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    Clinical Trial Results:
    A Randomized, Phase 3, Double-Masked, Parallel Group, Multicenter Study to Compare the Efficacy and Safety of ALT-L9 Versus Eylea® in Patients With Neovascular Age-Related Macular Degeneration (ALTERA)

    Summary
    EudraCT number
    		 2021-004530-11
    Trial protocol
    		 CZ   HU   SK   LV   AT   ES   BG   EE   LT  
    Global end of trial date
    20 Feb 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Mar 2025
    First version publication date
    07 Mar 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ALT-L9-03
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Altos Biologics Inc.
    Sponsor organisation address
    8F, 15, Teheran-ro 84-gil, Gangnam-gu, Seoul, Korea, Republic of, 06179
    Public contact
    SoJin Lee, Altos Biologics Inc., +82 2 2039 9520, sjlee@altosbio.com
    Scientific contact
    SoJin Lee, Altos Biologics Inc., +82 2 2039 9520, sjlee@altosbio.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
    18 Apr 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Feb 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to demonstrate that the biosimilar candidate ALT-L9 2 mg/50 microliter (mcL) was equivalent to Eylea® (aflibercept) in subjects with wet (neovascular) age-related macular degeneration (nAMD) in terms of best-corrected visual acuity (BCVA).
    Protection of trial subjects
    This study was conducted in accordance with the accepted version of the Declaration of Helsinki and/or all relevant federal regulations in compliance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use good clinical practice (ICH GCP) guidelines, Japanese GCP and Korean GCP, and according to the appropriate regulatory requirements in the countries where the study was conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Jun 2022
    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
    Austria: 7
    Country: Number of subjects enrolled
    Bulgaria: 16
    Country: Number of subjects enrolled
    Czechia: 56
    Country: Number of subjects enrolled
    Estonia: 6
    Country: Number of subjects enrolled
    Hungary: 97
    Country: Number of subjects enrolled
    Latvia: 35
    Country: Number of subjects enrolled
    Lithuania: 9
    Country: Number of subjects enrolled
    Poland: 92
    Country: Number of subjects enrolled
    Slovakia: 19
    Country: Number of subjects enrolled
    Spain: 22
    Country: Number of subjects enrolled
    Japan: 33
    Country: Number of subjects enrolled
    Korea, Republic of: 39
    Worldwide total number of subjects
    431
    EEA total number of subjects
    359
    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)
    49
    From 65 to 84 years
    345
    85 years and over
    37

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects took part in the study at 79 investigative sites in Japan, Republic of Korea, Austria, Bulgaria, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Slovakia and Spain from 02 June 2022 to 20 February 2024.

    Pre-assignment
    Screening details
    		 A total of 642 subjects with Neovascular Age-Related Macular Degeneration (nAMD) were screened, of which 211 subjects were screen failures and 431 subjects were randomized to receive ALT-L9 or Eylea.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ALT-L9
    Arm description
    		 Subjects received single dose of ALT-L9 40 milligrams per milliliter (mg/mL) (2 mg/50 microliter [mcL] aflibercept), ophthalmic intravitreal (IVT) injection, in study eye, once every 4 weeks, for up to Week 8 and once every 8 weeks up to Week 48.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Aflibercept biosimilar
    Investigational medicinal product code
    ALT-L9
    Other name
    Pharmaceutical forms
    Solution for injection in vial
    Routes of administration
    Intravitreal use
    Dosage and administration details
    ALT-L9 40 mg/mL (2 mg/50 mcL aflibercept), ophthalmic IVT injection, in study eye, once every 4 weeks, for up to Week 8 and once every 8 weeks up to Week 48. The 40 mg/mL concentration of aflibercept was contained in a single vial.

    Arm title
    		 Eylea®
    Arm description
    		 Subjects received single dose of Eylea® 40 mg/mL (2 mg/50 mcL aflibercept), ophthalmic IVT injection, in study eye, once every 4 weeks, for up to Week 8 and once every 8 weeks up to Week 48.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Eylea®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Intravitreal use
    Dosage and administration details
    Eylea® 40 mg/mL (2 mg/50 mcL aflibercept), ophthalmic IVT injection, in study eye, once every 4 weeks, for up to Week 8 and once every 8 weeks up to Week 48. The 40 mg/mL concentration of aflibercept was contained in a PFS.

    Number of subjects in period 1
    		ALT-L9 Eylea®
    Started
    216
    215
    Completed
    204
    201
    Not completed
    12
    14
         Consent withdrawn by subject
    3
    4
         Physician decision
    1
    -
         Adverse event, non-fatal
    4
    8
         Death
    1
    -
         Unspecified
    2
    1
         Lost to follow-up
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    ALT-L9
    Reporting group description
    		 Subjects received single dose of ALT-L9 40 milligrams per milliliter (mg/mL) (2 mg/50 microliter [mcL] aflibercept), ophthalmic intravitreal (IVT) injection, in study eye, once every 4 weeks, for up to Week 8 and once every 8 weeks up to Week 48.

