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   44339   clinical trials with a EudraCT protocol, of which   7369   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 Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults with Severe Hypertriglyceridemia

    Summary
    EudraCT number
    		 2021-000687-30
    Trial protocol
    		 DE   HU   NL   PL  
    Global end of trial date
    31 Aug 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Sep 2024
    First version publication date
    04 Sep 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    AROAPOC3-2001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04720534
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Arrowhead Pharmaceuticals, Inc.
    Sponsor organisation address
    177 East Colorado Boulevard, Suite 700, Pasadena, CA, United States, 91105
    Public contact
    Chief Operating Officer,, Arrowhead Pharmaceuticals, Inc., +1 6263043400, info@arrowheadpharma.com
    Scientific contact
    Chief Operating Officer,, Arrowhead Pharmaceuticals, Inc., +1 6263043400, info@arrowheadpharma.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
    31 Aug 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Aug 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study is to evaluate the safety and efficacy of ARO-APOC3 in adults with Severe Hypertriglyceridemia (SHTG) and to select a dosing regimen for later stage clinical studies in this patient population.
    Protection of trial subjects
    All eligible participants will have the study explained by the PI or designee. They will receive a full explanation, in lay terms, of the aims of the study, the discomforts, risks and benefits in taking part as well as of insurance and other procedures for compensation in case of injury. It will be explained that the study is for research purposes only and is not expected to provide any therapeutic benefit to the individual. It will be pointed out that they can withdraw from the study at any time without prejudice.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Apr 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 33
    Country: Number of subjects enrolled
    Canada: 24
    Country: Number of subjects enrolled
    New Zealand: 9
    Country: Number of subjects enrolled
    United States: 89
    Country: Number of subjects enrolled
    Netherlands: 7
    Country: Number of subjects enrolled
    Poland: 13
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Hungary: 53
    Worldwide total number of subjects
    229
    EEA total number of subjects
    74
    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)
    187
    From 65 to 84 years
    42
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 There were 76 study centers in 8 countries (Australia, Canada, Germany, Hungary, The Netherlands, New Zealand, Poland, and the United States [US]).

    Pre-assignment
    Screening details
    		 Subjects who met all the protocol eligibility criteria during Screening were enrolled and randomly assigned to treatment in a double-blind fashion. Subjects were randomly assigned 3:1 to receive 1 of 3 ARO-APOC3 dosing regimens (ARO-APOC3 10 mg, 25 mg, or 50 mg) or matched placebo.

    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
    		 Subject, Investigator, Monitor
    Blinding implementation details
    Treatment assignment (active vs placebo) is blinded in this clinical study. Dose group assignment is not blinded, due to required injection volume differences dictated by the respective dose group. Therefore, during the Double Blind Treatment Period, participants will receive an injection of either active or placebo volume matched to the assigned dose group.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Each dose of placebo (normal saline 0.9%), will be administered by SC injection by the Investigator or appropriately trained and qualified clinical staff designated by the Investigator.

    Arm title
    		 ARO-APOC3 10 mg
    Arm description
    		 Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ARO-APOC3 Injection
    Investigational medicinal product code
    ARO-APOC3
    Other name
    plozasiran
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Each dose of active drug (ARO-ANG3) will be administered by SC injection by the Investigator or appropriately trained and qualified clinical staff designated by the Investigator.

    Arm title
    		 ARO-APOC3 25 mg
    Arm description
    		 Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ARO-APOC3 Injection
    Investigational medicinal product code
    ARO-APOC3
    Other name
    plozasiran
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Each dose of active drug (ARO-ANG3) will be administered by SC injection by the Investigator or appropriately trained and qualified clinical staff designated by the Investigator.

    Arm title
    		 ARO-APOC3 50 mg
    Arm description
    		 Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ARO-APOC3 Injection
    Investigational medicinal product code
    ARO-APOC3
    Other name
    plozasiran
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Each dose of active drug (ARO-ANG3) will be administered by SC injection by the Investigator or appropriately trained and qualified clinical staff designated by the Investigator.

    Number of subjects in period 1
    		Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Started
    62
    55
    55
    57
    Completed
    58
    50
    52
    53
    Not completed
    4
    5
    3
    4
         Consent withdrawn by subject
    3
    1
    1
    1
         Physician decision
    -
    -
    -
    1
         Other, not specified
    -
    2
    -
    1
         Adverse event
    -
    1
    -
    1
         Lost to follow-up
    1
    1
    2
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.

    Reporting group title
    ARO-APOC3 10 mg
    Reporting group description
    		 Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.

    Reporting group title
    ARO-APOC3 25 mg
    Reporting group description
    		 Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.

    Reporting group title
    ARO-APOC3 50 mg
    Reporting group description
    		 Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.

    Reporting group values
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg Total
    Number of subjects
    		 62 55 55 57 229
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 55.8 ( 11.22 ) 52.9 ( 9.55 ) 56.0 ( 10.64 ) 54.3 ( 11.00 ) -
    Gender categorical
    Units: Subjects
        Female
    		 15 8 12 16 51
        Male
    		 47 47 43 41 178
    Race
    Units: Subjects
        White
    		 56 48 48 53 205
        Black or African American
    		 1 2 3 1 7
        American Indian or Alaska Native
    		 1 0 0 0 1
        Asian
    		 3 1 2 3 9
        Native Hawaiian or Other Pacific Islander
    		 0 0 2 0 2
        Unknown
    		 0 1 0 0 1
        Other, Not Specified
    		 1 3 0 0 4
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 13 7 7 6 33
        Not Hispanic or Latino
    		 48 47 48 51 194
        Not Reported
    		 1 1 0 0 2

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.

    Reporting group title
    ARO-APOC3 10 mg
    Reporting group description
    		 Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.

    Reporting group title
    ARO-APOC3 25 mg
    Reporting group description
    		 Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.

    Reporting group title
    ARO-APOC3 50 mg
    Reporting group description
    		 Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.

    Primary: Percent Change From Baseline at Week 24 in Fasting TG

    		 Close Top of page
    End point title
    		 Percent Change From Baseline at Week 24 in Fasting TG
    End point description
    Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Observed cases.
    End point type
    Primary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Number of subjects analysed
    59
    50
    54
    55
    Units: percentage change
        least squares mean (standard error)
    -17.2 ( 5.27 )
    -66.0 ( 5.61 )
    -70.2 ( 5.51 )
    -74.2 ( 5.44 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ARO-APOC3 10 mg
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [1]
    Method
    		 Mixed models repeated measures (MMRM)
    Parameter type
    		 Difference
    Point estimate
    -48.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -64
         upper limit
    		 -33.7
    Notes
    [1] - MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms. Observed cases of the data from baseline through Week 48 are included.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ARO-APOC3 25 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [2]
    Method
    		 Mixed models repeated measures (MMRM)
    Parameter type
    		 Difference
    Point estimate
    -53.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -68.1
         upper limit
    		 -38
    Notes
    [2] - MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms. Observed cases of the data from baseline through Week 48 are included.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ARO-APOC3 50 mg
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [3]
    Method
    		 Mixed models repeated measures (MMRM)
    Parameter type
    		 Difference
    Point estimate
    -57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -71.9
         upper limit
    		 -42.1
    Notes
    [3] - MMRM model includes treatment arm, study visit, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms. Observed cases of the data from baseline through Week 48 are included.

    Secondary: Percent Change From Baseline Over Time Through Week 48 in Fasting TG

    		 Close Top of page
    End point title
    		 Percent Change From Baseline Over Time Through Week 48 in Fasting TG
    End point description
    Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). n=Observed cases at given time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
    End point values
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Number of subjects analysed
    60
    54
    55
    57
    Units: percentage change
    least squares mean (standard error)
        Week 4; n=60, 53, 55, 57
    7.2 ( 4.61 )
    -63.3 ( 4.88 )
    -79.5 ( 4.81 )
    -77.6 ( 4.72 )
        Week 8; n=60, 54, 54, 56
    -0.7 ( 5.19 )
    -54.0 ( 5.46 )
    -73.2 ( 5.45 )
    -72.8 ( 5.34 )
        Week 12; n=57, 53, 54, 54
    -7.3 ( 7.05 )
    -53.9 ( 7.35 )
    -64.9 ( 7.29 )
    -70.3 ( 7.24 )
        Week 16; n=59, 50, 54, 53
    -2.9 ( 5.91 )
    -70.5 ( 6.32 )
    -80.1 ( 6.17 )
    -76.3 ( 6.15 )
        Week 20; n=58, 51, 51, 53
    2.4 ( 6.66 )
    -67.7 ( 7.07 )
    -75.3 ( 7.02 )
    -75.6 ( 6.91 )
        Week 24; n=59, 50, 54, 55
    -17.2 ( 5.27 )
    -66.0 ( 5.61 )
    -70.2 ( 5.51 )
    -74.2 ( 5.44 )
        Week 28; n=60, 50, 52, 54
    -11.7 ( 5.83 )
    -60.0 ( 6.33 )
    -70.3 ( 6.23 )
    -70.8 ( 6.11 )
        Week 36; n=57, 49, 51, 54
    -7.6 ( 9.08 )
    -37.7 ( 9.70 )
    -64.0 ( 9.54 )
    -53.6 ( 9.35 )
        Week 48; n=57, 50, 50, 53
    -6.6 ( 7.71 )
    -31.4 ( 8.20 )
    -58.0 ( 8.15 )
    -53.4 ( 7.97 )
    Attachments
    		 Untitled (Filename: Statistical Analyses-Percent Change from Baseline Over Time Through Week 48 in Fasting TG by Visit.docx)
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline at Week 24 in Apolipoprotein (Apo)C-III

    		 Close Top of page
    End point title
    		 Percent Change From Baseline at Week 24 in Apolipoprotein (Apo)C-III
    End point description
    Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Number of subjects analysed
    59
    49
    54
    55
    Units: percentage change
        least squares mean (standard error)
    114.2 ( 73.08 )
    -69.6 ( 76.90 )
    -73.7 ( 76.04 )
    -79.4 ( 73.19 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ARO-APOC3 10 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.076 [4]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -183.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -387
         upper limit
    		 19.4
    Notes
    [4] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ARO-APOC3 25 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0677 [5]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -187.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -389.6
         upper limit
    		 13.8
    Notes
    [5] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ARO-APOC3 50 mg
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0568 [6]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -193.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -392.9
         upper limit
    		 5.6
    Notes
    [6] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.

    Secondary: Percent Change From Baseline Over Time Through Week 48 in Apolipoprotein (Apo)C-III

    		 Close Top of page
    End point title
    		 Percent Change From Baseline Over Time Through Week 48 in Apolipoprotein (Apo)C-III
    End point description
    Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). n=Observed cases at given time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
    End point values
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Number of subjects analysed
    60
    54
    55
    57
    Units: percentage change
    least squares mean (standard error)
        Week 4; n=60, 52, 55, 57
    209.3 ( 73.06 )
    -67.3 ( 76.79 )
    -84.4 ( 76.00 )
    -84.6 ( 73.12 )
        Week 8; n=60, 53, 54, 56
    146.3 ( 73.06 )
    -59.8 ( 76.76 )
    -78.8 ( 76.03 )
    -79.9 ( 73.14 )
        Week 12; n=57, 52, 54, 54
    122.2 ( 73.13 )
    -55.5 ( 76.79 )
    -71.8 ( 76.04 )
    -73.2 ( 73.21 )
        Week 16; n=59, 49, 54, 53
    134.4 ( 73.09 )
    -77.1 ( 76.90 )
    -86.4 ( 76.04 )
    -87.1 ( 73.25 )
        Week 20; n=58, 50, 51, 53
    118.8 ( 73.11 )
    -71.7 ( 76.87 )
    -81.2 ( 76.13 )
    -84.0 ( 73.26 )
        Week 24; n=59, 49, 54, 55
    114.2 ( 73.08 )
    -69.6 ( 76.90 )
    -73.7 ( 76.04 )
    -79.4 ( 73.19 )
        Week 28; n=60, 49, 52, 54
    140.2 ( 73.06 )
    -64.4 ( 76.89 )
    -71.9 ( 76.09 )
    -74.7 ( 73.21 )
        Week 36; n=57, 48, 51, 54
    152.0 ( 73.13 )
    -50.2 ( 76.92 )
    -60.9 ( 76.12 )
    -59.9 ( 73.21 )
        Week 48; n=57, 49, 50, 53
    135.8 ( 73.14 )
    -34.5 ( 76.89 )
    -49.6 ( 76.16 )
    -48.3 ( 73.25 )
    Attachments
    		 Untitled (Filename: Statistical Analyses-Percent Change from Baseline at Week 24 and Over Time Through Week 48 in ApoC-III.docx)
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 Percent Change From Baseline at Week 24 in Fasting Non-High-Density Lipoprotein Cholesterol (non-HDL-C)
    End point description
    Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Number of subjects analysed
    59
    49
    54
    55
    Units: percentage change
        least squares mean (standard error)
    -1.5 ( 3.76 )
    -29.4 ( 4.04 )
    -28.4 ( 3.90 )
    -21.7 ( 3.83 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ARO-APOC3 10 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [7]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -27.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -38.6
         upper limit
    		 -17.2
    Notes
    [7] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ARO-APOC3 25 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [8]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -26.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -37.4
         upper limit
    		 -16.4
    Notes
    [8] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ARO-APOC3 50 mg
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0002 [9]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -20.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.6
         upper limit
    		 -9.7
    Notes
    [9] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.

    Secondary: Percent Change From Baseline Over Time Through Week 48 in Fasting Non-High-Density Lipoprotein Cholesterol (non-HDL-C)

    		 Close Top of page
    End point title
    		 Percent Change From Baseline Over Time Through Week 48 in Fasting Non-High-Density Lipoprotein Cholesterol (non-HDL-C)
    End point description
    Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). n=Observed cases at given time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
    End point values
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Number of subjects analysed
    60
    54
    55
    57
    Units: percentage change
    least squares mean (standard error)
        Week 4; n=60, 52, 55, 57
    6.3 ( 3.35 )
    -27.0 ( 3.57 )
    -34.7 ( 3.46 )
    -26.1 ( 3.37 )
        Week 8; n=60, 53, 54, 56
    4.5 ( 3.77 )
    -19.7 ( 4.00 )
    -30.7 ( 3.92 )
    -20.7 ( 3.82 )
        Week 12; n=57, 52, 54, 54
    1.4 ( 4.54 )
    -19.3 ( 4.77 )
    -30.0 ( 4.67 )
    -22.3 ( 4.61 )
        Week 16; n=59, 49, 54, 53
    1.8 ( 3.73 )
    -27.9 ( 4.00 )
    -37.8 ( 3.87 )
    -23.7 ( 3.81 )
        Week 20; n=58, 50, 51, 53
    5.7 ( 3.96 )
    -26.7 ( 4.22 )
    -34.6 ( 4.13 )
    -22.9 ( 4.04 )
        Week 24; n=59, 49, 54, 55
    -1.5 ( 3.76 )
    -29.4 ( 4.04 )
    -28.4 ( 3.90 )
    -21.7 ( 3.83 )
        Week 28; n=60, 49, 52, 54
    -2.3 ( 3.82 )
    -27.4 ( 4.14 )
    -31.3 ( 4.02 )
    -24.0 ( 3.92 )
        Week 36; n=57, 48, 51, 54
    -0.3 ( 4.57 )
    -19.2 ( 4.91 )
    -23.8 ( 4.78 )
    -13.1 ( 4.65 )
        Week 48; n=57, 49, 50, 53
    0.5 ( 4.58 )
    -10.0 ( 4.92 )
    -23.0 ( 4.83 )
    -13.5 ( 4.69 )
    Attachments
    		 Untitled (Filename: Statistical Analyses-Percent Change from Baseline at Week 24 and Over Time Through Week 48 in Fasting non-HDL-C.docx)
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline at Week 24 in Fasting High-Density Lipoprotein Cholesterol (HDL-C)

    		 Close Top of page
    End point title
    		 Percent Change From Baseline at Week 24 in Fasting High-Density Lipoprotein Cholesterol (HDL-C)
    End point description
    Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Observed cases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Number of subjects analysed
    59
    49
    54
    55
    Units: percentage change
        least squares mean (standard error)
    10.6 ( 5.87 )
    54.2 ( 6.32 )
    62.8 ( 6.09 )
    67.6 ( 6.00 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ARO-APOC3 10 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [10]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    43.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 26.8
         upper limit
    		 60.2
    Notes
    [10] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ARO-APOC3 25 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [11]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    52.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 35.8
         upper limit
    		 68.6
    Notes
    [11] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ARO-APOC3 50 mg
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [12]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 40.7
         upper limit
    		 73.3
    Notes
    [12] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.

    Secondary: Percent Change From Baseline Over Time Through Week 48 in Fasting High-Density Lipoprotein Cholesterol (HDL-C)

    		 Close Top of page
    End point title
    		 Percent Change From Baseline Over Time Through Week 48 in Fasting High-Density Lipoprotein Cholesterol (HDL-C)
    End point description
    Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). n=Participants with an assessment at given time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
    End point values
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Number of subjects analysed
    60
    54
    55
    57
    Units: percentage change
    least squares mean (standard error)
        Week 4; n=60, 52, 55, 57
    4.3 ( 5.48 )
    53.4 ( 5.86 )
    76.2 ( 5.67 )
    88.1 ( 5.56 )
        Week 8; n=60, 53, 54, 56
    6.2 ( 5.45 )
    45.4 ( 5.79 )
    73.5 ( 5.66 )
    67.7 ( 5.54 )
        Week 12; n=57, 52, 54, 54
    11.3 ( 5.50 )
    39.9 ( 5.81 )
    60.2 ( 5.66 )
    62.5 ( 5.59 )
        Week 16; n=59, 49, 54, 53
    5.7 ( 5.78 )
    66.2 ( 6.23 )
    87.1 ( 5.99 )
    82.6 ( 5.94 )
        Week 20; n=58, 50, 51, 53
    8.8 ( 6.20 )
    61.2 ( 6.63 )
    78.7 ( 6.48 )
    81.2 ( 6.36 )
        Week 24; n=59, 49, 54, 55
    10.6 ( 5.87 )
    54.2 ( 6.32 )
    62.8 ( 6.09 )
    67.6 ( 6.00 )
        Week 28; n=60, 49, 52, 54
    10.2 ( 5.55 )
    48.2 ( 6.00 )
    67.2 ( 5.81 )
    68.0 ( 5.70 )
        Week 36; n=57, 48, 51, 54
    11.7 ( 5.83 )
    34.5 ( 6.29 )
    51.1 ( 6.09 )
    47.2 ( 5.95 )
        Week 48; n=57, 49, 50, 53
    6.1 ( 5.40 )
    23.5 ( 5.80 )
    32.4 ( 5.65 )
    37.8 ( 5.51 )
    Attachments
    		 Untitled (Filename: Statistical Analyses-Percent Change from Baseline at Week 24 and Over Time Through Week 48 in Fasting HDL-C.docx)
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline at Week 24 in Fasting Total Apolipoprotein B (ApoB)

    		 Close Top of page
    End point title
    		 Percent Change From Baseline at Week 24 in Fasting Total Apolipoprotein B (ApoB)
    End point description
    Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Participants with an assessment at given time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Number of subjects analysed
    59
    49
    54
    55
    Units: percentage change
        least squares mean (standard error)
    8.0 ( 5.85 )
    6.0 ( 6.31 )
    -5.3 ( 6.06 )
    0.7 ( 6.01 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ARO-APOC3 10 mg
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8155 [13]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.8
         upper limit
    		 14.8
    Notes
    [13] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ARO-APOC3 25 mg
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1124 [14]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -13.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29.8
         upper limit
    		 3.2
    Notes
    [14] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ARO-APOC3 50 mg
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3791 [15]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -7.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.8
         upper limit
    		 9.1
    Notes
    [15] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.

    Secondary: Percent Change From Baseline Over Time Through Week 48 in Fasting Total Apolipoprotein B (ApoB)

    		 Close Top of page
    End point title
    		 Percent Change From Baseline Over Time Through Week 48 in Fasting Total Apolipoprotein B (ApoB)
    End point description
    Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). n=Participants with an assessment at given time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
    End point values
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Number of subjects analysed
    60
    54
    55
    57
    Units: percentage change
    least squares mean (standard error)
        Week 4; n=60, 52, 55, 57
    16.2 ( 6.70 )
    -2.3 ( 7.10 )
    -9.0 ( 6.95 )
    -1.9 ( 6.84 )
        Week 8; n=60, 53, 54, 56
    16.0 ( 4.74 )
    -0.8 ( 4.97 )
    -7.2 ( 4.89 )
    1.5 ( 4.82 )
        Week 12; n=57, 52, 54, 54
    4.2 ( 3.70 )
    0.5 ( 3.80 )
    -11.2 ( 3.74 )
    -1.3 ( 3.73 )
        Week 16; n=59, 49, 54, 53
    5.3 ( 4.13 )
    -0.8 ( 4.34 )
    -13.1 ( 4.22 )
    -0.6 ( 4.20 )
        Week 20; n=58, 50, 51, 53
    1.6 ( 3.98 )
    -0.7 ( 4.17 )
    -10.3 ( 4.10 )
    4.4 ( 4.06 )
        Week 24; n=59, 49, 54, 55
    8.0 ( 5.85 )
    6.0 ( 6.31 )
    -5.3 ( 6.06 )
    0.7 ( 6.01 )
        Week 28; n=60, 49, 52, 54
    3.9 ( 3.70 )
    -1.3 ( 3.92 )
    -6.0 ( 3.83 )
    0.6 ( 3.79 )
        Week 36; n=57, 48, 51, 54
    8.9 ( 4.10 )
    -0.4 ( 4.35 )
    2.5 ( 4.24 )
    8.5 ( 4.17 )
        Week 48; n=57, 49, 50, 53
    5.7 ( 4.06 )
    6.4 ( 4.28 )
    -0.2 ( 4.21 )
    2.4 ( 4.14 )
    Attachments
    		 Untitled (Filename: Statistical Analyses-Percent Change from Baseline at Week 24 and Over Time Through Week 48 in Fasting Total ApoB.docx)
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline at Week 24 in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C)

    		 Close Top of page
    End point title
    		 Percent Change From Baseline at Week 24 in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C)
    End point description
    LDL-C analyses used both Martin-Hopkins methodology and ultracentrifugation. Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). n=participants with given assessment at given time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Number of subjects analysed
    60
    54
    55
    57
    Units: percentage change
    least squares mean (standard error)
        Martin-Hopkins methodology; n=53, 44, 52, 50
    -5.5 ( 123.7 )
    301.9 ( 128.17 )
    -15.4 ( 120.30 )
    2.0 ( 123.04 )
        Ultracentrifugation; n=58, 49, 54, 55
    18.0 ( 10.48 )
    49.0 ( 11.06 )
    43.7 ( 10.76 )
    78.2 ( 10.60 )
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Martin-Hopkins methodology
    Comparison groups
    Placebo v ARO-APOC3 10 mg
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0737 [16]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    307.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29.8
         upper limit
    		 644.6
    Notes
    [16] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Martin-Hopkins methodology
    Comparison groups
    Placebo v ARO-APOC3 25 mg
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9525 [17]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -9.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -337.4
         upper limit
    		 317.6
    Notes
    [17] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Martin-Hopkins methodology
    Comparison groups
    Placebo v ARO-APOC3 50 mg
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9644 [18]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    7.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -323.3
         upper limit
    		 338.3
    Notes
    [18] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.
    Statistical analysis title
    		 Statistical Analysis 4
    Comparison groups
    Placebo v ARO-APOC3 10 mg
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0395 [19]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.5
         upper limit
    		 60.6
    Notes
    [19] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.
    Statistical analysis title
    		 Statistical Analysis 5
    Comparison groups
    Placebo v ARO-APOC3 25 mg
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0825 [20]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    25.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.4
         upper limit
    		 54.9
    Notes
    [20] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.
    Statistical analysis title
    		 Statistical Analysis 6
    Comparison groups
    Placebo v ARO-APOC3 50 mg
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [21]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    60.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 31.3
         upper limit
    		 89.2
    Notes
    [21] - MMRM model includes treatment arm, study visit, stratification factor, and baseline value as model terms. The model also includes treatment by visit and treatment by baseline as interaction terms.

    Secondary: Percent Change From Baseline Over Time Through Week 48 in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C)

    		 Close Top of page
    End point title
    		 Percent Change From Baseline Over Time Through Week 48 in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C)
    End point description
    LDL-C analyses used both Martin-Hopkins methodology (MHM) and ultracentrifugation (UC). Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). n=Participants with given assessment at given time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
    End point values
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Number of subjects analysed
    60
    54
    55
    57
    Units: percentage change
    least squares mean (standard error)
        MHM Week 4; n=50, 46, 53, 51
    -29.3 ( 123.78 )
    267.3 ( 128.13 )
    -13.5 ( 120.28 )
    0.6 ( 123.00 )
        MHM Week 8; n=52, 47, 51, 49
    -11.3 ( 123.74 )
    297.4 ( 128.11 )
    -11.7 ( 120.29 )
    5.3 ( 123.01 )
        MHM Week 12; n=48, 46, 52, 49
    -13.6 ( 123.75 )
    300.7 ( 128.12 )
    -17.3 ( 120.29 )
    3.2 ( 123.02 )
        MHM Week 16; n=50, 44, 52, 47
    -14.3 ( 123.72 )
    340.3 ( 128.15 )
    -20.4 ( 120.29 )
    5.6 ( 123.04 )
        MHM Week 20; n=48, 45, 49, 48
    -7.3 ( 123.72 )
    306.7 ( 128.15 )
    -17.4 ( 120.31 )
    4.9 ( 123.05 )
        MHM Week 24; n=53, 44, 52, 50
    -5.5 ( 123.67 )
    301.9 ( 128.17 )
    -15.4 ( 120.30 )
    2.0 ( 123.04 )
        MHM Week 28; n=52, 44, 50, 49
    -12.1 ( 123.68 )
    283.2 ( 128.20 )
    -12.1 ( 120.34 )
    -4.7 ( 123.06 )
        MHM Week 36; n=48, 42, 49, 47
    -5.5 ( 123.73 )
    254.7 ( 128.28 )
    -0.7 ( 120.38 )
    1.6 ( 123.10 )
        MHM Week 48; n=50, 43, 48, 48
    -11.5 ( 123.77 )
    286.5 ( 128.34 )
    -9.0 ( 120.44 )
    -5.3 ( 123.12 )
        UC Week 4; n=59, 52, 55, 57
    4.4 ( 9.65 )
    50.3 ( 10.10 )
    47.3 ( 9.88 )
    69.1 ( 9.67 )
        UC Week 8; n=59, 53, 54, 56
    15.8 ( 10.44 )
    49.8 ( 10.92 )
    45.8 ( 10.73 )
    65.4 ( 10.51 )
        UC Week 12; n=55, 52, 53, 53
    17.1 ( 10.17 )
    50.9 ( 10.57 )
    36.0 ( 10.38 )
    65.8 ( 10.22 )
        UC Week 16; n=57, 49, 54, 53
    19.3 ( 12.14 )
    62.6 ( 12.80 )
    41.7 ( 12.46 )
    87.1 ( 12.31 )
        UC Week 20; n=56, 50, 50, 53
    16.8 ( 11.79 )
    62.7 ( 12.38 )
    42.3 ( 12.16 )
    85.9 ( 11.93 )
        UC Week 24; n=58, 49, 54, 55
    18.0 ( 10.48 )
    49.0 ( 11.06 )
    43.7 ( 10.76 )
    78.2 ( 10.60 )
        UC Week 28; n=59, 49, 51, 54
    15.4 ( 10.14 )
    50.8 ( 10.76 )
    42.3 ( 10.51 )
    61.6 ( 10.30 )
        UC Week 36; n=56, 48, 51, 54
    18.4 ( 9.89 )
    35.5 ( 10.47 )
    51.5 ( 10.20 )
    61.3 ( 9.97 )
        UC Week 48; n=56, 49, 50, 53
    21.3 ( 10.73 )
    33.5 ( 11.36 )
    34.4 ( 11.14 )
    44.6 ( 10.87 )
    Attachments
    		 Untitled (Filename: Statistical Analyses-Percent Change from Baseline at Week 24 and Over Time Through Week 48 in Fasting LDL-C.docx)
    Untitled (Filename: Statistical Analyses - Percent Change from Baseline at Week 24 and Over Time Through Week 48 in Fasting LDL-C using UC.docx)
    No statistical analyses for this end point

    Secondary: Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12

    		 Close Top of page
    End point title
    		 Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12 [22]
    End point description
    Full PK Analysis Set: Full Analysis Set (FAS) participants (all randomized participants who receive at least 1 dose of IP during the study period) who have sufficient plasma concentration data to facilitate determination of PK parameters.
    End point type
    Secondary
    End point timeframe
    Day 1: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose; Week 12: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol, placebo arm was not analyzed for this measure.
    End point values
    		 ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Number of subjects analysed
    9
    9
    10
    Units: ng/mL
    arithmetic mean (standard deviation)
        Day 1, Pre-Dose; n=9, 9, 9
    0.000 ( 0.0000 )
    0.000 ( 0.0000 )
    0.000 ( 0.0000 )
        Day 1, 15 Minutes Post-Dose; n=9, 9, 8
    10.258 ( 12.4741 )
    21.207 ( 21.7982 )
    34.352 ( 27.3986 )
        Day 1, 1 Hour Post-Dose; n=9, 8, 9
    18.124 ( 18.1760 )
    37.396 ( 27.9849 )
    58.508 ( 29.0222 )
        Day 1, 3 Hours Post-Dose; n=9, 8, 9
    20.217 ( 16.8127 )
    50.596 ( 53.3270 )
    58.493 ( 30.5510 )
        Day 1, 6 Hours Post-Dose; n=9, 7, 9
    17.147 ( 14.6145 )
    51.813 ( 44.2610 )
    64.019 ( 26.3749 )
        Day 1, 24 Hours Post-Dose; n=9, 6, 9
    7.921 ( 16.9181 )
    10.316 ( 11.5852 )
    11.587 ( 6.4288 )
        Week 12, Pre-Dose; n=8, 8, 10
    0.000 ( 0.0000 )
    0.000 ( 0.0000 )
    0.000 ( 0.0000 )
        Week 12, 15 Minutes Post-Dose; n=8, 7, 10
    10.188 ( 9.4024 )
    23.576 ( 29.1713 )
    38.500 ( 32.4047 )
        Week 12, 1 Hour Post-Dose; n=8, 8, 10
    17.090 ( 12.7636 )
    35.513 ( 26.5491 )
    57.939 ( 26.8754 )
        Week 12, 3 Hours Post-Dose; n=8, 8, 10
    15.101 ( 9.5156 )
    42.591 ( 39.0808 )
    65.482 ( 44.5255 )
        Week 12, 6 Hours Post-Dose; n=7, 7, 10
    11.131 ( 6.6894 )
    56.230 ( 52.4345 )
    73.444 ( 42.1339 )
        Week 12, 24 Hours Post-Dose; n=8, 7, 10
    3.143 ( 5.5271 )
    6.241 ( 7.5820 )
    12.125 ( 8.5500 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    		 Close Top of page
    End point title
    		 Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
    End point description
    An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with this treatment. A serious AE (SAE) is an AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is a medically important event or reaction. TEAEs are AEs that occur following investigational product (IP) administration or a pre-existing condition exacerbated following IP administration. Safety Analysis Set: All participants who receive at least 1 dose of IP.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Number of subjects analysed
    61
    54
    55
    56
    Units: participants
        All Treatment-Emergent Adverse Events (TEAEs)
    43
    43
    36
    49
        Treatment-related TEAEs
    8
    13
    8
    10
        Serious TEAEs
    10
    4
    2
    7
        TEAEs leading to study drug discontinuation
    0
    1
    0
    0
        Deaths
    0
    0
    0
    0
    No statistical analyses for this end point

    Post-hoc: Ad Hoc Analysis: Percent Change from Baseline at Week 24 and Over Time Through Week 48 in ApoC-III

    		 Close Top of page
    End point title
    		 Ad Hoc Analysis: Percent Change from Baseline at Week 24 and Over Time Through Week 48 in ApoC-III
    End point description
    Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP), excluding participants with values below the limit of quantification (BLQ) at Baseline, along with one site. n=Observed cases at given time point.
    End point type
    Post-hoc
    End point timeframe
    Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)
    End point values
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Number of subjects analysed
    57
    53
    55
    57
    Units: percentage change
    least squares mean (standard error)
        Week 4; n=57, 51, 55, 57
    7.0 ( 3.88 )
    -65.1 ( 4.04 )
    -82.9 ( 3.94 )
    -83.2 ( 3.81 )
        Week 8; n=57, 52, 54, 56
    4.7 ( 4.19 )
    -57.3 ( 4.36 )
    -77.2 ( 4.26 )
    -78.7 ( 4.14 )
        Week 12; n=54, 51, 54, 54
    0.0 ( 4.79 )
    -53.2 ( 4.97 )
    -70.3 ( 4.84 )
    -72.2 ( 4.74 )
        Week 16; n=56, 49, 54, 53
    2.8 ( 3.94 )
    -74.8 ( 4.13 )
    -84.9 ( 4.00 )
    -86.3 ( 3.92 )
        Week 20; n=56, 50, 51, 53
    7.8 ( 4.60 )
    -69.9 ( 4.81 )
    -79.7 ( 4.72 )
    -82.6 ( 4.60 )
        Week 24; n=56, 48, 54, 55
    -0.8 ( 4.29 )
    -68.1 ( 4.51 )
    -72.1 ( 4.37 )
    -78.2 ( 4.26 )
        Week 28; n=57, 49, 52, 54
    -2.2 ( 4.19 )
    -63.0 ( 4.42 )
    -70.2 ( 4.31 )
    -73.2 ( 4.19 )
        Week 36; n=54, 48, 51, 54
    0.2 ( 4.98 )
    -48.5 ( 5.23 )
    -59.1 ( 5.10 )
    -58.3 ( 4.95 )
        Week 48; n=54, 49, 50, 53
    5.6 ( 6.19 )
    -33.7 ( 6.48 )
    -48.0 ( 6.37 )
    -46.8 ( 6.19 )
    Attachments
    		 Untitled (Filename: Statistical Analyses-Percent Change from Baseline at Week 24 and Over Time Through Week 48 in ApoC-III, MMRM with Observed.docx)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to 48 Weeks
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.

    Reporting group title
    ARO-APOC3 10 mg
    Reporting group description
    		 Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.

    Reporting group title
    ARO-APOC3 25 mg
    Reporting group description
    		 Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.

    Reporting group title
    ARO-APOC3 50 mg
    Reporting group description
    		 Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.

    Serious adverse events
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 61 (16.39%)
    4 / 54 (7.41%)
    2 / 55 (3.64%)
    7 / 56 (12.50%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer stage III
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Concussion
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Peripheral artery thrombosis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Pancreatitis acute
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic pseudocyst
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis necrotising
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis relapsing
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia bacterial
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo ARO-APOC3 10 mg ARO-APOC3 25 mg ARO-APOC3 50 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    44 / 61 (72.13%)
    44 / 54 (81.48%)
    36 / 55 (65.45%)
    50 / 56 (89.29%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Bowen's disease
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Haemangioma of liver
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Lentigo maligna
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Malignant melanoma
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    4 / 61 (6.56%)
    0 / 54 (0.00%)
    2 / 55 (3.64%)
    5 / 56 (8.93%)
         occurrences all number
    5
    0
    2
    5
    Haematoma
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypotension
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Peripheral artery aneurysm
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Peripheral artery thrombosis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 61 (3.28%)
    2 / 54 (3.70%)
    1 / 55 (1.82%)
    2 / 56 (3.57%)
         occurrences all number
    2
    3
    1
    2
    Fatigue
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 54 (3.70%)
    2 / 55 (3.64%)
    1 / 56 (1.79%)
         occurrences all number
    1
    2
    2
    1
    Injection site pain
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 54 (3.70%)
    2 / 55 (3.64%)
    1 / 56 (1.79%)
         occurrences all number
    0
    2
    2
    1
    Chest pain
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    1
    0
    0
    1
    Injection site erythema
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    1
    2
    Injection site pruritus
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    2
    0
    0
    1
    Influenza like illness
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Malaise
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Vessel puncture site bruise
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Erectile dysfunction
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    1 / 55 (1.82%)
    1 / 56 (1.79%)
         occurrences all number
    1
    1
    2
    1
    Epistaxis
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 54 (3.70%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    2
    0
    1
    Nasal congestion
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    1
    0
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    2 / 56 (3.57%)
         occurrences all number
    0
    0
    0
    2
    Sinus congestion
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 54 (3.70%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Dyspnoea at rest
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypoxia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Obstructive sleep apnoea syndrome
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Productive cough
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Upper respiratory tract congestion
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    1 / 55 (1.82%)
    1 / 56 (1.79%)
         occurrences all number
    2
    1
    1
    1
    Insomnia
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    1
    1
    0
    1
    Investigations
    Glycosylated haemoglobin increased
         subjects affected / exposed
    2 / 61 (3.28%)
    4 / 54 (7.41%)
    2 / 55 (3.64%)
    2 / 56 (3.57%)
         occurrences all number
    3
    4
    2
    2
    Lipase increased
         subjects affected / exposed
    2 / 61 (3.28%)
    2 / 54 (3.70%)
    2 / 55 (3.64%)
    4 / 56 (7.14%)
         occurrences all number
    2
    2
    2
    5
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    2 / 55 (3.64%)
    0 / 56 (0.00%)
         occurrences all number
    1
    1
    2
    0
    Blood glucose increased
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 54 (3.70%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    4
    1
    0
    Amylase increased
         subjects affected / exposed
    2 / 61 (3.28%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Anion gap increased
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    1
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Blood insulin increased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Blood pressure increased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Blood testosterone decreased
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    1
    1
    Glucose urine present
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Insulin C-peptide increased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    2
    0
    1
    Activated partial thromboplastin time abnormal
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    C-reactive protein increased
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cardiac murmur
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Electrocardiogram change
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Globulins decreased
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Glomerular filtration rate decreased
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    International normalised ratio increased
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Low density lipoprotein increased
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Occult blood positive
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Platelet count increased
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Protein urine present
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Serum ferritin decreased
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Diabetes mellitus
         subjects affected / exposed
    2 / 61 (3.28%)
    4 / 54 (7.41%)
    1 / 55 (1.82%)
    3 / 56 (5.36%)
         occurrences all number
    2
    4
    1
    3
    Hyperuricaemia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    2 / 56 (3.57%)
         occurrences all number
    0
    0
    1
    2
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 61 (1.64%)
    3 / 54 (5.56%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    1
    3
    1
    0
    Muscle strain
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    2 / 56 (3.57%)
         occurrences all number
    0
    1
    0
    2
    Procedural pain
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    1 / 56 (1.79%)
         occurrences all number
    1
    0
    1
    1
    Skin laceration
         subjects affected / exposed
    2 / 61 (3.28%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Contusion
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Epicondylitis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Exposure to toxic agent
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Graft complication
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hand fracture
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Ligament rupture
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Limb injury
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Muscle rupture
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rib fracture
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Skin abrasion
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Soft tissue injury
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Thermal burn
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tooth injury
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Wrist fracture
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Atrioventricular block first degree
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    1
    0
    0
    1
    Palpitations
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 54 (3.70%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Atrial fibrillation
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Bradycardia
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Bundle branch block left
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Bundle branch block right
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 61 (4.92%)
    8 / 54 (14.81%)
    6 / 55 (10.91%)
    2 / 56 (3.57%)
         occurrences all number
    3
    10
    6
    3
    Migraine
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    1
    1
    0
    1
    Dizziness
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Hypoaesthesia
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Sciatica
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cervicogenic headache
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Diabetic neuropathy
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Epilepsy
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Facial paralysis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypersomnia
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Lacunar infarction
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Paraesthesia
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Radiculopathy
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Syncope
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 61 (3.28%)
    2 / 54 (3.70%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    2
    2
    0
    1
    Leukocytosis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Lymphocytosis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pancytopenia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Splenomegaly
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Vertigo
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vitreous floaters
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    5 / 61 (8.20%)
    3 / 54 (5.56%)
    1 / 55 (1.82%)
    1 / 56 (1.79%)
         occurrences all number
    5
    3
    1
    1
    Abdominal pain
         subjects affected / exposed
    2 / 61 (3.28%)
    2 / 54 (3.70%)
    0 / 55 (0.00%)
    3 / 56 (5.36%)
         occurrences all number
    2
    2
    0
    3
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 61 (4.92%)
    2 / 54 (3.70%)
    0 / 55 (0.00%)
    2 / 56 (3.57%)
         occurrences all number
    3
    2
    0
    2
    Nausea
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 54 (3.70%)
    2 / 55 (3.64%)
    2 / 56 (3.57%)
         occurrences all number
    1
    2
    2
    3
    Abdominal pain upper
         subjects affected / exposed
    2 / 61 (3.28%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    2 / 56 (3.57%)
         occurrences all number
    2
    1
    0
    2
    Haemorrhoids
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 54 (3.70%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Inguinal hernia
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Vomiting
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Abdominal pain lower
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Constipation
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    1
    0
    1
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    1
    0
    1
    Abdominal tenderness
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Diverticulum
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Gastritis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Hiatus hernia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Intestinal polyp
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Large intestine polyp
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Toothache
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vomiting projectile
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Hepatobiliary disorders
    Hepatic steatosis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    2 / 55 (3.64%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Gallbladder polyp
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    1
    1
    Hepatic cyst
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hepatomegaly
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    3 / 55 (5.45%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    3
    0
    Dermatitis
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Dry skin
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Dermatitis allergic
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dermatitis contact
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Drug eruption
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Ingrowing nail
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Neuropathic ulcer
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Night sweats
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Rash papular
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rash pruritic
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Skin discolouration
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    1 / 55 (1.82%)
    1 / 56 (1.79%)
         occurrences all number
    1
    1
    1
    1
    Nephrolithiasis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    2 / 55 (3.64%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Chronic kidney disease
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    2 / 55 (3.64%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Renal cyst
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Calculus urinary
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dysuria
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Haematuria
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Microalbuminuria
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Testicular failure
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    5 / 61 (8.20%)
    3 / 54 (5.56%)
    1 / 55 (1.82%)
    4 / 56 (7.14%)
         occurrences all number
    5
    3
    1
    4
    Back pain
         subjects affected / exposed
    1 / 61 (1.64%)
    5 / 54 (9.26%)
    1 / 55 (1.82%)
    1 / 56 (1.79%)
         occurrences all number
    1
    5
    1
    1
    Myalgia
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 54 (3.70%)
    2 / 55 (3.64%)
    0 / 56 (0.00%)
         occurrences all number
    2
    2
    2
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 54 (3.70%)
    2 / 55 (3.64%)
    0 / 56 (0.00%)
         occurrences all number
    0
    2
    2
    0
    Pain in extremity
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    1 / 55 (1.82%)
    2 / 56 (3.57%)
         occurrences all number
    0
    1
    1
    2
    Osteoarthritis
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 54 (3.70%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    2
    0
    1
    Fibromyalgia
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 54 (3.70%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Muscle spasms
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Muscular weakness
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 54 (3.70%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Neck pain
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    1
    2
    Arthritis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Bursitis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Intervertebral disc degeneration
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Joint effusion
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Joint swelling
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Musculoskeletal stiffness
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Rhabdomyolysis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Tendon disorder
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tenosynovitis stenosans
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Infections and infestations
    COVID-19
         subjects affected / exposed
    9 / 61 (14.75%)
    11 / 54 (20.37%)
    9 / 55 (16.36%)
    9 / 56 (16.07%)
         occurrences all number
    10
    11
    9
    10
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 61 (6.56%)
    5 / 54 (9.26%)
    4 / 55 (7.27%)
    7 / 56 (12.50%)
         occurrences all number
    5
    6
    4
    8
    Urinary tract infection
         subjects affected / exposed
    6 / 61 (9.84%)
    6 / 54 (11.11%)
    1 / 55 (1.82%)
    4 / 56 (7.14%)
         occurrences all number
    6
    9
    2
    5
    Bronchitis
         subjects affected / exposed
    2 / 61 (3.28%)
    4 / 54 (7.41%)
    0 / 55 (0.00%)
    4 / 56 (7.14%)
         occurrences all number
    2
    4
    0
    5
    Sinusitis
         subjects affected / exposed
    0 / 61 (0.00%)
    3 / 54 (5.56%)
    4 / 55 (7.27%)
    2 / 56 (3.57%)
         occurrences all number
    0
    3
    4
    2
    Ear infection
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    4 / 56 (7.14%)
         occurrences all number
    1
    0
    0
    5
    Influenza
         subjects affected / exposed
    2 / 61 (3.28%)
    1 / 54 (1.85%)
    2 / 55 (3.64%)
    0 / 56 (0.00%)
         occurrences all number
    2
    1
    3
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 54 (3.70%)
    0 / 55 (0.00%)
    2 / 56 (3.57%)
         occurrences all number
    1
    2
    0
    2
    Cellulitis
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 54 (3.70%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    1
    2
    0
    2
    Tooth infection
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    2 / 56 (3.57%)
         occurrences all number
    1
    1
    0
    2
    Pharyngitis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    1 / 56 (1.79%)
         occurrences all number
    1
    0
    1
    1
    Conjunctivitis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Cystitis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    1
    0
    1
    Gastroenteritis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    1
    1
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    2 / 56 (3.57%)
         occurrences all number
    0
    0
    0
    2
    Wound infection
         subjects affected / exposed
    2 / 61 (3.28%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Acute sinusitis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Bacterial vulvovaginitis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Coronavirus infection
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Cytomegalovirus colitis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Diverticulitis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Eye infection
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Fungal infection
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrointestinal infection
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hordeolum
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Otitis media
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Periodontitis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pneumonia fungal
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin infection
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tonsillitis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Tooth abscess
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Viral infection
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Joint injury
         subjects affected / exposed
    2 / 61 (3.28%)
    1 / 54 (1.85%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    2
    1
    1
    0
    Metabolism and nutrition disorders
    Type 2 diabetes mellitus
         subjects affected / exposed
    3 / 61 (4.92%)
    1 / 54 (1.85%)
    4 / 55 (7.27%)
    6 / 56 (10.71%)
         occurrences all number
    4
    1
    4
    6
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 54 (3.70%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    3
    1
    0
    0
    Hypoglycaemia
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Vitamin D deficiency
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Gout
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Hyperglycaemia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hyperinsulinaemia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Hypernatraemia
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hyperphosphataemia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Hypomagnesaemia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Impaired fasting glucose
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    1 / 56 (1.79%)
         occurrences all number
    0
    0
    0
    1
    Increased appetite
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 54 (0.00%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Iron deficiency
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 54 (1.85%)
    0 / 55 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Latent autoimmune diabetes in adults
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 54 (0.00%)
    1 / 55 (1.82%)
    0 / 56 (0.00%)
         occurrences all number
    0
    0
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Jan 2021
    - Increased the projected number of investigative sites - Revised the Treatment Modification guidelines in subjects with elevated liver function enzymes - Revised inclusion criterion related to prior evidence of triglycerides (TG) ≥ 500 - Revised exclusion criterion related to planned major surgery, coronary interventions, and blood donations - Corrected TG randomization stratification reference timepoint - Clarified clinical events documentation relative to adverse events (AE) assessments - Added a pharmacokinetic (PK) sample collection timepoint at Week 48/end of study (EOS) - Clarified that magnetic resonance imaging -proton density fat fraction (MRI-PDFF) should have been collected as unscheduled visit in case of early termination prior to Week 24 - Clarified that subjects on statin lipid-lowering therapy must have been on an optimal regimen - Revised lipid monitoring thresholds and follow-up procedures - Clarified that the study blind applied to treatment allocation and not to dose group allocation - Clarified that efficacy analysis will include treatment by baseline interaction terms - Revised liver related study modification and follow-up guidelines for subjects with baseline predose evidence of liver disease
    19 Apr 2021
    - Data Safety Committee (DSC) recommendations and Treatment Stopping Rules updated to align with the DSC Charter and United States Food and Drug Administration (US FDA) Guidance - Eligibility Criteria updated to add: qualifying mean triglyceride value; defined stable regimen durations for specific background medications; laboratory sign exclusions; exclusion for known genetically confirmed familial chylomicronemia syndrome (FCS) - Clarified Secondary and Exploratory Endpoints - Revised schedule of assessments (SOA) to include three distinct Screening visits and updated fasting requirement to at least 10 hours prior to any lipid testing collection - Revised Lipid Monitoring to provide unblinded low-density lipoprotein cholesterol (LDL-C) values after Week 24 if results cross predefined threshold relative to baseline
    01 Nov 2021
    - Updated Sponsor Medical Monitor - Reduction in the total number of subjects to be enrolled - Update to Treatment Stopping Rules - Eligibility Criteria updated - Updated genetic testing panel to include GPD1 mutation associated with FCS - Updates to the SOA - Added Risk-Benefit Analysis - Revised TG monitoring requirements to include only those subjects with a history of acute pancreatitis within 2 years of Day 1 - Added acute pancreatitis events counseling, detection, and reporting requirements - Added an independent pancreatitis adjudication committee - Updates to Laboratory Testing - Clarification that the mean of the two fasting screening values together with the fasting Day 1 TG value was to serve as the baseline value for the primary endpoint analysis - Updated the circumstances under which the Sponsor may have terminated the study - Updated SAE reporting time-frame - Added Data Protection section - Updated Liver Related Study Modification and Follow-Up Guidelines for Participants (Appendix 1)
    21 Nov 2022
    - Clarified glycemic parameters and study discontinuation due to increased glycated hemoglobin (HbA1c) - Allowed adjustments to treatment medication at the discretion of the PI
    26 Jan 2023
    - Added plan for interim analysis

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 30 19:42:03 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA