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    Clinical Trial Results:
    A Double-blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults with Mixed Dyslipidemia

    Summary
    EudraCT number
    		 2021-000688-57
    Trial protocol
    		 HU   PL  
    Global end of trial date
    14 Aug 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Aug 2024
    First version publication date
    28 Aug 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    AROAPOC3-2002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04998201
    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., +1 626-304-3400, info@arrowheadpharma.com
    Scientific contact
    Chief Operating Officer, Arrowhead Pharmaceuticals, Inc., +1 626-304-3400, 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
    14 Aug 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Aug 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to evaluate the safety and efficacy of ARO-APOC3 in adults with mixed dyslipidemia (MD) and to select a dose and dosing regimen for later stage clinical studies in this patient population.
    Protection of trial subjects
    All eligible participants had the study explained by the PI or designee. They received 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 was explained that the study is for research purposes only and was not expected to provide any therapeutic benefit to the individual. It was pointed out that they could withdraw from the study at any time without prejudice.
    Background therapy
    		 All subjects were required to maintain a stable regimen of optimal statin therapy during screening and throughout the treatment period.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    07 Sep 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 38
    Country: Number of subjects enrolled
    Australia: 10
    Country: Number of subjects enrolled
    New Zealand: 12
    Country: Number of subjects enrolled
    United States: 169
    Country: Number of subjects enrolled
    Poland: 18
    Country: Number of subjects enrolled
    Hungary: 106
    Worldwide total number of subjects
    353
    EEA total number of subjects
    124
    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)
    206
    From 65 to 84 years
    145
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants who successfully passed the requirements during the Screening period were enrolled into the study. All dose cohorts were enrolled in parallel with participants randomized 3:1 to receive ARO-APOC3 or 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
    		 Investigator, Subject
    Blinding implementation details
    Treatment assignment (active versus placebo) was blinded in this clinical study. Dose group assignment was not blinded, due to required injection volume differences dictated by the respective dose group. Therefore, participants received an injection of either active or placebo volume matched to the assigned dose group. Syringes were blinded in the Pharmacy with translucent wrapping to mask the blinded staff and participants to treatment assignment in accordance with instructions provided.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Volume-matched placebo at Day 1 and Week 12
    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
    Subcutaneous (SC) injection on Day 1 and Week 12 for a total of 2 injections

    Arm title
    		 ARO-APOC3 10 mg Q12W
    Arm description
    		 ARO-APOC3 10 mg at Day 1 and Week 12 (Q12W)
    Arm type
    		 Experimental

    Investigational medicinal product name
    ARO-APOC3 Injection
    Investigational medicinal product code
    ARO-APOC3
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    SC injection on Day 1 and Week 12 for a total of 2 injections

    Arm title
    		 ARO-APOC3 25mg Q12W
    Arm description
    		 ARO-APOC3 25 mg at Day 1 and Week 12 (Q12W)
    Arm type
    		 Experimental

    Investigational medicinal product name
    ARO-APOC3 Injection
    Investigational medicinal product code
    ARO-APOC3
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    SC injection on Day 1 and Week 12 for a total of 2 injections

    Arm title
    		 ARO-APOC3 50mg Q12W
    Arm description
    		 ARO-APOC3 50 mg (n=60) or volume-matched placebo (n=20) at Day 1 and Week 12 (Q12W)
    Arm type
    		 Experimental

    Investigational medicinal product name
    ARO-APOC3 Injection
    Investigational medicinal product code
    ARO-APOC3
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    SC injection on Day 1 and Week 12 for a total of 2 injections

    Arm title
    		 ARO-APOC3 50mg Q24W
    Arm description
    		 ARO-APOC3 50 mg at Day 1 and Week 24 (Q24W)
    Arm type
    		 Experimental

    Investigational medicinal product name
    ARO-APOC3 Injection
    Investigational medicinal product code
    ARO-APOC3
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    SC injection on Day 1 and Week 24 for a total of 2 injections

    Number of subjects in period 1
    		Placebo ARO-APOC3 10 mg Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Started
    87
    67
    67
    66
    66
    Completed
    78
    60
    64
    61
    61
    Not completed
    9
    7
    3
    5
    5
         Consent withdrawn by subject
    3
    3
    1
    1
    2
         Physician decision
    3
    1
    -
    2
    -
         Death
    -
    -
    1
    -
    1
         Other, not specified
    -
    -
    -
    -
    1
         Adverse event
    -
    1
    -
    -
    1
         Lost to follow-up
    2
    2
    1
    1
    -
         Protocol deviation
    1
    -
    -
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Volume-matched placebo at Day 1 and Week 12

    Reporting group title
    ARO-APOC3 10 mg Q12W
    Reporting group description
    		 ARO-APOC3 10 mg at Day 1 and Week 12 (Q12W)

    Reporting group title
    ARO-APOC3 25mg Q12W
    Reporting group description
    		 ARO-APOC3 25 mg at Day 1 and Week 12 (Q12W)

    Reporting group title
    ARO-APOC3 50mg Q12W
    Reporting group description
    		 ARO-APOC3 50 mg (n=60) or volume-matched placebo (n=20) at Day 1 and Week 12 (Q12W)

    Reporting group title
    ARO-APOC3 50mg Q24W
    Reporting group description
    		 ARO-APOC3 50 mg at Day 1 and Week 24 (Q24W)

    Reporting group values
    		 Placebo ARO-APOC3 10 mg Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W Total
    Number of subjects
    		 87 67 67 66 66 353
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 58.9 ( 9.70 ) 60.2 ( 11.71 ) 61.3 ( 11.28 ) 62.6 ( 10.53 ) 61.3 ( 11.84 ) -
    Gender categorical
    Units: Subjects
        Female
    		 41 31 37 37 43 189
        Male
    		 46 36 30 29 23 164
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 16 18 12 12 15 73
        Not Hispanic or Latino
    		 71 49 55 53 51 279
        Not Reported
    		 0 0 0 1 0 1
    Race
    Units: Subjects
        White
    		 79 62 60 63 62 326
        Black or African American
    		 4 2 2 0 0 8
        American Indian or Alaska Native
    		 0 0 1 0 0 1
        Asian
    		 3 2 3 1 1 10
        Native Hawaiian or Other Pacific Islander
    		 0 0 1 0 1 2
        Unknown
    		 0 0 0 0 1 1
        Other
    		 1 1 0 2 1 5
    Mean Triglycerides (TG)
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 237.22 ( 76.179 ) 253.15 ( 81.425 ) 234.08 ( 72.746 ) 250.25 ( 81.329 ) 248.01 ( 80.553 ) -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Volume-matched placebo at Day 1 and Week 12