    Reporting group title
    Eylea®
    Reporting group description
    		 Subjects received single dose of Eylea® 40 mg/mL (2 mg/50 mcL aflibercept), ophthalmic IVT injection, in study eye, once every 4 weeks, for up to Week 8 and once every 8 weeks up to Week 48.

    Reporting group values
    		 ALT-L9 Eylea® Total
    Number of subjects
    		 216 215 431
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 74.4 ( 7.83 ) 73.9 ( 7.97 ) -
    Gender categorical
    Units: Subjects
        Female
    		 132 126 258
        Male
    		 84 89 173

    End points

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    End points reporting groups
    Reporting group title
    ALT-L9
    Reporting group description
    		 Subjects received single dose of ALT-L9 40 milligrams per milliliter (mg/mL) (2 mg/50 microliter [mcL] aflibercept), ophthalmic intravitreal (IVT) injection, in study eye, once every 4 weeks, for up to Week 8 and once every 8 weeks up to Week 48.

    Reporting group title
    Eylea®
    Reporting group description
    		 Subjects received single dose of Eylea® 40 mg/mL (2 mg/50 mcL aflibercept), ophthalmic IVT injection, in study eye, once every 4 weeks, for up to Week 8 and once every 8 weeks up to Week 48.

    Primary: Change from Baseline in Best-corrected Visual Acuity (BCVA) at Week 8 as Measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score

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    End point title
    		 Change from Baseline in Best-corrected Visual Acuity (BCVA) at Week 8 as Measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score
    End point description
    BCVA was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The BCVA letter score ranges from 0 to 100 (best score). A positive change indicates an improvement, and a negative change indicates worsening. The Intent-to-treat (ITT) set included all randomized subjects, irrespective of any deviation from the protocol or premature discontinuation. Here, "n" refers to subjects who were evaluable for this endpoint and for specified estimands.
    End point type
    Primary
    End point timeframe
    Baseline and at Week 8
    End point values
    		 ALT-L9 Eylea®
    Number of subjects analysed
    216
    215
    Units: score on a scale
    least squares mean (standard error)
        Primary Estimand (n=216,215)
    5.771 ( 0.5821 )
    7.863 ( 0.5888 )
        Secondary Estimand (n=216,215)
    6.272 ( 0.6240 )
    7.972 ( 0.6248 )
        Tertiary Estimand (n=213,214)
    5.782 ( 0.5870 )
    7.862 ( 0.5905 )
    Statistical analysis title
    		 Primary Estimand: ALT-L9 vs Eylea
    Comparison groups
    ALT-L9 v Eylea®
    Number of subjects included in analysis
    431
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [1]
    Method
    Parameter type
    		 Least-square Mean Difference
    Point estimate
    -2.092
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.431
         upper limit
    		 -0.753
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.6834
    Notes
    [1] - A predefined margin of ±3.49 letters was used for analysis.
    Statistical analysis title
    		 Secondary Estimand: ALT-L9 vs Eylea
    Comparison groups
    ALT-L9 v Eylea®
    Number of subjects included in analysis
    431
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [2]
    Method
    Parameter type
    		 Least-square Mean Difference
    Point estimate
    -1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.113
         upper limit
    		 -0.287
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.7209
    Notes
    [2] - A predefined margin of ±3.49 letters was used for analysis.
    Statistical analysis title
    		 Tertiary Estimand: ALT-L9 vs Eylea
    Comparison groups
    ALT-L9 v Eylea®
    Number of subjects included in analysis
    431
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [3]
    Method
    Parameter type
    		 Least-square Mean Difference
    Point estimate
    -2.079
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.425
         upper limit
    		 -0.734
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.6846
    Notes
    [3] - A predefined margin of ±3.49 letters was used for analysis.

