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    Clinical Trial Results:
    A randomized, double-blind, placebo-controlled multicenter study of Secukinumab (AIN457) to examine the clinical efficacy and the NSAID-sparing effect of Secukinumab over 16 weeks in patients with ankylosing spondylitis (ASTRUM)

    Summary
    EudraCT number
    		 2015-004575-74
    Trial protocol
    		 DE  
    Global end of trial date
    24 Sep 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Oct 2020
    First version publication date
    02 Oct 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CAIN457FDE03
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02763046
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharmaceuticals
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.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
    24 Sep 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Sep 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to demonstrate that the efficacy of secukinumab 150 mg subcutaneous (s.c.) injection (with nonsteroidal anti-inflammatory drug (NSAID) tapering) is superior to placebo based on the proportion of patients achieving an Assessment of SpondyloArthritis international Society (ASAS) 20 response at Week 12. To show superiority, both secukinumab treatment arms were pooled and compared against placebo.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 May 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 211
    Worldwide total number of subjects
    211
    EEA total number of subjects
    211
    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)
    197
    From 65 to 84 years
    14
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants took part in 40 investigative sites in Germany.

    Pre-assignment
    Screening details
    		 Participants were randomized 1:1:1 to one of the following treatment groups: secukinumab 150 mg s.c. with delayed NSAID tapering, secukinumab 150 mg s.c. with early NSAID tapering and placebo.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Secukinumab - delayed NSAID tapering
    Arm description
    		 Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (delayed tapering).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Secukinumab
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (delayed tapering).

    Arm title
    		 Secukinumab - early NSAID tapering
    Arm description
    		 Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (early tapering).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Secukinumab
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (early tapering).

    Arm title
    		 Placebo
    Arm description
    		 Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20). NSAID tapering allowed from Week 4.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20). NSAID tapering allowed from Week 4.

    Number of subjects in period 1
    		Secukinumab - delayed NSAID tapering Secukinumab - early NSAID tapering Placebo
    Started
    71
    70
    70
    Completed
    62
    65
    62
    Not completed
    9
    5
    8
         Physician decision
    1
    -
    1
         Adverse event, non-fatal
    5
    4
    -
         Subject/guardian decision
    2
    -
    4
         Lack of efficacy
    1
    1
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Secukinumab - delayed NSAID tapering
    Reporting group description
    		 Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (delayed tapering).

    Reporting group title
    Secukinumab - early NSAID tapering
    Reporting group description
    		 Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (early tapering).

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20). NSAID tapering allowed from Week 4.

    Reporting group values
    		 Secukinumab - delayed NSAID tapering Secukinumab - early NSAID tapering Placebo Total
    Number of subjects
    		 71 70 70 211
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 64 68 65 197
        From 65-84 years
    		 7 2 5 14
        85 years and over
    		 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 46.2 ± 13.36 44.1 ± 11.02 45.4 ± 12.55 -
    Sex: Female, Male
    Units: Participants
        Female
    		 30 28 31 89
        Male
    		 41 42 39 122
    Race/Ethnicity, Customized
    Units: Subjects
        Caucasian
    		 69 67 68 204
        Black
    		 1 0 0 1
        Asian
    		 0 2 1 3
        Other
    		 1 1 1 3

    End points

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    End points reporting groups
    Reporting group title
    Secukinumab - delayed NSAID tapering
    Reporting group description
    		 Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (delayed tapering).

    Reporting group title
    Secukinumab - early NSAID tapering
    Reporting group description
    		 Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (early tapering).

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20). NSAID tapering allowed from Week 4.

    Subject analysis set title
    Secukinumab - pooled
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The 2 secukinumab arms (delayed NSAID tapering and early NSAID tapering) pooled.