    Reporting group title
    ARO-APOC3 10 mg Q12W
    Reporting group description
    		 ARO-APOC3 10 mg at Day 1 and Week 12 (Q12W)

    Reporting group title
    ARO-APOC3 25mg Q12W
    Reporting group description
    		 ARO-APOC3 25 mg at Day 1 and Week 12 (Q12W)

    Reporting group title
    ARO-APOC3 50mg Q12W
    Reporting group description
    		 ARO-APOC3 50 mg (n=60) or volume-matched placebo (n=20) at Day 1 and Week 12 (Q12W)

    Reporting group title
    ARO-APOC3 50mg Q24W
    Reporting group description
    		 ARO-APOC3 50 mg at Day 1 and Week 24 (Q24W)

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

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    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 Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Number of subjects analysed
    81
    61
    63
    62
    61
    Units: percentage change
        least squares mean (standard error)
    -1.7 ( 3.07 )
    -51.5 ( 3.54 )
    -57.7 ( 3.49 )
    -64.1 ( 3.51 )
    -45.9 ( 3.52 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ARO-APOC3 10 mg Q12W
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [1]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -49.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -59
         upper limit
    		 -40.6
    Notes
    [1] - Mixed Model Repeated Measures (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.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ARO-APOC3 25mg Q12W
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [2]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -65.1
         upper limit
    		 -46.8
    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.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ARO-APOC3 50mg Q12W
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [3]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -62.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -71.5
         upper limit
    		 -53.2
    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.
    Statistical analysis title
    		 Statistical Analysis 4
    Comparison groups
    Placebo v ARO-APOC3 50mg Q24W
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [4]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -44.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -53.4
         upper limit
    		 -35
    Notes
    [4] - 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.

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

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    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 Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Number of subjects analysed
    87
    67
    67
    66
    66
    Units: percentage change
    least squares mean (standard error)
        Week 4; n=85, 62, 67, 63, 63
    -0.5 ( 2.77 )
    -51.4 ( 3.21 )
    -61.5 ( 3.14 )
    -66.4 ( 3.20 )
    -62.5 ( 3.19 )
        Week 8; n=83, 64, 66, 64, 64
    -0.4 ( 2.45 )
    -48.6 ( 2.78 )
    -58.1 ( 2.77 )
    -65.0 ( 2.78 )
    -59.7 ( 2.78 )
        Week 12; n=80, 63, 61, 64, 61
    -0.1 ( 3.07 )
    -43.8 ( 3.46 )
    -53.6 ( 3.50 )
    -57.9 ( 3.45 )
    -51.7 ( 3.49 )
        Week 16; n=77, 63, 63, 63, 65
    -1.8 ( 2.87 )
    -58.0 ( 3.21 )
    -62.0 ( 3.21 )
    -68.3 ( 3.21 )
    -50.6 ( 3.17 )
        Week 20; n=82, 59, 61, 61, 63
    1.2 ( 2.85 )
    -54.6 ( 3.32 )
    -62.0 ( 3.28 )
    -64.7 ( 3.28 )
    -49.1 ( 3.23 )
        Week 24; n=81, 61, 63, 62, 61
    -1.7 ( 3.07 )
    -51.5 ( 3.54 )
    -57.7 ( 3.49 )
    -64.1 ( 3.51 )
    -45.9 ( 3.52 )
        Week 28; n=82, 61, 64, 62, 61
    3.5 ( 2.95 )
    -46.2 ( 3.41 )
    -55.7 ( 3.35 )
    -61.7 ( 3.38 )
    -63.4 ( 3.39 )
        Week 36; n=80, 61, 63, 60, 61
    6.1 ( 4.66 )
    -44.7 ( 5.35 )
    -51.5 ( 5.25 )
    -54.9 ( 5.34 )
    -60.1 ( 5.32 )
        Week 48; n=78, 60, 64, 61, 61
    1.7 ( 4.35 )
    -33.2 ( 4.96 )
    -42.8 ( 4.86 )
    -50.2 ( 4.94 )
    -55.0 ( 4.93 )
    Attachments
    		 Untitled (Filename: Percent Change from Baseline Over Time Through Week 48 in Fasting TG - SA.docx)
    No statistical analyses for this end point

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

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    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 Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Number of subjects analysed
    79
    59
    63
    62
    61
    Units: percentage change
        least squares mean (standard error)
    23.9 ( 21.90 )
    -58.9 ( 24.86 )
    -44.3 ( 24.54 )
    -65.7 ( 24.71 )
    -57.9 ( 24.70 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ARO-APOC3 10 mg Q12W
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0128 [5]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -82.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -147.9
         upper limit
    		 -17.7
    Notes
    [5] - Mixed Model Repeated Measures (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.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v ARO-APOC3 25mg Q12W
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0387 [6]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -68.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -132.9
         upper limit
    		 -3.5
    Notes
    [6] - Mixed Model Repeated Measures (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.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v ARO-APOC3 50mg Q12W
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0069 [7]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -89.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -154.5
         upper limit
    		 -24.7
    Notes
    [7] - Mixed Model Repeated Measures (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.
    Statistical analysis title
    		 Statistical Analysis 4
    Comparison groups
    Placebo v ARO-APOC3 50mg Q24W
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0136 [8]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -81.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -146.7
         upper limit
    		 -16.9
    Notes
    [8] - Mixed Model Repeated Measures (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.