    Secondary: Proportion of Subjects With a Loss of at Least 5, 10, or 15 Letters in BCVA Letter Score in the Study Eye Over Time up to Week 52, Compared With Baseline, Using the ETDRS Protocol

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    End point title
    		 Proportion of Subjects With a Loss of at Least 5, 10, or 15 Letters in BCVA Letter Score in the Study Eye Over Time up to Week 52, Compared With Baseline, Using the ETDRS Protocol
    End point description
    BCVA was measured on the ETDRS chart. The BCVA letter score ranges from 0 to 100 (best score). A positive change indicates an improvement, and a negative change indicates worsening. The ITT set included all randomized subjects, irrespective of any deviation from the protocol or premature discontinuation.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    		 ALT-L9 Eylea®
    Number of subjects analysed
    216
    215
    Units: percentage of subjects
    number (not applicable)
        Primary Estimand: >=5 letters
    10.6
    4.0
        Secondary Estimand: >=5 letters
    8.1
    3.7
        Tertiary Estimand: >=5 letters
    10.3
    4.0
        Primary Estimand: >=10 letters
    6.4
    2.0
        Secondary Estimand: >=10 letters
    3.5
    1.5
        Tertiary Estimand: >=10 letters
    6.4
    2.0
        Primary Estimand: >=15 letters
    3.4
    1.0
        Secondary Estimand: >=15 letters
    2.0
    0.6
        Tertiary Estimand: >=15 letters
    3.4
    1.0
    No statistical analyses for this end point

    Secondary: Change From Baseline in Central Subfield Thickness (CST) in the Study Eye Up to Week 4 and Week 52 as Measured by Spectral Domain-optical Coherence Tomography (SD-OCT)

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    End point title
    		 Change From Baseline in Central Subfield Thickness (CST) in the Study Eye Up to Week 4 and Week 52 as Measured by Spectral Domain-optical Coherence Tomography (SD-OCT)
    End point description
    CST was measured in the study eye by SD-OCT. The ITT set included all randomized subjects, irrespective of any deviation from the protocol or premature discontinuation. Here, "n" refers to subjects who were evaluable for specified estimands.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Weeks 4 and 52
    End point values
    		 ALT-L9 Eylea®
    Number of subjects analysed
    216
    215
    Units: microns
    least squares mean (standard error)
        Week 4: Primary Estimand (n=216,215)
    -100.485 ( 6.2919 )
    -93.569 ( 6.3687 )
        Week 4: Secondary Estimand (n=216,215)
    -98.250 ( 6.7016 )
    -93.151 ( 6.8495 )
        Week 4: Tertiary Estimand (n=213,213)
    -101.102 ( 6.2981 )
    -93.734 ( 6.3697 )
        Week 52: Primary Estimand (n=216,215)
    -116.023 ( 7.4471 )
    -111.281 ( 7.5733 )
        Week 52: Secondary Estimand (n=216,215)
    -113.450 ( 8.1122 )
    -111.471 ( 8.2944 )
        Week 52: Tertiary Estimand (n=203,195)
    -119.154 ( 7.3191 )
    -108.528 ( 7.4820 )
    No statistical analyses for this end point

    Secondary: Proportion of Subjects With a Gain of at least 5, 10, or 15 Letters in BCVA Letter Score in the Study Eye Over Time up to Week 52, Compared With Baseline, Using the ETDRS Protocol

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    End point title
    		 Proportion of Subjects With a Gain of at least 5, 10, or 15 Letters in BCVA Letter Score in the Study Eye Over Time up to Week 52, Compared With Baseline, Using the ETDRS Protocol
    End point description
    BCVA was measured on the ETDRS chart. The BCVA letter score ranges from 0 to 100 (best score). A positive change indicates an improvement, and a negative change indicates worsening. The ITT set included all randomized subjects, irrespective of any deviation from the protocol or premature discontinuation.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    		 ALT-L9 Eylea®
    Number of subjects analysed
    216
    215
    Units: percentage of subjects
    number (not applicable)
        Primary Estimand: >=5 letters
    68.8
    72.9
        Secondary Estimand: >=5 letters
    71.0
    74.2
        Tertiary Estimand: >=5 letters
    69.6
    73.1
        Primary Estimand: >=10 letters
    41.5
    44.6
        Secondary Estimand: >=10 letters
    43.9
    47.2
        Tertiary Estimand: >=10 letters
    42.2
    44.3
        Primary Estimand: >=15 letters
    19.2
    21.8
        Secondary Estimand: >=15 letters
    21.5
    25.0
        Tertiary Estimand: >=15 letters
    19.6
    21.4
    No statistical analyses for this end point

    Secondary: Proportion of Subjects With Existing Intraretinal or Subretinal Fluid in the Study Eye Over Time up to Week 4 and Week 52, Compared With Baseline, as Measured by SD-OCT

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    End point title
    		 Proportion of Subjects With Existing Intraretinal or Subretinal Fluid in the Study Eye Over Time up to Week 4 and Week 52, Compared With Baseline, as Measured by SD-OCT
    End point description
    Existing intraretinal or subretinal fluid was measured in the study eye by SD-OCT. The ITT set included all randomized subjects, irrespective of any deviation from the protocol or premature discontinuation.
    End point type
    Secondary
    End point timeframe
    Up to Weeks 4 and 52
    End point values
    		 ALT-L9 Eylea®
    Number of subjects analysed
    216
    215
    Units: percentage of subjects
    number (not applicable)
        Week 4: Primary Estimand
    62.2
    56.9
        Week 4: Secondary Estimand
    61.7
    56.2
        Week 4: Tertiary Estimand
    62.1
    56.8
        Week 52: Primary Estimand
    39.7
    39.1
        Week 52: Secondary Estimand
    42.4
    40.5
        Week 52: Tertiary Estimand
    38.2
    37.5
    No statistical analyses for this end point

    Secondary: Change From Baseline in BCVA Letter Score in The Study Eye Over Time up to Week 52 Using the ETDRS Protocol

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    End point title
    		 Change From Baseline in BCVA Letter Score in The Study Eye Over Time up to Week 52 Using the ETDRS Protocol
    End point description
    BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score). A positive change indicates an improvement, and a negative change indicates worsening. The ITT set included all randomized subjects, irrespective of any deviation from the protocol or premature discontinuation. Here, "n" refers to subjects who were evaluable for specified estimands.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    		 ALT-L9 Eylea®
    Number of subjects analysed
    216
    215
    Units: score on a scale
    least squares mean (standard error)
        Primary Estimand (n=216, 215)
    7.315 ( 0.7871 )
    9.259 ( 0.8018 )
        Secondary Estimand (n=216, 215)
    8.171 ( 0.9405 )
    9.551 ( 0.8940 )
        Tertiary Estimand (n=204, 201)
    7.415 ( 0.7872 )
    9.228 ( 0.8014 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in the Total Size of the Active Choroidal Neovascularization (CNV) Area in the Study Eye Over Time up to Week 52, as Measured by Fluorescein Angiography (FA)

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    End point title
    		 Change From Baseline in the Total Size of the Active Choroidal Neovascularization (CNV) Area in the Study Eye Over Time up to Week 52, as Measured by Fluorescein Angiography (FA)
    End point description
    Active CNV leakage of the study eye was assessed with fluorescein angiography. The active CNV leakage was defined as result of >0 (mm^2). ITT set included all randomized subjects, irrespective of any deviation from the protocol or premature discontinuation. Here, "n" refers to subjects who were evaluable for this endpoint and for specified estimands.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    		 ALT-L9 Eylea®
    Number of subjects analysed
    216
    215
    Units: square millimeter (mm^2)
    least squares mean (standard error)
        Primary Estimand (n=216,215)
    -1.890 ( 0.4174 )
    -2.123 ( 0.4188 )
        Secondary Estimand (n=216,215)
    -1.992 ( 0.5344 )
    -2.130 ( 0.5201 )
        Tertiary Estimand (n=199,194)
    -1.857 ( 0.4205 )
    -2.100 ( 0.4242 )
    No statistical analyses for this end point

    Secondary: Number of Subjects with Treatment-related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) for Systemic and Ocular Category

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    End point title
    		 Number of Subjects with Treatment-related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) for Systemic and Ocular Category
    End point description
    A treatment-related TEAEs and SAEs were clinical event with plausible time relationship to study drug administration, and that cannot be explained by concurrent disease or other drugs or chemicals. The SAF included all randomized subjects who receive at least 1 administration (full or partial) of the study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    		 ALT-L9 Eylea®
    Number of subjects analysed
    216
    215
    Units: subjects
        Systemic Category: Related TEAEs
    0
    2
        Systemic Category: Related SAEs
    0
    2
        Ocular Category: Related TEAEs
    3
    3
        Ocular Category: Related SAEs
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-emergent AEs (TEAEs) and Serious AEs (SAEs) for Systemic and Ocular Category

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    End point title
    		 Number of Subjects With Treatment-emergent AEs (TEAEs) and Serious AEs (SAEs) for Systemic and Ocular Category
    End point description
    A TEAE was defined as any event not present before the initiation of the study treatment or any event already present that worsens in either intensity or frequency following exposure to the treatments. An SAE is any untoward medical occurrence, in the view of either the investigator or Sponsor, that meets one or more of the following criteria: results in death, is life-threatening, results in inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect. The SAF included of all randomized subjects who receive at least 1 administration (full or partial) of the study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    		 ALT-L9 Eylea®
    Number of subjects analysed
    216
    215
    Units: subjects
        Systemic Category: TEAEs
    116
    112
        Systemic Category: SAEs
    25
    25
        Ocular Category: TEAEs
    90
    75
        Ocular Category: SAEs
    1
    3
    No statistical analyses for this end point

    Secondary: Proportion of Subjects With Active CNV Leakage in the Study Eye Over Time up to Week 52, Compared With Baseline, as Measured by FA

