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    Clinical Trial Results:
    A Randomized, Double-blind, Placebo-controlled, Dose-response Study of the Efficacy and Safety of MEDI7352 in Subjects with Painful Osteoarthritis of the Knee

    Summary
    EudraCT number
    		 2020-003797-51
    Trial protocol
    		 DE   DK  
    Global end of trial date
    16 Aug 2023

    Results information
    Results version number
    		 v2(current)
    This version publication date
    11 Dec 2024
    First version publication date
    30 Aug 2024
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    D5680C00003
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04675034
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca
    Sponsor organisation address
    151 85, Sodertalje, Sweden,
    Public contact
    Global Clinical Lead, AstraZeneca Clinical Study Information Center, +1 8772409479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca Clinical Study Information Center, +1 8772409479, information.center@astrazeneca.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 Sep 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Aug 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study is to assess the efficacy of MEDI7352 compared with placebo on chronic pain in participants with painful osteoarthritis (OA) of the knee at Week 12.
    Protection of trial subjects
    The conduct of this clinical study met all local and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Conference on Harmonization guideline: Good Clinical Practice, and applicable regulatory requirements. Participants signed an informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Dec 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Denmark: 3
    Country: Number of subjects enrolled
    Estonia: 14
    Country: Number of subjects enrolled
    Germany: 11
    Country: Number of subjects enrolled
    Poland: 129
    Country: Number of subjects enrolled
    Spain: 76
    Country: Number of subjects enrolled
    United Kingdom: 112
    Worldwide total number of subjects
    345
    EEA total number of subjects
    233
    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)
    185
    From 65 to 84 years
    160
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study was conducted at 50 sites in 6 countries (the United Kingdom, Denmark, Estonia, Germany, Poland, and Spain).

    Pre-assignment
    Screening details
    		 A total of 345 participants were randomized, of which 344 participants received at least one dose of study drug.

    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, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MEDl7352 Dose Level 1
    Arm description
    		 Participants received 6 doses of subcutaneous (SC) MEDl7352 Dose Level 1 injection once every 2 weeks (Q2W) during a 12-week parallel-group treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI7352
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Six doses of SC MEDl7352 Dose Level 1 Q2W given during a 12-week parallel-group treatment period.

    Arm title
    		 MEDl7352 Dose Level 2
    Arm description
    		 Participants received 6 doses of SC MEDl7352 Dose Level 2 injection Q2W during a 12-week parallel-group treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI7352
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Six doses of SC MEDl7352 Dose Level 2 Q2W given during a 12-week parallel-group treatment period.

    Arm title
    		 MEDl7352 Dose Level 3
    Arm description
    		 Participants received 6 doses of SC MEDl7352 Dose Level 3 injection Q2W during a 12-week parallel-group treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI7352
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Six doses of SC MEDl7352 Dose Level 3 Q2W given during a 12-week parallel-group treatment period.

    Arm title
    		 MEDl7352 Dose Level 4
    Arm description
    		 Participants received 6 doses of SC MEDl7352 Dose Level 4 injection Q2W during a 12-week parallel-group treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI7352
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Six doses of SC MEDl7352 Dose Level 4 Q2W given during a 12-week parallel-group treatment period.

    Arm title
    		 Placebo
    Arm description
    		 Participants received 6 doses of SC placebo injection matched to MEDl7352 Q2W during a 12-week parallel-group treatment period.
    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
    Six doses of SC placebo injection matched to MEDl7352 Q2W given during a 12-week parallel-group treatment period.

    Number of subjects in period 1
    		MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Started
    70
    68
    69
    68
    70
    Treated
    70
    68
    69
    68
    69
    Completed
    59
    64
    65
    57
    61
    Not completed
    11
    4
    4
    11
    9
         Consent withdrawn by subject
    9
    3
    4
    8
    6
         Lost to follow-up
    1
    1
    -
    2
    -
         Protocol deviation
    1
    -
    -
    1
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MEDl7352 Dose Level 1
    Reporting group description
    		 Participants received 6 doses of subcutaneous (SC) MEDl7352 Dose Level 1 injection once every 2 weeks (Q2W) during a 12-week parallel-group treatment period.

    Reporting group title
    MEDl7352 Dose Level 2
    Reporting group description
    		 Participants received 6 doses of SC MEDl7352 Dose Level 2 injection Q2W during a 12-week parallel-group treatment period.

    Reporting group title
    MEDl7352 Dose Level 3
    Reporting group description
    		 Participants received 6 doses of SC MEDl7352 Dose Level 3 injection Q2W during a 12-week parallel-group treatment period.

    Reporting group title
    MEDl7352 Dose Level 4
    Reporting group description
    		 Participants received 6 doses of SC MEDl7352 Dose Level 4 injection Q2W during a 12-week parallel-group treatment period.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received 6 doses of SC placebo injection matched to MEDl7352 Q2W during a 12-week parallel-group treatment period.

    Reporting group values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo Total
    Number of subjects
    		 70 68 69 68 70 345
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0
        Adults (18-64 years)
    		 32 33 40 38 42 185
        From 65-84 years
    		 38 35 29 30 28 160
        85 years and over
    		 0 0 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 65.8 ( 7.90 ) 63.3 ( 7.73 ) 63.8 ( 6.91 ) 63.3 ( 7.52 ) 62.5 ( 8.03 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 43 51 48 46 42 230
        Male
    		 27 17 21 22 28 115
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0
        Asian
    		 0 1 2 3 3 9
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0
        Black or African American
    		 0 0 0 0 0 0
        White
    		 69 66 67 65 67 334
        More than one race
    		 0 0 0 0 0 0
        Unknown or Not Reported
    		 1 1 0 0 0 2
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 1 1 2 1 0 5
        Not Hispanic or Latino
    		 69 67 67 67 70 340
        Unknown or Not Reported
    		 0 0 0 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    MEDl7352 Dose Level 1
    Reporting group description
    		 Participants received 6 doses of subcutaneous (SC) MEDl7352 Dose Level 1 injection once every 2 weeks (Q2W) during a 12-week parallel-group treatment period.

    Reporting group title
    MEDl7352 Dose Level 2
    Reporting group description
    		 Participants received 6 doses of SC MEDl7352 Dose Level 2 injection Q2W during a 12-week parallel-group treatment period.

    Reporting group title
    MEDl7352 Dose Level 3
    Reporting group description
    		 Participants received 6 doses of SC MEDl7352 Dose Level 3 injection Q2W during a 12-week parallel-group treatment period.

    Reporting group title
    MEDl7352 Dose Level 4
    Reporting group description
    		 Participants received 6 doses of SC MEDl7352 Dose Level 4 injection Q2W during a 12-week parallel-group treatment period.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received 6 doses of SC placebo injection matched to MEDl7352 Q2W during a 12-week parallel-group treatment period.

    Primary: Change From Baseline in Weekly Average of Daily Numerical Rating Scale (NRS) Pain Score to Week 12

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    End point title
    		 Change From Baseline in Weekly Average of Daily Numerical Rating Scale (NRS) Pain Score to Week 12
    End point description
    Change from baseline in weekly average of daily NRS pain score to Week 12 is reported. The NRS is an 11-point Likert scale used to assess pain, where participants were asked to describe their average pain in the target knee by identifying a number from 0 = “no pain” to 10 = “most severe pain imaginable over the previous 24 hours”. This was recorded on a daily basis at approximately the same time every morning via electronic patient recorded outcome (ePRO) diary. A two-step multiple imputation procedure was used to address missing post-baseline scores. Full analysis set (FAS) included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received.
    End point type
    Primary
    End point timeframe
    Baseline (Day -7 to Day -1, inclusive) through Week 12
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    70
    68
    69
    68
    70
    Units: Units on a scale
        arithmetic mean (standard deviation)
    -2.19 ( 2.243 )
    -3.00 ( 2.342 )
    -2.83 ( 2.522 )
    -2.81 ( 2.835 )
    -2.35 ( 2.364 )
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Least Square (LS) mean and treatment group difference with associated 95% confidence intervals (CIs) are modelled using ANCOVA on imputed data including treatment group, baseline score and Kellgren and Lawrence (KL) grade.
    Comparison groups
    MEDl7352 Dose Level 1 v Placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.36
    Method
    		 ANCOVA
    Parameter type
    		 Combined estimate for LS mean
    Point estimate
    -0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.968
         upper limit
    		 0.67
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.416
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Least Square mean and treatment group difference with associated 95% CIs are modelled using ANCOVA on imputed data including treatment group, baseline score and KL grade.
    Comparison groups
    MEDl7352 Dose Level 2 v Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.029
    Method
    		 ANCOVA
    Parameter type
    		 Combined estimate for LS mean
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.619
         upper limit
    		 0.027
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.418
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Least Square mean and treatment group difference with associated 95% CIs are modelled using ANCOVA on imputed data including treatment group, baseline score and KL grade.
    Comparison groups
    MEDl7352 Dose Level 3 v Placebo
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.026
    Method
    		 ANCOVA
    Parameter type
    		 Combined estimate for LS mean
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.618
         upper limit
    		 0.009
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.413
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Least Square mean and treatment group difference with associated 95% CIs are modelled using ANCOVA on imputed data including treatment group, baseline score and KL grade.
    Comparison groups
    MEDl7352 Dose Level 4 v Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.083
    Method
    		 ANCOVA
    Parameter type
    		 Combined estimate for LS mean
    Point estimate
    -0.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.423
         upper limit
    		 0.245
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.424

    Secondary: Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale to Week 12

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    End point title
    		 Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale to Week 12
    End point description
    The WOMAC multiscale index is used to assess pain, stiffness, and joint functionality in the past 48 hours in participants with OA of the knee or hip. The WOMAC pain subscale consists of 5 questions assessing the participant's pain due to osteoarthritis (OA) in the target knee. Each question was scored on a NRS scale from 0 to 10, and the WOMAC pain subscale score is calculated as the mean score from all 5 questions, where higher scores represent higher pain. A two-step multiple imputation procedure was used to address missing post-baseline scores. Change from baseline in WOMAC pain subscale to Week 12 is reported. FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received.
    End point type
    Secondary
    End point timeframe
    Week 0 (Day 1; baseline) through Week 12
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    70
    68
    69
    68
    70
    Units: Units on a scale
        arithmetic mean (standard deviation)
    -1.88 ( 2.047 )
    -2.88 ( 2.407 )
    -2.62 ( 2.305 )
    -2.57 ( 2.992 )
    -2.62 ( 2.558 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in WOMAC Physical Function Subscale to Week 12

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    End point title
    		 Change From Baseline in WOMAC Physical Function Subscale to Week 12
    End point description
    The WOMAC multiscale index is used to assess pain, stiffness, and joint functionality in the past 48 hours in participants with OA of the knee or hip. The WOMAC physical function (PF) subscale consists of 17 questions assessing the participant’s difficulty in performing activities of daily living due to OA in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC PF subscale score is calculated as the mean score from all 17 questions, where higher scores represent worse function. A two-step multiple imputation procedure was used to address missing post-baseline scores. Change from baseline in WOMAC physical function to Week 12 is reported. FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received.
    End point type
    Secondary
    End point timeframe
    Week 0 (Day 1; baseline) through Week 12
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    70
    68
    69
    68
    70
    Units: Units on a scale
        arithmetic mean (standard deviation)
    -1.48 ( 2.233 )
    -2.56 ( 2.352 )
    -2.45 ( 1.909 )
    -2.22 ( 2.887 )
    -2.14 ( 2.338 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Patient's Global Assessment (PGA) of OA to Week 12

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    End point title
    		 Change From Baseline in Patient's Global Assessment (PGA) of OA to Week 12
    End point description
    The PGA of OA was a 5-point Likert scale used to assess symptoms and activity impairment due to OA of the knee. Participants were asked to identify a number from 1 = “very good (asymptomatic and no limitation to normal activities)” to 5 = “very poor (very severe symptoms which are intolerable and inability to carry out all normal activities)” based on the question “Considering all the ways that OA of the knee affects you, how are you feeling today?”. A two-step multiple imputation procedure was used to address missing post-baseline scores. Change from baseline in PGA of OA to Week 12 is reported. FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received.
    End point type
    Secondary
    End point timeframe
    Week 0 (Day 1; baseline) through Week 12
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    70
    68
    69
    68
    70
    Units: Units on a scale
        arithmetic mean (standard deviation)
    -0.34 ( 0.933 )
    -0.72 ( 1.123 )
    -0.81 ( 1.032 )
    -0.69 ( 1.377 )
    -0.57 ( 1.003 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in WOMAC Pain Subscale Over Time

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    End point title
    		 Change From Baseline in WOMAC Pain Subscale Over Time
    End point description
    The WOMAC multiscale index is used to assess pain, stiffness, and joint functionality in the past 48 hours in participants with OA of the knee or hip. The WOMAC pain subscale consists of 5 questions assessing the participant's pain due to OA in the target knee. Each question was scored on an NRS scale from 0 to 10, and the WOMAC pain subscale score is calculated as the mean score from all 5 questions, where higher scores represent higher pain. Change from baseline in WOMAC pain subscale to Weeks 2,4,6, 8, 10, and 18 is reported. FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this endpoint. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), and 18 (Day 126)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    63
    63
    63
    65
    61
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Week 2(n=63,63,63,65,58)
    -1.32 ( 1.501 )
    -1.79 ( 1.988 )
    -1.58 ( 1.571 )
    -1.88 ( 1.953 )
    -1.30 ( 1.968 )
        Week 4(n=57,61,60,59,61)
    -1.62 ( 1.635 )
    -2.33 ( 2.230 )
    -2.41 ( 1.939 )
    -2.60 ( 2.077 )
    -2.08 ( 2.000 )
        Week 6(n=59,61,57,56,55)
    -2.01 ( 1.541 )
    -2.76 ( 2.223 )
    -2.73 ( 1.852 )
    -3.07 ( 2.065 )
    -2.40 ( 2.114 )
        Week 8(n=54,56,57,49,46)
    -2.01 ( 1.840 )
    -2.96 ( 2.259 )
    -2.91 ( 1.954 )
    -3.33 ( 1.964 )
    -2.56 ( 2.431 )
        Week 10(n=53,56,52,48,46)
    -2.14 ( 1.886 )
    -3.22 ( 2.282 )
    -2.89 ( 2.052 )
    -3.54 ( 2.055 )
    -2.89 ( 2.283 )
        Week 18(n=45,51,51,39,43)
    -2.00 ( 2.090 )
    -3.02 ( 2.388 )
    -2.61 ( 2.107 )
    -3.50 ( 1.988 )
    -2.97 ( 2.219 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in WOMAC PF Subscale Over Time

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    End point title
    		 Change From Baseline in WOMAC PF Subscale Over Time
    End point description
    The WOMAC multiscale index is used to assess pain, stiffness, and joint functionality in the past 48 hours in participants with OA of the knee or hip. The WOMAC PF subscale consists of 17 questions assessing the participant’s difficulty in performing activities of daily living due to OA in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC PF subscale score is calculated as the mean score from all 17 questions, where higher scores represent worse function. Change from baseline in WOMAC physical function to Weeks 2,4,6, 8, 10, and 18 is reported. FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this endpoint. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), and 18 (Day 126)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    63
    63
    63
    65
    61
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Week 2(n=63,63,63,65,58)
    -1.06 ( 1.621 )
    -1.64 ( 1.877 )
    -1.56 ( 1.417 )
    -1.80 ( 1.778 )
    -0.96 ( 1.728 )
        Week 4(n=57,61,60,59,61)
    -1.59 ( 1.812 )
    -2.07 ( 1.933 )
    -2.20 ( 1.701 )
    -2.39 ( 2.062 )
    -1.62 ( 1.708 )
        Week 6(n=59,61,57,56,55)
    -1.77 ( 1.670 )
    -2.43 ( 1.946 )
    -2.43 ( 1.436 )
    -2.71 ( 2.001 )
    -1.92 ( 1.945 )
        Week 8(n=54,56,57,49,46)
    -1.64 ( 1.856 )
    -2.82 ( 1.960 )
    -2.68 ( 1.792 )
    -3.06 ( 1.858 )
    -2.06 ( 2.114 )
        Week 10(n=53,56,52,48,46)
    -1.74 ( 1.994 )
    -2.85 ( 1.944 )
    -2.65 ( 1.671 )
    -3.30 ( 1.979 )
    -2.26 ( 2.063 )
        Week 18(n=45,51,51,39,43)
    -1.55 ( 2.267 )
    -2.71 ( 2.141 )
    -2.37 ( 1.722 )
    -3.17 ( 1.812 )
    -2.24 ( 1.810 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in WOMAC Overall Score Over Time