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

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    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 Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Number of subjects analysed
    87
    67
    67
    66
    66
    Units: percentage change
    least squares mean (standard error)
        Week 4; n=84, 61, 67, 63, 63
    19.3 ( 21.81 )
    -60.7 ( 24.78 )
    -69.7 ( 24.45 )
    -78.4 ( 24.66 )
    -82.7 ( 24.64 )
        Week 8; n=81, 63, 65, 64, 64
    19.0 ( 21.84 )
    -57.3 ( 24.72 )
    -61.9 ( 24.48 )
    -71.8 ( 24.64 )
    -78.1 ( 24.62 )
        Week 12; n=79, 62, 61, 64, 61
    20.3 ( 21.90 )
    -48.7 ( 24.77 )
    -18.9 ( 24.57 )
    -59.2 ( 24.66 )
    -71.5 ( 24.68 )
        Week 16; n=77, 62, 63, 64, 65
    10.9 ( 21.92 )
    -69.9 ( 24.79 )
    -63.8 ( 24.54 )
    -78.9 ( 24.67 )
    -67.7 ( 24.62 )
        Week 20; n=80, 58, 60, 61, 63
    21.8 ( 21.88 )
    -64.0 ( 24.87 )
    -63.3 ( 24.58 )
    -69.3 ( 24.72 )
    -62.6 ( 24.65 )
        Week 24; n=79, 59, 63, 62, 61
    23.9 ( 21.90 )
    -58.9 ( 24.86 )
    -44.3 ( 24.54 )
    -65.7 ( 24.71 )
    -57.9 ( 24.70 )
        Week 28; n=81, 60, 64, 62, 62
    35.6 ( 21.90 )
    -51.7 ( 24.87 )
    -32.8 ( 24.55 )
    -53.3 ( 24.71 )
    -82.5 ( 24.70 )
        Week 36; n=79, 60, 63, 60, 61
    30.6 ( 21.96 )
    -46.3 ( 24.91 )
    -24.9 ( 24.58 )
    -34.5 ( 24.74 )
    -75.8 ( 24.70 )
        Week 48; n=77, 59, 64, 61, 61
    27.3 ( 21.97 )
    -31.2 ( 24.97 )
    -13.9 ( 24.58 )
    -17.4 ( 24.78 )
    -64.8 ( 24.72 )
    Attachments
    		 Untitled (Filename: Percent Change from Baseline at Week 24 and Over Time Through Week 48 in ApoC-III - SA.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 Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Number of subjects analysed
    81
    61
    63
    62
    61
    Units: percentage change
        least squares mean (standard error)
    -2.7 ( 2.56 )
    -19.3 ( 2.93 )
    -20.1 ( 2.90 )
    -26.9 ( 2.92 )
    -10.3 ( 2.92 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ARO-APOC3 10 mg Q12W
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [9]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -16.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.3
         upper limit
    		 -9
    Notes
    [9] - 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 25mg Q12W
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [10]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -17.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.1
         upper limit
    		 -9.8
    Notes
    [10] - 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 50mg Q12W
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [11]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -24.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -31.9
         upper limit
    		 -16.6
    Notes
    [11] - 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 4
    Comparison groups
    Placebo v ARO-APOC3 50mg Q24W
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0492 [12]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -7.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.3
         upper limit
    		 0
    Notes
    [12] - 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 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 Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Number of subjects analysed
    87
    67
    67
    66
    66
    Units: percentage change
    least squares mean (standard error)
        Week 4; n=85, 62, 67, 63, 63
    -1.2 ( 2.19 )
    -17.3 ( 2.53 )
    -23.3 ( 2.48 )
    -26.3 ( 2.52 )
    -19.6 ( 2.53 )
        Week 8; n=83, 64, 66, 64, 64
    -1.0 ( 2.37 )
    -18.2 ( 2.69 )
    -22.4 ( 2.67 )
    -27.8 ( 2.70 )
    -16.2 ( 2.70 )
        Week 12; n=80, 63, 61, 64, 61
    -0.4 ( 2.65 )
    -15.5 ( 3.00 )
    -19.4 ( 3.01 )
    -21.9 ( 3.00 )
    -16.0 ( 3.02 )
        Week 16; n=77, 63, 63, 63, 65
    -1.4 ( 2.49 )
    -21.2 ( 2.80 )
    -23.8 ( 2.80 )
    -28.5 ( 2.81 )
    -15.5 ( 2.79 )
        Week 20; n=82, 59, 61, 61, 63
    -1.9 ( 2.82 )
    -20.9 ( 3.24 )
    -21.5 ( 3.21 )
    -27.3 ( 3.22 )
    -11.7 ( 3.20 )
        Week 24; n=81, 61, 63, 62, 61
    -2.7 ( 2.56 )
    -19.3 ( 2.93 )
    -20.1 ( 2.90 )
    -26.9 ( 2.92 )
    -10.3 ( 2.92 )
        Week 28; n=82, 61, 64, 62, 61
    0.4 ( 2.91 )
    -17.1 ( 3.33 )
    -17.7 ( 3.29 )
    -25.6 ( 3.32 )
    -20.5 ( 3.33 )
        Week 36; n=80, 61, 63, 60, 61
    0.0 ( 2.71 )
    -17.1 ( 3.09 )
    -17.1 ( 3.05 )
    -23.4 ( 3.10 )
    -17.3 ( 3.09 )
        Week 48; n=78, 60, 64, 61, 61
    1.7 ( 2.96 )
    -12.1 ( 3.37 )
    -12.1 ( 3.29 )
    -21.8 ( 3.35 )
    -20.0 ( 3.35 )
    Attachments
    		 Untitled (Filename: Percent Change from Baseline at Week 24 and Over Time Through Week 48 in Fasting non-HDL-C - SA.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 Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Number of subjects analysed
    81
    61
    63
    62
    61
    Units: percentage change
        least squares mean (standard error)
    4.7 ( 3.34 )
    37.9 ( 3.81 )
    46.8 ( 3.82 )
    50.5 ( 3.80 )
    32.8 ( 3.82 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    ARO-APOC3 10 mg Q12W v Placebo
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [13]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    33.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 23.2
         upper limit
    		 43.1
    Notes
    [13] - 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 25mg Q12W
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [14]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 32.1
         upper limit
    		 52
    Notes
    [14] - 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 50mg Q12W
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [15]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    45.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 35.8
         upper limit
    		 55.7
    Notes
    [15] - 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 4
    Comparison groups
    Placebo v ARO-APOC3 50mg Q24W
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [16]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18
         upper limit
    		 38
    Notes
    [16] - 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 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 Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Number of subjects analysed
    87
    67
    67
    66
    66
    Units: percentage change
    least squares mean (standard error)
        Week 4; n=85, 62, 67, 63, 63
    3.6 ( 3.38 )
    39.3 ( 3.88 )
    48.3 ( 3.86 )
    55.4 ( 3.88 )
    55.5 ( 3.90 )
        Week 8; n=83, 64, 66, 64, 64
    2.0 ( 3.18 )
    32.1 ( 3.61 )
    46.4 ( 3.63 )
    54.3 ( 3.62 )
    52.8 ( 3.64 )
        Week 12; n=80, 63, 61, 64, 61
    2.5 ( 3.19 )
    31.4 ( 3.60 )
    40.1 ( 3.66 )
    49.0 ( 3.61 )
    45.1 ( 3.65 )
        Week 16; n=77, 63, 63, 63, 65
    3.2 ( 3.46 )
    45.8 ( 3.90 )
    56.4 ( 3.93 )
    64.2 ( 3.91 )
    41.6 ( 3.91 )
        Week 20; n=82, 59, 61, 61, 63
    2.8 ( 3.27 )
    45.0 ( 3.75 )