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    End point title
    		 Proportion of Subjects With Active CNV Leakage in the Study Eye Over Time up to Week 52, Compared With Baseline, as Measured by FA
    End point description
    Active CNV leakage of the study eye was assessed with fluorescein angiography. The active CNV leakage was defined as result of >0 (mm^2). ITT set included all randomized subjects, irrespective of any deviation from the protocol or premature discontinuation.
    End point type
    Secondary
    End point timeframe
    Up to Week 52
    End point values
    		 ALT-L9 Eylea®
    Number of subjects analysed
    216
    215
    Units: percentage of subjects
    number (not applicable)
        Primary Estimand
    61.7
    55.1
        Secodary Estimand
    64.4
    56.6
        Tertiary Estimand
    62.3
    54.9
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to Week 52
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    ALT-L9
    Reporting group description
    		 Subjects received single dose of ALT-L9 40 mg/mL (2 mg/50 mcL aflibercept), ophthalmic IVT injection, in study eye, once every 4 weeks, for up to Week 8 and once every 8 weeks up to Week 48.

    Reporting group title
    Eylea®
    Reporting group description
    		 Subjects received single dose of Eylea® 40 mg/mL (2 mg/50 mcL aflibercept), ophthalmic IVT injection, in study eye, once every 4 weeks, for up to Week 8 and once every 8 weeks up to Week 48.

    Serious adverse events
    		 ALT-L9 Eylea®
    Total subjects affected by serious adverse events
         subjects affected / exposed
    26 / 216 (12.04%)
    28 / 215 (13.02%)
         number of deaths (all causes)
    1
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Follicular thyroid cancer
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glioma
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hormone-dependent prostate cancer
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polycythaemia vera
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Salivary gland neoplasm
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Arteriosclerosis
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Cystocele
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterovaginal prolapse
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety disorder
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Ischaemic stroke
         subjects affected / exposed
    1 / 216 (0.46%)
    3 / 215 (1.40%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombotic cerebral infarction
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trigeminal palsy
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood loss anaemia
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Blindness
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastric ulcer haemorrhage
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Pemphigoid
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal stenosis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethritis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vulval abscess
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endophthalmitis
         subjects affected / exposed
    1 / 216 (0.46%)
    2 / 215 (0.93%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 ALT-L9 Eylea®
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    204 / 216 (94.44%)
    180 / 215 (83.72%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Salivary gland neoplasm
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Adenoma benign
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Bowen's disease
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Glioma
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Laryngeal cancer
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Metastases to bone
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Neoplasm
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Oesophageal carcinoma
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Polycythaemia vera
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    11 / 216 (5.09%)
    10 / 215 (4.65%)
         occurrences all number
    13
    11
    Arteriosclerosis
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Blood pressure fluctuation
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Hot flush
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Hypertensive crisis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Subclavian artery stenosis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Thrombophlebitis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Venous thrombosis limb
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    White coat hypertension
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 216 (0.46%)
    3 / 215 (1.40%)
         occurrences all number
    1
    3
    Peripheral swelling
         subjects affected / exposed
    2 / 216 (0.93%)
    1 / 215 (0.47%)
         occurrences all number
    2
    1
    Pyrexia
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Chest pain
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Hernia
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    2 / 216 (0.93%)
    1 / 215 (0.47%)
         occurrences all number
    2
    1
    Contrast media allergy
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    2 / 216 (0.93%)
    1 / 215 (0.47%)
         occurrences all number
    2
    1
    Uterine polyp
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Cystocele
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Endometrial hyperplasia
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Uterine prolapse
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Uterovaginal prolapse
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    6 / 216 (2.78%)
    1 / 215 (0.47%)
         occurrences all number
    6
    1
    Upper respiratory tract inflammation
         subjects affected / exposed
    1 / 216 (0.46%)
    2 / 215 (0.93%)
         occurrences all number
    1
    2
    Rhinorrhoea
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Lung opacity
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Paranasal sinus inflammation
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Rhinitis allergic
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 216 (0.00%)
    3 / 215 (1.40%)
         occurrences all number
    0
    3
    Anxiety
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Anxiety disorder
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Body dysmorphic disorder
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Delirium
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Depression
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Sleep disorder
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Product issues
    Device dislocation
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Blood pressure increased
         subjects affected / exposed
    4 / 216 (1.85%)
    1 / 215 (0.47%)
         occurrences all number
    4
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    3 / 216 (1.39%)
    1 / 215 (0.47%)
         occurrences all number
    3
    1
    Blood triglycerides increased
         subjects affected / exposed
    0 / 216 (0.00%)
    3 / 215 (1.40%)
         occurrences all number
    0
    3
    Blood urea increased
         subjects affected / exposed
    1 / 216 (0.46%)
    2 / 215 (0.93%)
         occurrences all number
    1
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Blood glucose increased
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Anti-thyroid antibody increased
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Blood glucose decreased
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Blood phosphorus decreased
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Body temperature increased
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Fibrin D dimer increased
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Glomerular filtration rate decreased
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Influenza A virus test positive
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Platelet count increased
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Ultrasound liver abnormal
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Vitamin B12 decreased
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Intraocular pressure increased
         subjects affected / exposed
    4 / 216 (1.85%)
    3 / 215 (1.40%)
         occurrences all number
    7
    5
    Optical coherence tomography abnormal
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Tooth fracture
         subjects affected / exposed
    0 / 216 (0.00%)
    2 / 215 (0.93%)
         occurrences all number
    0
    2
    Rib fracture
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Bone contusion
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Contusion
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Hand fracture
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Head injury
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Humerus fracture
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Limb injury
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Patella fracture
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Pelvic fracture
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Post-traumatic pain
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Skin wound
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Synovial rupture
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Ulna fracture
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Upper limb fracture
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Wrist fracture
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Corneal abrasion
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Craniofacial fracture
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Injury of conjunctiva
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Type IIa hyperlipidaemia
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Cardiac failure chronic
         subjects affected / exposed
    1 / 216 (0.46%)
    2 / 215 (0.93%)
         occurrences all number
    1
    2
    Angina pectoris
         subjects affected / exposed
    0 / 216 (0.00%)
    2 / 215 (0.93%)
         occurrences all number
    0
    2
    Arrhythmia
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 216 (0.00%)
    2 / 215 (0.93%)
         occurrences all number
    0
    2
    Palpitations
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Atrial fibrillation
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Cardiac asthma
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Chronic coronary syndrome
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Coronary artery disease
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Tricuspid valve incompetence
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    7 / 216 (3.24%)
    4 / 215 (1.86%)
         occurrences all number
    8
    5
    Intracranial aneurysm
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    2
    Lumbar radiculopathy
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    2
    Cognitive disorder
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Dizziness
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Memory impairment
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Polyneuropathy
         subjects affected / exposed
    0 / 216 (0.00%)
    2 / 215 (0.93%)
         occurrences all number
    0
    2
    Trigeminal palsy
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    2
    Balance disorder
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Carotid artery stenosis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Encephalomalacia
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Loss of consciousness
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Lumbosacral radiculopathy
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Migraine
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Neuropathy peripheral
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Paresis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Peripheral sensorimotor neuropathy
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Sciatica
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Spinal cord herniation
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Thrombotic cerebral infarction
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Vascular dementia
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 216 (1.39%)
    0 / 215 (0.00%)
         occurrences all number
    3
    0
    Blood loss anaemia
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Leukocytosis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Leukopenia
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Vertigo positional
         subjects affected / exposed
    0 / 216 (0.00%)
    2 / 215 (0.93%)
         occurrences all number
    0
    2
    Cerumen impaction
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Ear pain
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Tinnitus
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Vestibular disorder
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Neovascular age-related macular degeneration
         subjects affected / exposed
    23 / 216 (10.65%)
    13 / 215 (6.05%)
         occurrences all number
    24
    13
    Visual acuity reduced
         subjects affected / exposed
    12 / 216 (5.56%)
    10 / 215 (4.65%)
         occurrences all number
    12
    11
    Cataract
         subjects affected / exposed
    8 / 216 (3.70%)
    4 / 215 (1.86%)
         occurrences all number
    8
    5
    Subretinal fluid
         subjects affected / exposed
    6 / 216 (2.78%)
    4 / 215 (1.86%)
         occurrences all number
    6
    4
    Conjunctival haemorrhage
         subjects affected / exposed
    2 / 216 (0.93%)
    6 / 215 (2.79%)
         occurrences all number
    2
    6
    Posterior capsule opacification
         subjects affected / exposed
    3 / 216 (1.39%)
    5 / 215 (2.33%)
         occurrences all number
    3
    5
    Vitreous floaters
         subjects affected / exposed
    4 / 216 (1.85%)
    3 / 215 (1.40%)
         occurrences all number
    4
    3
    Retinal oedema
         subjects affected / exposed
    3 / 216 (1.39%)
    3 / 215 (1.40%)
         occurrences all number
    3
    3
    Retinal pigment epithelial tear
         subjects affected / exposed
    3 / 216 (1.39%)
    3 / 215 (1.40%)
         occurrences all number
    3
    3
    Macular fibrosis
         subjects affected / exposed
    2 / 216 (0.93%)
    3 / 215 (1.40%)
         occurrences all number
    2
    3
    Retinal haemorrhage
         subjects affected / exposed
    2 / 216 (0.93%)
    3 / 215 (1.40%)
         occurrences all number
    2
    3
    Vitreous detachment
         subjects affected / exposed
    3 / 216 (1.39%)
    2 / 215 (0.93%)
         occurrences all number
    3
    2
    Macular degeneration
         subjects affected / exposed
    3 / 216 (1.39%)
    1 / 215 (0.47%)
         occurrences all number
    3
    1
    Visual impairment
         subjects affected / exposed
    1 / 216 (0.46%)
    3 / 215 (1.40%)
         occurrences all number
    1
    3
    Eye pain
         subjects affected / exposed
    3 / 216 (1.39%)
    0 / 215 (0.00%)
         occurrences all number
    4
    0
    Cataract subcapsular
         subjects affected / exposed
    1 / 216 (0.46%)
    2 / 215 (0.93%)
         occurrences all number
    1
    2
    Choroidal neovascularisation
         subjects affected / exposed
    3 / 216 (1.39%)
    0 / 215 (0.00%)
         occurrences all number
    3
    0
    Conjunctival hyperaemia
         subjects affected / exposed
    2 / 216 (0.93%)
    1 / 215 (0.47%)
         occurrences all number
    2
    1
    Cystoid macular oedema
         subjects affected / exposed
    1 / 216 (0.46%)
    2 / 215 (0.93%)
         occurrences all number
    1
    2
    Eye irritation
         subjects affected / exposed
    2 / 216 (0.93%)
    1 / 215 (0.47%)
         occurrences all number
    2
    1
    Optic disc haemorrhage
         subjects affected / exposed
    3 / 216 (1.39%)
    0 / 215 (0.00%)
         occurrences all number
    3
    0
    Blepharitis
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Cataract cortical
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Chalazion
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Corneal erosion
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Detachment of retinal pigment epithelium
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Lacrimation increased
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Retinal exudates
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Vision blurred
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Vitreous haemorrhage
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Age-related macular degeneration
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Anterior chamber cell
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Arteriosclerotic retinopathy
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Asthenopia
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Conjunctival suffusion
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Cornea verticillata
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Corneal oedema
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Corneal scar
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Dacryostenosis acquired
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Detachment of macular retinal pigment epithelium
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Diplopia
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Dry eye
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Epiretinal membrane
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Eye discharge
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Eye inflammation
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Eye pruritus
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Eyelid pain
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Foreign body sensation in eyes
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Macular hole
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Macular oedema
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Macular pseudohole
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Macular scar
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Metamorphopsia
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Optic disc traction syndrome
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Optic nerve sheath haemorrhage
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Photophobia
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Photopsia
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Punctate keratitis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Retinal cyst
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Retinal depigmentation
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Retinal detachment
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Retinal drusen
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Retinal pigment epitheliopathy
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Retinal vein occlusion
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Retinoschisis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Subretinal fibrosis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Visual field defect
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    2 / 216 (0.93%)
    3 / 215 (1.40%)
         occurrences all number
    2
    3
    Abdominal pain
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 216 (0.00%)
    2 / 215 (0.93%)
         occurrences all number
    0
    2
    Constipation
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Nausea
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Abdominal discomfort
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Dental caries
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Diverticulum intestinal
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Gastritis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Haemorrhoids
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Inguinal hernia
