subjects Analysed" signifies subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 160 mg Q4W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
    Number of subjects analysed
    42
    22
    21
    22
    40
    45
    42
    33
    Units: Percent change
        least squares mean (standard error)
    13.3 ± 3.36
    -56.6 ± 4.92
    -66.3 ± 5.01
    -63.8 ± 5.22
    -73.0 ± 3.76
    -67.1 ± 3.46
    -78.9 ± 3.58
    -81.9 ± 4.48
    Statistical analysis title
    		 Placebo versus Vupanorsen: 80 mg Q4W
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 80 mg Q4W
    Number of subjects included in analysis
    64
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -69.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -81.6
         upper limit
    		 -58.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.97
    Statistical analysis title
    		 Placebo versus Vupanorsen: 60 mg Q2W
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 60 mg Q2W
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -79.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -91.5
         upper limit
    		 -67.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.03
    Statistical analysis title
    		 Placebo versus Vupanorsen: 120 mg Q4W
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 120 mg Q4W
    Number of subjects included in analysis
    64
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -77.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -89.4
         upper limit
    		 -64.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.22
    Statistical analysis title
    		 Placebo versus Vupanorsen: 80 mg Q2W
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 80 mg Q2W
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -86.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -96.2
         upper limit
    		 -76.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.04
    Statistical analysis title
    		 Placebo versus Vupanorsen: 160 mg Q4W
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 160 mg Q4W
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -80.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -89.9
         upper limit
    		 -70.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.82
    Statistical analysis title
    		 Placebo versus Vupanorsen: 120 mg Q2W
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 120 mg Q2W
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -92.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -101.9
         upper limit
    		 -82.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.92
    Statistical analysis title
    		 Placebo versus Vupanorsen: 160 mg Q2W
    Statistical analysis description
    MMRM with baseline value, treatment, visit, interaction term of treatment by visit as fixed effects and unstructured covariance structure was used.
    Comparison groups
    Placebo v Vupanorsen: 160 mg Q2W
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference
    Point estimate
    -95.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -106.2
         upper limit
    		 -84.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.59

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From start of study intervention up to 12 weeks after last dose of study intervention (maximum for 36 weeks)
    Adverse event reporting additional description
    Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorised as serious in 1 subject and as non-serious in another, or a subject may have experienced both a serious and non-serious event.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects were randomised to receive vupanorsen (PF-07285557) matched placebo SC injection. Single or double administration was given at Q2W or Q4W to match active treatment groups. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 80 mg Q4W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 80 mg single SC injection at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 60 mg Q2W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 60 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 120 mg Q4W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 60 mg double SC injection (120 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 160 mg Q4W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 80 mg double SC injection (160 mg total) in different locations at Q4W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 80 mg Q2W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 80 mg single SC injection at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 120 mg Q2W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 60 mg double SC injection (120 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Reporting group title
    Vupanorsen: 160 mg Q2W
    Reporting group description
    		 Subjects were randomised to receive vupanorsen 80 mg double SC injection (160 mg in total) in different locations at Q2W. Administration locations were upper arm, thigh, or abdomen quadrant, as preferred by the subject. Treatment duration was up to 24 weeks. Subjects were followed up to 12 weeks after last dose of study intervention.