    50.6 ( 3.76 )
    58.2 ( 3.74 )
    40.3 ( 3.73 )
        Week 24; n=81, 61, 63, 62, 61
    4.7 ( 3.34 )
    37.9 ( 3.81 )
    46.8 ( 3.82 )
    50.5 ( 3.80 )
    32.8 ( 3.82 )
        Week 28; n=82, 61, 64, 62, 61
    2.1 ( 3.47 )
    35.8 ( 3.98 )
    45.3 ( 3.96 )
    49.5 ( 3.96 )
    54.0 ( 3.99 )
        Week 36; n=80, 61, 63, 60, 61
    1.6 ( 3.25 )
    30.8 ( 3.72 )
    37.0 ( 3.71 )
    43.1 ( 3.72 )
    49.7 ( 3.73 )
        Week 48; n=78, 60, 64, 61, 61
    4.5 ( 3.53 )
    25.4 ( 4.02 )
    30.5 ( 3.98 )
    34.3 ( 4.00 )
    44.5 ( 4.01 )
    Attachments
    		 Untitled (Filename: Percent Change from Baseline at Week 24 and Over Time Through Week 48 in Fasting HDL-C - SA.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 Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Number of subjects analysed
    79
    59
    63
    62
    61
    Units: percentage change
        least squares mean (standard error)
    0.8 ( 2.57 )
    -9.5 ( 2.94 )
    -12.2 ( 2.89 )
    -18.3 ( 2.91 )
    -5.7 ( 2.91 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v ARO-APOC3 10 mg Q12W
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0089 [17]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -10.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.9
         upper limit
    		 -2.6
    Notes
    [17] - 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 25mg Q12W
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0009 [18]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.6
         upper limit
    		 -5.4
    Notes
    [18] - 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 50mg Q12W
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [19]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -19.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.7
         upper limit
    		 -11.5
    Notes
    [19] - 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 4
    Comparison groups
    Placebo v ARO-APOC3 50mg Q24W
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0965 [20]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -6.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.1
         upper limit
    		 1.2
    Notes
    [20] - 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 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 Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Number of subjects analysed
    87
    67
    67
    66
    66
    Units: percentage change
    least squares mean (standard error)
        Week 4; n=84, 61, 67, 63, 63
    -1.3 ( 1.99 )
    -10.3 ( 2.30 )
    -15.5 ( 2.24 )
    -18.5 ( 2.28 )
    -13.5 ( 2.29 )
        Week 8; n=81, 63, 65, 64, 64
    -0.5 ( 2.26 )
    -11.0 ( 2.56 )
    -15.5 ( 2.54 )
    -20.3 ( 2.55 )
    -10.9 ( 2.56 )
        Week 12; n=79, 62, 61, 64, 61
    0.9 ( 2.53 )
    -8.5 ( 2.87 )
    -14.3 ( 2.86 )
    -14.8 ( 2.85 )
    -10.8 ( 2.87 )
        Week 16; n=77, 62, 63, 64, 65
    0.2 ( 2.30 )
    -12.8 ( 2.60 )
    -17.2 ( 2.57 )
    -20.6 ( 2.58 )
    -9.4 ( 2.58 )
        Wek 20; n=80, 58, 60, 61, 63
    0.5 ( 2.61 )
    -13.0 ( 3.00 )
    -14.3 ( 2.96 )
    -19.3 ( 2.97 )
    -7.3 ( 2.95 )
        Week 24; n=79, 59, 63, 62, 61
    0.8 ( 2.57 )
    -9.5 ( 2.94 )
    -12.2 ( 2.89 )
    -18.3 ( 2.91 )
    -5.7 ( 2.91 )
        Week 28; n=81, 60, 64, 62, 62
    5.1 ( 2.98 )
    -9.0 ( 3.41 )
    -10.0 ( 3.35 )
    -16.3 ( 3.38 )
    -12.1 ( 3.38 )
        Week 36; n=79, 60, 63, 60, 61
    3.7 ( 2.68 )
    -7.8 ( 3.07 )
    -9.3 ( 3.00 )
    -15.4 ( 3.05 )
    -9.9 ( 3.04 )
        Week 48; n=77, 59, 64, 61, 61
    3.3 ( 2.75 )
    -4.7 ( 3.14 )
    -6.4 ( 3.06 )
    -12.2 ( 3.11 )
    -11.9 ( 3.11 )
    Attachments
    		 Untitled (Filename: Percent Change from Baseline at Week 24 and Over Time Through Week 48 in Fasting Total ApoB - SA.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
    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 Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Number of subjects analysed
    81
    61
    63
    62
    61
    Units: percentage change
        least squares mean (standard error)
    -0.1 ( 3.62 )
    1.4 ( 4.14 )
    3.9 ( 4.10 )
    -4.3 ( 4.13 )
    7.3 ( 4.14 )
    Statistical analysis title
    		 Statisical Analysis 1
    Comparison groups
    Placebo v ARO-APOC3 10 mg Q12W
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7856 [21]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.3
         upper limit
    		 12.3
    Notes
    [21] - 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
    		 Statisical Analysis 2
    Comparison groups
    Placebo v ARO-APOC3 25mg Q12W
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4602 [22]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.7
         upper limit
    		 14.8
    Notes
    [22] - 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
    		 Statisical Analysis 3
    Comparison groups
    Placebo v ARO-APOC3 50mg Q12W
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4429 [23]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    -4.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15
         upper limit
    		 6.6
    Notes
    [23] - 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
    		 Statisical Analysis 4
    Comparison groups
    Placebo v ARO-APOC3 50mg Q24W
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1763 [24]
    Method
    		 MMRM
    Parameter type
    		 Difference
    Point estimate
    7.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.4
         upper limit
    		 18.3
    Notes
    [24] - 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 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
    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 Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Number of subjects analysed
    87
    67
    67
    66
    66
    Units: percentage change
    least squares mean (standard error)
        Week 4; n=85, 62, 67, 63, 63
    0.6 ( 3.18 )
    5.0 ( 3.67 )
    1.1 ( 3.59 )
    0.4 ( 3.66 )
    3.2 ( 3.67 )
        Week 8; n=83, 64, 66, 64, 64
    1.7 ( 3.24 )
    0.7 ( 3.68 )
    0.6 ( 3.65 )
    -3.6 ( 3.69 )
    7.4 ( 3.70 )
        Week 12; n=80, 63, 61, 64, 61
    1.8 ( 3.68 )
    2.5 ( 4.16 )
    2.5 ( 4.18 )
    1.6 ( 4.16 )
    3.2 ( 4.20 )
        Week 16; n=77, 63, 63, 63, 65
    1.5 ( 3.65 )
    2.2 ( 4.11 )
    0.4 ( 4.10 )
    -2.7 ( 4.11 )
    3.2 ( 4.09 )
        Week 20; n=82, 59, 61, 61, 63
    -0.3 ( 3.78 )
    1.3 ( 4.35 )
    4.0 ( 4.31 )
    -3.9 ( 4.33 )
    7.2 ( 4.30 )
        Week 24; n=81, 61, 63, 62, 61
    -0.1 ( 3.62 )
    1.4 ( 4.14 )
    3.9 ( 4.10 )
    -4.3 ( 4.13 )
    7.3 ( 4.14 )
        Week 28; n=82, 61, 64, 62, 61
    1.6 ( 3.86 )
    0.2 ( 4.42 )
    6.1 ( 4.37 )
    -3.6 ( 4.41 )
    2.0 ( 4.42 )
        Week 36; n=80, 61, 63, 60, 61
    1.6 ( 3.80 )
    0.0 ( 4.33 )
    5.3 ( 4.28 )
    -3.5 ( 4.35 )
    5.7 ( 4.34 )
        Week 48; n=78, 60, 64, 61, 61
    1.7 ( 3.88 )
    2.0 ( 4.43 )
    6.9 ( 4.32 )
    -4.0 ( 4.40 )
    -0.1 ( 4.40 )
    Attachments
    		 Untitled (Filename: Percent Change from Baseline at Week 24 and Over Time Through Week 48 in Fasting LDL-C - SA.docx)
    No statistical analyses for this end point

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

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    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.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 Placebo ARO-APOC3 10 mg Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Number of subjects analysed
    87
    67
    67
    66
    66
    Units: participants
        All Treatment-Emergent Adverse Events (TEAEs)
    55
    46
    45
    47
    49
        Treatment-related TEAEs
    8
    7
    9
    12
    8
        Serious TEAEs
    5
    2
    5
    7
    5
        TEAEs leading to study drug discontinuation
    2
    0
    0
    1
    0
        Deaths
    0
    0
    1
    2
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to Week 48
    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
    		 Volume-matched placebo at Day 1 and Week 12

    Reporting group title
    ARO-APOC3 10 mg Q12W
    Reporting group description
    		 ARO-APOC3 10 mg at Day 1 and Week 12 (Q12W)

    Reporting group title
    ARO-APOC3 25mg Q12W
    Reporting group description
    		 ARO-APOC3 25 mg at Day 1 and Week 12 (Q12W)

    Reporting group title
    ARO-APOC3 50mg Q12W
    Reporting group description
    		 ARO-APOC3 50 mg (n=60) or volume-matched placebo (n=20) at Day 1 and Week 12 (Q12W)

    Reporting group title
    ARO-APOC3 50mg Q24W
    Reporting group description
    		 ARO-APOC3 50 mg at Day 1 and Week 24 (Q24W)

    Serious adverse events
    		 Placebo ARO-APOC3 10 mg Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 87 (5.75%)
    2 / 67 (2.99%)
    5 / 67 (7.46%)
    7 / 66 (10.61%)
    5 / 66 (7.58%)
         number of deaths (all causes)
    0
    0
    1
    2
    1
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Parathyroid tumour benign
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm rupture
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Artery dissection
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Completed suicide
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Lacunar infarction
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Coeliac artery aneurysm
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Subcutaneous abscess
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal abscess
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo ARO-APOC3 10 mg Q12W ARO-APOC3 25mg Q12W ARO-APOC3 50mg Q12W ARO-APOC3 50mg Q24W
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    55 / 87 (63.22%)
    47 / 67 (70.15%)
    44 / 67 (65.67%)
    48 / 66 (72.73%)
    48 / 66 (72.73%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Seborrhoeic keratosis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    4
    Adrenal adenoma
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    2 / 66 (3.03%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Benign neoplasm of skin
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Blepharal papilloma
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Fibroma
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Lipoma
         subjects affected / exposed
    1 / 87 (1.15%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Malignant melanoma in situ
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Melanocytic naevus
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 87 (3.45%)
    2 / 67 (2.99%)
    2 / 67 (2.99%)
    1 / 66 (1.52%)
    3 / 66 (4.55%)
         occurrences all number
    3
    2
    2
    1
    3
    Blood pressure inadequately controlled
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Aortic aneurysm
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Aortic stenosis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Haematoma
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Hot flush
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    1 / 87 (1.15%)
    1 / 67 (1.49%)
    2 / 67 (2.99%)
    0 / 66 (0.00%)
    2 / 66 (3.03%)
         occurrences all number
    1
    1
    2
    0
    2
    Injection site erythema
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    2 / 66 (3.03%)
         occurrences all number
    0
    0
    0
    1
    3
    Chest discomfort
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    0
    0
    1
    Influenza like illness
         subjects affected / exposed
    3 / 87 (3.45%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    4
    0
    1
    0
    1
    Oedema
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Oedema peripheral
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    0
    0
    1
    Peripheral swelling
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Swelling face
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Dystrophic calcification
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Injection site pain
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    Injection site reaction
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Secretion discharge
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Sensation of foreign body
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Immune system disorders
    Food allergy
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Seasonal allergy
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Social circumstances
    Postmenopause
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Erectile dysfunction
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    2 / 66 (3.03%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    Fibrocystic breast disease
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Prostatomegaly
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Emphysema
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 87 (1.15%)
    1 / 67 (1.49%)
    2 / 67 (2.99%)
    1 / 66 (1.52%)
    3 / 66 (4.55%)
         occurrences all number
    1
    1
    2
    1
    4
    Dyspnoea
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    2 / 66 (3.03%)
         occurrences all number
    2
    0
    0
    0
    2
    Nasal congestion
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    2 / 66 (3.03%)
         occurrences all number
    0
    0
    0
    0
    2
    Asthma
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    0
    0
    1
    Hydrothorax
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Upper respiratory tract inflammation
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    1
    1
    Acquired diaphragmatic eventration
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Bronchial hyperreactivity
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Bronchiectasis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Dry throat
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Obstructive sleep apnoea syndrome
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    2 / 67 (2.99%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    2
    0
    2
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    1 / 87 (1.15%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    2 / 67 (2.99%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    2
    0
    1
    Anxiety
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Bipolar disorder
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Depression
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Investigations
    Blood urine present
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    2 / 66 (3.03%)
         occurrences all number
    0
    0
    0
    0
    2
    Glycosylated haemoglobin increased
         subjects affected / exposed
    2 / 87 (2.30%)
    2 / 67 (2.99%)
    1 / 67 (1.49%)
    2 / 66 (3.03%)
    2 / 66 (3.03%)
         occurrences all number
    2
    2
    1
    2
    2
    Amylase increased
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    1
    1
    1
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 87 (2.30%)
    1 / 67 (1.49%)
    3 / 67 (4.48%)
    3 / 66 (4.55%)
    1 / 66 (1.52%)
         occurrences all number
    2
    1
    3
    3
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    0
    0
    2
    Blood pressure increased
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    2 / 67 (2.99%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    2
    0
    1
    Blood urea increased
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Glomerular filtration rate decreased
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    2 / 66 (3.03%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    2
    2
    Haemoglobin decreased
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    2 / 67 (2.99%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    2
    0
    1
    Lipase increased
         subjects affected / exposed
    2 / 87 (2.30%)
    1 / 67 (1.49%)
    3 / 67 (4.48%)
    3 / 66 (4.55%)
    1 / 66 (1.52%)
         occurrences all number
    4
    1
    3
    4
    1
    Pancreatic enzymes increased
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    0
    0
    1
    Troponin increased
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Weight decreased
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    0
    0
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Anion gap increased
         subjects affected / exposed
    0 / 87 (0.00%)
    2 / 67 (2.99%)
    1 / 67 (1.49%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    2
    1
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 87 (0.00%)
    2 / 67 (2.99%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Bilirubin conjugated increased
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    2 / 66 (3.03%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    Blood glucose increased
         subjects affected / exposed
    1 / 87 (1.15%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    Blood insulin increased
         subjects affected / exposed
    3 / 87 (3.45%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    2 / 66 (3.03%)
    0 / 66 (0.00%)
         occurrences all number
    3
    1
    0
    2
    0
    Blood iron decreased
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Blood uric acid increased
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    2 / 67 (2.99%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    2 / 87 (2.30%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    2 / 66 (3.03%)
    0 / 66 (0.00%)
         occurrences all number
    3
    1
    0
    2
    0
    Cardiac murmur
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Cells in urine
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Electrocardiogram T wave inversion
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Electrocardiogram abnormal
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    1 / 67 (1.49%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    Haematocrit increased
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Human metapneumovirus test positive
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Insulin C-peptide increased
         subjects affected / exposed
    2 / 87 (2.30%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    2
    1
    0
    1
    0
    International normalised ratio increased
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Laboratory test abnormal
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Neutrophil percentage increased
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Platelet count increased
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Prostatic specific antigen increased
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Prothrombin time prolonged
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    White blood cell count increased
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Injury, poisoning and procedural complications
    Injection related reaction
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Skin abrasion
         subjects affected / exposed
    2 / 87 (2.30%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    2
    1
    0
    0
    1
    Skin laceration
         subjects affected / exposed
    1 / 87 (1.15%)
    2 / 67 (2.99%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    1
    2
    0
    0
    1
    Contusion
         subjects affected / exposed
    2 / 87 (2.30%)
    2 / 67 (2.99%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    3
    2
    1
    0
    0
    Dental restoration failure
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Eye contusion
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Eye injury
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Eyelid injury
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Fall
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Foot fracture
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Hand fracture
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Heat exhaustion
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Ligament sprain
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Limb injury
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    3 / 67 (4.48%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    3
    0
    0
    Lisfranc fracture
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Meniscus injury
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Muscle strain
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    Post procedural complication
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Post-traumatic pain
         subjects affected / exposed
    0 / 87 (0.00%)
    2 / 67 (2.99%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Scratch
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Skin wound
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Stress fracture
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Thermal burn
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Traumatic haematoma
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Wrist fracture
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    1
    1
    Arrhythmia supraventricular
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Bundle branch block left
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Cardiac failure chronic
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Left atrial enlargement
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Left ventricular hypertrophy
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    1 / 67 (1.49%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Tachycardia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    2 / 67 (2.99%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 87 (3.45%)
    2 / 67 (2.99%)
    3 / 67 (4.48%)
    4 / 66 (6.06%)
    5 / 66 (7.58%)
         occurrences all number
    3
    3
    3
    5
    8
    Paraesthesia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    2 / 66 (3.03%)
         occurrences all number
    0
    0
    0
    0
    2
    Carotid artery stenosis
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    1
    1
    0
    1
    Carpal tunnel syndrome
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    1
    1
    Complex regional pain syndrome
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Cubital tunnel syndrome
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    2
    Epilepsy
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    1
    2
    Hypoaesthesia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    0
    1
    1
    Lacunar infarction
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Occipital neuralgia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Sciatica
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    1
    1
    Syncope
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    1
    1
    Cerebral artery stenosis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Diabetic neuropathy
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Dizziness
         subjects affected / exposed
    3 / 87 (3.45%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    3
    0
    1
    0
    0
    Loss of consciousness
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Memory impairment
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Migraine
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    3
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Polyneuropathy
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Presyncope
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Radiculopathy
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Vertebrobasilar insufficiency
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    2 / 67 (2.99%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    2
    1
    1
    Thrombocytosis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Coagulopathy
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Eosinophilia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Iron deficiency anaemia
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Lymphadenopathy
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Ear and labyrinth disorders
    Ear discomfort
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Vertigo
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    2 / 66 (3.03%)
         occurrences all number
    2
    0
    0
    0
    2
    Diabetic retinopathy
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    2 / 66 (3.03%)
         occurrences all number
    0
    0
    0
    0
    2
    Dermatochalasis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Eyelid ptosis
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    1
    0
    0
    1
    Myopia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Dry eye
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    2 / 66 (3.03%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Eye pain
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Presbyopia
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Visual impairment
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Gastrointestinal disorders
    Diverticulum intestinal
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    2 / 66 (3.03%)
         occurrences all number
    0
    1
    0
    0
    2
    Hiatus hernia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    2 / 66 (3.03%)
         occurrences all number
    0
    0
    0
    0
    2
    Abdominal pain
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    4 / 66 (6.06%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    4
    1
    Dyspepsia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    2 / 67 (2.99%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    2
    0
    1
    Enteritis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Gastrointestinal ulcer
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 87 (1.15%)
    1 / 67 (1.49%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    1
    1
    1
    0
    1
    Malabsorption
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Nausea
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    1 / 67 (1.49%)
    2 / 66 (3.03%)
    1 / 66 (1.52%)
         occurrences all number
    0
    1
    3
    2
    1
    Pancreatolithiasis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Umbilical hernia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    1
    1
    Vomiting
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    2 / 66 (3.03%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    1
    2
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Colitis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Constipation
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    3 / 87 (3.45%)
    3 / 67 (4.48%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    6
    3
    0
    0
    0
    Dysphagia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Flatulence
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Food poisoning
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    2 / 67 (2.99%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Gastritis
         subjects affected / exposed
    0 / 87 (0.00%)
    2 / 67 (2.99%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Gastrointestinal pain
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Haemorrhoids
         subjects affected / exposed
    2 / 87 (2.30%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    2
    1
    0
    2
    0
    Impaired gastric emptying
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Inguinal hernia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Intestinal polyp
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Large intestine polyp
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Pancreatitis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    2
    Non-alcoholic fatty liver
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Hepatic cyst
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Hepatic steatosis
         subjects affected / exposed
    1 / 87 (1.15%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Hepatomegaly
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Skin lesion
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    2 / 66 (3.03%)
         occurrences all number
    0
    0
    0
    0
    2
    Actinic keratosis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    0
    0
    1
    Dermatitis allergic
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Psoriasis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    2
    Rosacea
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Skin ulcer
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Alopecia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Dermal cyst
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    2 / 66 (3.03%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    Dermatitis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Ecchymosis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Hidradenitis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Onychoclasis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Pruritus allergic
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Rash
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    2 / 67 (2.99%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    2
    1
    0
    Sebaceous hyperplasia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Urticaria
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    2 / 66 (3.03%)
    2 / 66 (3.03%)
         occurrences all number
    0
    0
    0
    2
    2
    Chronic kidney disease
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Haematuria
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    2 / 66 (3.03%)
    1 / 66 (1.52%)
         occurrences all number
    2
    0
    0
    2
    1
    Hypertonic bladder
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    0
    0
    1
    Renal cyst
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    1
    1
    0
    1
    Ureterolithiasis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Urethral stenosis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Acute kidney injury
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Chromaturia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Dysuria
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Leukocyturia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Proteinuria
         subjects affected / exposed
    3 / 87 (3.45%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    2 / 66 (3.03%)
    0 / 66 (0.00%)
         occurrences all number
    4
    0
    0
    2
    0
    Renal impairment
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Urinary retention
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Endocrine disorders
    Hyperparathyroidism
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Hypothyroidism
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Thyroid mass
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 87 (3.45%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    2 / 66 (3.03%)
    4 / 66 (6.06%)
         occurrences all number
    5
    0
    1
    2
    5
    Osteoarthritis
         subjects affected / exposed
    2 / 87 (2.30%)
    1 / 67 (1.49%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    3 / 66 (4.55%)
         occurrences all number
    2
    1
    1
    0
    3
    Myalgia
         subjects affected / exposed
    1 / 87 (1.15%)
    2 / 67 (2.99%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    2 / 66 (3.03%)
         occurrences all number
    1
    2
    1
    0
    2
    Diffuse idiopathic skeletal hyperostosis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    0
    0
    1
    Muscle spasms
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    2
    0
    0
    1
    Osteopenia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    1
    1
    Arthritis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Back pain
         subjects affected / exposed
    2 / 87 (2.30%)
    2 / 67 (2.99%)
    2 / 67 (2.99%)
    4 / 66 (6.06%)
    0 / 66 (0.00%)
         occurrences all number
    2
    2
    2
    4
    0
    Bursitis
         subjects affected / exposed
    1 / 87 (1.15%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Exostosis
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Flank pain
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Joint range of motion decreased
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Mixed connective tissue disease
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Neck pain
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Nodal osteoarthritis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Periarthritis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Scleroderma
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Spinal osteoarthritis
         subjects affected / exposed
    1 / 87 (1.15%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Spondylolisthesis
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    7 / 87 (8.05%)
    3 / 67 (4.48%)
    7 / 67 (10.45%)
    2 / 66 (3.03%)
    9 / 66 (13.64%)
         occurrences all number
    8
    3
    7
    2
    10
    COVID-19
         subjects affected / exposed
    12 / 87 (13.79%)
    8 / 67 (11.94%)
    11 / 67 (16.42%)
    9 / 66 (13.64%)
    6 / 66 (9.09%)
         occurrences all number
    12
    8
    11
    9
    6
    Bronchitis
         subjects affected / exposed
    1 / 87 (1.15%)
    4 / 67 (5.97%)
    2 / 67 (2.99%)
    3 / 66 (4.55%)
    5 / 66 (7.58%)
         occurrences all number
    1
    4
    2
    3
    5
    Cystitis
         subjects affected / exposed
    2 / 87 (2.30%)
    4 / 67 (5.97%)
    2 / 67 (2.99%)
    1 / 66 (1.52%)
    4 / 66 (6.06%)
         occurrences all number
    5
    4
    3
    2
    7
    Sinusitis
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 67 (0.00%)
    2 / 67 (2.99%)
    0 / 66 (0.00%)
    4 / 66 (6.06%)
         occurrences all number
    2
    0
    2
    0
    4
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    2 / 66 (3.03%)
         occurrences all number
    1
    0
    0
    1
    2
    Pneumonia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    2 / 66 (3.03%)
         occurrences all number
    0
    0
    1
    0
    2
    Urinary tract infection
         subjects affected / exposed
    7 / 87 (8.05%)
    4 / 67 (5.97%)
    6 / 67 (8.96%)
    6 / 66 (9.09%)
    2 / 66 (3.03%)
         occurrences all number
    8
    4
    6
    7
    3
    Abscess neck
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Acute sinusitis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    1
    1
    1
    Conjunctivitis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    1
    1
    1
    Ear infection
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    1
    1
    Hordeolum
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    2
    Oral candidiasis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Viral pharyngitis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Abscess oral
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Bacteriuria
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Body tinea
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Cellulitis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Dermatophytosis of nail
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Diarrhoea infectious
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Diverticulitis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Fungal skin infection
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Helicobacter infection
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Influenza
         subjects affected / exposed
    1 / 87 (1.15%)
    2 / 67 (2.99%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    1
    2
    0
    1
    0
    Laryngitis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Localised infection
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Meningitis viral
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    2 / 87 (2.30%)
    2 / 67 (2.99%)
    1 / 67 (1.49%)
    2 / 66 (3.03%)
    0 / 66 (0.00%)
         occurrences all number
    2
    2
    1
    2
    0
    Otitis media
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Otitis media acute
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Paronychia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Pharyngitis
         subjects affected / exposed
    4 / 87 (4.60%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    2 / 66 (3.03%)
    0 / 66 (0.00%)
         occurrences all number
    4
    0
    2
    2
    0
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Post-acute COVID-19 syndrome
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Pyuria
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Skin infection
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Tinea versicolour
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Tooth abscess
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Tooth infection
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Vaginal infection
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Viral infection
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    1 / 67 (1.49%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    Metabolism and nutrition disorders
    Type 2 diabetes mellitus
         subjects affected / exposed
    4 / 87 (4.60%)
    5 / 67 (7.46%)
    4 / 67 (5.97%)
    8 / 66 (12.12%)
    11 / 66 (16.67%)
         occurrences all number
    4
    5
    4
    8
    11
    Decreased appetite
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    0
    0
    2
    Diabetes mellitus
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    2 / 66 (3.03%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    2
    1
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    2
    1
    Hyperlipidaemia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    0
    1
    Hypokalaemia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    1 / 66 (1.52%)
         occurrences all number
    1
    0
    0
    0
    1
    Hypophosphataemia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    1 / 66 (1.52%)
         occurrences all number
    0
    0
    0
    1
    1
    Acidosis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Glucose tolerance impaired
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Hyperkalaemia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Hyperuricaemia
         subjects affected / exposed
    0 / 87 (0.00%)
    2 / 67 (2.99%)
    2 / 67 (2.99%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    2
    2
    1
    0
    Hypochloraemia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Hypoglycaemia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 66 (1.52%)
    0 / 66 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Hyponatraemia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Impaired fasting glucose
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Lactose intolerance
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Metabolic acidosis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Vitamin D deficiency
         subjects affected / exposed
    0 / 87 (0.00%)
    2 / 67 (2.99%)
    2 / 67 (2.99%)
    0 / 66 (0.00%)
    0 / 66 (0.00%)
         occurrences all number
    0
    2
    2
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 May 2022
    - Requirements for the study design to strengthen reporting criteria for SAEs - Amend requirements to suspend dosing in subjects - To allow a documented prior history of elevated TG between ≥150 mg/dL and ≤499 mg/dL (≥1.69 and ≤5.64 mmol/L) on 1 occasion is adequate to identify the study population targeted for inclusion - To extend the timeframe between the first and second qualifying fasting TG collection by 3 days - Inclusion criteria were updated to allow use of anticoagulation therapy, thyroid hormone therapy, and testosterone replacement therapy. - The PK endpoint was clarified and was redefined as an exploratory endpoint because it is not a main focus of the study. - Additional details were available regarding the primary analysis method and secondary endpoint analysis. Clarified the timing of the final clinical study report. - Updated the table and footnotes in the schedule of events table to clarify assessments and associated timepoints and to be consistent with updated sections of the protocol. - Included the final results from clinical study AROAPOC31001. - Added a new subsection to describe Benefit-Risk assessment for plozasiran. - Clarification that the timepoint begins with the lipid parameter collected at the Week 24 visit. - Time window for Screening visit 3 was extended to 17 days to lessen study burden on study subjects and investigative site staff. Text was updated to more accurately describe dosing visits. - Added guidance regarding the method to determine LDL-C eligibility. - To clarify that use of spermicide is not required when using a condom. - Updated the reporting requirements for pregnancy for consistency with existing procedure.
    17 May 2022
    (continued) - Updated that Day 1 predose assessment and 2 fasting TG values during the Screening period was to account for result fluctuations and provide a more stable measurement to represent the baseline TG level. Additional details were available regarding the statistical analyses, including the estimand (ICH E9 [R1] addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials), the baseline\definition for lipid-related lipoprotein and serum PD assessments. - Updated study discontinuation criteria. - Added measures taken to protect personal data collected in the course of study conduct
    22 Nov 2022
    - Added text to footnote 6 of the SOA: HbA1c was to be evaluated on an ongoing basis against treatment discontinuation criteria (Appendix 3). - Definition of HbA1c revised from “Glycosylated hemoglobin” to “Glycated hemoglobin”. Added OLE to the list. - Added guidelines for new study drug discontinuation rules in response to HbA1c elevation. - Added mitigation steps and reference to study drug discontinuation criteria in response HbA1c elevation. - Provided information on the administrative analysis and the increased HbA1c levels in relation to Benefit-Risk analysis. - Added the following text: “In response to diabetes evaluations, adjustments to treatment medication are allowed at the discretion of the PI”. - Added new Appendix 3.
    26 Jan 2023
    - Added text describing a planned 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
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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