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    Clinical Trial Results:
    A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER, DOSE-RANGING STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PF-04236921 IN SUBJECTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

    Summary
    EudraCT number
    2011-000420-15
    Trial protocol
    DE   HU  
    Global end of trial date
    26 Mar 2014

    Results information
    Results version number
    v2(current)
    This version publication date
    16 Mar 2016
    First version publication date
    30 Jul 2015
    Other versions
    v1
    Version creation reason
    • Correction of full data set
    SAE event information

    Trial information

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    Trial identification
    Sponsor protocol code
    B0151006
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01405196
    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
    01 Jul 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Mar 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to evaluate and compare the efficacy of 3 dose levels of PF-04236921 to placebo in subjects with active SLE using the SLE Responder Index (SRI).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    16 Dec 2011
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    6 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 92
    Country: Number of subjects enrolled
    Argentina: 28
    Country: Number of subjects enrolled
    Chile: 1
    Country: Number of subjects enrolled
    Colombia: 10
    Country: Number of subjects enrolled
    Germany: 3
    Country: Number of subjects enrolled
    Hungary: 9
    Country: Number of subjects enrolled
    Korea, Republic of: 1
    Country: Number of subjects enrolled
    Moldova, Republic of: 15
    Country: Number of subjects enrolled
    Peru: 4
    Country: Number of subjects enrolled
    Poland: 13
    Country: Number of subjects enrolled
    Romania: 7
    Worldwide total number of subjects
    183
    EEA total number of subjects
    32
    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)
    179
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    The study started on 8 November 2011 and completed on 26 March 2014. Subjects were enrolled from 11 countries (Argentina, Chile, Columbia, Germany, Hungary, Republic of Korea, Republic of Moldova, Peru, Poland, Romania and United states).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    PF-04236921 10 milligram (10 mg)
    Arm description
    Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-04236921
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    10 mg dose of PF-04236921 subcutaneously at Week 0, Week 8 and Week 16.

    Arm title
    PF-04236921 50 mg
    Arm description
    Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-04236921
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    50 mg dose of PF-04236921 subcutaneously at Week 0, Week 8 and Week 16.

    Arm title
    PF-04236921 200 mg
    Arm description
    Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-04236921
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    200 mg dose of PF-04236921 subcutaneously at Week 0, Week 8 and Week 16.

    Arm title
    Placebo
    Arm description
    Placebo matching to PF-04236921 administered subcutaneously in the anterolateral right and left thighs.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo administered subcutaneously in the anterolateral right and left thighs at Week 0, Week 8 and Week 16.

    Number of subjects in period 1
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg PF-04236921 200 mg Placebo
    Started
    45
    47
    46
    45
    Completed
    34
    35
    23
    36
    Not completed
    11
    12
    23
    9
         Study Terminated by Sponsor
    -
    -
    9
    -
         Consent withdrawn by subject
    4
    6
    3
    6
         Unspecified
    2
    2
    5
    -
         Adverse Event
    2
    2
    -
    2
         Lost to follow-up
    2
    2
    3
    1
         Subject Died
    1
    -
    3
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    PF-04236921 10 milligram (10 mg)
    Reporting group description
    Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.

    Reporting group title
    PF-04236921 50 mg
    Reporting group description
    Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.

    Reporting group title
    PF-04236921 200 mg
    Reporting group description
    Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.

    Reporting group title
    Placebo
    Reporting group description
    Placebo matching to PF-04236921 administered subcutaneously in the anterolateral right and left thighs.

    Reporting group values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg PF-04236921 200 mg Placebo Total
    Number of subjects
    45 47 46 45 183
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    39.9 ± 11.48 38.3 ± 10.49 41.3 ± 11.29 42.3 ± 13.04 -
    Gender categorical
    Units: Subjects
        Female
    43 44 43 38 168
        Male
    2 3 3 7 15

    End points

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    End points reporting groups
    Reporting group title
    PF-04236921 10 milligram (10 mg)
    Reporting group description
    Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.

    Reporting group title
    PF-04236921 50 mg
    Reporting group description
    Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.

    Reporting group title
    PF-04236921 200 mg
    Reporting group description
    Subjects received PF-04236921 subcutaneously in the anterolateral right and left thighs.

    Reporting group title
    Placebo
    Reporting group description
    Placebo matching to PF-04236921 administered subcutaneously in the anterolateral right and left thighs.

    Primary: Percentage of Subjects Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 24

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    End point title
    Percentage of Subjects Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 24 [1]
    End point description
    SRI components: Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI 2K),British Isles Lupus Activity Group(BILAG) 2004,Physician’s Global Assessment(PhGA).Subjects classified as responder if they did not meet definition of treatment failure and met all the following criteria: greater than or equal to (>=)4 point reduction in SLEDAI 2K score; no new BILAG A organ domain score/2 new BILAG B organ domain scores; less than (<) 0.3 point increase in PhGA score. Treatment failure: any new/increased use of corticosteroids,immunosuppressants/antimalarial drug,death,hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with study participation. SLEDAI-2K:assesses improvement in disease activity(0 to 105;higher score=higher severity). BILAG:assesses disease extent, severity (A [severe] to E [no disease]). PhGA: assesses worsening in subject’s general health status(0[none] to 3[severe]). Full Analysis Set (FAS) excluding 200-mg dose group.
    End point type
    Primary
    End point timeframe
    Week 24
    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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg Placebo
    Number of subjects analysed
    35 [2]
    36 [3]
    42 [4]
    Units: Percentage of Subjects
        number (not applicable)
    59.9
    39.2
    40.1
    Notes
    [2] - Here, 'N' signifies subjects who completed through the Week 24 visit for each group respectively.
    [3] - Here, 'N' signifies subjects who completed through the Week 24 visit for each group respectively.
    [4] - Here, 'N' signifies subjects who completed through the Week 24 visit for each group respectively.
    Statistical analysis title
    Analysis for SRI: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the Odds ratio (ORs) as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.076 [5]
    Method
    Mixed models analysis
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.23
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.89
         upper limit
    5.62
    Notes
    [5] - P-value was displayed without adjusting for multiplicity.
    Statistical analysis title
    Analysis for SRI: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.528 [6]
    Method
    Mixed models analysis
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.96
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.38
         upper limit
    2.41
    Notes
    [6] - P-value was displayed without adjusting for multiplicity.

    Secondary: Percentage of Subjects Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, and 20

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    End point title
    Percentage of Subjects Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, and 20 [7]
    End point description
    SRI components: SLEDAI 2K, BILAG 2004, PhGA. Subjects classified as responder if they did not meet definition of treatment failure and met all the following criteria: >=4 point reduction in SLEDAI 2K score; no new BILAG A organ domain score/2 new BILAG B organ domain scores; <0.3 point increase in PhGA score. Treatment failure: any new/increased use of corticosteroids,immunosuppressants/antimalarial drug,death,hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with study participation. SLEDAI-2K:assesses improvement in disease activity(0 to 105;higher score=higher severity). BILAG:assesses disease extent, severity (A [severe] to E [no disease]). PhGA: assesses worsening in subject’s general health status(0[none] to 3[severe]). Full Analysis Set (FAS) excluding 200-mg dose group; 'n' = subjects evaluable at specified time point.
    End point type
    Secondary
    End point timeframe
    Week 4, 8, 12, 16, 20
    Notes
    [7] - 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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg Placebo
    Number of subjects analysed
    45
    47
    45
    Units: Percentage of Subjects
    number (not applicable)
        Week 4 (n=43, 44, 45)
    12.2
    7.1
    4.8
        Week 8 (n=43, 43, 43)
    26.8
    21.5
    26.3
        Week 12 (n=39, 41, 42)
    33.7
    20
    36.3
        Week 16 (n=36, 39, 41)
    48.9
    28.9
    37.1
        Week 20 (n=36, 39, 43)
    54.7
    36.8
    38.3
    Statistical analysis title
    Analysis at Week 4: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.77
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.62
         upper limit
    12.4
    Statistical analysis title
    Analysis at Week 4: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.54
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.31
         upper limit
    7.71
    Statistical analysis title
    Analysis at Week 8: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.03
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.4
         upper limit
    2.67
    Statistical analysis title
    Analysis at Week 8: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.77
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.29
         upper limit
    2.05
    Statistical analysis title
    Analysis at Week 12: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.89
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.35
         upper limit
    2.24
    Statistical analysis title
    Analysis at Week 12: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.44
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.16
         upper limit
    1.16
    Statistical analysis title
    Analysis at Week 16: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.62
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.64
         upper limit
    4.09
    Statistical analysis title
    Analysis at Week 16: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.69
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.27
         upper limit
    1.77
    Statistical analysis title
    Analysis at Week 20: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.95
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.78
         upper limit
    4.84
    Statistical analysis title
    Analysis at Week 20: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.94
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.38
         upper limit
    2.32

    Secondary: Percentage of Subjects Achieving Modified Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, 20, and 24

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    End point title
    Percentage of Subjects Achieving Modified Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, 20, and 24 [8]
    End point description
    SRI components include: modified SLEDAI 2K (SLEDAI 2K without standard parameters "Low complement" and "Leukopenia"), BILAG 2004, PhGA. Subjects classified as responder if they did not meet definition of treatment failure and met all the following criteria: >=4 point reduction in SLEDAI 2K score; no new BILAG A organ domain score or 2 new BILAG B organ domain scores; <0.3 point increase in PhGA score. Treatment failure: any new/increased use of corticosteroids, immunosuppressants/antimalarial drug, death, hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with study participation. Modified SLEDAI-2K: assesses improvement in disease activity (0 to 102; higher score = higher severity). BILAG: assesses disease extent, severity (A [severe] to E [no disease]). PhGA: assesses worsening in subject’s general health status (0[none] to 3[severe]). FAS excluding the subjects in the 200-mg dose group; 'n' = subjects evaluable at specified time point.
    End point type
    Secondary
    End point timeframe
    Week 4, 8, 12, 16, 20, 24
    Notes
    [8] - 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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg Placebo
    Number of subjects analysed
    45
    47
    45
    Units: Percentage of Subjects
    number (not applicable)
        Week 4 (n=43, 44, 45)
    9.5
    7
    9.2
        Week 8 (n=43, 43, 43)
    23.8
    25.7
    30.2
        Week 12 (n=39, 41, 42)
    35.6
    24.9
    42.6
        Week 16 (n=36, 39, 41)
    50.2
    34
    41
        Week 20 (n=36, 39, 43)
    56.5
    46.9
    42.2
        Week 24 (n=35, 36, 42)
    61.2
    41.4
    41.6
    Statistical analysis title
    Analysis at Week 4: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.05
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.28
         upper limit
    3.88
    Statistical analysis title
    Analysis at Week 4: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.75
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.19
         upper limit
    3.01
    Statistical analysis title
    Analysis at Week 8: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.72
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.28
         upper limit
    1.85
    Statistical analysis title
    Analysis at Week 8: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.8
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.32
         upper limit
    2.02
    Statistical analysis title
    Analysis at Week 12: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.75
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.3
         upper limit
    1.83
    Statistical analysis title
    Analysis at Week 12: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    Placebo v PF-04236921 50 mg
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.45
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.18
         upper limit
    1.13
    Statistical analysis title
    Analysis at Week 16: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.45
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.58
         upper limit
    3.6
    Statistical analysis title
    Analysis at Week 16: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    Placebo v PF-04236921 50 mg
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.74
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.3
         upper limit
    1.84
    Statistical analysis title
    Analysis at Week 20: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    Placebo v PF-04236921 10 milligram (10 mg)
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.78
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.72
         upper limit
    4.37
    Statistical analysis title
    Analysis at Week 20: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.21
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.5
         upper limit
    2.92
    Statistical analysis title
    Analysis at Week 24: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    Placebo v PF-04236921 10 milligram (10 mg)
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.22
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.89
         upper limit
    5.55
    Statistical analysis title
    Analysis at Week 24: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.4
         upper limit
    2.46

    Secondary: Percentage of Subjects Achieving British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response at Week 4, 8, 12, 16, 20, and 24

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    End point title
    Percentage of Subjects Achieving British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response at Week 4, 8, 12, 16, 20, and 24 [9]
    End point description
    BICLA include: BILAG-2004, SLEDAI-2K, PhGA of disease activity. Subjects classified as responder if they did not meet definition of treatment failure and met all the following criteria: BILAG-2004 improvement(all A scores at baseline improved to B/C/D, all B scores improved to C or D); no worsening in disease activity(no new BILAG-2004 A scores or =<1 new B score); no worsening of total SLEDAI-2K score; no <10 percent [%] worsening in analogue PhGA. Treatment failure: any new/increased use of corticosteroids, immunosuppressants/antimalarial, death, hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with study participation. BILAG:assesses disease extent, severity (A[severe] to E[no disease]). SLEDAI-2K:assesses improvement in disease activity (0 to 105; higher score=higher severity). PhGA: assesses worsening in subject’s general health status(0[none] to 3[severe]). FAS excluding 200-mg dose group; 'n' = subjects evaluable at specified time point.
    End point type
    Secondary
    End point timeframe
    Week 4, 8, 12, 16, 20, 24
    Notes
    [9] - 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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg Placebo
    Number of subjects analysed
    45
    47
    45
    Units: Percentage of Subjects
    number (not applicable)
        Week 4 (n=43, 44, 45)
    26.2
    21.7
    21
        Week 8 (n=43, 43, 43)
    26.2
    29
    30.6
        Week 12 (n=39, 41, 42)
    33.6
    39.6
    33.3
        Week 16 (n=36, 39, 41)
    45.5
    39.2
    26.2
        Week 20 (n=35, 39, 43)
    43.7
    31.6
    21.7
        Week 24 (n=35, 36, 42)
    49.7
    40.5
    25.1
    Statistical analysis title
    Analysis at Week 4: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.34
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.53
         upper limit
    3.35
    Statistical analysis title
    Analysis at Week 4: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.04
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.41
         upper limit
    2.65
    Statistical analysis title
    Analysis at Week 8: PF-04236921 10 mg v. Placebo
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.81
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.33
         upper limit
    1.96
    Statistical analysis title
    Analysis at Week 8: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.93
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.39
         upper limit
    2.23
    Statistical analysis title
    Analysis at Week 12: PF-04236921 10 mg v. Placebo
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.01
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.42
         upper limit
    2.45
    Statistical analysis title
    Analysis at Week 12: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.31
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.55
         upper limit
    3.1
    Statistical analysis title
    Analysis at Week 16: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.36
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.95
         upper limit
    5.88
    Statistical analysis title
    Analysis at Week 16: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    Placebo v PF-04236921 50 mg
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.82
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.74
         upper limit
    4.46
    Statistical analysis title
    Analysis at Week 20: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    Placebo v PF-04236921 10 milligram (10 mg)
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.8
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    1.1
         upper limit
    7.12
    Statistical analysis title
    Analysis at Week 20: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.67
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.66
         upper limit
    4.21
    Statistical analysis title
    Analysis at Week 24: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.95
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    1.18
         upper limit
    7.41
    Statistical analysis title
    Analysis at Week 24: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.03
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.82
         upper limit
    5.06

    Secondary: Percentage of Subjects Achieving Pre-defined Criteria for Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Components at Week 24

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    End point title
    Percentage of Subjects Achieving Pre-defined Criteria for Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Components at Week 24 [10]
    End point description
    SRI components: SLEDAI 2K, BILAG 2004, PhGA. Subjects classified as responder if they did not meet definition of treatment failure, met all the following criteria: >=4 point reduction in SLEDAI 2K score; no new BILAG A organ domain score/2 new BILAG B organ domain scores;<0.3 point increase in PhGA score. Treatment failure: any new/increased use of corticosteroids,immunosuppressants/antimalarial drug,death, hospitalization/treatment discontinuation due to SLE,any flare of lupus interfering with study participation. SLEDAI-2K:assesses improvement in disease activity(0 to 105;higher score=higher severity).BILAG:assesses disease extent, severity (A[severe] to E[no disease]). PhGA: assesses worsening in subject’s general health (0[none] to 3[severe]). FAS excluding 200-mg dose group; 'n' = subjects evaluable for specified categories. Model percent estimates reported only for 'Reduction in SLEDAI Score', 'No Worsening in PhGA' categories; for remaining categories, raw percentages reported.
    End point type
    Secondary
    End point timeframe
    Week 24
    Notes
    [10] - 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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg Placebo
    Number of subjects analysed
    34 [11]
    36 [12]
    41 [13]
    Units: Percentage of Subjects
    number (not applicable)
        4 or More Points Reduction in SLEDAI Score
    60.7
    44.9
    49.3
        No New 1A/2B BILAG
    100
    100
    90.2
        No Worsening in PhGA
    97.4
    97.5
    93.1
        Treatment Failure
    0
    2.8
    4.9
    Notes
    [11] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
    [12] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
    [13] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
    Statistical analysis title
    SLEDAI component: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    >=4 points reduction in SLEDAI score: Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.205 [14]
    Method
    Mixed models analysis
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.59
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.63
         upper limit
    4.02
    Notes
    [14] - P-value was displayed without adjusting for multiplicity.
    Statistical analysis title
    SLEDAI Component: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    >=4 points reduction in SLEDAI score: Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.625 [15]
    Method
    Mixed models analysis
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.84
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.34
         upper limit
    2.08
    Notes
    [15] - P-value was displayed without adjusting for multiplicity.
    Statistical analysis title
    PhGA Component: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    No worsening in PhGA: Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.198 [16]
    Method
    Mixed models analysis
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.81
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.38
         upper limit
    20.65
    Notes
    [16] - P-value was displayed without adjusting for multiplicity.
    Statistical analysis title
    PhGA Component: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    No worsening in PhGA: Point estimates of the ORs as well as their confidence intervals were calculated from the generalized linear mix model that included fixed factors of the stratification factors, treatment, visit and treatment by visit.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.192 [17]
    Method
    Mixed models analysis
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.88
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.39
         upper limit
    21.3
    Notes
    [17] - P-value was displayed without adjusting for multiplicity.

    Secondary: Number of Subjects With Clinically Significant Laboratory Tests Results

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    End point title
    Number of Subjects With Clinically Significant Laboratory Tests Results
    End point description
    Pre-defined criteria were established for each laboratory test to define values that would be identified as of potential clinical importance. Laboratory values included Alanine Aminotransferase(ALT) [>5.0-10.0*Upper limit of normal range(ULN)], Albumin[<26-20 gram per liter(g/L)/<20 g/L], Amylase[>2.0-5.0*ULN], Aspartate Aminotransferase (AST)[>5.0-10.0*ULN], Creatine Kinase(CK)[>5.0-10.0*ULN/ >10.0*ULN], Glucose(Hyperglycemia)[>13.9-27.8millimoles/liter(mmol/L)],Hemoglobin(HGB)[<80-65g/L/<65g/L],Lipase[>2.0-5.0*ULN], Lymphocytes(Lymph.)(Absolute[Abs])[<0.5-0.2*10^3/microliter(UL)/<0.2*10^3/UL],Platelets[<50-25*10^3/UL/<25*10^3/UL],potassium (low)[<3.0-2.5 mmol/L], Sodium(low)[<130-120 mmol/L], Total Neutrophils(TN) (Abs)[<1.0-0.5*10^3/UL/ <0.5*10^3/UL], Triglycerides[>5.7-11.4 mmol/L], White Blood Cell Count(WBC)[<2.0-1.0*10^3/UL/<1.0*10^3/UL]. Safety population: all subjects who had at least 1 dose of investigational product; 'n'= subjects evaluable for specified parameter.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg PF-04236921 200 mg Placebo
    Number of subjects analysed
    45
    47
    46
    45
    Units: Subjects
        ALT (n=45, 47, 45, 45)
    2
    0
    0
    0
        Albumin: <26-20 g/L (n=45, 47, 45, 45)
    1
    1
    1
    1
        Albumin: <20 g/L (n=45, 47, 45, 45)
    0
    1
    0
    0
        Amylase (n=45, 47, 45, 45)
    1
    1
    1
    1
        AST (n=45, 47, 45, 45)
    0
    1
    0
    1
        CK: >5.0 -10.0*ULN (n=45,47,45,45)
    0
    1
    1
    0
        CK >10.0*ULN (n=45,47,45,45)
    0
    1
    1
    0
        Glucose (Hyperglycemia) (n=45,47,45,45)
    1
    1
    0
    2
        HGB: <80 - 65 g/L (n=45,47,45,45)
    1
    0
    0
    1
        HGB: <65 g/L (n=45,47,45,45)
    1
    0
    0
    0
        Lipase (n=45,47,45,45)
    0
    1
    1
    0
        Lymph.(Abs)<0.5-0.2* 10^3/UL(n=45,47,45,45)
    6
    9
    4
    8
        Lymphocytes (Abs) <0.2*10^3/UL (n=45,47,45,45)
    1
    0
    0
    0
        Platelets <50 - 25*10^3/UL (n=45,47,45,45)
    0
    0
    0
    2
        Platelets <25*10^3/UL (n=45,47,45,45)
    0
    0
    0
    1
        Potassium (low) (n=45,47,45,45)
    2
    1
    1
    1
        Sodium (low) (n=45,47,45,45)
    0
    0
    1
    0
        TN (Abs)<1.0-0.5*10^3/UL (n=45,47,45,45)
    4
    5
    3
    2
        TN (Abs) <0.5*10^3/UL (n=45,47,45,45)
    1
    1
    1
    0
        Triglycerides (n=44,47,45,45)
    0
    1
    0
    2
        WBC <2.0 - 1.0*10^3/UL (n=45,47,45,45)
    4
    2
    2
    2
        WBC <1.0*10^3/UL (n=45,47,45,45)
    1
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects who Discontinued due to Adverse Events

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    End point title
    Number of Subjects who Discontinued due to Adverse Events
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Number of subjects who discontinued due to AEs were reported. Safety population defined as all subjects who had at least one dose of investigational product.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg PF-04236921 200 mg Placebo
    Number of subjects analysed
    45
    47
    46
    45
    Units: Subjects
    3
    2
    3
    3
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

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    End point title
    Number of Subjects With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 52 that were absent before treatment or that worsened relative to pretreatment state. Number of subjects with treatment-emergent AEs or SAEs (excluding infectious AEs or SAEs) were reported. AEs include both SAEs and non-SAEs.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg PF-04236921 200 mg Placebo
    Number of subjects analysed
    45
    47
    46
    45
    Units: Subjects
        AEs
    34
    36
    38
    40
        SAEs
    4
    2
    7
    8
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-Emergent Infectious Adverse Events (AEs) or Serious Adverse Events (SAEs)

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    End point title
    Number of Subjects With Treatment-Emergent Infectious Adverse Events (AEs) or Serious Adverse Events (SAEs)
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 52 that were absent before treatment or that worsened relative to pretreatment state. Number of subjects with treatment-emergent infectious AEs or SAEs were reported. AEs include both SAEs and non-SAEs. Safety population defined as all subjects who had at least one dose of investigational product.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg PF-04236921 200 mg Placebo
    Number of subjects analysed
    45
    47
    46
    45
    Units: Subjects
        Infectious AEs
    25
    28
    25
    26
        Infectious SAEs
    2
    3
    4
    4
    No statistical analyses for this end point

    Secondary: Number of Subjects With Potentially Clinically Important (PCI) Electrocardiogram (ECG) Findings

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    End point title
    Number of Subjects With Potentially Clinically Important (PCI) Electrocardiogram (ECG) Findings
    End point description
    Criteria for PCI findings in ECG were defined as: heart rate <=40 beats per minute (bpm) or >=120 bpm; PR interval >=220 millisecond (msec); QT interval >=480 msec; QRS interval >=120 msec; QT interval corrected using the Fridericia formula (QTcF) >=500msec; no sinus rhythm. Safety population defined as all subjects who had at least one dose of investigational product.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg PF-04236921 200 mg Placebo
    Number of subjects analysed
    42 [18]
    46 [19]
    44 [20]
    44 [21]
    Units: Subjects
        Heart Rate <=40 beats/min or >=120 beats/min
    0
    0
    0
    0
        PR Interval >=200 msec
    2
    1
    1
    2
        QT Interval >=480 msec
    2
    0
    0
    0
        QRS Interval >=120 msec
    3
    1
    2
    2
        QTcF >=500 msec
    2
    0
    0
    0
        Rhythm (Not Sinus Rhythm)
    0
    0
    0
    1
    Notes
    [18] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
    [19] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
    [20] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
    [21] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Potentially Clinically Important Vital Signs Findings

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    End point title
    Number of Subjects With Potentially Clinically Important Vital Signs Findings
    End point description
    Criteria for PCI findings in vital signs were defined as: sitting systolic blood pressure (Increase from baseline >=20 millimeter of mercury (mm Hg) and >=160 mm Hg or a decrease from baseline >=20 mm Hg and <=90 mm Hg) and sitting diastolic blood pressure (increase from baseline >=15 mm Hg and >=90 mm Hg or decrease from baseline >=15 mm Hg and <=60 mm Hg), pulse rate (increase from baseline >=15 beats/min and >=120 beats/min or decrease from baseline >=15 beats/min and <=50 beats /min), body temperature (increase of >=2 degree Fahrenheit (F) and temperature >=101 degree F) and weight (change of >=7% in body weight). Safety population defined as all subjects who had at least one dose of investigational product.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg PF-04236921 200 mg Placebo
    Number of subjects analysed
    45
    47
    46
    45
    Units: Subjects
        Sitting Systolic Blood Pressure
    8
    3
    3
    5
        Sitting Diastolic Blood Pressure
    14
    14
    12
    14
        Sitting Pulse Rate
    1
    1
    0
    1
        Temperature
    0
    0
    0
    0
        Weight
    12
    23
    14
    14
    No statistical analyses for this end point

    Secondary: Number of Subjects With Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (Nabs)

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    End point title
    Number of Subjects With Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (Nabs)
    End point description
    Human serum samples were analyzed for the presence or absence of anti-PF-04236921 antibodies. A positive ADA sample was further tested for neutralizing antibodies using a validated assay. Safety population defined as all subjects who had at least one dose of investigational product.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg PF-04236921 200 mg Placebo
    Number of subjects analysed
    45
    47
    46
    45
    Units: Subjects
        Anti-drug Antibodies
    1
    0
    1
    0
        Neutralizing Antibodies
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Serum concentration of PF-04236921

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    End point title
    Serum concentration of PF-04236921 [22]
    End point description
    Serum PF-04236921 concentrations over time were summarized. Pharmacokinetic analysis set was the subset of subjects from safety analysis set (all subjects who received at least 1 dose of investigational product) who provided at least 1 pharmacokinetic concentration. Here, 'n' signifies number of observations (non-missing concentrations) at the specified time points for each group respectively.
    End point type
    Secondary
    End point timeframe
    Day 1, Week 2, 4, 6, 8, 12, 16, 20, 24
    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: Serum concentration of PF-04236921 was not planned to be reported for placebo group.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg PF-04236921 200 mg
    Number of subjects analysed
    45
    47
    46
    Units: nanogram per milliliter (ng/mL)
    arithmetic mean (standard deviation)
        Day 1 (n=42, 45, 43)
    26.3 ± 110.8
    31 ± 146.9
    15.2 ± 99.8
        Week 2 (n=37, 41, 40)
    1297 ± 759.4
    5640 ± 2274
    22780 ± 9896
        Week 4 (n=39, 42, 38)
    991.8 ± 527.6
    4337 ± 1495
    17550 ± 5757.1
        Week 6 (n=39, 40, 37)
    608.4 ± 330.1
    3396 ± 1410
    13460 ± 5416.6
        Week 8 (n=39, 38, 30)
    463.4 ± 254.9
    2709 ± 1317.5
    11110 ± 5023.7
        Week 12 (n=32, 33, 28)
    1210 ± 607
    6482 ± 2487.4
    25240 ± 8114
        Week 16 (n=31, 36, 23)
    703.2 ± 407.4
    3886 ± 1322.1
    16990 ± 6203.4
        Week 20 (n=30, 34, 17)
    1452 ± 726.8
    6978 ± 2954
    31050 ± 11368
        Week 24 (n=31, 34, 18)
    871.9 ± 450.4
    4417 ± 2402.4
    20150 ± 12091
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Corticosteroid Dose Reduced by Both Greater Than or Equal to (>=) 25 Percent (%) From Baseline and Less Than or Equal to (<=) 7.5 Milligrams per day (mg/day)

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    End point title
    Percentage of Subjects With Corticosteroid Dose Reduced by Both Greater Than or Equal to (>=) 25 Percent (%) From Baseline and Less Than or Equal to (<=) 7.5 Milligrams per day (mg/day) [23]
    End point description
    Subjects were given supplemental corticosteroids at baseline to control disease activity. The steroid taper was based on subject’s symptoms. Subjects recorded their steroid usage on a diary card. FAS excluding subjects in 200-mg dose group; Least Observation Carried Forward(LOCF) method was used to impute missing data.
    End point type
    Secondary
    End point timeframe
    Week 12, 16, 20, 24
    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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg PF-04236921 200 mg
    Number of subjects analysed
    15 [24]
    24 [25]
    23 [26]
    Units: Percentage of Subjects
    number (not applicable)
        Week 12
    13.3
    20.8
    8.7
        Week 16
    20
    25
    8.7
        Week 20
    26.7
    25
    8.7
        Week 24
    26.7
    20.8
    8.7
    Notes
    [24] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
    [25] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
    [26] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Normalized Serological Activity

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    End point title
    Percentage of Subjects With Normalized Serological Activity [27]
    End point description
    Serologic activity was to be assessed in the subgroup of subjects who had positive serologic activity at baseline.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    Notes
    [27] - 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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg Placebo
    Number of subjects analysed
    0 [28]
    0 [29]
    0 [30]
    Units: Percentage of Subjects
        number (not applicable)
    Notes
    [28] - Data was not analyzed as number of subjects with abnormal values at baseline was minimal (<=25%).
    [29] - Data was not analyzed as number of subjects with abnormal values at baseline was minimal (<=25%).
    [30] - Data was not analyzed as number of subjects with abnormal values at baseline was minimal (<=25%).
    No statistical analyses for this end point

    Secondary: Patient Global Visual Analog Scale (VAS) Scores at Baseline

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    End point title
    Patient Global Visual Analog Scale (VAS) Scores at Baseline [31]
    End point description
    Subjects assessed their disease activity using a 100 mm VAS. Subjects answered the following question “Considering all the ways your disease affects you, how are you feeling today?” Response was recorded by placing a mark on the scale between 0 (very well) and 100 (extremely bad). FAS excluding the subjects in the 200-mg dose group.
    End point type
    Secondary
    End point timeframe
    Baseline
    Notes
    [31] - 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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg Placebo
    Number of subjects analysed
    45
    47
    45
    Units: mm
        arithmetic mean (standard error)
    50.44 ± 2.865
    47.7 ± 2.88
    49.47 ± 3.349
    No statistical analyses for this end point

    Secondary: Change From Baseline in Patient Global Visual Analog Scale (VAS) at Week 2, 4, 6, 8, 12, 16, 20 and 24

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    End point title
    Change From Baseline in Patient Global Visual Analog Scale (VAS) at Week 2, 4, 6, 8, 12, 16, 20 and 24 [32]
    End point description
    Subjects assessed their disease activity using a 100 mm VAS. Subjects answered the following question “Considering all the ways your disease affects you, how are you feeling today?” Response was recorded by placing a mark on the scale between 0 (very well) and 100 (extremely bad). FAS excluding the subjects in the 200-mg dose group; 'n' =subjects evaluable at specified time point. LOCF method was used to impute missing values.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24
    Notes
    [32] - 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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg Placebo
    Number of subjects analysed
    45
    47
    45
    Units: mm
    least squares mean (confidence interval 95%)
        Week 2 (n=44, 47, 43)
    -9.17 (-15.09 to -3.26)
    -1.54 (-7.22 to 4.15)
    -3.58 (-9.49 to 2.34)
        Week 4 (n=45, 47, 45)
    -3.24 (-9.09 to 2.62)
    -4.01 (-9.69 to 1.68)
    -1.24 (-7.02 to 4.55)
        Week 6 (n=45, 47, 45)
    -5.48 (-11.33 to 0.37)
    -3.62 (-9.31 to 2.06)
    -7.24 (-13.02 to -1.45)
        Week 8 (n=45, 47, 45)
    -4.17 (-10.02 to 1.68)
    -6.03 (-11.71 to -0.34)
    -7.11 (-12.89 to -1.32)
        Week 12 (n=45, 47, 45)
    -9.21 (-15.07 to -3.36)
    -4.2 (-9.88 to 1.49)
    -6.88 (-12.67 to -1.1)
        Week 16 (n=45, 47, 45)
    -8.75 (-14.6 to -2.89)
    -10.2 (-15.88 to -4.51)
    -5.99 (-11.78 to -0.21)
        Week 20 (n=45, 47, 45)
    -11.52 (-17.38 to -5.67)
    -9.03 (-14.71 to -3.34)
    -6.77 (-12.56 to -0.99)
        Week 24 (n=45, 47, 45)
    -9.17 (-15.02 to -3.32)
    -7.45 (-13.14 to -1.77)
    -10.64 (-16.42 to -4.85)
    Statistical analysis title
    Analysis at Week 2: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    -5.41
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.3
         upper limit
    1.49
    Statistical analysis title
    Analysis at Week 4: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    Placebo v PF-04236921 10 milligram (10 mg)
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean difference
    Point estimate
    -1.39
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -8.21
         upper limit
    5.42
    Statistical analysis title
    Analysis at Week 6: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean difference
    Point estimate
    1.3
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -5.71
         upper limit
    8.32
    Statistical analysis title
    Analysis at Week 8: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean difference
    Point estimate
    4.67
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -2.22
         upper limit
    11.57
    Statistical analysis title
    Analysis at Week 12: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean difference
    Point estimate
    -3.98
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.04
         upper limit
    3.07
    Statistical analysis title
    Analysis at Week 16: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean difference
    Point estimate
    -2.89
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.87
         upper limit
    4.1
    Statistical analysis title
    Analysis at Week 20: PF-04236921 10 mg v Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean difference
    Point estimate
    -6.21
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.37
         upper limit
    0.94
    Statistical analysis title
    Analysis at Week 24: PF-04236921 10 mg v Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean difference
    Point estimate
    1.98
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -5.17
         upper limit
    9.13
    Statistical analysis title
    Analysis at Week 2: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    Placebo v PF-04236921 50 mg
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean difference
    Point estimate
    2.07
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -4.7
         upper limit
    8.84
    Statistical analysis title
    Analysis at Week 4: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    Placebo v PF-04236921 50 mg
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean difference
    Point estimate
    -2.81
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.62
         upper limit
    4
    Statistical analysis title
    Analysis at Week 4: PF-04236921 50 mg v.Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    Placebo v PF-04236921 50 mg
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean difference
    Point estimate
    3.97
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -2.95
         upper limit
    10.9
    Statistical analysis title
    Analysis at Week 8: PF-04236921 50 mg v.Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    Placebo v PF-04236921 50 mg
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean difference
    Point estimate
    2.56
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -4.29
         upper limit
    9.4
    Statistical analysis title
    Analysis at Week 12: PF-04236921 50 mg v.Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    Placebo v PF-04236921 50 mg
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean difference
    Point estimate
    3.14
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -3.67
         upper limit
    9.94
    Statistical analysis title
    Analysis at Week 16: PF-04236921 50 mg v.Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    Placebo v PF-04236921 50 mg
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean difference
    Point estimate
    -4.94
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -11.91
         upper limit
    2.03
    Statistical analysis title
    Analysis at Week 20: PF-04236921 50 mg v.Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    Placebo v PF-04236921 50 mg
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean difference
    Point estimate
    -2.64
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.61
         upper limit
    4.32
    Statistical analysis title
    Analysis at Week 24: PF-04236921 50 mg v.Placebo
    Statistical analysis description
    Analysis was done using linear mixed effect model that included fixed factors of the stratification factors, treatment, visit, treatment by visit and baseline VAS.
    Comparison groups
    Placebo v PF-04236921 50 mg
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean difference
    Point estimate
    2.66
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -4.48
         upper limit
    9.8

    Secondary: Change From Baseline in European Quality of Life 5 Dimensions Questionnaire (EQ-5D) at Week 4, 8, 12, 16, 20 and 24

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    End point title
    Change From Baseline in European Quality of Life 5 Dimensions Questionnaire (EQ-5D) at Week 4, 8, 12, 16, 20 and 24 [33]
    End point description
    EQ-5D is a standardized, subject-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a single index value characterizing current health status using a 100-point VAS (0= worst imaginable health state, 100= best imaginable health state).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, 8, 12, 16, 20, 24
    Notes
    [33] - 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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg Placebo
    Number of subjects analysed
    0 [34]
    0 [35]
    0 [36]
    Units: Units on a scale
        arithmetic mean (standard deviation)
    ±
    ±
    ±
    Notes
    [34] - Data was not analyzed as SF-36 scale was sufficient for evaluating subject reported quality of life.
    [35] - Data was not analyzed as SF-36 scale was sufficient for evaluating subject reported quality of life.
    [36] - Data was not analyzed as SF-36 scale was sufficient for evaluating subject reported quality of life.
    No statistical analyses for this end point

    Secondary: Thirty six-Item Short-Form Health Survey (SF-36) Physical Component Score (PCS) and Mental Component Score (MCS) at Baseline

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    End point title
    Thirty six-Item Short-Form Health Survey (SF-36) Physical Component Score (PCS) and Mental Component Score (MCS) at Baseline [37]
    End point description
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as PCS and MCS. The score for each aspect and PCS/MCS is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). FAS excluding the subjects in the 200-mg dose group.
    End point type
    Secondary
    End point timeframe
    Baseline
    Notes
    [37] - 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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg Placebo
    Number of subjects analysed
    43 [38]
    46 [39]
    45
    Units: Units on a scale
    arithmetic mean (standard error)
        MCS
    39.5 ± 1.81
    42.36 ± 1.426
    39.94 ± 1.45
        PCS
    33.47 ± 1.169
    34.36 ± 1.25
    34.64 ± 1.523
    Notes
    [38] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
    [39] - Here, 'N' signifies subjects evaluable for this end point for each group respectively.
    No statistical analyses for this end point

    Secondary: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) PCS and MCS at Week 4, 8, 12, 16, 20 and 24

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    End point title
    Change From Baseline in 36-Item Short-Form Health Survey (SF-36) PCS and MCS at Week 4, 8, 12, 16, 20 and 24 [40]
    End point description
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as PCS and MCS. The score for each aspect and PCS/MCS is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). LOCF method was used to impute missing values. Here, 'n' =subjects evaluable at specified time point. 
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, 8, 12, 16, 20, 24
    Notes
    [40] - 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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg Placebo
    Number of subjects analysed
    45
    47
    45
    Units: Units on a scale
    least squares mean (confidence interval 95%)
        MCS: Week 4 (n=43, 45, 45)
    1.97 (-0.69 to 4.64)
    1.45 (-1.14 to 4.04)
    1.45 (-1.12 to 4.02)
        MCS: Week 8 (n=43, 46, 45)
    1.57 (-1.1 to 4.23)
    1.97 (-0.59 to 4.52)
    2.05 (-0.52 to 4.62)
        MCS: Week 12 (n=43, 46, 45)
    3.8 (1.13 to 6.46)
    2.5 (-0.06 to 5.05)
    2.52 (-0.05 to 5.09)
        MCS: Week 16 (n=43, 46, 45)
    4.73 (2.07 to 7.4)
    2.79 (0.24 to 5.35)
    2.95 (0.38 to 5.52)
        MCS: Week 20 (n=43, 46, 45)
    4.49 (1.82 to 7.15)
    1.71 (-0.85 to 4.26)
    3.28 (0.71 to 5.85)
        MCS: Week 24 (n=43, 46, 45)
    2.94 (0.28 to 5.6)
    2.14 (-0.41 to 4.7)
    2.85 (0.28 to 5.42)
        PCS: Week 4 (n=43, 45, 45)
    3.95 (1.75 to 6.15)
    3.24 (1.1 to 5.38)
    1.28 (-0.85 to 3.4)
        PCS: Week 8 (n=43, 46, 45)
    5.48 (3.27 to 7.68)
    4.79 (2.68 to 6.9)
    2.11 (-0.01 to 4.23)
        PCS: Week 12 (n=43, 46, 45)
    6.06 (3.86 to 8.26)
    4.66 (2.55 to 6.77)
    2.82 (0.7 to 4.95)
        PCS: Week 16 (n=43, 46, 45)
    6.25 (4.05 to 8.45)
    4.5 (2.39 to 6.61)
    2.48 (0.36 to 4.6)
        PCS: Week 20 (n=43, 46, 45)
    6.39 (4.19 to 8.59)
    5.63 (3.52 to 7.74)
    3.29 (1.17 to 5.42)
        PCS: Week 24 (n=43, 46, 45)
    5.98 (3.77 to 8.18)
    5.53 (3.42 to 7.64)
    2.94 (0.82 to 5.06)
    Statistical analysis title
    MCS Analysis Week 4: PF-04236921 10 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.53
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -2.53
         upper limit
    3.59
    Statistical analysis title
    MCS Analysis Week 8: PF-04236921 10 mg vs Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.48
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -3.54
         upper limit
    2.58
    Statistical analysis title
    MCS Analysis Week 16: PF-04236921 10 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.78
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -1.28
         upper limit
    4.84
    Statistical analysis title
    MCS Analysis Week 12:PF-04236921 10 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.28
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -1.78
         upper limit
    4.34
    Statistical analysis title
    MCS Analysis Week 20: PF-04236921 10 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.2
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -1.86
         upper limit
    4.26
    Statistical analysis title
    MCS Analysis Week 24: PF-04236921 10 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.09
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -2.98
         upper limit
    3.15
    Statistical analysis title
    MCS Analysis Week 4: PF-04236921 50 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    0
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -3.03
         upper limit
    3.03
    Statistical analysis title
    MCS Analysis Week 8: PF-04236921 50 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.09
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -3.09
         upper limit
    2.92
    Statistical analysis title
    MCS Analysis Week 12: PF-04236921 50 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -3.03
         upper limit
    2.99
    Statistical analysis title
    MCS Analysis Week 16: PF-04236921 50 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.16
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -3.17
         upper limit
    2.85
    Statistical analysis title
    MCS Analysis Week 20: PF-04236921 50 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    -1.58
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -4.58
         upper limit
    1.43
    Statistical analysis title
    MCS Analysis Week 24: PF-04236921 50 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.71
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -3.72
         upper limit
    2.3
    Statistical analysis title
    PCS Analysis Week 4: PF-04236921 10 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    2.67
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.14
         upper limit
    5.2
    Statistical analysis title
    PCS Analysis Week 8: PF-04236921 10 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    3.36
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.84
         upper limit
    5.89
    Statistical analysis title
    PCS Analysis Week 12: PF-04236921 10 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    3.23
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.7
         upper limit
    5.76
    Statistical analysis title
    PCS Analysis Week 16: PF-04236921 10 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    3.77
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    1.24
         upper limit
    6.3
    Statistical analysis title
    PCS Analysis Week 20: PF-04236921 10 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    3.1
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.57
         upper limit
    5.63
    Statistical analysis title
    PCS Analysis Week 24: PF-04236921 10 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    3.03
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.5
         upper limit
    5.56
    Statistical analysis title
    PCS Analysis Week 4: PF-04236921 50 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.96
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -0.53
         upper limit
    4.46
    Statistical analysis title
    PCS Analysis Week 8: PF-04236921 50 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    2.68
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.2
         upper limit
    5.17
    Statistical analysis title
    PCS Analysis Week 12: PF-04236921 50 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.84
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -0.65
         upper limit
    4.32
    Statistical analysis title
    PCS Analysis Week 16: PF-04236921 50 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    2.01
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -0.47
         upper limit
    4.5
    Statistical analysis title
    PCS Analysis Week 20: PF-04236921 50 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    2.34
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -0.15
         upper limit
    4.82
    Statistical analysis title
    PCS Analysis Week 24: PF-04236921 50 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    2.59
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.11
         upper limit
    5.08

    Secondary: Change From Baseline in Vitality Scores at Week 4, 8, 12, 16, 20 and 24

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    End point title
    Change From Baseline in Vitality Scores at Week 4, 8, 12, 16, 20 and 24 [41]
    End point description
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. Vitality sub-score is a component of SF-36 Health Survey Questionnaire and assesses energy and fatigue. The vitality score ranged from 0-100 (100=highest level of functioning). FAS excluding the subjects in the 200-mg dose group. LOCF method was used to impute missing values. As the SF-36 MCS component results were not significant at any timepoint, the decision was made to evaluate the vitality domain, at only Week 24 timepoint. Here, results for only Week 24 time point are reported.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, 8, 12, 16, 20, 24
    Notes
    [41] - 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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg Placebo
    Number of subjects analysed
    43
    46
    45
    Units: Units on a scale
        least squares mean (standard error)
    10.3 ± 3.088
    7.45 ± 2.983
    6.42 ± 3.022
    Statistical analysis title
    Vitality Analysis: PF04236921 10 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the treatment difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.374
    Method
    ANCOVA
    Parameter type
    Treatment Difference
    Point estimate
    3.87
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.71
         upper limit
    12.46
    Statistical analysis title
    Vitality Analysis: PF04236921 50 mg v Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the treatment difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.81
    Method
    ANCOVA
    Parameter type
    Treatment Difference
    Point estimate
    1.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.4
         upper limit
    9.46

    Secondary: Change From Baseline in Short Form-6 Dimension (SF-6D) at Week 4, 8, 12, 16, 20 and 24

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    End point title
    Change From Baseline in Short Form-6 Dimension (SF-6D) at Week 4, 8, 12, 16, 20 and 24 [42]
    End point description
    The SF-6D focuses on seven of the eight health domains covered by the SF-36 version2(v2) Health Survey: physical functioning, role participation (combined role-physical and role-emotional), social functioning, bodily pain, mental health, and vitality. Only the general health domain is not included. The SF-6D index is scored from 0.0 (worst health state) to 1.0 (best health state).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, 8, 12, 16, 20, 24
    Notes
    [42] - 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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg Placebo
    Number of subjects analysed
    0 [43]
    0 [44]
    0 [45]
    Units: Units on a scale
        arithmetic mean (standard deviation)
    ±
    ±
    ±
    Notes
    [43] - Data was not analyzed as SF-36 scale was sufficient for evaluating subject reported quality of life.
    [44] - Data was not analyzed as SF-36 scale was sufficient for evaluating subject reported quality of life.
    [45] - Data was not analyzed as SF-36 scale was sufficient for evaluating subject reported quality of life.
    No statistical analyses for this end point

    Secondary: Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) Score at Baseline

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    End point title
    Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) Score at Baseline [46]
    End point description
    FACIT-F is a 13-item questionnaire. Subjects scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the subject’s response to the questions (with the exception of 2 negatively stated), greater was the subject’s fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the subject’s response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). FAS excluding the subjects in the 200-mg dose group.
    End point type
    Secondary
    End point timeframe
    Baseline
    Notes
    [46] - 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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg Placebo
    Number of subjects analysed
    45
    47
    45
    Units: Units on a scale
        arithmetic mean (standard deviation)
    25.91 ± 1.7
    29.38 ± 1.506
    25.96 ± 1.76
    No statistical analyses for this end point

    Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) Score at Week 4, 8, 12, 16, 20 and 24

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    End point title
    Change From Baseline in Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) Score at Week 4, 8, 12, 16, 20 and 24 [47]
    End point description
    FACIT-F is a 13-item questionnaire. Subjects scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the subject’s response to the questions (with the exception of 2 negatively stated), greater was the subject’s fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the subject’s response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). Here, 'n' signifies subjects evaluable for this end point at the specified time points. LOCF method was used to impute missing values.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, 8, 12, 16, 20, 24
    Notes
    [47] - 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: As per planned analysis, for this end point, FAS population excluding the subjects in 200 mg group was used. Hence, the arm "PF-04236921 200 mg" was excluded from the analysis.
    End point values
    PF-04236921 10 milligram (10 mg) PF-04236921 50 mg Placebo
    Number of subjects analysed
    45
    47
    45
    Units: Units on a scale
    least squares mean (confidence interval 95%)
        Week 4 (n=43, 45, 45)
    3.16 (0.25 to 6.07)
    2.77 (-0.05 to 5.6)
    1.08 (-1.72 to 3.89)
        Week 8 (n=43, 46, 45)
    4.39 (1.49 to 7.3)
    3.41 (0.62 to 6.2)
    2.44 (-0.37 to 5.24)
        Week 12 (n=43, 46, 45)
    5.07 (2.16 to 7.97)
    3.59 (0.8 to 6.38)
    2.26 (-0.54 to 5.06)
        Week 16 (n=43, 46, 45)
    5.81 (2.9 to 8.72)
    5.53 (2.74 to 8.32)
    1.93 (-0.88 to 4.73)
        Week 20 (n=43, 46, 45)
    5.37 (2.46 to 8.28)
    4.32 (1.53 to 7.11)
    3.42 (0.61 to 6.22)
        Week 24 (n=43, 46, 45)
    4.39 (1.49 to 7.3)
    3.3 (0.51 to 6.09)
    2.7 (-0.1 to 5.51)
    Statistical analysis title
    Analysis at Week 4: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the Least Square (LS) mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    2.08
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -1.26
         upper limit
    5.42
    Statistical analysis title
    Analysis at Week 8: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.95
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -1.38
         upper limit
    5.29
    Statistical analysis title
    Analysis at Week 12: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    2.81
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -0.53
         upper limit
    6.15
    Statistical analysis title
    Analysis at Week 16: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    3.88
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.54
         upper limit
    7.22
    Statistical analysis title
    Analysis at Week 20: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.95
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -1.39
         upper limit
    5.29
    Statistical analysis title
    Analysis at Week 24: PF-04236921 10 mg v. Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 10 milligram (10 mg) v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.69
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -1.65
         upper limit
    5.03
    Statistical analysis title
    Analysis at Week 4: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.69
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -1.61
         upper limit
    4.99
    Statistical analysis title
    Analysis at Week 8: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.97
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -2.31
         upper limit
    4.26
    Statistical analysis title
    Analysis at Week 12: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.33
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -1.96
         upper limit
    4.61
    Statistical analysis title
    Analysis at Week 16: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    Placebo v PF-04236921 50 mg
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    3.6
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.32
         upper limit
    6.89
    Statistical analysis title
    Analysis at Week 20: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.91
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -2.38
         upper limit
    4.19
    Statistical analysis title
    Analysis at Week 24: PF-04236921 50 mg v. Placebo
    Statistical analysis description
    Analysis was done using the ANCOVA model; CI parameter being the LS mean difference from that model.
    Comparison groups
    PF-04236921 50 mg v Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.6
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -2.68
         upper limit
    3.88

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs/SAEs were collected from baseline up to Week 52
    Adverse event reporting additional description
    An AE may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. SAEs consist of all the SAEs including infectious SAEs; non-SAEs consist of all the non-SAEs including infectious non-SAEs.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    PF-04236921 10 mg
    Reporting group description
    Subjects received 10 mg dose of PF-04236921 subcutaneously in the anterolateral right and left thighs at Week 0, Week 8 and Week 16.

    Reporting group title
    PF-04236921 50 mg
    Reporting group description
    Subjects received 50 mg dose of PF-04236921 subcutaneously in the anterolateral right and left thighs at Week 0, Week 8 and Week 16.

    Reporting group title
    PF-04236921 200 mg
    Reporting group description
    Subjects received 200 mg dose of PF-04236921 subcutaneously in the anterolateral right and left thighs at Week 0, Week 8 and Week 16.

    Reporting group title
    Placebo
    Reporting group description
    Placebo matching to PF-04236921 administered subcutaneously in the anterolateral right and left thighs at Week 0, Week 8 and Week 16.

    Serious adverse events
    PF-04236921 10 mg PF-04236921 50 mg PF-04236921 200 mg Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 45 (8.89%)
    3 / 47 (6.38%)
    7 / 46 (15.22%)
    8 / 45 (17.78%)
         number of deaths (all causes)
    1
    0
    3
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Aortic stenosis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    1 / 46 (2.17%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Surgical and medical procedures
    Knee arthroplasty
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
    0 / 46 (0.00%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metrorrhagia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian haemorrhage
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    1 / 46 (2.17%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Arthroscopy
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardio
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    1 / 46 (2.17%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    1 / 46 (2.17%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    1 / 46 (2.17%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    1 / 46 (2.17%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
    2 / 46 (4.35%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 2
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    1 / 46 (2.17%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vasculitis cerebral
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Visual impairment
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    1 / 46 (2.17%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    1 / 46 (2.17%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
    0 / 46 (0.00%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia, obstructive
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    1 / 46 (2.17%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    1 / 46 (2.17%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Systemic lupus erythematosus
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    2 / 45 (4.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    1 / 46 (2.17%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
    1 / 46 (2.17%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disseminated tuberculosis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    1 / 46 (2.17%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Infectious mononucleosis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Latent tuberculosis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis chronic
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
    0 / 46 (0.00%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
    1 / 46 (2.17%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    PF-04236921 10 mg PF-04236921 50 mg PF-04236921 200 mg Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    20 / 45 (44.44%)
    24 / 47 (51.06%)
    32 / 46 (69.57%)
    26 / 45 (57.78%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    4 / 45 (8.89%)
    2 / 47 (4.26%)
    4 / 46 (8.70%)
    1 / 45 (2.22%)
         occurrences all number
    4
    2
    4
    1
    General disorders and administration site conditions
    Injection site pain
         subjects affected / exposed
    0 / 45 (0.00%)
    3 / 47 (6.38%)
    2 / 46 (4.35%)
    1 / 45 (2.22%)
         occurrences all number
    0
    3
    2
    1
    Pyrexia
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 47 (4.26%)
    0 / 46 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    0
    2
    0
    3
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 47 (2.13%)
    3 / 46 (6.52%)
    2 / 45 (4.44%)
         occurrences all number
    1
    1
    3
    2
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    3 / 45 (6.67%)
    1 / 47 (2.13%)
    2 / 46 (4.35%)
    0 / 45 (0.00%)
         occurrences all number
    3
    1
    2
    0
    Investigations
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    3 / 46 (6.52%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    3
    1
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    3 / 46 (6.52%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 47 (2.13%)
    1 / 46 (2.17%)
    3 / 45 (6.67%)
         occurrences all number
    1
    1
    1
    3
    Oropharyngeal pain
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 47 (2.13%)
    4 / 46 (8.70%)
    2 / 45 (4.44%)
         occurrences all number
    1
    1
    4
    2
    Cough
         subjects affected / exposed
    4 / 45 (8.89%)
    1 / 47 (2.13%)
    1 / 46 (2.17%)
    3 / 45 (6.67%)
         occurrences all number
    4
    1
    1
    3
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 45 (2.22%)
    3 / 47 (6.38%)
    2 / 46 (4.35%)
    2 / 45 (4.44%)
         occurrences all number
    1
    3
    2
    2
    Headache
         subjects affected / exposed
    4 / 45 (8.89%)
    8 / 47 (17.02%)
    5 / 46 (10.87%)
    2 / 45 (4.44%)
         occurrences all number
    4
    8
    5
    2
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 45 (4.44%)
    3 / 47 (6.38%)
    2 / 46 (4.35%)
    1 / 45 (2.22%)
         occurrences all number
    2
    3
    2
    1
    Abdominal pain upper
         subjects affected / exposed
    3 / 45 (6.67%)
    0 / 47 (0.00%)
    1 / 46 (2.17%)
    0 / 45 (0.00%)
         occurrences all number
    3
    0
    1
    0
    Diarrhoea
         subjects affected / exposed
    2 / 45 (4.44%)
    3 / 47 (6.38%)
    5 / 46 (10.87%)
    5 / 45 (11.11%)
         occurrences all number
    2
    3
    5
    5
    Nausea
         subjects affected / exposed
    3 / 45 (6.67%)
    4 / 47 (8.51%)
    6 / 46 (13.04%)
    7 / 45 (15.56%)
         occurrences all number
    3
    4
    6
    7
    Vomiting
         subjects affected / exposed
    1 / 45 (2.22%)
    2 / 47 (4.26%)
    2 / 46 (4.35%)
    3 / 45 (6.67%)
         occurrences all number
    1
    2
    2
    3
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    0 / 45 (0.00%)
    3 / 47 (6.38%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    3
    0
    1
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 47 (2.13%)
    3 / 46 (6.52%)
    2 / 45 (4.44%)
         occurrences all number
    1
    1
    3
    2
    Pruritus
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 47 (2.13%)
    0 / 46 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    1
    1
    0
    3
    Rash
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 47 (4.26%)
    4 / 46 (8.70%)
    1 / 45 (2.22%)
         occurrences all number
    0
    2
    4
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 45 (2.22%)
    4 / 47 (8.51%)
    3 / 46 (6.52%)
    4 / 45 (8.89%)
         occurrences all number
    1
    4
    3
    4
    Back pain
         subjects affected / exposed
    1 / 45 (2.22%)
    3 / 47 (6.38%)
    3 / 46 (6.52%)
    0 / 45 (0.00%)
         occurrences all number
    1
    3
    3
    0
    Flank pain
         subjects affected / exposed
    0 / 45 (0.00%)
    3 / 47 (6.38%)
    0 / 46 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    3
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
    4 / 46 (8.70%)
    2 / 45 (4.44%)
         occurrences all number
    0
    1
    4
    2
    Systemic lupus erythematosus
         subjects affected / exposed
    3 / 45 (6.67%)
    5 / 47 (10.64%)
    2 / 46 (4.35%)
    1 / 45 (2.22%)
         occurrences all number
    3
    5
    2
    1
    Metabolism and nutrition disorders
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 45 (2.22%)
    4 / 47 (8.51%)
    1 / 46 (2.17%)
    1 / 45 (2.22%)
         occurrences all number
    1
    4
    1
    1
    Hyperglycaemia
         subjects affected / exposed
    3 / 45 (6.67%)
    0 / 47 (0.00%)
    2 / 46 (4.35%)
    0 / 45 (0.00%)
         occurrences all number
    3
    0
    2
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 45 (2.22%)
    3 / 47 (6.38%)
    3 / 46 (6.52%)
    2 / 45 (4.44%)
         occurrences all number
    1
    3
    3
    2
    Hypoglycaemia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
    0 / 46 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    0
    0
    0
    3
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    5 / 45 (11.11%)
    6 / 47 (12.77%)
    3 / 46 (6.52%)
    3 / 45 (6.67%)
         occurrences all number
    5
    7
    4
    3
    Gastroenteritis
         subjects affected / exposed
    1 / 45 (2.22%)
    3 / 47 (6.38%)
    2 / 46 (4.35%)
    3 / 45 (6.67%)
         occurrences all number
    1
    3
    5
    3
    Pharyngitis
         subjects affected / exposed
    2 / 45 (4.44%)
    3 / 47 (6.38%)
    2 / 46 (4.35%)
    4 / 45 (8.89%)
         occurrences all number
    2
    3
    2
    6
    Sinusitis
         subjects affected / exposed
    1 / 45 (2.22%)
    3 / 47 (6.38%)
    4 / 46 (8.70%)
    0 / 45 (0.00%)
         occurrences all number
    1
    3
    5
    0
    Upper respiratory tract infection
         subjects affected / exposed
    5 / 45 (11.11%)
    6 / 47 (12.77%)
    11 / 46 (23.91%)
    7 / 45 (15.56%)
         occurrences all number
    8
    6
    13
    8
    Urinary tract infection
         subjects affected / exposed
    8 / 45 (17.78%)
    5 / 47 (10.64%)
    3 / 46 (6.52%)
    7 / 45 (15.56%)
         occurrences all number
    8
    9
    3
    15

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Jul 2011
    1. Changed primary endpoint of subjects achieving SLE responder Index from Week 20 or 24 to Week 24 only. 2. Combined BILAG, SLEDAI-2K and Physician’s Global Assessment endpoints into a single endpoint of components and disposition of SRI. Added corticosteroid taper endpoint. Added endpoint for normalized serologic activity Endpoints. Clarified mean change in patient global VAS, EQ-5D, SF-36 PCS, MCS and Vitality Score –all domains over time including SF-6D, FACIT. 3. AE assessment section was modified to include the monitoring of hypersensitivity reactions to the investigational product.
    01 Mar 2013
    1. Due to new safety data, tuberculosis (TB) testing was added at week 12, 24, 36 and week 52 throughout the study. 2. New safety language regarding neutrophil monitoring and monitoring of tuberculosis was added. Subjects were re-evaluated at frequent intervals to monitor the absolute neutrophil counts (ANC) and for signs or symptoms of infections. If the ANC counts increased to >=750 cells per cubic millimeter (cells/mm^3) within 15 days of the next dose at either Week 8 or Week 16, the subject was discontinued and entered the follow up period. Subjects were also discontinued if they developed any symptoms or signs of febrile neutropenia during this period. Following follow up measures were added to this protocol to ensure the continued safety of subjects and to further mitigate the risk of TB infection: a) Serial TB testing (Purified Protein Derivative [PPD] or quantiferon test [QFT]) was implemented to monitor for new cases of TB during the course of study. b) Subjects were carefully monitored throughout study for signs, symptoms of TB such as chest pain, difficulty breathing, wheezing, fever, coughing up mucus or blood, excessive sweating(especially at night), lymphadenopathy, new fatigue, or new unplanned weight loss. c) If a subject converted from a negative to positive TB test during trial by serial testing, they were thoroughly evaluated to exclude TB. d) If it was confirmed that a subject had developed latent or active TB in the study based upon above evaluations, the subject received further doses of test article, and was treated standard antimycobacterial therapy. e) If treatment with steroids was required to treat a documented lupus flare, or intercurrent medical condition, a thorough evaluation was performed to exclude TB infection prior to initiating steroid therapy.
    30 Apr 2013
    Further dosing in the 200 mg treatment arm was stopped due to safety reasons and excluded from the primary analysis.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

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