    Serious adverse events
    		 Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 160 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 44 (9.09%)
    2 / 23 (8.70%)
    2 / 24 (8.33%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    6 / 45 (13.33%)
    3 / 46 (6.52%)
    1 / 36 (2.78%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Investigations
    SARS-CoV-2 test positive
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acoustic neuroma
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Thrombosis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Ischaemic stroke
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal stenosis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Placebo Vupanorsen: 80 mg Q4W Vupanorsen: 60 mg Q2W Vupanorsen: 120 mg Q4W Vupanorsen: 160 mg Q4W Vupanorsen: 80 mg Q2W Vupanorsen: 120 mg Q2W Vupanorsen: 160 mg Q2W
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    31 / 44 (70.45%)
    15 / 23 (65.22%)
    17 / 24 (70.83%)
    12 / 23 (52.17%)
    28 / 45 (62.22%)
    30 / 45 (66.67%)
    29 / 46 (63.04%)
    31 / 36 (86.11%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Hot flush
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    Hypertension
         subjects affected / exposed
    3 / 44 (6.82%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    3 / 36 (8.33%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    0
    3
    Hypotension
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Peripheral coldness
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Chest discomfort
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    Chest pain
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    2
    0
    0
    0
    0
    0
    Chills
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Fatigue
         subjects affected / exposed
    2 / 44 (4.55%)
    1 / 23 (4.35%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    2 / 45 (4.44%)
    1 / 45 (2.22%)
    3 / 46 (6.52%)
    0 / 36 (0.00%)
         occurrences all number
    2
    1
    1
    0
    2
    2
    3
    0
    Hunger
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Injection site bruising
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    1
    Injection site dermatitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    3
    4
    0
    0
    1
    Injection site erythema
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    1 / 24 (4.17%)
    2 / 23 (8.70%)
    1 / 45 (2.22%)
    2 / 45 (4.44%)
    3 / 46 (6.52%)
    4 / 36 (11.11%)
         occurrences all number
    0
    2
    1
    2
    2
    3
    5
    6
    Injection site pain
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    1
    0
    Injection site rash
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    0
    1
    0
    Injection site reaction
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    3 / 24 (12.50%)
    4 / 23 (17.39%)
    4 / 45 (8.89%)
    4 / 45 (8.89%)
    6 / 46 (13.04%)
    8 / 36 (22.22%)
         occurrences all number
    0
    2
    7
    10
    7
    5
    9
    27
    Injection site recall reaction
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    2 / 24 (8.33%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
    5 / 46 (10.87%)
    3 / 36 (8.33%)
         occurrences all number
    0
    0
    2
    1
    0
    3
    5
    4
    Injection site vesicles
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Malaise
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    2 / 45 (4.44%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    2
    1
    0
    Pain
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Peripheral swelling
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    1
    Therapeutic response unexpected
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Thirst
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    Vessel puncture site bruise
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Seasonal allergy
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Reproductive system and breast disorders
    Abnormal uterine bleeding
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Atrophic vulvovaginitis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Erectile dysfunction
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Genital atrophy
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Prostatitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Vulvovaginal dryness
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    Dyspnoea
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    2
    0
    0
    0
    1
    1
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    Haemoptysis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Productive cough
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Pulmonary mass
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    1
    Sinus pain
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Sputum increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Psychiatric disorders
    Adjustment disorder
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Anxiety
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    2 / 23 (8.70%)
    2 / 45 (4.44%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    2
    2
    1
    0
    0
    Depression
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Insomnia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Major depression
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    Alanine aminotransferase abnormal
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    4 / 46 (8.70%)
    9 / 36 (25.00%)
         occurrences all number
    2
    0
    0
    0
    1
    1
    5
    10
    Albumin urine present
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    2 / 46 (4.35%)
    4 / 36 (11.11%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    2
    4
    Blood calcium increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Blood glucose increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Blood potassium abnormal
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Blood pressure decreased
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Blood pressure increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Body temperature increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Creatinine renal clearance abnormal
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Electrocardiogram QRS complex prolonged
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    Electrocardiogram abnormal
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Haematocrit increased
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Liver function test abnormal
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    2 / 46 (4.35%)
    3 / 36 (8.33%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    2
    3
    Liver function test increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    Magnetic resonance imaging spinal abnormal
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Mean cell haemoglobin concentration decreased
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Mean cell volume increased
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Urine albumin/creatinine ratio abnormal
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Urine albumin/creatinine ratio increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Urine analysis abnormal
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    2 / 24 (8.33%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Transaminases increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
    1 / 46 (2.17%)
    6 / 36 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    1
    6
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Arthropod bite
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Back injury
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Epicondylitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Fall
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    1
    0
    0
    Foot fracture
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Head injury
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Injection related reaction
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Ligament sprain
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    1
    0
    Muscle rupture
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Post procedural discomfort
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Procedural pain
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    Skin abrasion
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    Vaccination complication
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Brugada syndrome
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Myocardial injury
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    2 / 45 (4.44%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    0
    0
    Headache
         subjects affected / exposed
    2 / 44 (4.55%)
    1 / 23 (4.35%)
    1 / 24 (4.17%)
    1 / 23 (4.35%)
    3 / 45 (6.67%)
    2 / 45 (4.44%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    2
    1
    1
    1
    4
    3
    4
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Migraine
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    Paraesthesia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    2 / 45 (4.44%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    2
    0
    0
    0
    Radiculopathy
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Sciatica
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Sensory disturbance
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Eosinophilia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Vertigo
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    Conjunctivitis allergic
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Ulcerative keratitis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Vitreous floaters
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Abdominal distension
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    Abdominal pain
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    1
    0
    0
    Acid peptic disease
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Constipation
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    1 / 46 (2.17%)
    1 / 36 (2.78%)
         occurrences all number
    1
    1
    0
    1
    1
    1
    1
    1
    Crohn's disease
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Dental necrosis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Diarrhoea
         subjects affected / exposed
    3 / 44 (6.82%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    2 / 46 (4.35%)
    2 / 36 (5.56%)
         occurrences all number
    3
    1
    0
    0
    2
    1
    2
    3
    Diverticulum
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Dyspepsia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    1
    0
    1
    1
    0
    0
    1
    Faeces soft
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    2 / 45 (4.44%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    2 / 36 (5.56%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    3
    Haematochezia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Nausea
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    1 / 45 (2.22%)
    2 / 45 (4.44%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    3
    0
    0
    1
    1
    2
    0
    0
    Oesophageal pain
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Toothache
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    2 / 46 (4.35%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    Vomiting
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    2
    0
    0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Drug-induced liver injury
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    3 / 46 (6.52%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    3
    0
    Hepatic steatosis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Nonalcoholic fatty liver disease
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Actinic keratosis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Alopecia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Dermatitis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    Dermatitis allergic
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    2
    0
    0
    0
    2
    0
    0
    0
    Dermatitis contact
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Erythema
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    Miliaria
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Petechiae
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    1 / 46 (2.17%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    1
    Rash
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    3
    1
    0
    Rosacea
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Skin discolouration
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Skin lesion
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    Skin mass
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    2 / 24 (8.33%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    Calculus bladder
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Chronic kidney disease
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Dysuria
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Haematuria
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    Microalbuminuria
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    Nephrolithiasis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    Pollakiuria
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Proteinuria
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    2 / 45 (4.44%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    Renal cyst
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Renal failure
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    Urge incontinence
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Urinary incontinence
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 44 (4.55%)
    1 / 23 (4.35%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    4 / 45 (8.89%)
    3 / 46 (6.52%)
    1 / 36 (2.78%)
         occurrences all number
    2
    2
    1
    0
    1
    4
    3
    4
    Arthritis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Bone cyst
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Bursitis
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    Flank pain
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    2 / 36 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    Intervertebral disc degeneration
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Joint stiffness
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Joint swelling
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Muscle fatigue
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Muscle spasms
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    Muscular weakness
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    3 / 36 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Myalgia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    3 / 45 (6.67%)
    2 / 45 (4.44%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    3
    3
    0
    0
    Neck pain
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    1
    0
    Osteoarthritis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    2 / 24 (8.33%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    3 / 24 (12.50%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    3 / 45 (6.67%)
    2 / 46 (4.35%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    4
    0
    0
    3
    2
    0
    Plantar fascial fibromatosis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    Scoliosis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Spinal pain
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Temporomandibular joint syndrome
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Tendonitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Tenosynovitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Back pain
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 23 (0.00%)
    2 / 24 (8.33%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    6 / 45 (13.33%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    2
    0
    2
    0
    1
    6
    0
    0
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Bronchitis
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    2 / 45 (4.44%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    2
    0
    0
    5
    2
    0
    0
    1
    COVID-19
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    0
    0
    Cellulitis
         subjects affected / exposed
    2 / 44 (4.55%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    0
    Cystitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Fungal infection
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    Fungal skin infection
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Gastrointestinal bacterial infection
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Helicobacter infection
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Herpes zoster
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Infection parasitic
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Injection site cellulitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Kidney infection
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Otitis externa
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Pharyngitis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    1
    0
    Sinusitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Tinea cruris
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Tooth abscess
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    Tooth infection
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    2 / 46 (4.35%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    Urinary tract infection
         subjects affected / exposed
    3 / 44 (6.82%)
    1 / 23 (4.35%)
    1 / 24 (4.17%)
    1 / 23 (4.35%)
    1 / 45 (2.22%)
    3 / 45 (6.67%)
    1 / 46 (2.17%)
    3 / 36 (8.33%)
         occurrences all number
    3
    1
    1
    1
    1
    4
    1
    1
    Viral infection
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Vulvovaginal candidiasis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Vulvovaginal mycotic infection
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 46 (2.17%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    Dehydration
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Diabetes mellitus
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Glucose tolerance impaired
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Gout
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    2 / 24 (8.33%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    2
    0
    0
    0
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Hypoglycaemia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Increased appetite
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    0 / 46 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    1
    1
    1
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Sep 2020
    New appendix was added to describe alternative measures that were allowed during a public emergency, such as COVID-19.

    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-Wed May 08 15:16:42 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA