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    Clinical Trial Results:
    A PHASE 2B, MULTI-SITE, RANDOMIZED, DOUBLE-BLIND, VEHICLE-CONTROLLED, PARALLEL-GROUP STUDY OF THE EFFICACY, SAFETY, LOCAL TOLERABILITY AND PHARMACOKINETICS OF 2 DOSE STRENGTHS AND 2 REGIMENS OF TOFACITINIB OINTMENT IN SUBJECTS WITH CHRONIC PLAQUE PSORIASIS

    Summary
    EudraCT number
    2012-005645-20
    Trial protocol
    DK  
    Global end of trial date
    16 Sep 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    16 Sep 2016
    First version publication date
    16 Sep 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    A3921082
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York,, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.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
    16 Sep 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    16 Sep 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Sep 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The Primary Objectives were: To characterize the efficacy of tofacitinib ointment (10 mg/g and 20 mg/g) applied once daily (QD) or twice daily (BID) over 12 weeks in subjects with mild or moderate chronic plaque psoriasis compared to the corresponding placebo ointment (vehicle) (QD or BID). To characterize safety of tofacitinib ointment (10 mg/g and 20 mg/g) applied QD or BID over 12 weeks in subjects with mild or moderate chronic plaque psoriasis. To characterize local tolerability of tofacitinib ointment (10 mg/g and 20 mg/g) applied QD or BID over 12 weeks in subjects with mild or moderate chronic plaque psoriasis. The Secondary Objectives were: To characterize effects on patient reported outcome (PRO) measures of tofacitinib ointment (10 mg/g and 20 mg/g) applied QD or BID over 12 weeks of treatment in subjects with mild or moderate chronic plaque psoriasis.
    Protection of trial subjects
    The study was conducted in accordance with legal and regulatory requirements, as well as the general principles set forth in the International Ethical Guidelines for Biomedical Research Involving Human Subjects (Council for International Organizations of Medical Sciences 2002), Guidelines for Good Clinical Practice (ICH 1996), and the Declaration of Helsinki (World Medical Association 1996 and 2008). The informed consent document was in compliance with International Conference on Harmonisation (ICH) GCP, local regulatory requirements, and legal requirements. The informed consent document used during the informed consent process was reviewed by the sponsor, approved by the IRB/IEC, and available for inspection. The investigator was to inform Pfizer immediately of any urgent safety measures taken by the investigator to protect the study subjects against any immediate hazard, and of any serious breaches of this protocol or of ICH GCP that the investigator became aware of.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    13 May 2013
    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
    Canada: 127
    Country: Number of subjects enrolled
    Denmark: 5
    Country: Number of subjects enrolled
    Poland: 109
    Country: Number of subjects enrolled
    United States: 230
    Worldwide total number of subjects
    471
    EEA total number of subjects
    114
    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)
    393
    From 65 to 84 years
    77
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    Advertisements approved by ethics committees and investigator databases could be used as recruitment procedures.

    Pre-assignment
    Screening details
    Subjects were screened within 28 days (+4 days) prior to Visit 1 (Baseline/Day 1) to confirm that they were suitable and potentially eligible for the study. Screening procedures could be performed over more than one visit in the 28 days (+4 days) prior to Visit 1 (Baseline/Day 1).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Carer
    Blinding implementation details
    Carer equals the physician treating the subject Investigator equals the sponsor of the trial.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID
    Arm description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment, 20 mg/g, BID for 12 weeks.
    Arm type
    Active comparator

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    20 mg/g BID

    Arm title
    Mild/Moderate: Tofacitinib 10 mg/g BID
    Arm description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment, 10 mg/g, BID for 12 weeks.
    Arm type
    Active comparator

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    10 mg/g BID

    Arm title
    Mild/Moderate: Placebo (vehicle) BID
    Arm description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied placebo ointment (vehicle), BID for 12 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    placebo BID

    Arm title
    Mild/Moderate: Tofacitinib 20 mg/g QD
    Arm description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment, 20 mg/g, QD for 12 weeks.
    Arm type
    Active comparator

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    20 mg/g QD

    Arm title
    Mild/Moderate: Tofacitinib 10 mg/g QD
    Arm description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment 10 mg/g, QD for 12 weeks.
    Arm type
    Active comparator

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    10 mg/g QD

    Arm title
    Mild/Moderate: Placebo (vehicle) QD
    Arm description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied placebo ointment (vehicle), QD for 12 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    placebo QD

    Arm title
    Severe: Tofacitinib 20 mg/g BID
    Arm description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment, 20 mg/g, BID for 12 weeks.
    Arm type
    Active comparator

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    20 mg/g BID

    Arm title
    Severe: Tofacitinib 10 mg/g BID
    Arm description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment, 10 mg/g, BID for 12 weeks.
    Arm type
    Active comparator

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    10 mg/g BID

    Arm title
    Severe: Placebo (vehicle) BID
    Arm description
    Participants with a baseline PGA-C score of severe (4) applied placebo ointment (vehicle), BID for 12 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    placebo BID

    Arm title
    Severe: Tofacitinib 20 mg/g QD
    Arm description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment, 20 mg/g, QD for 12 weeks.
    Arm type
    Active comparator

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    20 mg/g QD

    Arm title
    Severe: Tofacitinib 10 mg/g QD
    Arm description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment 10 mg/g, QD for 12 weeks.
    Arm type
    Active comparator

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    10 mg/g QD

    Arm title
    Severe: Placebo (vehicle) QD
    Arm description
    Participants with a baseline PGA-C score of severe (4) applied placebo ointment (vehicle), QD for 12 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    placebo QD

    Number of subjects in period 1
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD Severe: Tofacitinib 20 mg/g BID Severe: Tofacitinib 10 mg/g BID Severe: Placebo (vehicle) BID Severe: Tofacitinib 20 mg/g QD Severe: Tofacitinib 10 mg/g QD Severe: Placebo (vehicle) QD
    Started
    71
    70
    71
    70
    74
    74
    7
    7
    7
    7
    6
    7
    Completed
    55
    52
    48
    51
    57
    48
    6
    5
    4
    2
    4
    3
    Not completed
    16
    18
    23
    19
    17
    26
    1
    2
    3
    5
    2
    4
         Protocol deviation
    1
    1
    2
    -
    -
    1
    -
    -
    -
    -
    -
    -
         Non-compliance with study treatment
    2
    1
    1
    -
    -
    1
    -
    -
    -
    -
    -
    -
         Lack of efficacy
    5
    8
    7
    6
    9
    8
    1
    1
    2
    2
    2
    -
         Adverse event, serious fatal
    -
    1
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
         Not specified
    2
    3
    2
    2
    2
    1
    -
    -
    -
    -
    -
    -
         Adverse event, non-fatal
    -
    -
    4
    6
    3
    7
    -
    1
    1
    1
    -
    2
         Consent withdrawn by subject
    6
    3
    3
    3
    3
    5
    -
    -
    -
    1
    -
    1
         Lost to follow-up
    -
    1
    4
    2
    -
    3
    -
    -
    -
    1
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment, 20 mg/g, BID for 12 weeks.

    Reporting group title
    Mild/Moderate: Tofacitinib 10 mg/g BID
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment, 10 mg/g, BID for 12 weeks.

    Reporting group title
    Mild/Moderate: Placebo (vehicle) BID
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied placebo ointment (vehicle), BID for 12 weeks.

    Reporting group title
    Mild/Moderate: Tofacitinib 20 mg/g QD
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment, 20 mg/g, QD for 12 weeks.

    Reporting group title
    Mild/Moderate: Tofacitinib 10 mg/g QD
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment 10 mg/g, QD for 12 weeks.

    Reporting group title
    Mild/Moderate: Placebo (vehicle) QD
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied placebo ointment (vehicle), QD for 12 weeks.

    Reporting group title
    Severe: Tofacitinib 20 mg/g BID
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment, 20 mg/g, BID for 12 weeks.

    Reporting group title
    Severe: Tofacitinib 10 mg/g BID
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment, 10 mg/g, BID for 12 weeks.

    Reporting group title
    Severe: Placebo (vehicle) BID
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied placebo ointment (vehicle), BID for 12 weeks.

    Reporting group title
    Severe: Tofacitinib 20 mg/g QD
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment, 20 mg/g, QD for 12 weeks.

    Reporting group title
    Severe: Tofacitinib 10 mg/g QD
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment 10 mg/g, QD for 12 weeks.

    Reporting group title
    Severe: Placebo (vehicle) QD
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied placebo ointment (vehicle), QD for 12 weeks.

    Reporting group values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD Severe: Tofacitinib 20 mg/g BID Severe: Tofacitinib 10 mg/g BID Severe: Placebo (vehicle) BID Severe: Tofacitinib 20 mg/g QD Severe: Tofacitinib 10 mg/g QD Severe: Placebo (vehicle) QD Total
    Number of subjects
    71 70 71 70 74 74 7 7 7 7 6 7 471
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    58 57 59 59 65 64 6 6 5 5 5 4 393
        From 65-84 years
    13 13 12 11 8 10 1 1 2 2 1 3 77
        85 years and over
    0 0 0 0 1 0 0 0 0 0 0 0 1
    Gender, Male/Female
    Units: Participants
        Female
    28 23 30 33 24 32 1 3 1 1 0 0 176
        Male
    43 47 41 37 50 42 6 4 6 6 6 7 295

    End points

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    End points reporting groups
    Reporting group title
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment, 20 mg/g, BID for 12 weeks.

    Reporting group title
    Mild/Moderate: Tofacitinib 10 mg/g BID
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment, 10 mg/g, BID for 12 weeks.

    Reporting group title
    Mild/Moderate: Placebo (vehicle) BID
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied placebo ointment (vehicle), BID for 12 weeks.

    Reporting group title
    Mild/Moderate: Tofacitinib 20 mg/g QD
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment, 20 mg/g, QD for 12 weeks.

    Reporting group title
    Mild/Moderate: Tofacitinib 10 mg/g QD
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment 10 mg/g, QD for 12 weeks.

    Reporting group title
    Mild/Moderate: Placebo (vehicle) QD
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied placebo ointment (vehicle), QD for 12 weeks.

    Reporting group title
    Severe: Tofacitinib 20 mg/g BID
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment, 20 mg/g, BID for 12 weeks.

    Reporting group title
    Severe: Tofacitinib 10 mg/g BID
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment, 10 mg/g, BID for 12 weeks.

    Reporting group title
    Severe: Placebo (vehicle) BID
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied placebo ointment (vehicle), BID for 12 weeks.

    Reporting group title
    Severe: Tofacitinib 20 mg/g QD
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment, 20 mg/g, QD for 12 weeks.

    Reporting group title
    Severe: Tofacitinib 10 mg/g QD
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment 10 mg/g, QD for 12 weeks.

    Reporting group title
    Severe: Placebo (vehicle) QD
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied placebo ointment (vehicle), QD for 12 weeks.

    Primary: Percentage of Participants Achieving a PGA-C Response of Clear (0) or Almost Clear (1) and Greater Than or Equal to (≥) 2 Grade/point Improvement from Baseline at Week 12

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    End point title
    Percentage of Participants Achieving a PGA-C Response of Clear (0) or Almost Clear (1) and Greater Than or Equal to (≥) 2 Grade/point Improvement from Baseline at Week 12 [1]
    End point description
    Clinical signs of plaque psoriasis (erythema [E], induration [I], and scaling [S]) were scored separately according to a 5-point severity scale (0 to 4) to provide PGA subscores, which described the overall severity of each clinical sign. The PGA-C was a static assessment; i.e., without regard to a previous assessment. The PGA subscores are then summed and averaged after which the total average was rounded to the nearest whole number to determine the PGA-C score and category. A higher score indicated a higher level of severity. 0 is equal to (=) cleared except for any residual discoloration and 1=almost clear, majority of lesions had individual scores for E+I+S that when summed, averaged, and rounded equaled 1.
    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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    71
    70
    71
    70
    74
    74
    Units: Percentage of Participants
        number (not applicable)
    21.1
    12.9
    16.9
    20
    21.6
    17.6
    Statistical analysis title
    Mild/Moderate BID: Tofacitinib 20 mg/g vs Placebo
    Statistical analysis description
    The mild/moderate full analysis set (FASm) included all participants in the FAS with a baseline PGA-C disease severity of mild (2) or moderate (3). A participant with a missing value was considered a non-responder.
    Comparison groups
    Mild/Moderate: Placebo (vehicle) BID v Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    other [2]
    P-value
    = 0.5425
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in response rates
    Point estimate
    3.9
    Confidence interval
         level
    80%
         sides
    2-sided
         lower limit
    -4.3
         upper limit
    12
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.36
    Notes
    [2] - Large sample approximation to the difference in binomial proportions adjusted for the baseline PGA-C disease severity using the Cochran‑Mantel-Haenszel approach.
    Statistical analysis title
    Mild/Moderate BID: Tofacitinib 10 mg/g vs Placebo
    Statistical analysis description
    FASm included all participants in the FAS with a baseline PGA-C disease severity of mild (2) or moderate (3). A participant with a missing value was considered a non-responder.
    Comparison groups
    Mild/Moderate: Tofacitinib 10 mg/g BID v Mild/Moderate: Placebo (vehicle) BID
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [3]
    P-value
    = 0.4976
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in response rates
    Point estimate
    -4
    Confidence interval
         level
    80%
         sides
    2-sided
         lower limit
    -11.5
         upper limit
    3.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.87
    Notes
    [3] - Large sample approximation to the difference in binomial proportions adjusted for the baseline PGA-C disease severity using the Cochran‑Mantel-Haenszel approach
    Statistical analysis title
    Mild/Moderate QD: Tofacitinib 20 mg/g vs Placebo
    Statistical analysis description
    FASm included all participants in the FAS with a baseline PGA-C disease severity of mild (2) or moderate (3). A participant with a missing value was considered a non-responder.
    Comparison groups
    Mild/Moderate: Tofacitinib 20 mg/g QD v Mild/Moderate: Placebo (vehicle) QD
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    other [4]
    P-value
    = 0.6039
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in response rates
    Point estimate
    3.3
    Confidence interval
         level
    80%
         sides
    2-sided
         lower limit
    -4.9
         upper limit
    11.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.36
    Notes
    [4] - Large sample approximation to the difference in binomial proportions adjusted for the baseline PGA-C disease severity using the Cochran‑Mantel-Haenszel approach
    Statistical analysis title
    Mild/Moderate QD: Tofacitinib 10 mg/g vs Placebo
    Statistical analysis description
    FASm included all participants in the FAS with a baseline PGA-C disease severity of mild (2) or moderate (3). A participant with a missing value was considered a non-responder.
    Comparison groups
    Mild/Moderate: Tofacitinib 10 mg/g QD v Mild/Moderate: Placebo (vehicle) QD
    Number of subjects included in analysis
    148
    Analysis specification
    Pre-specified
    Analysis type
    other [5]
    P-value
    = 0.5279
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in response rate
    Point estimate
    4
    Confidence interval
         level
    80%
         sides
    2-sided
         lower limit
    -4.1
         upper limit
    12.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.34
    Notes
    [5] - Large sample approximation to the difference in binomial proportions adjusted for the baseline PGA-C disease severity using the Cochran‑Mantel-Haenszel approach

    Primary: Percentage of Participants Achieving a PGA-C Response of Clear (0) or Almost Clear (1) and ≥2 Grade/point Improvement from Baseline at Week 8

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    End point title
    Percentage of Participants Achieving a PGA-C Response of Clear (0) or Almost Clear (1) and ≥2 Grade/point Improvement from Baseline at Week 8 [6]
    End point description
    Clinical signs of plaque psoriasis (E, I, and S) were scored separately according to a 5-point severity scale (0 to 4) to provide PGA subscores, which described the overall severity of each clinical sign. The PGA-C was a static assessment; i.e., without regard to a previous assessment. The PGA subscores are then summed and averaged after which the total average was rounded to the nearest whole number to determine the PGA-C score and category. A higher score indicated a higher level of severity. 0 is equal to (=) cleared except for any residual discoloration and 1=almost clear, majority of lesions had individual scores for E+I+S that when summed, averaged, and rounded equaled 1.
    End point type
    Primary
    End point timeframe
    Baseline, Week 8
    Notes
    [6] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    71
    70
    71
    70
    74
    74
    Units: Percentage of Participants
        number (not applicable)
    22.5
    10
    11.3
    18.6
    14.9
    8.1
    Statistical analysis title
    Mild/Moderate BID: Tofacitinib 20 mg/g vs Placebo
    Statistical analysis description
    FASm. A participant with a missing value was considered a non-responder.
    Comparison groups
    Mild/Moderate: Placebo (vehicle) BID v Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    other [7]
    P-value
    = 0.071
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in response rates
    Point estimate
    10.8
    Confidence interval
         level
    80%
         sides
    2-sided
         lower limit
    3.1
         upper limit
    18.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.99
    Notes
    [7] - Large sample approximation to the difference in binomial proportions adjusted for the baseline PGA-C disease severity using the Cochran‑Mantel-Haenszel approach
    Statistical analysis title
    Mild/Moderate BID: Tofacitinib 10 mg/g vs Placebo
    Statistical analysis description
    FASm. A participant with a missing value was considered a non-responder.
    Comparison groups
    Mild/Moderate: Tofacitinib 10 mg/g BID v Mild/Moderate: Placebo (vehicle) BID
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [8]
    P-value
    = 0.8175
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in response rates
    Point estimate
    -1.2
    Confidence interval
         level
    80%
         sides
    2-sided
         lower limit
    -7.9
         upper limit
    5.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.2
    Notes
    [8] - Large sample approximation to the difference in binomial proportions adjusted for the baseline PGA-C disease severity using the Cochran‑Mantel-Haenszel approach
    Statistical analysis title
    Mild/Moderate QD: Tofacitinib 20 mg/g vs Placebo
    Statistical analysis description
    FASm. A participant with a missing value was considered a non-responder.
    Comparison groups
    Mild/Moderate: Tofacitinib 20 mg/g QD v Mild/Moderate: Placebo (vehicle) QD
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    other [9]
    P-value
    = 0.0513
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in response rates
    Point estimate
    11
    Confidence interval
         level
    80%
         sides
    2-sided
         lower limit
    3.8
         upper limit
    18.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.63
    Notes
    [9] - Large sample approximation to the difference in binomial proportions adjusted for the baseline PGA-C disease severity using the Cochran‑Mantel-Haenszel approach
    Statistical analysis title
    Mild/Moderate QD: Tofacitinib 10 mg/g vs Placebo
    Statistical analysis description
    FASm. A participant with a missing value was considered a non-responder.
    Comparison groups
    Mild/Moderate: Tofacitinib 10 mg/g QD v Mild/Moderate: Placebo (vehicle) QD
    Number of subjects included in analysis
    148
    Analysis specification
    Pre-specified
    Analysis type
    other [10]
    P-value
    = 0.2021
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in response rates
    Point estimate
    6.7
    Confidence interval
         level
    80%
         sides
    2-sided
         lower limit
    0
         upper limit
    13.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.23
    Notes
    [10] - Large sample approximation to the difference in binomial proportions adjusted for the baseline PGA-C disease severity using the Cochran‑Mantel-Haenszel approach

    Secondary: Percentage of Participants Achieving a PGA-C Response of Clear (0) or Almost Clear (1) at Week 12

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    End point title
    Percentage of Participants Achieving a PGA-C Response of Clear (0) or Almost Clear (1) at Week 12 [11]
    End point description
    Clinical signs of plaque psoriasis (E, I, and S) were scored separately according to a 5-point severity scale (0 to 4) to provide PGA subscores, which described the overall severity of each clinical sign. The PGA-C was a static assessment; i.e., without regard to a previous assessment. The PGA subscores are then summed and averaged after which the total average was rounded to the nearest whole number to determine the PGA-C score and category. A higher score indicated a higher level of severity. 0 is equal to (=) cleared except for any residual discoloration and 1=almost clear, majority of lesions had individual scores for E+I+S that when summed, averaged, and rounded equaled 1.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [11] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    71
    70
    71
    70
    74
    74
    Units: Percentage of Participants
        number (not applicable)
    33.8
    25.7
    23.9
    27.1
    29.7
    23
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving a PGA-C Response of Clear (0) or Almost Clear (1) at Week 8

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    End point title
    Percentage of Participants Achieving a PGA-C Response of Clear (0) or Almost Clear (1) at Week 8 [12]
    End point description
    Clinical signs of plaque psoriasis (E, I, and S) were scored separately according to a 5-point severity scale (0 to 4) to provide PGA subscores, which described the overall severity of each clinical sign. The PGA-C was a static assessment; i.e., without regard to a previous assessment. The PGA subscores are then summed and averaged after which the total average was rounded to the nearest whole number to determine the PGA-C score and category. A higher score indicated a higher level of severity. 0 is equal to (=) cleared except for any residual discoloration and 1=almost clear, majority of lesions had individual scores for E+I+S that when summed, averaged, and rounded equaled 1.
    End point type
    Secondary
    End point timeframe
    Week 8
    Notes
    [12] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    71
    70
    71
    70
    74
    74
    Units: Percentage of Participants
        number (not applicable)
    36.6
    20
    22.5
    32.9
    21.6
    12.2
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving a Gestalt Physician's Global Assessment (PGA-G) Response of Clear (0) or Almost Clear (1) and ≥2 Grade/point Improvement from Baseline at Week 12

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    End point title
    Percentage of Participants Achieving a Gestalt Physician's Global Assessment (PGA-G) Response of Clear (0) or Almost Clear (1) and ≥2 Grade/point Improvement from Baseline at Week 12 [13]
    End point description
    Clinical signs of plaque psoriasis (E, I and S) were scored separately according to a 5-point severity scale (0 to 4) to provide PGA subscores, which described the overall severity of each clinical sign. After scoring each of the PGA subscores, a clinical evaluator of psoriasis performed an assessment of the overall severity of psoriasis and assigned a PGA-G score and category. 0=Clear, except for any residual discoloration (post-inflammatory hyperpigmentation and/or hypopigmentation) and 1=almost clear, the psoriasis is not entirely cleared and remaining plaques are light pink (not including post inflammatory hyperpigmentation), and/or have barely palpable elevation and/or have occasional fine scale. The PGA-G was a static assessment; i.e., without regard to a previous assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [13] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    71
    70
    71
    70
    74
    74
    Units: Percentage of Participants
        number (not applicable)
    18.3
    11.4
    14.1
    15.7
    18.9
    12.2
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving a PGA-G Response of Clear (0) or Almost Clear (1) and ≥2 Grade/point Improvement from Baseline at Week 8

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    End point title
    Percentage of Participants Achieving a PGA-G Response of Clear (0) or Almost Clear (1) and ≥2 Grade/point Improvement from Baseline at Week 8 [14]
    End point description
    Clinical signs of plaque psoriasis (E, I and S) were scored separately according to a 5-point severity scale (0 to 4) to provide PGA subscores, which described the overall severity of each clinical sign. After scoring each of the PGA subscores, a clinical evaluator of psoriasis performed an assessment of the overall severity of psoriasis and assigned a PGA-G score and category. 0=Clear, except for any residual discoloration (post-inflammatory hyperpigmentation and/or hypopigmentation) and 1=almost clear, the psoriasis is not entirely cleared and remaining plaques are light pink (not including post inflammatory hyperpigmentation), and/or have barely palpable elevation and/or have occasional fine scale. The PGA-G was a static assessment; i.e., without regard to a previous assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    Notes
    [14] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    71
    70
    71
    70
    74
    74
    Units: Percentage of Participants
        number (not applicable)
    21.1
    7.1
    11.3
    15.7
    9.5
    4.1
    No statistical analyses for this end point

    Secondary: Percent Change from Baseline to Week 12 in Psoriasis Area and Severity Index (PASI)

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    End point title
    Percent Change from Baseline to Week 12 in Psoriasis Area and Severity Index (PASI) [15]
    End point description
    Combined assessment of lesion severity and area affected into single score. Body was divided into 4 regions: head, arms, trunk, legs. For each region, percent (%) area of skin involved was estimated: 0=0% to 6=90–100%. Severity was estimated by clinical signs: erythema, induration, scaling; scale: 0=none to 4=maximum. Final PASI = sum of severity parameters for each region*area score*weight of region (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4); total possible score range: 0=no disease to 72=maximal disease. The maximum PASI score was <72 since the PASI assessment excluded scalp, palms, finger nails, soles, and toe nails.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [15] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    58
    57
    55
    53
    62
    52
    Units: Percent Change from Baseline
        arithmetic mean (standard deviation)
    -36.6 ± 40.88
    -35.7 ± 43.78
    -32 ± 49.47
    -38.6 ± 36.37
    -31.4 ± 42.36
    -30 ± 38.68
    No statistical analyses for this end point

    Secondary: Percent Change from Baseline to Week 8 in PASI

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    End point title
    Percent Change from Baseline to Week 8 in PASI [16]
    End point description
    Combined assessment of lesion severity and area affected into single score. Body was divided into 4 regions: head, arms, trunk, legs. For each region, percent area of skin involved was estimated: 0=0% to 6=90-100%. Severity was estimated by clinical signs: erythema, induration, scaling; scale: 0=none to 4=maximum. Final PASI = sum of severity parameters for each region*area score*weight of region (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4); total possible score range: 0=no disease to 72=maximal disease. The maximum PASI score was <72 since the PASI assessment excluded scalp, palms, finger nails, soles, and toe nails.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    Notes
    [16] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    61
    64
    55
    60
    67
    58
    Units: Percent Change from Baseline
        arithmetic mean (standard deviation)
    -36.7 ± 36.01
    -29.1 ± 40.86
    -28.8 ± 37.06
    -36.5 ± 33.87
    -29 ± 29.47
    -27.1 ± 32.93
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving at Least a 75% Reduction in PASI Response (PASI75), Relative to Baseline at Week 12

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    End point title
    Percentage of Participants Achieving at Least a 75% Reduction in PASI Response (PASI75), Relative to Baseline at Week 12 [17]
    End point description
    Combined assessment of lesion severity and area affected into single score. Body was divided into 4 regions: head, arms, trunk, legs. For each region, percent area of skin involved was estimated: 0=0% to 6=90-100%. Severity was estimated by clinical signs: erythema, induration, scaling; scale: 0=none to 4=maximum. Final PASI = sum of severity parameters for each region*area score*weight of region (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4); total possible score range: 0=no disease to 72=maximal disease. The maximum PASI score was <72 since the PASI assessment excluded scalp, palms, finger nails, soles, and toe nails.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [17] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    71
    70
    71
    70
    74
    74
    Units: Percentage of Participants
        number (not applicable)
    16.9
    12.9
    12.7
    15.7
    10.8
    6.8
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving PASI75, Relative to Baseline at Week 8

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    End point title
    Percentage of Participants Achieving PASI75, Relative to Baseline at Week 8 [18]
    End point description
    Combined assessment of lesion severity and area affected into single score. Body was divided into 4 regions: head, arms, trunk, legs. For each region, percent area of skin involved was estimated: 0=0% to 6=90-100%. Severity was estimated by clinical signs: erythema, induration, scaling; scale: 0=none to 4=maximum. Final PASI = sum of severity parameters for each region*area score*weight of region (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4); total possible score range: 0=no disease to 72=maximal disease. The maximum PASI score was <72 since the PASI assessment excluded scalp, palms, finger nails, soles, and toe nails.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    Notes
    [18] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    71
    70
    71
    70
    74
    74
    Units: Percentage of Participants
        number (not applicable)
    14.1
    8.6
    7
    15.7
    6.8
    6.8
    No statistical analyses for this end point

    Secondary: Percent Change from Baseline to Week 12 in Body Surface Area (BSA) Affected with Psoriasis

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    End point title
    Percent Change from Baseline to Week 12 in Body Surface Area (BSA) Affected with Psoriasis [19]
    End point description
    Assessment of BSA with psoriasis was performed separately for 4 body regions: head and neck, upper limbs, trunk (including axillae and groin), and lower limbs (including buttocks). The percent surface area with psoriasis was estimated by means of the handprint method, where the full palmar hand of the participant represents approximately 1% of the total BSA. The number of handprints of psoriatic skin in a body region can be used to determine the extent (%) to which a body regions is involved with psoriasis. BSA (%)=the sum of the BSAs of the 4 body regions. BSA assessment excluded head and neck, palms, finger nails, soles and toe nails.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [19] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    58
    57
    55
    53
    62
    52
    Units: Percent Change from Baseline
        arithmetic mean (standard deviation)
    -32.8 ± 40.92
    -27.5 ± 36.4
    -27.7 ± 43.43
    -24.6 ± 36.29
    -15.6 ± 36.63
    -11.2 ± 56.38
    No statistical analyses for this end point

    Secondary: Percent Change from Baseline to Week 8 in BSA Affected with Psoriasis

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    End point title
    Percent Change from Baseline to Week 8 in BSA Affected with Psoriasis [20]
    End point description
    Assessment of BSA with psoriasis was performed separately for 4 body regions: head and neck, upper limbs, trunk (including axillae and groin), and lower limbs (including buttocks). The percent surface area with psoriasis was estimated by means of the handprint method, where the full palmar hand of the participant represents approximately 1% of the total BSA. The number of handprints of psoriatic skin in a body region can be used to determine the extent (%) to which a body regions is involved with psoriasis. BSA (%)=the sum of the BSAs of the 4 body regions. BSA assessment excluded head and neck, palms, finger nails, soles and toe nails.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    Notes
    [20] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    61
    64
    55
    60
    67
    58
    Units: Percent Change from Baseline
        arithmetic mean (standard deviation)
    -25.4 ± 44.75
    -22.5 ± 35.87
    -20.5 ± 34.9
    -17.8 ± 28.59
    -9 ± 30.08
    -11.7 ± 38.29
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 12 in Clinic-Based Itch Severity Item (ISI) Scores

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    End point title
    Change from Baseline to Week 12 in Clinic-Based Itch Severity Item (ISI) Scores [21]
    End point description
    The severity of itch (pruritus) due to psoriasis was assessed using the ISI. Participants were asked to assess their “worst itching due to psoriasis over the past 24 hours” on a numeric rating scale anchored by the terms “no itching” (0) and “worst possible itching” (10) at the ends. Participants completed the ISI assessments at the clinic (i.e., clinic-based).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [21] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    57
    57
    55
    52
    62
    52
    Units: Score on a Scale
        arithmetic mean (standard deviation)
    -2.88 ± 3.14
    -2.89 ± 3.32
    -1.73 ± 2.46
    -2.38 ± 3.182
    -1.94 ± 3.151
    -1.5 ± 2.961
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 8 in Clinic-Based ISI Scores

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    End point title
    Change from Baseline to Week 8 in Clinic-Based ISI Scores [22]
    End point description
    The severity of itch (pruritus) due to psoriasis was assessed using the ISI. Participants were asked to assess their “worst itching due to psoriasis over the past 24 hours” on a numeric rating scale anchored by the terms “no itching” (0) and “worst possible itching” (10) at the ends. Participants completed the ISI assessments at the clinic (i.e., clinic-based).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    61
    64
    55
    59
    66
    58
    Units: Score on a Scale
        arithmetic mean (standard deviation)
    -3.07 ± 2.971
    -2.38 ± 2.984
    -1.45 ± 2.847
    -2.49 ± 2.769
    -1.91 ± 3.166
    -1.34 ± 3.285
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 12 in the Dermatology Life Quality Index (DLQI) Total Score

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    End point title
    Change from Baseline to Week 12 in the Dermatology Life Quality Index (DLQI) Total Score [23]
    End point description
    DLQI is the dermatology-specific quality of life measure used for psoriatic population. The 10-item questionnaire assesses participant health-related quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment). The DLQI questions are rated by the participant as 0 (not at all/not relevant) to 3 (very much) with a total score range of 0 (best) to 30 (worst); higher scores indicate poor quality of life.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [23] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    58
    57
    55
    53
    62
    52
    Units: Score on a Scale
        arithmetic mean (standard deviation)
    -4.6 ± 5.55
    -3.2 ± 5.32
    -2.6 ± 5.45
    -5.6 ± 7.04
    -3.3 ± 5.97
    -2.3 ± 6.34
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 8 in the DLQI Total Score

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    End point title
    Change from Baseline to Week 8 in the DLQI Total Score [24]
    End point description
    DLQI is the dermatology-specific quality of life measure used for psoriatic population. The 10-item questionnaire assesses participant health-related quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment). The DLQI questions are rated by the participant as 0 (not at all/not relevant) to 3 (very much) with a total score range of 0 (best) to 30 (worst); higher scores indicate poor quality of life.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    Notes
    [24] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    61
    64
    55
    60
    67
    58
    Units: Score on a Scale
        arithmetic mean (standard deviation)
    -4.6 ± 5.16
    -2.6 ± 4.98
    -2.8 ± 4.01
    -5 ± 5.85
    -2.7 ± 4.79
    -2.2 ± 5.63
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving a Patient's Global Assessment (PtGA) Response of Clear (0) or Almost Clear (1) and ≥2 Grade/point Improvement from Baseline at Week 12 for Participants with a PtGA Score ≥2 at Baseline

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    End point title
    Percentage of Participants Achieving a Patient's Global Assessment (PtGA) Response of Clear (0) or Almost Clear (1) and ≥2 Grade/point Improvement from Baseline at Week 12 for Participants with a PtGA Score ≥2 at Baseline [25]
    End point description
    The PtGA asks the participant to evaluate the overall cutaneous disease at that point in time on a single item, 5-point scale (0=clear; 1=almost clear; 2=mild; 3=moderate; 4=severe).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [25] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    57
    57
    55
    53
    62
    52
    Units: Percentage of Participants
        number (not applicable)
    8.8
    17.5
    7.3
    13.2
    14.5
    7.7
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving a PtGA Response of Clear (0) or Almost Clear (1) and ≥2 Grade/point Improvement from Baseline at Week 8 for Participants with a PtGA Score ≥2 at Baseline

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    End point title
    Percentage of Participants Achieving a PtGA Response of Clear (0) or Almost Clear (1) and ≥2 Grade/point Improvement from Baseline at Week 8 for Participants with a PtGA Score ≥2 at Baseline [26]
    End point description
    The PtGA asks the participant to evaluate the overall cutaneous disease at that point in time on a single item, 5-point scale (0=clear; 1=almost clear; 2=mild; 3=moderate; 4=severe).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    Notes
    [26] - 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: A statistical analysis for this outcome measure was not included, because this study was an estimation trial, not a confirmatory trial.
    End point values
    Mild/Moderate: Tofacitinib 20 mg/gram (mg/g) BID Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Placebo (vehicle) QD
    Number of subjects analysed
    60
    64
    55
    60
    67
    58
    Units: Percentage of Participants
        number (not applicable)
    5
    6.3
    10.9
    10
    6
    1.7
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit.
    Adverse event reporting additional description
    The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study. All AEs (including treatment area AEs) are presented.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Mild/Moderate: Tofacitinib 10 mg/g BID
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment, 10 mg/g, BID for 12 weeks.

    Reporting group title
    Mild/Moderate: Tofacitinib 20 mg/g BID
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment, 20 mg/g, BID for 12 weeks.

    Reporting group title
    Mild/Moderate: Placebo (vehicle) BID
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied placebo ointment (vehicle), BID for 12 weeks.

    Reporting group title
    Mild/Moderate: Tofacitinib 10 mg/g QD
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment 10 mg/g, QD for 12 weeks.

    Reporting group title
    Mild/Moderate: Tofacitinib 20 mg/g QD
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied tofacitinib ointment, 20 mg/g, QD for 12 weeks.

    Reporting group title
    Mild/Moderate: Placebo (vehicle) QD
    Reporting group description
    Participants with a baseline PGA-C score of mild (2) or moderate (3) applied placebo ointment (vehicle), QD for 12 weeks.

    Reporting group title
    Severe: Tofacitinib 20 mg/g BID
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment, 20 mg/g, BID for 12 weeks.

    Reporting group title
    Severe: Tofacitinib 10 mg/g BID
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment, 10 mg/g, BID for 12 weeks.

    Reporting group title
    Severe: Placebo (vehicle) BID
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied placebo ointment (vehicle), BID for 12 weeks.

    Reporting group title
    Severe: Tofacitinib 20 mg/g QD
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment, 20 mg/g, QD for 12 weeks.

    Reporting group title
    Severe: Tofacitinib 10 mg/g QD
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied tofacitinib ointment 10 mg/g, QD for 12 weeks.

    Reporting group title
    Severe: Placebo (vehicle) QD
    Reporting group description
    Participants with a baseline PGA-C score of severe (4) applied placebo ointment (vehicle), QD for 12 weeks.

    Serious adverse events
    Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Tofacitinib 20 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Placebo (vehicle) QD Severe: Tofacitinib 20 mg/g BID Severe: Tofacitinib 10 mg/g BID Severe: Placebo (vehicle) BID Severe: Tofacitinib 20 mg/g QD Severe: Tofacitinib 10 mg/g QD Severe: Placebo (vehicle) QD
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 70 (7.14%)
    0 / 71 (0.00%)
    2 / 71 (2.82%)
    2 / 74 (2.70%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
         number of deaths (all causes)
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Arrhythmia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psoriatic arthropathy
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Mild/Moderate: Tofacitinib 10 mg/g BID Mild/Moderate: Tofacitinib 20 mg/g BID Mild/Moderate: Placebo (vehicle) BID Mild/Moderate: Tofacitinib 10 mg/g QD Mild/Moderate: Tofacitinib 20 mg/g QD Mild/Moderate: Placebo (vehicle) QD Severe: Tofacitinib 20 mg/g BID Severe: Tofacitinib 10 mg/g BID Severe: Placebo (vehicle) BID Severe: Tofacitinib 20 mg/g QD Severe: Tofacitinib 10 mg/g QD Severe: Placebo (vehicle) QD
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    29 / 70 (41.43%)
    30 / 71 (42.25%)
    27 / 71 (38.03%)
    28 / 74 (37.84%)
    34 / 70 (48.57%)
    40 / 74 (54.05%)
    2 / 7 (28.57%)
    4 / 7 (57.14%)
    4 / 7 (57.14%)
    3 / 7 (42.86%)
    2 / 6 (33.33%)
    2 / 7 (28.57%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypertension
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Hypotension
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Vasculitis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Lipoma
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    Application site pain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    2 / 74 (2.70%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Application site papules
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Asthenia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Chest pain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Fatigue
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    1 / 74 (1.35%)
    1 / 70 (1.43%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    1
    0
    0
    0
    0
    0
    0
    Application site pruritus
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Depression
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Insomnia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    Stress
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Reproductive system and breast disorders
    Erectile dysfunction
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Injury, poisoning and procedural complications
    Accident at work
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Arthropod bite
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Burns first degree
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Drug dispensing error
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Fall
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    2
    0
    0
    0
    0
    0
    0
    0
    Foot fracture
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Laceration
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Muscle strain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    1 / 74 (1.35%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    1
    0
    0
    0
    0
    0
    Post-traumatic neck syndrome
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Procedural pain
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Scar
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Skin abrasion
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 70 (2.86%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 70 (2.86%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    2
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Blood cholesterol increased
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood triglycerides increased
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Eosinophil percentage increased
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Liver function test abnormal
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    Low density lipoprotein increased
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Vitamin B12 decreased
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    White blood cell count decreased
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Catarrh
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dry throat
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Dyspnoea
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    2 / 70 (2.86%)
    3 / 74 (4.05%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    3
    0
    0
    0
    0
    0
    0
    Paranasal sinus discomfort
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Respiratory tract congestion
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Sinus congestion
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Sneezing
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    Cough
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Leukocytosis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Leukopenia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Pancytopenia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    1
    0
    0
    0
    Dysaesthesia
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Headache
         subjects affected / exposed
    2 / 70 (2.86%)
    0 / 71 (0.00%)
    2 / 71 (2.82%)
    3 / 74 (4.05%)
    3 / 70 (4.29%)
    2 / 74 (2.70%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    2
    0
    2
    3
    3
    2
    0
    0
    0
    0
    0
    0
    Migraine
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Tension headache
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Eye disorders
    Erythema of eyelid
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Eyelid oedema
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Lacrimation increased
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Ear and labyrinth disorders
    Cerumen impaction
         subjects affected / exposed
    2 / 70 (2.86%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Ear discomfort
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    Chronic gastritis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dental caries
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 71 (2.82%)
    1 / 71 (1.41%)
    1 / 74 (1.35%)
    3 / 70 (4.29%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    1
    1
    3
    0
    0
    0
    0
    0
    0
    0
    Dyspepsia
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Food poisoning
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Gastritis
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Hiatus hernia
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Inguinal hernia
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    1 / 70 (1.43%)
    2 / 71 (2.82%)
    1 / 71 (1.41%)
    3 / 74 (4.05%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    2
    2
    2
    4
    1
    0
    1
    0
    0
    0
    0
    0
    Tongue ulceration
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    1 / 74 (1.35%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    2
    1
    1
    0
    0
    0
    0
    0
    0
    0
    Abdominal tenderness
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Constipation
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Nephrolithiasis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Proteinuria
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    1 / 70 (1.43%)
    3 / 74 (4.05%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    2
    0
    0
    0
    0
    0
    0
    Glycosuria
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dermal cyst
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dermatitis contact
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 71 (1.41%)
    2 / 71 (2.82%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dry skin
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    2 / 74 (2.70%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Erythema
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    2
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Intertrigo
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Nail psoriasis
         subjects affected / exposed
    1 / 70 (1.43%)
    2 / 71 (2.82%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Onychoclasis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    1 / 71 (1.41%)
    2 / 74 (2.70%)
    2 / 70 (2.86%)
    4 / 74 (5.41%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    2
    2
    3
    2
    4
    0
    0
    1
    0
    0
    0
    Psoriasis
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    6 / 74 (8.11%)
    7 / 70 (10.00%)
    6 / 74 (8.11%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    1
    0
    8
    12
    6
    1
    0
    0
    4
    0
    2
    Rash macular
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Skin burning sensation
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    Skin fissures
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    0
    0
    0
    0
    0
    0
    Skin lesion
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    2 / 74 (2.70%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    2
    1
    0
    0
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Back pain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    Exostosis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Joint range of motion decreased
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Joint stiffness
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Neck pain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    Psoriatic arthropathy
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    1 / 70 (1.43%)
    2 / 74 (2.70%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    1
    1
    2
    0
    0
    0
    0
    0
    0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Intervertebral disc degeneration
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Osteoarthritis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    2 / 74 (2.70%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    0
    0
    0
    0
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Hyperlipidaemia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    2 / 74 (2.70%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    2
    1
    0
    0
    0
    0
    0
    0
    0
    Hypoglycaemia
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Infections and infestations
    Bacteriuria
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Bronchitis
         subjects affected / exposed
    1 / 70 (1.43%)
    2 / 71 (2.82%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    1 / 70 (1.43%)
    1 / 74 (1.35%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    2
    0
    1
    1
    1
    1
    0
    1
    0
    0
    0
    Chronic tonsillitis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Ear infection
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Fungal infection
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    2 / 70 (2.86%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    0
    0
    0
    0
    0
    0
    Gastrointestinal viral infection
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Gingivitis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Infected bites
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Influenza
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    1 / 74 (1.35%)
    2 / 70 (2.86%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    1
    2
    0
    0
    0
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    2 / 70 (2.86%)
    3 / 71 (4.23%)
    1 / 71 (1.41%)
    7 / 74 (9.46%)
    5 / 70 (7.14%)
    11 / 74 (14.86%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    2
    3
    1
    7
    6
    13
    0
    1
    0
    0
    0
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Oral herpes
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Otitis externa
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Paronychia
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Pharyngitis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Pulpitis dental
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Pyelonephritis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Rash pustular
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Rhinitis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    1 / 70 (1.43%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Sepsis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Sinusitis
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 71 (1.41%)
    2 / 71 (2.82%)
    1 / 74 (1.35%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    2
    1
    0
    1
    0
    0
    0
    0
    0
    0
    Tooth abscess
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Tooth infection
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 71 (2.82%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    10 / 70 (14.29%)
    2 / 71 (2.82%)
    6 / 71 (8.45%)
    0 / 74 (0.00%)
    2 / 70 (2.86%)
    1 / 74 (1.35%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    11
    2
    7
    0
    2
    1
    1
    0
    0
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    2 / 70 (2.86%)
    0 / 71 (0.00%)
    6 / 71 (8.45%)
    2 / 74 (2.70%)
    1 / 70 (1.43%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    2
    0
    6
    2
    1
    1
    0
    0
    0
    1
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    1 / 74 (1.35%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Cystitis
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Cystitis escherichia
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Erysipelas
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Impetigo
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    0 / 74 (0.00%)
    0 / 70 (0.00%)
    0 / 74 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Dec 2013
    Added Text for clarity in Sections: Protocol Summary, Schedule of Activities, Section 1.1.4, Section 3, Section 4, Section 5.2, Section 6, Section 7.1, Section 7.3.1, Section 7.4, Section 7.5, Section 7.7, Section 7.8, Section 8.2, Section 8.3, Section 8.5, Section 8.9, Section 8.10, Section 8.12.3, Section 9.5, Section 9.7, Section 9.9, Section 12.2, Section 12.3, Appendix 2.1, Appendix 4, Appendix 5.

    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.
    Efficacy results for participants in the severe population were not reported since this was considered an exploratory population.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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