    Primary: Proportion of patients who achieved ASAS20 response in the pooled secukinumab group compared with the placebo group at Week 12

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    End point title
    		 Proportion of patients who achieved ASAS20 response in the pooled secukinumab group compared with the placebo group at Week 12 [1]
    End point description
    ASAS (Assessment of SpondyloArthritis International Society criteria) 20 response is defined as an improvement from baseline of ≥20% and ≥1 unit on a scale of 0-10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit on a scale of 0-10 in the remaining domain. The four main ASAS domains are: Patient's global assessment of disease activity, back pain, function represented by ability to perform specific tasks (from Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]) and inflammation represented by mean duration and severity of morning stiffness. Non-responder imputation was applied for missing data.
    End point type
    Primary
    End point timeframe
    Baseline, Week 12
    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: For the analysis of the primary endpoint both secukinumab treatment arms were pooled and compared against placebo.
    End point values
    		 Placebo Secukinumab - pooled
    Number of subjects analysed
    70
    141
    Units: Percentage of participants
        number (not applicable)
    44.3
    51.1
    Statistical analysis title
    		 ASAS20 response - Week 12
    Comparison groups
    Placebo v Secukinumab - pooled
    Number of subjects included in analysis
    211
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3512
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 2.36

    Secondary: Proportion of patients who achieved ASAS20 response in each secukinumab group (delayed NSAID tapering and early NSAID tapering) compared with the placebo group

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    End point title
    		 Proportion of patients who achieved ASAS20 response in each secukinumab group (delayed NSAID tapering and early NSAID tapering) compared with the placebo group
    End point description
    ASAS (Assessment of SpondyloArthritis International Society criteria) 20 response is defined as an improvement from baseline of ≥20% and ≥1 unit on a scale of 0-10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit on a scale of 0-10 in the remaining domain. The four main ASAS domains are: Patient's global assessment of disease activity, back pain, function represented by ability to perform specific tasks (from Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]) and inflammation represented by mean duration and severity of morning stiffness. Non-responder imputation was applied for missing data.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 16
    End point values
    		 Secukinumab - delayed NSAID tapering Secukinumab - early NSAID tapering Placebo
    Number of subjects analysed
    71
    70
    70
    Units: Percentage of Participants
    number (not applicable)
        Week 12
    52.1
    50.0
    44.3
        Week 16
    56.3
    50.0
    41.4
    Statistical analysis title
    		 ASAS20 response - Week 12
    Comparison groups
    Secukinumab - delayed NSAID tapering v Placebo
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.401
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 2.6
    Statistical analysis title
    		 ASAS20 response - Week 12
    Comparison groups
    Secukinumab - early NSAID tapering v Placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4382
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 2.55
    Statistical analysis title
    		 ASAS20 response - Week 16
    Comparison groups
    Secukinumab - delayed NSAID tapering v Placebo
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0934
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 3.5
    Statistical analysis title
    		 ASAS20 response - Week 16
    Comparison groups
    Secukinumab - early NSAID tapering v Placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2619
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 2.9

    Secondary: Mean change from baseline in ASAS-NSAID score at Week 12

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    End point title
    		 Mean change from baseline in ASAS-NSAID score at Week 12
    End point description
    ASAS-NSAID score is used to present the NSAID (nonsteroidal anti-inflammatory drug) intake by considering the type of NSAID, the total dose and the number of days taking NSAID during a period of interest (PI). For the NSAID equivalence scoring system, "no NSAID intake" was set to a score value of 0, and the reference dose of 150 mg/day diclofenac was set to a score value of 100. The Daily diclofenac-equivalent dose score was derived by converting each daily dose of NSAID to a percentage dose equivalent of 150 mg diclofenac. ASAS-NSAID score = (equivalent NSAID score) x (days of intake during PI) x (days per week)/(PI in days). A negative change from baseline indicates less NSAID consumption.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    		 Secukinumab - delayed NSAID tapering Secukinumab - early NSAID tapering Placebo Secukinumab - pooled
    Number of subjects analysed
    71
    70
    70
    141
    Units: Score on scale
        arithmetic mean (standard deviation)
    -44.9 ± 47.32
    -40.3 ± 71.48
    -31.5 ± 36.54
    -42.6 ± 60.53
    Statistical analysis title
    		 ASAS-NSAID score - Week 12
    Comparison groups
    Placebo v Secukinumab - pooled
    Number of subjects included in analysis
    211
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0997
    Method
    		 Mixed Model for Repeated Measures (MMRM)
    Parameter type
    		 LS (least square) Mean
    Point estimate
    -10.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.55
         upper limit
    		 1.96
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.25
    Statistical analysis title
    		 ASAS-NSAID score - Week 12
    Comparison groups
    Secukinumab - delayed NSAID tapering v Placebo
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0888
    Method
    		 Mixed Model for Repeated Measures (MMRM)
    Parameter type
    		 LS Mean
    Point estimate
    -12.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.47
         upper limit
    		 1.87
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.23
    Statistical analysis title
    		 ASAS-NSAID score - Week 12
    Comparison groups
    Secukinumab - early NSAID tapering v Placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2484
    Method
    		 Mixed Model for Repeated Measures (MMRM)
    Parameter type
    		 LS Mean
    Point estimate
    -8.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.36
         upper limit
    		 5.79
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.18

    Secondary: Mean change from baseline in ASAS-NSAID score in each secukinumab group after 12 weeks of exposure (at Week 12 in the secukinumab-delayed NSAID tapering group and at Week 16 in the secukinumab-early NSAID tapering group)

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    End point title
    		 Mean change from baseline in ASAS-NSAID score in each secukinumab group after 12 weeks of exposure (at Week 12 in the secukinumab-delayed NSAID tapering group and at Week 16 in the secukinumab-early NSAID tapering group) [2]
    End point description
    ASAS-NSAID score is used to present the NSAID (nonsteroidal anti-inflammatory drug) intake by considering the type of NSAID, the total dose and the number of days taking NSAID during a period of interest (PI). For the NSAID equivalence scoring system, "no NSAID intake" was set to a score value of 0, and the reference dose of 150 mg/day diclofenac was set to a score value of 100. The Daily diclofenac-equivalent dose score was derived by converting each daily dose of NSAID to a percentage dose equivalent of 150 mg diclofenac. ASAS-NSAID score = (equivalent NSAID score) x (days of intake during PI) x (days per week)/(PI in days). A negative change from baseline indicates less NSAID consumption. For this endpoint the analysis was performed after 12 weeks of exposure to secukinumab which was achieved at Week 12 in the secukinumab delayed NSAID tapering group but at Week 16 in the secukinumab early NSAID tapering group.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12 (delayed NSAID tapering), Week 16 (early NSAID tapering)
    Notes
    [2] - 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: This endpoints refers to the secukinumab arms only. No statistics were planned for the placebo group.
    End point values
    		 Secukinumab - delayed NSAID tapering Secukinumab - early NSAID tapering
    Number of subjects analysed
    71
    70
    Units: Score on scale
        arithmetic mean (standard deviation)
    -44.9 ± 47.32
    -42.5 ± 68.62
    Statistical analysis title
    		 delayed tapering (W12) vs early tapering (W16)
    Comparison groups
    Secukinumab - delayed NSAID tapering v Secukinumab - early NSAID tapering
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7735
    Method
    		 Mixed Model for Repeated Measures (MMRM)
    Parameter type
    		 LS Mean
    Point estimate
    -2.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.11
         upper limit
    		 11.98

    Secondary: Mean change from baseline in the BASDAI total score

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    End point title
    		 Mean change from baseline in the BASDAI total score
    End point description
    The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to ankylosing spondylitis: 1) Fatigue, 2) Spinal pain, 3) Peripheral arthritis, 4) Enthesitis, 5) Intensity, and 6) Duration of morning stiffness. Participants need to score each item with a score from 0 to 10 (captured as a continuous visual analog scale). Total score is obtained from the average of symptom scores ranging 0 (no problem) to 10 (worst problem), with a higher score indicating more severe symptoms. A negative change from baseline in the total 0-10 BASDAI score indicates improvement.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 16
    End point values
    		 Secukinumab - delayed NSAID tapering Secukinumab - early NSAID tapering Placebo Secukinumab - pooled
    Number of subjects analysed
    71
    70
    70
    141
    Units: Score on scale
    arithmetic mean (standard deviation)
        Week 12
    -2.1 ± 2.16
    -2.0 ± 2.10
    -1.8 ± 2.00
    -2.1 ± 2.12
        Week 16
    -2.3 ± 1.90
    -2.0 ± 1.96
    -1.7 ± 1.96
    -2.2 ± 1.93
    Statistical analysis title
    		 Week 12
    Comparison groups
    Placebo v Secukinumab - pooled
    Number of subjects included in analysis
    211
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1926
    Method
    		 Mixed Model for Repeated Measures (MMRM)
    Parameter type
    		 LS Mean
    Point estimate
    -0.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.99
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3
    Statistical analysis title
    		 Week 12
    Comparison groups
    Secukinumab - delayed NSAID tapering v Placebo
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1914
    Method
    		 Mixed Model for Repeated Measures (MMRM)
    Parameter type
    		 LS Mean
    Point estimate
    -0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.14
         upper limit
    		 0.23
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.35
    Statistical analysis title
    		 Week 12
    Comparison groups
    Secukinumab - early NSAID tapering v Placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3397
    Method
    		 Mixed Model for Repeated Measures (MMRM)
    Parameter type
    		 LS Mean
    Point estimate
    -0.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.01
         upper limit
    		 0.35
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.34
    Statistical analysis title
    		 Week 16
    Comparison groups
    Secukinumab - delayed NSAID tapering v Placebo
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0384
    Method
    		 Mixed Model for Repeated Measures (MMRM)
    Parameter type
    		 LS Mean
    Point estimate
    -0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.33
         upper limit
    		 -0.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.33
    Statistical analysis title
    		 Week 16
    Comparison groups
    Secukinumab - early NSAID tapering v Placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2116
    Method
    		 Mixed Model for Repeated Measures (MMRM)
    Parameter type
    		 LS Mean
    Point estimate
    -0.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.05
         upper limit
    		 0.23
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.33

    Secondary: Mean change from baseline in health-related Quality of Life as measured by the Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) Score

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    End point title
    		 Mean change from baseline in health-related Quality of Life as measured by the Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) Score
    End point description
    The Short Form-36 Health Survey (SF-36) measures the impact of disease on overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 comprise the physical component of the SF-36 (SF-36 PCS) that is evaluated in this study. Scores on each item 1-4 were summed and averaged (range = 0-100 with higher scores indicating better levels of function and/or better health). A positive change from Baseline indicates improvement.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    		 Secukinumab - delayed NSAID tapering Secukinumab - early NSAID tapering Placebo Secukinumab - pooled
    Number of subjects analysed
    71
    70
    70
    141
    Units: Score on scale
        arithmetic mean (standard deviation)
    4.8 ± 7.03
    6.1 ± 6.92
    4.8 ± 7.43
    5.5 ± 6.98
    Statistical analysis title
    		 Week 12
    Comparison groups
    Placebo v Secukinumab - pooled
    Number of subjects included in analysis
    211
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5384
    Method
    		 Mixed Model for Repeated Measures (MMRM)
    Parameter type
    		 LS Mean
    Point estimate
    0.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.38
         upper limit
    		 2.63
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.02
    Statistical analysis title
    		 Week 12
    Comparison groups
    Secukinumab - delayed NSAID tapering v Placebo
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9251
    Method
    		 Mixed Model for Repeated Measures (MMRM)
    Parameter type
    		 LS Mean
    Point estimate
    -0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.43
         upper limit
    		 2.21
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.18
    Statistical analysis title
    		 Week 12
    Comparison groups
    Secukinumab - early NSAID tapering v Placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2432
    Method
    		 Mixed Model for Repeated Measures (MMRM)
    Parameter type
    		 LS Mean
    Point estimate
    1.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.93
         upper limit
    		 3.66
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.16

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events (AEs) were collected from first dose of study treatment until end of study treatment plus 4 weeks post-treatment (median duration of 24 weeks).
    Adverse event reporting additional description
    Any signs or symptoms that occurs from first study drug treatment until 30 days after last study drug treatment. AEs were analyzed by treatment period: Treatment Period 1 from first study drug administration through Week 16 (until the day before visit Week 16) and Treatment Period 2 (from the day of injection at visit Week 16 until study end).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    Secukinumab - delayed NSAID tapering – Treatment Period 1
    Reporting group description
    		 Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (delayed tapering). Treatment Period 1: from first study drug administration at baseline through Week 16 (concretely: until the day before the injection of study drug scheduled at visit Week 16). This corresponds to the placebo-controlled period of the study.

    Reporting group title
    Secukinumab - early NSAID tapering - Treatment Period 1
    Reporting group description
    		 Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (early tapering). Treatment Period 1: from first study drug administration at baseline through Week 16 (concretely: until the day before the injection of study drug scheduled at visit Week 16). This corresponds to the placebo-controlled period of the study.

    Reporting group title
    Placebo - Treatment Period 1
    Reporting group description
    		 Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20). NSAID tapering allowed from Week 4. Treatment Period 1: from first study drug administration at baseline through Week 16 (concretely: until the day before the injection of study drug scheduled at visit Week 16). This corresponds to the placebo-controlled period of the study.

    Reporting group title
    Secukinumab - delayed NSAID tapering - Treatment Period 2
    Reporting group description
    		 Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (delayed tapering). Treatment Period 2: from the day of injection at visit Week 16 onwards until study end.

    Reporting group title
    Secukinumab - early NSAID tapering - Treatment Period 2
    Reporting group description
    		 Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (early tapering). Treatment Period 2: from the day of injection at visit Week 16 onwards until study end.

    Reporting group title
    Placebo - Treatment Period 2
    Reporting group description
    		 Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20). NSAID tapering allowed from Week 4. Treatment Period 2: from the day of injection at visit Week 16 onwards until study end.

    Serious adverse events
    		 Secukinumab - delayed NSAID tapering – Treatment Period 1 Secukinumab - early NSAID tapering - Treatment Period 1 Placebo - Treatment Period 1 Secukinumab - delayed NSAID tapering - Treatment Period 2 Secukinumab - early NSAID tapering - Treatment Period 2 Placebo - Treatment Period 2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 71 (5.63%)
    3 / 70 (4.29%)
    1 / 70 (1.43%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Eye disorders
    Iridocyclitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Oesophageal ulcer
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Vaginal cyst
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Psoriasis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Erysipelas
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Secukinumab - delayed NSAID tapering – Treatment Period 1 Secukinumab - early NSAID tapering - Treatment Period 1 Placebo - Treatment Period 1 Secukinumab - delayed NSAID tapering - Treatment Period 2 Secukinumab - early NSAID tapering - Treatment Period 2 Placebo - Treatment Period 2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    53 / 71 (74.65%)
    56 / 70 (80.00%)
    55 / 70 (78.57%)
    25 / 71 (35.21%)
    23 / 70 (32.86%)
    22 / 70 (31.43%)
    Vascular disorders
    Circulatory collapse
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Haematoma
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Hypertension
         subjects affected / exposed
    4 / 71 (5.63%)
    3 / 70 (4.29%)
    4 / 70 (5.71%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    4
    3
    4
    0
    0
    1
    Hypotension
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    General disorders and administration site conditions
    Discomfort
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Fatigue
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    2 / 70 (2.86%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    5
    0
    0
    0
    Feeling hot
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Impaired healing
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Injection site pruritus
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Injection site urticaria
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Peripheral swelling
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Polyp
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Thirst
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Immune system disorders
    Allergy to arthropod bite
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Seasonal allergy
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Menorrhagia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Uterine pain
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Vulvovaginal pain
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Cough
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 70 (0.00%)
    2 / 70 (2.86%)
    0 / 71 (0.00%)
    3 / 70 (4.29%)
    0 / 70 (0.00%)
         occurrences all number
    3
    0
    2
    0
    3
    0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 70 (2.86%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    3 / 70 (4.29%)
    0 / 70 (0.00%)
         occurrences all number
    0
    2
    1
    0
    3
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 70 (2.86%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Psychiatric disorders
    Apathy
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Depression
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    Insomnia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Nervousness
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Restlessness
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Sleep disorder
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Blood glucose increased
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Blood pressure decreased
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Blood pressure increased
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Laboratory test abnormal
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Liver function test increased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Red blood cell sedimentation rate increased
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Transaminases increased
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    White blood cell count decreased
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    White blood cell count increased
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    3
    0
    0
    0
    Bone contusion
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Contusion
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Fall
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Hand fracture
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Joint dislocation
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Ligament rupture
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Ligament sprain
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Limb injury
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Muscle injury
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Muscle strain
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Overdose
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Post-traumatic neck syndrome
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Reactive gastropathy
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Road traffic accident
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    Spinal column injury
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Wound
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Coronary artery disease
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Palpitations
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Nervous system disorders
    Ageusia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Autonomic nervous system imbalance
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Cervicobrachial syndrome
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    0
    Disturbance in attention
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Dizziness
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 70 (2.86%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    2
    1
    0
    0
    1
    Dysaesthesia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Dysgeusia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Headache
         subjects affected / exposed
    12 / 71 (16.90%)
    10 / 70 (14.29%)
    6 / 70 (8.57%)
    4 / 71 (5.63%)
    3 / 70 (4.29%)
    1 / 70 (1.43%)
         occurrences all number
    25
    18
    23
    4
    4
    1
    Intercostal neuralgia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Migraine
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    0
    Nerve compression
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Paraesthesia
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    2
    0
    1
    0
    0
    0
    Paresis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Presyncope
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Sciatica
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    1
    0
    1
    0
    Tension headache
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Tremor
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Leukopenia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Lymph node pain
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Lymphopenia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Monoclonal B-cell lymphocytosis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Monocytosis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Neutrophilia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Tinnitus
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Vertigo
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    3 / 70 (4.29%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    1
    0
    13
    1
    0
    1
    Eye disorders
    Diplopia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Dry eye
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Eye irritation
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Eye pain
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Iritis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Macular degeneration
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Presbyopia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Uveitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Visual impairment
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 71 (4.23%)
    3 / 70 (4.29%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    4
    4
    0
    0
    0
    0
    Abdominal pain lower
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    3 / 71 (4.23%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    3
    0
    1
    0
    0
    0
    Aphthous ulcer
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Colitis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Constipation
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    3 / 71 (4.23%)
    3 / 70 (4.29%)
    3 / 70 (4.29%)
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    3 / 70 (4.29%)
         occurrences all number
    3
    4
    3
    1
    1
    3
    Diarrhoea haemorrhagic
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Dry mouth
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 70 (2.86%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    2
    1
    0
    1
    0
    Dyspepsia
         subjects affected / exposed
    0 / 71 (0.00%)
    3 / 70 (4.29%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    3
    1
    0
    1
    0
    Dysphagia
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Enteritis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Frequent bowel movements
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Gastritis
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Gingival discomfort
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Haematochezia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Hiatus hernia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Inguinal hernia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Nausea
         subjects affected / exposed
    2 / 71 (2.82%)
    2 / 70 (2.86%)
    5 / 70 (7.14%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    2
    3
    5
    0
    0
    1
    Stomatitis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Toothache
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Hepatic steatosis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Dermatitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Dyshidrotic eczema
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    0
    Eczema
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Eczema asteatotic
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Erythema
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    2 / 70 (2.86%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    2
    0
    0
    0
    Guttate psoriasis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 70 (2.86%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Night sweats
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Palmoplantar pustulosis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Photosensitivity reaction
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Pruritus
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    3 / 70 (4.29%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    3
    0
    0
    0
    Psoriasis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Rash
         subjects affected / exposed
    2 / 71 (2.82%)
    1 / 70 (1.43%)
    3 / 70 (4.29%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    2
    1
    3
    0
    0
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Seborrhoea
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Skin exfoliation
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Skin fissures
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Skin irritation
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Solar dermatitis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Xeroderma
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Haematuria
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Proteinuria
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Renal failure
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Urinary incontinence
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Endocrine disorders
    Hyperprolactinaemia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Hypothyroidism
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Ankylosing spondylitis
         subjects affected / exposed
    3 / 71 (4.23%)
    1 / 70 (1.43%)
    6 / 70 (8.57%)
    2 / 71 (2.82%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    3
    1
    7
    2
    0
    1
    Arthralgia
         subjects affected / exposed
    2 / 71 (2.82%)
    2 / 70 (2.86%)
    2 / 70 (2.86%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    2
    2
    2
    1
    0
    0
    Arthritis
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    0
    1
    0
    0
    Back pain
         subjects affected / exposed
    4 / 71 (5.63%)
    1 / 70 (1.43%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    4
    1
    1
    0
    0
    0
    Bursitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Joint swelling
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Muscle spasms
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Muscle tightness
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    2 / 70 (2.86%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Myalgia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Osteoarthritis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    4
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    1 / 71 (1.41%)
    2 / 70 (2.86%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    1
    5
    4
    0
    1
    0
    Rheumatic fever
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Sacroiliitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Spinal pain
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    2 / 70 (2.86%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    3
    0
    0
    0
    Spondylitis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    2 / 70 (2.86%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    0
    Spondyloarthropathy
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    2 / 70 (2.86%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    2
    0
    0
    0
    Spondylolisthesis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Synovial cyst
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Tendon disorder
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Tendon pain
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Tendonitis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    1 / 70 (1.43%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    0
    Tenosynovitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Infections and infestations
    Bacterial vaginosis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Bronchitis
         subjects affected / exposed
    5 / 71 (7.04%)
    2 / 70 (2.86%)
    3 / 70 (4.29%)
    2 / 71 (2.82%)
    1 / 70 (1.43%)
    1 / 70 (1.43%)
         occurrences all number
    5
    2
    6
    2
    1
    1
    Candida infection
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    2 / 71 (2.82%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Cystitis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Epstein-Barr virus infection
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Erysipelas
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Folliculitis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    2
    0
    0
    1
    0
    Fungal infection
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Fungal skin infection
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    0
    Furuncle
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Gastroenteritis
         subjects affected / exposed
    2 / 71 (2.82%)
    4 / 70 (5.71%)
    3 / 70 (4.29%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    2
    4
    4
    1
    0
    1
    Gastroenteritis viral
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Gastrointestinal infection
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Gastrointestinal viral infection
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Herpes simplex
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Infected bite
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Influenza
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    0
    Laryngitis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Lyme disease
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    6 / 71 (8.45%)
    13 / 70 (18.57%)
    14 / 70 (20.00%)
    7 / 71 (9.86%)
    5 / 70 (7.14%)
    3 / 70 (4.29%)
         occurrences all number
    6
    17
    16
    7
    6
    3
    Oesophageal candidiasis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Onychomycosis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Oral candidiasis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Oral herpes
         subjects affected / exposed
    2 / 71 (2.82%)
    2 / 70 (2.86%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    2
    2
    0
    1
    1
    0
    Otitis externa
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Otitis media
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Pharyngitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Pulpitis dental
         subjects affected / exposed
    1 / 71 (1.41%)
    2 / 70 (2.86%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    2 / 71 (2.82%)
    4 / 70 (5.71%)
    3 / 70 (4.29%)
    1 / 71 (1.41%)
    1 / 70 (1.43%)
    3 / 70 (4.29%)
         occurrences all number
    2
    4
    4
    1
    1
    3
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Rhinitis
         subjects affected / exposed
    4 / 71 (5.63%)
    0 / 70 (0.00%)
    2 / 70 (2.86%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    5
    0
    2
    0
    0
    0
    Sinusitis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    2 / 70 (2.86%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences all number
    0
    0
    2
    0
    0
    1
    Subcutaneous abscess
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Trichomoniasis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 71 (1.41%)
    3 / 70 (4.29%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    2
    4
    1
    0
    0
    2
    Urinary tract infection
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Uterine infection
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 70 (1.43%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Diabetes mellitus
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Pseudohyperkalaemia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Pseudohypoglycaemia
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 70 (0.00%)
    0 / 70 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Dec 2018
    Based on the results from the MEASURE 3 (CAIN457F2314), MEASURE 4 (CAIN457F2320) and COAST V (Ixekizumab, NCT02696785) studies, the assumptions for the power calculation of the primary and a selection of secondary and exploratory objectives were re-evaluated, leading to changes in the statistical analysis plan. These 3 studies suggested that the placebo response might be somewhat higher, leading to a potentially smaller difference between active treatment and placebo than originally assumed during the planning of this trial. Therefore, in order to keep sufficient power, it was decided to pool the two secukinumab arms for the primary analysis. As a result of the secukinumab pooling introduced with the amendment, the number of randomized patients could be reduced to a smaller sample size (approximately 190 patients) than originally expected (about 204 patients), while maintaining adequate power for primary and secondary analyses.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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