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    End point title
    		 Change From Baseline in WOMAC Overall Score Over Time
    End point description
    The WOMAC overall score consisted of all 24 questions reported in the WOMAC questionnaire to assess: i) pain subscale, ii) PF subscale and iii) stiffness subscale. WOMAC overall score was calculated as the mean score from all 24 questions each scored on a Likert scale from 0 to 10 where higher scores represent worse outcome. FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this endpoint. Number analyzed (n) denotes those participants who were evaluable at the specified time point. Change from baseline in weekly average of WOMAC overall score to Weeks 2, 4, 6, 8, 10, 12, and 18 is reported.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), and 18 (Day 126)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    64
    63
    64
    65
    61
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Week 2(n=64,63,64,65,58)
    -1.11 ( 1.546 )
    -1.71 ( 1.836 )
    -1.58 ( 1.343 )
    -1.88 ( 1.735 )
    -1.04 ( 1.695 )
        Week 4(n=58,61,60,59,61)
    -1.66 ( 1.706 )
    -2.14 ( 1.958 )
    -2.25 ( 1.667 )
    -2.45 ( 2.000 )
    -1.74 ( 1.671 )
        Week 6(n=59,62,57,57,56)
    -1.85 ( 1.583 )
    -2.54 ( 1.968 )
    -2.52 ( 1.426 )
    -2.79 ( 1.951 )
    -1.98 ( 1.984 )
        Week 8(n=54,56,58,49,46)
    -1.75 ( 1.792 )
    -2.85 ( 1.995 )
    -2.69 ( 1.757 )
    -3.12 ( 1.822 )
    -2.19 ( 2.102 )
        Week 10(n=53,56,52,48,46)
    -1.86 ( 1.907 )
    -2.94 ( 1.995 )
    -2.72 ( 1.663 )
    -3.35 ( 1.954 )
    -2.43 ( 2.022 )
        Week 12(n=47,54,52,41,42)
    -1.82 ( 1.945 )
    -3.00 ( 2.087 )
    -2.76 ( 1.616 )
    -3.48 ( 2.121 )
    -2.56 ( 1.956 )
        Week 18(n=45,51,51,39,43)
    -1.68 ( 2.148 )
    -2.78 ( 2.153 )
    -2.46 ( 1.718 )
    -3.24 ( 1.784 )
    -2.42 ( 1.767 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in WOMAC Stiffness Scores Over Time

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    End point title
    		 Change From Baseline in WOMAC Stiffness Scores Over Time
    End point description
    The WOMAC stiffness function subscale consists of 2 questions assessing stiffness due to OA in the target knee. Stiffness is defined as a sensation of decreased ease of movement in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC stiffness function subscale score is calculated as the mean score from the 2 questions, where higher scores represent higher stiffness. Change from baseline in WOMAC stiffness score to Weeks 2, 4, 6, 8, 10, 12, and 18 is reported. FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this endpoint. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), and 18 (Day 126)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    64
    63
    64
    65
    61
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Week 2(n=64,63,64,65,58)
    -1.30 ( 1.887 )
    -2.06 ( 2.015 )
    -1.85 ( 1.927 )
    -2.13 ( 2.020 )
    -0.99 ( 1.805 )
        Week 4(n=58,61,60,59,61)
    -1.88 ( 1.938 )
    -2.26 ( 2.146 )
    -2.33 ( 2.127 )
    -2.55 ( 2.368 )
    -1.91 ( 2.009 )
        Week 6(n=59,62,57,57,56)
    -2.13 ( 1.837 )
    -2.79 ( 2.307 )
    -2.72 ( 1.871 )
    -2.97 ( 2.428 )
    -2.27 ( 2.314 )
        Week 8(n=54,56,58,49,46)
    -1.99 ( 2.125 )
    -2.85 ( 2.260 )
    -2.85 ( 2.103 )
    -3.07 ( 2.104 )
    -2.39 ( 2.633 )
        Week 10(n=53,56,52,48,46)
    -2.13 ( 2.060 )
    -2.99 ( 2.277 )
    -2.96 ( 1.977 )
    -3.29 ( 2.091 )
    -2.67 ( 2.329 )
        Week 12(n=47,54,52,41,42)
    -2.29 ( 2.034 )
    -3.06 ( 2.380 )
    -3.06 ( 2.040 )
    -3.43 ( 2.407 )
    -2.85 ( 2.372 )
        Week 18(n=45,51,51,39,43)
    -2.04 ( 2.192 )
    -2.76 ( 2.401 )
    -2.86 ( 1.988 )
    -3.17 ( 1.797 )
    -2.62 ( 2.152 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in PGA of OA Over Time

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    End point title
    		 Change From Baseline in PGA of OA Over Time
    End point description
    The PGA of OA was a 5-point Likert scale used to assess symptoms and activity impairment due to OA of the knee. Participants were asked to identify a number from 1 = “very good (asymptomatic and no limitation to normal activities)” to 5 = “very poor (very severe symptoms which are intolerable and inability to carry out all normal activities)” based on the question “Considering all the ways that OA of the knee affects you, how are you feeling today?”. Change from baseline in PGA of OA to Weeks 2, 4, 8, 10, and 18 is reported. FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants who were evaluable for the specified endpoint. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 10 (Day 70), and 18 (Day 126)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    62
    62
    60
    65
    60
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Week 2(n=62,62,60,65,57)
    -0.35 ( 0.812 )
    -0.56 ( 0.917 )
    -0.67 ( 0.933 )
    -0.42 ( 1.059 )
    -0.37 ( 0.698 )
        Week 4(n=56,60,57,59,60)
    -0.48 ( 0.738 )
    -0.68 ( 1.066 )
    -0.86 ( 1.043 )
    -0.86 ( 1.106 )
    -0.48 ( 0.792 )
        Week 8(n=53,55,54,49,45)
    -0.57 ( 0.910 )
    -0.80 ( 1.026 )
    -1.02 ( 1.090 )
    -1.04 ( 1.098 )
    -0.51 ( 0.843 )
        Week 10(n=52,55,49,48,45)
    -0.42 ( 0.723 )
    -0.76 ( 0.922 )
    -1.02 ( 1.010 )
    -1.06 ( 1.295 )
    -0.67 ( 0.826 )
        Week 18(n=44,50,48,39,43)
    -0.39 ( 0.655 )
    -0.66 ( 1.022 )
    -0.83 ( 1.117 )
    -1.10 ( 1.294 )
    -0.56 ( 0.700 )
    No statistical analyses for this end point

    Secondary: Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition

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    End point title
    		 Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition
    End point description
    OMERACT-OARSI responder index is calculated from WOMAC Pain subscale, WOMAC PF Subscale and PGA of OA. A participant is classified as responder if: 1. >=2-point absolute change from Baseline to Week X or >=50% improvement is reported in WOMAC pain or PF subscales; 2. At least 2 of following 3 conditions are true: >=1-point absolute change from Baseline to Week X or >=20% improvement is reported in WOMAC Pain subscale, >=1-point absolute change from Baseline to Week X or >=20% improvement is reported in WOMAC PF subscale or >=1-point absolute change from Baseline to Week X in PGA of OA. Percentage of responder participants are reported. FAS: all randomized participants analyzed according to intent-to-treat principle whereby randomized study treatment will be analyzed regardless of study treatment actually received. Number of participants analyzed (N): participants evaluated for this endpoint. Number analyzed (n): participants who were evaluable at the specified time point.
    End point type
    Secondary
    End point timeframe
    Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    65
    64
    68
    67
    65
    Units: Percentage of participants
    number (not applicable)
        Week 2(n=65,64,68,67,64)
    47.7
    62.5
    61.8
    59.7
    40.6
        Week 4(n=59,62,64,61,65)
    59.3
    67.7
    73.4
    65.6
    63.1
        Week 8(n=56,57,60,51,51)
    58.9
    80.7
    80.0
    86.3
    68.6
        Week 12(n=49,55,55,42,46)
    59.2
    80.0
    80.0
    85.7
    67.4
        Week 18(n=47,52,54,41,47)
    55.3
    78.8
    72.2
    80.5
    70.2
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Improvement of >= 2 points in PGA of OA

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    End point title
    		 Percentage of Participants With Improvement of >= 2 points in PGA of OA
    End point description
    The PGA of OA was a 5-point Likert scale used to assess symptoms and activity impairment due to OA of the knee. Participants were asked to identify a number from 1 = “very good (asymptomatic and no limitation to normal activities)” to 5 = “very poor (very severe symptoms which are intolerable and inability to carry out all normal activities)” based on the question “Considering all the ways that OA of the knee affects you, how are you feeling today?”. Percentage of participants with improvement of >= 2 points in PGA of OA at Weeks 2, 4, 8, 12, and 18 is reported. FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this endpoint. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
    End point type
    Secondary
    End point timeframe
    Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    62
    62
    60
    65
    60
    Units: Percentage of participants
    number (not applicable)
        Week 2(n=62,62,60,65,57)
    9.7
    9.7
    16.7
    12.3
    7.0
        Week 4(n=56,60,57,59,60)
    8.9
    26.7
    24.6
    22.0
    6.7
        Week 8(n=53,55,54,49,45)
    17.0
    23.6
    25.9
    28.6
    4.4
        Week 12(n=46,53,49,40,41)
    10.9
    18.9
    20.4
    32.5
    7.3
        Week 18(n=44,50,48,39,43)
    2.3
    20.0
    22.9
    25.6
    4.7
    No statistical analyses for this end point

    Secondary: Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time

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    End point title
    		 Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time
    End point description
    The NRS is an 11-point Likert scale used to assess pain, where participants were asked to describe their average pain in the target knee by identifying a number from 0 = “no pain” to 10 = “most severe pain imaginable over the previous 24 hours”. This will be recorded on a daily basis at approximately the same time every morning via ePRO diary. Change from baseline in weekly average of daily NRS to Weeks 2, 4, 6, 8, 10, and 18 is reported. FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this endpoint. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -7 to Day -1, inclusive), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), and 18 (Day 126)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    66
    64
    65
    66
    65
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Week 2(n=66,64,65,66,65)
    -1.62 ( 1.704 )
    -1.86 ( 1.949 )
    -1.97 ( 2.012 )
    -2.26 ( 2.129 )
    -1.10 ( 1.811 )
        Week 4(n=61,64,64,65,64)
    -1.88 ( 1.653 )
    -2.50 ( 2.163 )
    -2.68 ( 2.177 )
    -2.65 ( 2.333 )
    -1.66 ( 1.854 )
        Week 6(n=62,63,61,57,58)
    -2.17 ( 1.687 )
    -2.83 ( 2.248 )
    -3.00 ( 2.192 )
    -3.35 ( 2.498 )
    -1.97 ( 2.020 )
        Week 8(n=55,59,61,52,52)
    -2.27 ( 1.736 )
    -2.91 ( 2.084 )
    -3.09 ( 2.205 )
    -3.45 ( 2.365 )
    -2.18 ( 2.274 )
        Week 10(n=55,55,56,51,46)
    -2.38 ( 2.001 )
    -3.18 ( 1.930 )
    -3.24 ( 2.294 )
    -3.57 ( 2.274 )
    -2.28 ( 2.047 )
        Week 18(n=42,48,52,38,44)
    -2.08 ( 2.120 )
    -3.18 ( 2.237 )
    -2.90 ( 2.157 )
    -3.63 ( 2.383 )
    -2.45 ( 1.969 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time

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    End point title
    		 Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time
    End point description
    The NRS is an 11-point Likert scale used to assess pain, where participants were asked to describe their average pain in the target knee by identifying a number from 0 = “no pain” to 10 = “most severe pain imaginable over the previous 24 hours”. This will be recorded on a daily basis at approximately the same time every morning via ePRO diary. Percentage of participants with >= 30% and >= 50% reductions in weekly average of daily NRS pain score are reported. FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this endpoint. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -7 to Day -1, inclusive), Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    66
    64
    65
    66
    65
    Units: Percentage of participants
    number (not applicable)
        >=30%: Week 2(n=66,64,65,66,65)
    34.8
    34.4
    41.5
    43.9
    21.5
        >=30%: Week 4(n=61,64,64,65,64)
    47.5
    50.0
    64.1
    53.8
    29.7
        >=30%: Week 8(n=55,59,61,52,52)
    56.4
    67.8
    67.2
    61.5
    42.3
        >=30%: Week 12(n=50,55,55,44,46)
    58.0
    76.4
    65.5
    72.7
    47.8
        >=30%: Week 18(n=42,48,52,38,44)
    42.9
    72.9
    67.3
    65.8
    54.5
        >=50%: Week 2(n=66,64,65,66,65)
    15.2
    25.0
    29.2
    30.3
    13.8
        >=50%: Week 4(n=61,64,64,65,64)
    24.6
    32.8
    40.6
    36.9
    15.6
        >=50%: Week 8(n=55,59,61,52,52)
    32.7
    45.8
    54.1
    57.7
    26.9
        >=50%: Week 12(n=50,55,55,44,46)
    44.0
    54.5
    49.1
    54.5
    26.1
        >=50%: Week 18(n=42,48,52,38,44)
    26.2
    54.2
    50.0
    52.6
    29.5
    No statistical analyses for this end point

    Secondary: Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time

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    End point title
    		 Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time
    End point description
    The WOMAC multiscale index is used to assess pain, stiffness, and joint functionality in the past 48 hours in participants with OA of the knee or hip. The WOMAC pain subscale consists of 5 questions assessing the participant's pain due to OA in the target knee. Each question was scored on an NRS scale from 0 to 10, and the WOMAC pain subscale score is calculated as the mean score from all 5 questions, where higher scores represent higher pain. Percentage of participants with >= 30% and >= 50% reductions in WOMAC pain subscale score over time are reported. FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this endpoint. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    63
    63
    63
    65
    61
    Units: Percentage of participants
    number (not applicable)
        >=30%: Week 2(n=63,63,63,65,58)
    30.2
    39.7
    36.5
    50.8
    24.1
        >=30%: Week 4(n=57,61,60,59,61)
    40.4
    54.1
    61.7
    61.0
    47.5
        >=30%: Week 8(n=54,56,57,49,46)
    55.6
    64.3
    64.9
    71.4
    56.5
        >=30%: Week 12(n=47,54,52,40,42)
    59.6
    68.5
    67.3
    75.0
    66.7
        >=30%: Week 18(n=45,51,51,39,43)
    51.1
    70.6
    62.7
    76.9
    69.8
        >=50%: Week 2(n=63,63,63,65,58)
    14.3
    23.8
    17.5
    33.8
    10.3
        >=50%: Week 4(n=57,61,60,59,61)
    24.6
    31.1
    40.0
    55.9
    26.2
        >=50%: Week 8(n=54,56,57,49,46)
    35.2
    46.4
    49.1
    57.1
    34.8
        >=50%: Week 12(n=47,54,52,40,42)
    31.9
    51.9
    50.0
    62.5
    42.9
        >=50%: Week 18(n=45,51,51,39,43)
    33.3
    51.0
    43.1
    59.0
    41.9
    No statistical analyses for this end point

    Secondary: Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time

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    End point title
    		 Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time
    End point description
    The WOMAC PF subscale consists of 17 questions assessing the participant’s difficulty in performing activities of daily living due to OA in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC PF subscale score is calculated as the mean score from all 17 questions, where higher scores represent worse function. Percentage of participants with >= 30% and >= 50% reductions in WOMAC physical function subscale over time are reported. FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this endpoint. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    63
    63
    63
    65
    61
    Units: Percentage of participants
    number (not applicable)
        >=30%: Week 2(n=63,63,63,65,58)
    30.2
    42.9
    39.7
    47.7
    22.4
        >=30%: Week 4(n=57,61,60,59,61)
    47.4
    52.5
    61.7
    59.3
    37.7
        >=30%: Week 8(n=54,56,57,49,46)
    50.0
    64.3
    63.2
    69.4
    47.8
        >=30%: Week 12(n=47,54,52,40,42)
    42.6
    72.2
    67.3
    72.5
    54.8
        >=30%: Week 18(n=45,51,51,39,43)
    42.2
    72.5
    64.7
    74.4
    60.5
        >=50%: Week 2(n=63,63,63,65,58)
    14.3
    22.2
    23.8
    33.8
    12.1
        >=50%: Week 4(n=57,61,60,59,61)
    28.1
    31.1
    41.7
    54.2
    19.7
        >=50%: Week 8(n=54,56,57,49,46)
    33.3
    51.8
    47.4
    57.1
    26.1
        >=50%: Week 12(n=47,54,52,40,42)
    34.0
    46.3
    50.0
    62.5
    35.7
        >=50%: Week 18(n=45,51,51,39,43)
    33.3
    45.1
    39.2
    59.0
    34.9
    No statistical analyses for this end point

    Secondary: Serum Concentration of MEDI7352

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    End point title
    		 Serum Concentration of MEDI7352 [1]
    End point description
    Serum concentration of MEDI7352 is reported. Pharmacokinetic (PK) analysis set included participants who received at least one dose of double-blind study treatment per the protocol for whom any post-baseline PK data are available and who did not violate or deviate from the protocol in ways that would significantly affect the PK analyses. The arbitrary numbers 99.999 and 99999 signified mean and standard deviation, respectively, not reported as the Geometric mean and geometric CV% were not calculated as samples were lost (unfrozen) during shipment. Number of participants analyzed (N) denotes those participants who were analyzed for this endpoint. Number analyzed (n) denotes those participants who had adequate serum samples.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Day 7; pre-dose on Days 14, 28, 42, 56, and 70; and on Days 74, 77, 84, 126, and 224
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4
    Number of subjects analysed
    70
    68
    67
    68
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Day 1(n=0,0,0,0)
    99.999 ( 99999 )
    99.999 ( 99999 )
    99.999 ( 99999 )
    99.999 ( 99999 )
        Day 7(n=63,62,66,65)
    326.863 ( 98.989 )
    681.322 ( 159.914 )
    2149.062 ( 109.2763 )
    3582.265 ( 364.200 )
        Day 14(n=65,63,67,67)
    50.337 ( 538.604 )
    144.242 ( 475.607 )
    379.882 ( 488.933 )
    650.864 ( 624.642 )
        Day 28(n=57,58,62,56)
    11.025 ( 853.538 )
    28.332 ( 2745.856 )
    43.644 ( 6705.491 )
    222.665 ( 3963.855 )
        Day 42(n=55,54,59,50)
    5.895 ( 846.517 )
    12.375 ( 2578.767 )
    30.005 ( 11978.840 )
    116.951 ( 14993.947 )
        Day 56(n=0,53,58,51)
    99.999 ( 99999 )
    6.625 ( 2133.678 )
    20.546 ( 13626.951 )
    85.779 ( 15987.305 )
        Day 70(n=0,0,55,44)
    99.999 ( 99999 )
    99999 ( 99999 )
    17.124 ( 15147.088 )
    57.042 ( 18183.372 )
        Day 74(n=48,53,55,42)
    10.943 ( 1833.135 )
    22.074 ( 4305.129 )
    116.544 ( 25316.322 )
    551.099 ( 18558.506 )
        Day 77(n=45,50,52,44)
    5.011 ( 1322.708 )
    9.356 ( 3099.752 )
    47.108 ( 39692.068 )
    271.511 ( 36387.885 )
        Day 84(n=0,0,56,45)
    99.999 ( 99999 )
    99.999 ( 99999 )
    10.482 ( 6086.596 )
    43.062 ( 13640.856 )
        Day 126(n=0,0,0,0)
    99.999 ( 99999 )
    99.999 ( 99999 )
    99.999 ( 99999 )
    99.999 ( 99999 )
        Day 224(n=0,0,0,0)
    99.999 ( 99999 )
    99.999 ( 99999 )
    99.999 ( 99999 )
    99.999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352

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    End point title
    		 Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352
    End point description
    Number of participants with ADA to MEDI7352 are reported. Treatment-induced ADA positive: ADA negative at baseline (Bl) and positive at least 1 post-BL ADA assessment. Treatment-boosted ADA positive: ADA positive at BL, and BL titre is boosted by greater than variability of assay at >=1 post-BL timepoint. Persistent positive: ADA negative at BL and having at least 2 post-BL ADA positive results (>=16 weeks between first and last positive)/ADA positive at last post-BL test. Transiently positive: ADA negative at BL and at least 1 post-BL ADA positive measurement and not fulfilling conditions for persistently positive. ADA evaluable participants included all participants in safety analysis set who have non-missing BL and at least 1 non-missing post-BL ADA results. Number of participants analyzed (N): number of participants who were evaluable for specified endpoint. No. analyzed (n): participants who had adequate ADA sample.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Day 7; pre-dose on Days 14, 28, 42, 56, and 70; and on Days 74, 77, 84, 126, and 224
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    70
    68
    66
    67
    67
    Units: Participants
        Treatment-induced ADA positive
    52
    49
    42
    52
    6
        Treatment-boosted ADA positive
    6
    9
    8
    2
    2
        Persistent positive ADA
    43
    39
    33
    42
    4
        Transiently positive ADA
    9
    10
    9
    10
    2
    No statistical analyses for this end point

    Secondary: ADA Titre in Participants who were ADA Positive at Baseline and/or Post-baseline

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    End point title
    		 ADA Titre in Participants who were ADA Positive at Baseline and/or Post-baseline
    End point description
    The ADA titre in participants who were ADA positive at baseline and/or post-baseline is reported. ADA evaluable participants included all participants in safety analysis set who have non-missing baseline and at least 1 non-missing post-baseline ADA results. Number of participants analyzed (N): number of participants who were ADA positive at baseline and/or post-baseline. Number analyzed (n): participants who had adequate ADA sample.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Day 7; pre-dose on Days 14, 28, 42, 56, and 70; and on Days 74, 77, 84, 126, and 224
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    61
    59
    52
    54
    19
    Units: Ratio
        median (full range (min-max))
    960.0 (30 to 122880)
    960.0 (30 to 245760)
    960.0 (30 to 15360)
    720.0 (30 to 122880)
    240.0 (30 to 3840)
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

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    End point title
    		 Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
    End point description
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Day 1 through 41 weeks (maximum observed duration)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    70
    68
    69
    68
    69
    Units: Participants
        Any TEAEs
    51
    45
    54
    51
    41
        Any TESAEs
    3
    5
    3
    1
    2
    No statistical analyses for this end point

    Secondary: Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs

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    End point title
    		 Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs
    End point description
    Number of participants with clinically significant findings in physical examination reported as TEAE are reported. A physical examination included assessments of general appearance, skin, head and neck, examination of the oral cavity for any lesions, lymph nodes, thyroid, abdomen (bowel sounds, liver, and spleen palpation), back (including costovertebral angle tenderness), musculoskeletal/extremities, cardiovascular, and respiratory systems. Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Day 1 through 41 weeks (maximum observed duration)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    70
    68
    69
    68
    69
    Units: Participants
    0
    0
    0
    1
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination

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    End point title
    		 Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination
    End point description
    Number of participants with clinically significant abnormal findings in neurological examination is reported. The neurological examination included assessment of mental status, cranial nerves, motor examination (muscle strength and tone), upper and lower extremity deep tendon reflexes, plantar responses, sensory system examination, coordination, and gait. Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -45 to Day -1), Weeks 0 (Day 1), 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), 18 (Day 126), 28 (Day 168), 32 (Day 224), and 36 (Day 252)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    70
    68
    69
    68
    69
    Units: Participants
        Baseline
    0
    0
    0
    0
    0
        Week 0
    0
    0
    0
    0
    0
        Week 2
    1
    0
    0
    0
    0
        Week 4
    0
    0
    0
    0
    1
        Week 6
    0
    0
    0
    0
    0
        Week 8
    0
    0
    0
    0
    0
        Week 10
    0
    0
    0
    0
    0
        Week 12
    0
    0
    0
    1
    0
        Week 18
    0
    0
    0
    1
    0
        Week 28
    0
    0
    0
    1
    0
        Week 32
    0
    0
    0
    1
    0
        Week 36
    0
    0
    0
    2
    0
    No statistical analyses for this end point

    Secondary: Total Neuropathy Score-Nurse (TNSn) Over Time

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    End point title
    		 Total Neuropathy Score-Nurse (TNSn) Over Time
    End point description
    The TNSn, is a semiquantitative clinical assessment of peripheral nervous system function. The TNSn assessment is collected as scores of motor symptom, autonomic symptom, pin sensibility, sensory symptom, and vibration sensibility score. Each neuropathy item is scored on a 0 to 4 scale with total score ranging from 0 to 20. Higher total scores correlate with more severe neuropathy. Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this endpoint. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -45 to Day -1), Weeks 0 (Day 1), 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), 28 (Day 196), and 32 (Day 224)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    70
    66
    69
    68
    67
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Baseline(n=51,55,59,56,61)
    1.5 ( 2.40 )
    1.4 ( 1.94 )
    1.0 ( 1.56 )
    1.2 ( 1.69 )
    1.5 ( 2.02 )
        Week 0(n=70,66,69,68,67)
    1.3 ( 1.92 )
    1.7 ( 2.26 )
    1.4 ( 2.03 )
    1.5 ( 2.29 )
    1.8 ( 2.26 )
        Week 2(n=66,65,69,67,65)
    1.1 ( 1.84 )
    1.6 ( 2.42 )
    1.2 ( 1.97 )
    1.0 ( 1.70 )
    1.5 ( 2.18 )
        Week 4(n=61,64,64,64,65)
    1.0 ( 1.66 )
    1.3 ( 1.98 )
    0.9 ( 1.54 )
    0.9 ( 1.61 )
    1.4 ( 2.16 )
        Week 6(n=61,62,62,60,61)
    1.0 ( 1.55 )
    1.4 ( 2.23 )
    0.9 ( 1.73 )
    0.9 ( 1.48 )
    1.5 ( 2.51 )
        Week 8(n=56,57,62,52,52)
    1.0 ( 1.65 )
    1.1 ( 1.86 )
    0.6 ( 0.91 )
    0.8 ( 1.62 )
    1.2 ( 1.84 )
        Week 10(n=56,56,55,51,50)
    1.1 ( 1.85 )
    1.3 ( 2.06 )
    0.8 ( 1.53 )
    0.7 ( 1.20 )
    1.1 ( 2.10 )
        Week 12(n=48,58,59,52,49)
    0.9 ( 1.35 )
    1.2 ( 1.88 )
    0.8 ( 1.37 )
    0.7 ( 1.23 )
    1.1 ( 2.00 )
        Week 28(n=6,9,8,10,9)
    1.7 ( 2.25 )
    3.3 ( 2.69 )
    2.5 ( 2.83 )
    0.8 ( 0.92 )
    2.9 ( 2.67 )
        Week 32(n=41,49,51,43,48)
    1.5 ( 1.98 )
    1.0 ( 1.50 )
    0.5 ( 0.88 )
    0.9 ( 1.64 )
    1.0 ( 1.98 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Weight (kg) to Week 12

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    End point title
    		 Change From Baseline in Weight (kg) to Week 12
    End point description
    Change from baseline in weight (kg) to Week 12 is reported. Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Number of participants analyzed (N) denotes the number of participants evaluated at Week 12
    End point type
    Secondary
    End point timeframe
    Baseline (Day -45 to -1) and Week 12
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    66
    66
    65
    66
    64
    Units: kg
        arithmetic mean (standard deviation)
    -0.25 ( 2.048 )
    0.10 ( 2.343 )
    0.34 ( 1.932 )
    -0.03 ( 1.864 )
    -0.34 ( 2.004 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal Vital Signs Reported as TEAEs

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    End point title
    		 Number of Participants With Abnormal Vital Signs Reported as TEAEs
    End point description
    Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body temperature, supine and standing blood pressure, pulse rate, and respiratory rate). Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Day 1 through 41 weeks (maximum observed duration)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    70
    68
    69
    68
    69
    Units: Participants
        Bradycardia
    0
    0
    0
    0
    1
        Tachycardia
    1
    0
    0
    0
    0
        Tachycardia paroxysmal
    1
    0
    0
    0
    0
        Hypertension
    0
    2
    3
    0
    0
        Hypertensive crisis
    1
    0
    0
    0
    0
        Orthostatic hypotension
    1
    1
    1
    0
    1
        Pyrexia
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Change from Baseline in Survey of Autonomic Symptoms (SAS) Total Impact Score

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    End point title
    		 Change from Baseline in Survey of Autonomic Symptoms (SAS) Total Impact Score
    End point description
    SAS is an instrument that measures autonomic symptoms used for assessing autonomic neuropathies. It evaluates presence and severity of symptoms. SAS consists of 11 questions in women and 12 in men, with Yes/No answer to symptoms occurring 6 months prior to study drug administration. “Yes” responses further rated from 1 to 5 (1=not at all; 5=a lot) by asking participant how much each symptom is bothering, thus contributing to a total symptom impact score. Questions assess following domains: orthostatic intolerance [10 points (pts)]; vasomotor [6 pts]; secretomotor [7 pts]; gastrointestinal [28 pts]; bladder [9 pts]; pupillomotor [15 pts]. Higher score indicates worse autonomic dysfunction. Safety analysis set: participants who received at least 1 dose of any double-blind study drug and were analyzed according to received treatment. No. of participants analyzed (N): participants that are evaluable for specified endpoint. No. analyzed (n): participants who had adequate SAS impact score.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1; Week 0) and Day 252 (Week 36)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    40
    42
    44
    38
    44
    Units: Units on a scale
        arithmetic mean (standard deviation)
    -1.5 ( 4.78 )
    -1.1 ( 4.63 )
    -0.9 ( 4.13 )
    -1.6 ( 4.62 )
    -0.8 ( 3.50 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs)

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    End point title
    		 Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs)
    End point description
    Number of participants with clinically significant abnormal ECGs are reported. Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Number of participants analyzed (N) denotes the number of participants who were evaluable for the specified outcome measure. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
    End point type
    Secondary
    End point timeframe
    Weeks 0 (Day 1), 2 (Day 14), 4 (Day 28), 8 (Day 56), 10 (Day 70), 12 (Day 84), 28 (Day 168), and 32 (Day 224)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    70
    68
    69
    68
    69
    Units: Participants
        Week 0(n=70,68,69,68,69)
    0
    0
    0
    0
    0
        Week 2(n=66,64,68,68,66)
    0
    0
    0
    0
    0
        Week 4(n=62,63,63,60,64)
    0
    0
    0
    0
    0
        Week 8(n=55,57,60,52,49)
    0
    0
    0
    0
    0
        Week 10(n=54,55,56,48,50)
    0
    0
    0
    1
    0
        Week 12(n=66,66,67,65,65)
    0
    0
    0
    0
    0
        Week 28(n=8,10,11,10,9)
    0
    0
    0
    0
    0
        Week 32(n=48,50,54,45,49)
    0
    0
    1
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs

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    End point title
    		 Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
    End point description
    Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Day 1 through 41 weeks (maximum observed duration)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    70
    68
    69
    68
    69
    Units: Participants
        COVID-19
    16
    5
    10
    12
    8
        Anaemia
    0
    1
    1
    0
    0
        Leukopenia
    1
    0
    0
    0
    1
        Lymphopenia
    0
    0
    0
    1
    1
        Neutropenia
    0
    0
    0
    1
    1
        Hypercholesterolaemia
    1
    0
    1
    1
    0
        Hyperkalaemia
    0
    2
    0
    0
    0
        Hypertriglyceridaemia
    1
    0
    0
    2
    1
        Hypokalaemia
    0
    0
    1
    0
    1
        Hyponatraemia
    0
    0
    1
    0
    0
        Type 2 diabetes mellitus
    0
    0
    0
    0
    1
        Vitamin D deficiency
    0
    1
    0
    0
    0
        Glycosuria
    0
    1
    0
    0
    2
        Leukocyturia
    0
    2
    0
    0
    1
        Proteinuria
    0
    0
    2
    0
    2
        Activated partial thromboplastin time prolonged
    0
    0
    1
    0
    0
        Alanine aminotransferase increased
    0
    0
    0
    0
    1
        Aspartate aminotransferase increased
    0
    0
    0
    0
    1
        Blood creatine phosphokinase increased
    2
    1
    1
    0
    2
        Blood folate decreased
    1
    0
    0
    0
    0
        Blood glucose increased
    0
    1
    0
    1
    0
        Blood uric acid increased
    0
    0
    0
    1
    0
        C-reactive protein increased
    1
    0
    0
    1
    0
        Coagulation factor increased
    1
    0
    0
    0
    0
        Gamma-glutamyltransferase increased
    0
    1
    0
    0
    1
        Glycosylated haemoglobin increased
    1
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Change From Baseline in Weekly Average of Daily NRS Pain Score to Week 12 due to Baseline Biomarker C-reactive Protein

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    End point title
    		 Change From Baseline in Weekly Average of Daily NRS Pain Score to Week 12 due to Baseline Biomarker C-reactive Protein
    End point description
    Change from baseline in weekly average of daily NRS pain score to Week 12 due to baseline biomarker C-reactive protein is reported. The NRS is an 11-point Likert scale used to assess pain, where participants were asked to describe their average pain in the target knee by identifying a number from 0 = "no pain" to 10 = "most severe pain imaginable over the previous 24 hours". This was recorded on a daily basis at approximately the same time every morning via electronic patient recorded outcome (ePRO) diary. FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated at Week 12.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -7 to -1, inclusive) through Week 12
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    50
    55
    54
    43
    45
    Units: Units on a scale
        arithmetic mean (standard deviation)
    -2.55 ( 1.975 )
    -3.34 ( 2.004 )
    -3.30 ( 2.422 )
    -3.68 ( 2.313 )
    -2.38 ( 1.971 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Injection Site Reactions

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    End point title
    		 Number of Participants With Injection Site Reactions
    End point description
    Number of participants with injection site reactions are reported. Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Day 1 through 41 weeks (maximum observed duration)
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    70
    68
    69
    68
    69
    Units: Participants
    2
    3
    0
    4
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints

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    End point title
    		 Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints
    End point description
    Number of participants with abnormal X-ray and/or MRI of large joints is reported. Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -45 to -1) and Week 32
    End point values
    		 MEDl7352 Dose Level 1 MEDl7352 Dose Level 2 MEDl7352 Dose Level 3 MEDl7352 Dose Level 4 Placebo
    Number of subjects analysed
    70
    68
    69
    68
    69
    Units: Participants
        X-ray
    1
    0
    0
    1
    2
        MRI
    0
    1
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 through 41 weeks (maximum observed duration)
    Adverse event reporting additional description
    Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    MEDI7352 Dose Level 1
    Reporting group description
    		 Participants received 6 doses of subcutaneous (SC) MEDl7352 Dose Level 1 injection once every 2 weeks (Q2W) during 12-week treatment period.

    Reporting group title
    MEDI7352 Dose Level 2
    Reporting group description
    		 Participants received 6 doses of SC MEDl7352 Dose Level 2 injection Q2W during 12-week treatment period.

    Reporting group title
    MEDI7352 Dose Level 3
    Reporting group description
    		 Participants received 6 doses of SC MEDl7352 Dose Level 3 injection Q2W during 12-week treatment period.

    Reporting group title
    MEDI7352 Dose Level 4
    Reporting group description
    		 Participants received 6 doses of SC MEDl7352 Dose 4 Level injection Q2W during 12-week treatment period.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received 6 doses of SC placebo injection matched to MEDl7352 Q2W during 12-week treatment period.

    Serious adverse events
    		 MEDI7352 Dose Level 1 MEDI7352 Dose Level 2 MEDI7352 Dose Level 3 MEDI7352 Dose Level 4 Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 70 (4.29%)
    5 / 68 (7.35%)
    3 / 69 (4.35%)
    1 / 68 (1.47%)
    2 / 69 (2.90%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Investigations
    Liver function test abnormal
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Ovarian neoplasm
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         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
    Gastrointestinal carcinoma
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (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
    Breast cancer
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (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
    Traumatic renal injury
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (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
    Splenic rupture
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (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
    Multiple injuries
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (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
    Cardiac disorders
    Cardiovascular insufficiency
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (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
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (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
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (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
    Gastrointestinal disorders
    Large intestine polyp
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (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
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (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
    Dyspnoea
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (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
    Pleural effusion
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (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
    Respiratory failure
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (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
    Skin and subcutaneous tissue disorders
    Henoch-schonlein purpura
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Loss of bladder sensation
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (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
    Nephrolithiasis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (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
    Urinoma
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (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
    Musculoskeletal and connective tissue disorders
    Arthritis reactive
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (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
    Covid-19
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         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
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 MEDI7352 Dose Level 1 MEDI7352 Dose Level 2 MEDI7352 Dose Level 3 MEDI7352 Dose Level 4 Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    51 / 70 (72.86%)
    45 / 68 (66.18%)
    54 / 69 (78.26%)
    51 / 68 (75.00%)
    40 / 69 (57.97%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Haemangioma of liver
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Haemangioma of bone
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Acrochordon
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Lipoma
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Seborrhoeic keratosis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Tumour ulceration
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Vascular disorders
    Hot flush
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Hypertension
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 68 (2.94%)
    3 / 69 (4.35%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    2
    3
    0
    0
    Hypertensive crisis
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    1
    1
    0
    1
    Peripheral coldness
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Superficial vein prominence
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    General disorders and administration site conditions
    Feeling hot
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Asthenia
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Chest discomfort
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Chills
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    2 / 68 (2.94%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    2
    1
    Fatigue
         subjects affected / exposed
    2 / 70 (2.86%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    2
    1
    1
    0
    1
    Temperature regulation disorder
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Injection site bruising
         subjects affected / exposed
    2 / 70 (2.86%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    3 / 69 (4.35%)
         occurrences all number
    2
    1
    0
    0
    3
    Injection site erythema
         subjects affected / exposed
    2 / 70 (2.86%)
    6 / 68 (8.82%)
    6 / 69 (8.70%)
    9 / 68 (13.24%)
    2 / 69 (2.90%)
         occurrences all number
    2
    8
    7
    10
    2
    Injection site induration
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Injection site pain
         subjects affected / exposed
    0 / 70 (0.00%)
    5 / 68 (7.35%)
    4 / 69 (5.80%)
    1 / 68 (1.47%)
    2 / 69 (2.90%)
         occurrences all number
    0
    7
    5
    1
    2
    Injection site pruritus
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    2 / 69 (2.90%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    2
    0
    1
    Injection site reaction
         subjects affected / exposed
    2 / 70 (2.86%)
    3 / 68 (4.41%)
    0 / 69 (0.00%)
    4 / 68 (5.88%)
    0 / 69 (0.00%)
         occurrences all number
    3
    4
    0
    7
    0
    Injection site swelling
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Malaise
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    Peripheral swelling
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    2 / 68 (2.94%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    0
    2
    2
    Pyrexia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Influenza like illness
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    2
    Thirst
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Immune system disorders
    Allergy to arthropod sting
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Drug hypersensitivity
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Seasonal allergy
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Type iv hypersensitivity reaction
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Reproductive system and breast disorders
    Bartholin's cyst
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Pelvic pain
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    1 / 70 (1.43%)
    3 / 68 (4.41%)
    1 / 69 (1.45%)
    2 / 68 (2.94%)
    0 / 69 (0.00%)
         occurrences all number
    1
    3
    1
    2
    0
    Cough
         subjects affected / exposed
    5 / 70 (7.14%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    5
    1
    1
    0
    1
    Dysphonia
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Epistaxis
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Haemoptysis
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Aphonia
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Pleuritic pain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Productive cough
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Pulmonary mass
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Psychiatric disorders
    Alcohol abuse
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Anxiety
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Depressed mood
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Depression
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Insomnia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Irritability
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 70 (2.86%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    2
    1
    1
    0
    2
    Blood folate decreased
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Blood glucose increased
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Blood pressure increased
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    2 / 68 (2.94%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    3
    0
    Blood uric acid increased
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    C-reactive protein increased
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Coagulation factor increased
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Liver function test increased
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Glycosylated haemoglobin increased
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    Faecal calprotectin abnormal
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Drug screen positive
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Electrocardiogram qt prolonged
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Electrocardiogram t wave inversion
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Injury, poisoning and procedural complications
    Chillblains
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Cartilage injury
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Bone contusion
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Arthropod bite
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Animal bite
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    Adverse event following immunisation
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Accidental exposure to product
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Back injury
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Post procedural contusion
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Musculoskeletal injury
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Muscle strain
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    1
    0
    0
    1
    Muscle injury
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Limb injury
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 68 (2.94%)
    2 / 69 (2.90%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    2
    2
    0
    1
    Ligament sprain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    2 / 69 (2.90%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    2
    1
    1
    Joint injury
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 68 (1.47%)
    3 / 69 (4.35%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    2
    3
    0
    0
    Head injury
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    Fracture
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Foot fracture
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Fall
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    1
    2
    0
    0
    Post-traumatic pain
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Contusion
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    2 / 68 (2.94%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    1
    2
    2
    Tooth fracture
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Procedural pain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Skin injury
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Soft tissue injury
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Congenital, familial and genetic disorders
    Accessory spleen
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Vascular malformation
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Cardiac disorders
    Extrasystoles
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Tachycardia
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Tachycardia paroxysmal
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Atrial fibrillation
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Bradycardia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Nervous system disorders
    Areflexia
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Disturbance in attention
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Carpal tunnel syndrome
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Cervical radiculopathy
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Burning sensation
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 68 (2.94%)
    1 / 69 (1.45%)
    1 / 68 (1.47%)
    3 / 69 (4.35%)
         occurrences all number
    0
    2
    1
    1
    4
    Dizziness postural
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Headache
         subjects affected / exposed
    2 / 70 (2.86%)
    7 / 68 (10.29%)
    9 / 69 (13.04%)
    9 / 68 (13.24%)
    3 / 69 (4.35%)
         occurrences all number
    2
    8
    9
    11
    3
    Hypoaesthesia
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 68 (1.47%)
    4 / 69 (5.80%)
    2 / 68 (2.94%)
    0 / 69 (0.00%)
         occurrences all number
    1
    1
    4
    4
    0
    Migraine
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    Paraesthesia
         subjects affected / exposed
    4 / 70 (5.71%)
    3 / 68 (4.41%)
    2 / 69 (2.90%)
    4 / 68 (5.88%)
    1 / 69 (1.45%)
         occurrences all number
    5
    4
    3
    5
    1
    Tremor
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Presyncope
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    Resting tremor
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Sciatica
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Sensory loss
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Somnolence
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Polyneuropathy
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Leukopenia
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    Lymphadenopathy
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    1
    1
    Lymphopenia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    1
    1
    Neutropenia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    1
    1
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Ear congestion
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Tympanic membrane perforation
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    3 / 68 (4.41%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    Vertigo positional
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Eye disorders
    Amaurosis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Glaucoma
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Lacrimation increased
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Photopsia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Vitreous floaters
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 68 (2.94%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Abdominal mass
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Abdominal pain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    2 / 69 (2.90%)
    0 / 68 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    2
    0
    2
    Abdominal pain lower
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Hiatus hernia
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 68 (2.94%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Colitis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Constipation
         subjects affected / exposed
    2 / 70 (2.86%)
    2 / 68 (2.94%)
    1 / 69 (1.45%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
         occurrences all number
    2
    2
    1
    1
    1
    Dental discomfort
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    3 / 70 (4.29%)
    2 / 68 (2.94%)
    2 / 69 (2.90%)
    2 / 68 (2.94%)
    0 / 69 (0.00%)
         occurrences all number
    3
    2
    2
    3
    0
    Diverticulum intestinal
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Duodenitis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Dyspepsia
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Food poisoning
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Gastric ulcer
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Gastritis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    2 / 69 (2.90%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Mesenteric panniculitis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Nausea
         subjects affected / exposed
    1 / 70 (1.43%)
    2 / 68 (2.94%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    2
    1
    0
    0
    Noninfective gingivitis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Oesophageal stenosis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Oesophagitis
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 68 (2.94%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Toothache
         subjects affected / exposed
    1 / 70 (1.43%)
    2 / 68 (2.94%)
    2 / 69 (2.90%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    2
    2
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Tongue discomfort
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Hepatobiliary disorders
    Hepatomegaly
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Hepatic steatosis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Cholelithiasis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Cholestasis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Hepatic lesion
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Pustular psoriasis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Dermatitis contact
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Eczema
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Erythema
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    2 / 68 (2.94%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Miliaria
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Pruritus
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 68 (1.47%)
    4 / 69 (5.80%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    1
    1
    4
    1
    0
    Psoriasis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Dermal cyst
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Rash
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    2 / 69 (2.90%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Rosacea
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Skin lesion
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Glycosuria
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    1
    0
    0
    2
    Leukocyturia
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 68 (2.94%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    2
    0
    0
    1
    Micturition urgency
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Proteinuria
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    2 / 69 (2.90%)
    0 / 68 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    2
    0
    2
    Renal cyst
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Urinary incontinence
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    Urinary retention
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Urinary tract inflammation
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    7 / 70 (10.00%)
    6 / 68 (8.82%)
    5 / 69 (7.25%)
    3 / 68 (4.41%)
    4 / 69 (5.80%)
         occurrences all number
    7
    7
    5
    6
    4
    Musculoskeletal pain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    2 / 68 (2.94%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Muscular weakness
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Muscle tightness
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Muscle spasms
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    3 / 68 (4.41%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    0
    5
    2
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Limb discomfort
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Joint swelling
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    2
    Intervertebral disc degeneration
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Facet joint syndrome
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    2 / 69 (2.90%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Back pain
         subjects affected / exposed
    3 / 70 (4.29%)
    1 / 68 (1.47%)
    5 / 69 (7.25%)
    7 / 68 (10.29%)
    3 / 69 (4.35%)
         occurrences all number
    3
    3
    5
    9
    3
    Limb mass
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Myalgia
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    3 / 68 (4.41%)
    0 / 69 (0.00%)
         occurrences all number
    1
    1
    0
    3
    0
    Neck pain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    2 / 68 (2.94%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    2
    2
    2
    Osteoarthritis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    2
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    3 / 69 (4.35%)
         occurrences all number
    0
    2
    0
    1
    3
    Pain in jaw
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    Plantar fasciitis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Polymyalgia rheumatica
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Rapidly progressive osteoarthritis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    1
    2
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    2 / 68 (2.94%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    2
    1
    Soft tissue disorder
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Spinal pain
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    Subchondral insufficiency fracture
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Tendon disorder
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    2
    Tendon pain
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Tendonitis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    Trigger finger
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Infections and infestations
    Pharyngitis
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 68 (2.94%)
    0 / 69 (0.00%)
    2 / 68 (2.94%)
    1 / 69 (1.45%)
         occurrences all number
    0
    2
    0
    2
    1
    Periodontitis
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    2 / 68 (2.94%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    Oral herpes
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    6 / 70 (8.57%)
    4 / 68 (5.88%)
    6 / 69 (8.70%)
    5 / 68 (7.35%)
    9 / 69 (13.04%)
         occurrences all number
    7
    4
    7
    5
    11
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 70 (2.86%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    3 / 69 (4.35%)
         occurrences all number
    2
    0
    1
    0
    3
    Sinusitis
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Rhinitis
         subjects affected / exposed
    2 / 70 (2.86%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    3
    1
    1
    0
    1
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    3 / 68 (4.41%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    3
    0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Skin infection
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Pulpitis dental
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 70 (2.86%)
    3 / 68 (4.41%)
    4 / 69 (5.80%)
    3 / 68 (4.41%)
    2 / 69 (2.90%)
         occurrences all number
    2
    3
    4
    3
    2
    Urinary tract infection
         subjects affected / exposed
    2 / 70 (2.86%)
    5 / 68 (7.35%)
    2 / 69 (2.90%)
    4 / 68 (5.88%)
    1 / 69 (1.45%)
         occurrences all number
    2
    6
    4
    6
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Bronchitis
         subjects affected / exposed
    2 / 70 (2.86%)
    3 / 68 (4.41%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    2
    3
    0
    0
    0
    Cellulitis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Acarodermatitis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Conjunctivitis
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    1
    1
    0
    2
    Cystitis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    3 / 69 (4.35%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    5
    1
    0
    Ear infection
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 68 (2.94%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Ear infection fungal
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Erysipelas
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Fungal skin infection
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Influenza
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    1
    1
    Furuncle
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Epstein-barr virus infection
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Covid-19
         subjects affected / exposed
    16 / 70 (22.86%)
    5 / 68 (7.35%)
    10 / 69 (14.49%)
    12 / 68 (17.65%)
    8 / 69 (11.59%)
         occurrences all number
    16
    5
    10
    12
    8
    Metabolism and nutrition disorders
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    Hyponatraemia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
    2 / 68 (2.94%)
    1 / 69 (1.45%)
         occurrences all number
    2
    0
    0
    2
    1
    Hyperkalaemia
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 68 (2.94%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 68 (0.00%)
    1 / 69 (1.45%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
         occurrences all number
    2
    0
    1
    1
    0
    Vitamin d deficiency
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 68 (1.47%)
    0 / 69 (0.00%)
    0 / 68 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Mar 2021
    Added that on study Visit 4 (Day 14) and Visit 5 (Day 28), study participants will remain under observation for at least 2 hours after investigational product (IP) administration. Modified inclusion requirement that participants have history of inadequate pain relief from paracetamol, nonsteroidal anti-inflammatory drug (NSAID)/cyclooxygenase-2 (COX-2) inhibitors, and opioid analgesics to allow for inclusion of participants who refuse to take opioids or for whom opioids are unavailable. Added coronavirus disease 2019 (COVID-19) vaccine exclusion criterion and as prohibited concomitant medication. Changed exclusion criterion limiting blood loss within 2 months prior to screening from 50 mL to 500 mL. Reduced exclusion period prior to screening for corticosteroid or intra-articular hyaluronic acid injection on a target knee joint to 12 weeks, and for intra-articular hyaluronic acid injection on a non-target joint to 6 weeks. Removed 45-day limit on rescreening attempt. Extended validity of screening X-ray and magnetic resonance imaging (MRI) results from 45 to 90 days. Modified liver stopping criteria to include: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 × upper limit of normal (ULN) for more than 2 weeks and ALT or AST >= 3 × ULN and coexisting normalized ratio (internal normalized ratio [INR]) > 1.5 Updated guidance for evaluation of abnormal liver function tests. Removed systemic infections from AESIs and replaced with infections that meet the serious adverse event (SAE) or severe adverse event (AE) criteria.
    14 Oct 2021
    Increased duration of follow up period from 20 to 24 weeks, updated number and timing of follow up visits to reflect this. Added exploratory objective for urine C-telopeptide of crosslinked collagen type II (CTX-II). Inclusion and exclusion criteria were updated to expand the eligible participant population. Increased permitted low dose aspirin from 100 mg/day to 325 mg/day. Added limited (no more than 10 days per 8-week period) concomitant use of prescription or over the counter (OTC) NSAIDs for conditions not related to osteoarthritis (OA) to the list of permitted concomitant therapies. Removed stopping criterion “Renal toxicity, defined as serum creatinine ≥ 1.5 × ULN”. Added recommendation that participants had at least 3 weeks between last IP dose and joint replacement surgery. Added a minimum follow up period of 4 months for participants who underwent joint replacement surgery. Added serious or severe hypersensitivity reactions as adverse events of special interest (AESIs).
    28 Jun 2022
    Increased approximate number of participants to be recruited from 300 to 350, and for recruitment to continue until either statistical information equivalent to 255 participants completing the treatment period or 350 participants randomized was reached (previously when 255 participants completed treatment period). Changed the following COVID-19 requirements: i) Removed requirement for participants to have no signs of an acute viral respiratory illness at baseline and prior to all subsequent dosing visits. ii) Changed exclusion criteria to allow participants who have asymptomatic COVID-19 or have fully recovered from mild or moderate COVID-19 one month prior to randomization to be eligible for the study. iii) Changed requirement for participants diagnosed with COVID-19 to permanently discontinue IP to only require interruption of IP if other discontinuation criteria were not met.

    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.
    Concomitant medication and therapies data do not necessarily evaluate the safety and are therefore not considered as outcome measures in this study.
    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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