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Noninfective gingivitis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Oesophagitis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 216 (0.46%)
    2 / 215 (0.93%)
         occurrences all number
    1
    2
    Cholecystitis chronic
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Cholestasis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Gallbladder polyp
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Hepatic function abnormal
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Hepatic steatosis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    1 / 216 (0.46%)
    2 / 215 (0.93%)
         occurrences all number
    1
    2
    Rash
         subjects affected / exposed
    1 / 216 (0.46%)
    2 / 215 (0.93%)
         occurrences all number
    1
    2
    Pemphigoid
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    3
    Actinic keratosis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Dermatitis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Dermatitis allergic
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Eczema
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Pain of skin
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Rosacea
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Scab
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    0
    0
    Skin ulcer
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Urticaria
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Petechiae
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Chronic kidney disease
         subjects affected / exposed
    2 / 216 (0.93%)
    1 / 215 (0.47%)
         occurrences all number
    2
    1
    Renal cyst
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Renal failure
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Cystitis noninfective
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Haematuria
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Hypertensive nephropathy
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Leukocyturia
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Nephritis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Nephrolithiasis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Nephropathy
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Nephropathy toxic
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Renal impairment
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Stress urinary incontinence
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Urethral pain
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Urethral stenosis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Urinary bladder herniation
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Urinary tract discomfort
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Hyperthyroidism
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    2
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    4 / 216 (1.85%)
    5 / 215 (2.33%)
         occurrences all number
    6
    5
    Osteoarthritis
         subjects affected / exposed
    3 / 216 (1.39%)
    2 / 215 (0.93%)
         occurrences all number
    3
    2
    Pain in extremity
         subjects affected / exposed
    3 / 216 (1.39%)
    2 / 215 (0.93%)
         occurrences all number
    3
    2
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 216 (0.00%)
    4 / 215 (1.86%)
         occurrences all number
    0
    7
    Spinal stenosis
         subjects affected / exposed
    1 / 216 (0.46%)
    2 / 215 (0.93%)
         occurrences all number
    3
    2
    Arthralgia
         subjects affected / exposed
    1 / 216 (0.46%)
    2 / 215 (0.93%)
         occurrences all number
    1
    2
    Muscle spasms
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Myalgia
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Periarthritis
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    3
    0
    Bone pain
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Greater trochanteric pain syndrome
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal stiffness
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Osteoporotic fracture
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Polymyalgia rheumatica
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Sacral pain
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Spinal pain
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Spondylolisthesis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Sympathetic posterior cervical syndrome
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Tendon disorder
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Tenosynovitis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Vertebral foraminal stenosis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    11 / 216 (5.09%)
    21 / 215 (9.77%)
         occurrences all number
    11
    23
    COVID-19
         subjects affected / exposed
    11 / 216 (5.09%)
    3 / 215 (1.40%)
         occurrences all number
    12
    3
    Influenza
         subjects affected / exposed
    2 / 216 (0.93%)
    4 / 215 (1.86%)
         occurrences all number
    2
    4
    Urinary tract infection
         subjects affected / exposed
    3 / 216 (1.39%)
    1 / 215 (0.47%)
         occurrences all number
    5
    1
    Asymptomatic bacteriuria
         subjects affected / exposed
    2 / 216 (0.93%)
    2 / 215 (0.93%)
         occurrences all number
    2
    2
    Cystitis
         subjects affected / exposed
    2 / 216 (0.93%)
    2 / 215 (0.93%)
         occurrences all number
    2
    2
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 216 (0.46%)
    3 / 215 (1.40%)
         occurrences all number
    1
    3
    Viral infection
         subjects affected / exposed
    2 / 216 (0.93%)
    2 / 215 (0.93%)
         occurrences all number
    2
    2
    Otitis externa
         subjects affected / exposed
    1 / 216 (0.46%)
    2 / 215 (0.93%)
         occurrences all number
    1
    2
    Rhinitis
         subjects affected / exposed
    1 / 216 (0.46%)
    2 / 215 (0.93%)
         occurrences all number
    1
    2
    Enteritis infectious
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Gastroenteritis viral
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Herpes zoster
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Otitis media
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Sinusitis
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Erysipelas
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Laryngitis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Vulval abscess
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Bronchitis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Hepatitis C
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Lyme disease
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Onychomycosis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Periodontitis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Pneumonia aspiration
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Pyelonephritis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Skin infection
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Tonsillitis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Conjunctivitis
         subjects affected / exposed
    6 / 216 (2.78%)
    2 / 215 (0.93%)
         occurrences all number
    7
    2
    Hordeolum
         subjects affected / exposed
    0 / 216 (0.00%)
    2 / 215 (0.93%)
         occurrences all number
    0
    2
    Metabolism and nutrition disorders
    Hypercholesterolaemia
         subjects affected / exposed
    2 / 216 (0.93%)
    5 / 215 (2.33%)
         occurrences all number
    2
    5
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 216 (0.46%)
    4 / 215 (1.86%)
         occurrences all number
    1
    4
    Diabetes mellitus
         subjects affected / exposed
    2 / 216 (0.93%)
    1 / 215 (0.47%)
         occurrences all number
    2
    1
    Dyslipidaemia
         subjects affected / exposed
    2 / 216 (0.93%)
    1 / 215 (0.47%)
         occurrences all number
    2
    1
    Hypophosphataemia
         subjects affected / exposed
    0 / 216 (0.00%)
    2 / 215 (0.93%)
         occurrences all number
    0
    3
    Hyperkalaemia
         subjects affected / exposed
    2 / 216 (0.93%)
    0 / 215 (0.00%)
         occurrences all number
    2
    0
    Hyperuricaemia
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 215 (0.47%)
         occurrences all number
    1
    1
    Glucose tolerance impaired
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Gout
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Hyperlipidaemia
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Hyponatraemia
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Insulin resistance
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 215 (0.47%)
         occurrences all number
    0
    1
    Iron deficiency
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Lipid metabolism disorder
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 215 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Sep 2022
    Protocol Amendment 1: The primary change of this amendment is the removal of re-randomization at Week 32, which led to adjustments in the sample size and schedule of assessments.

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

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

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