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    Clinical Trial Results:
    A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study of Two Doses of R935788 in Rheumatoid Arthritis Patients Failing to Respond to Methotrexate

    Summary
    EudraCT number
    		 2008-000742-30
    Trial protocol
    		 HU   BG   PL  
    Global end of trial date
    01 Jun 2009

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Sep 2022
    First version publication date
    01 Sep 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    C-935788-010
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00665925
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Rigel Pharmaceuticals, Inc.
    Sponsor organisation address
    1180 Veterans Blvd, South San Francisco, CA, United States, 94080
    Public contact
    Lucy Yan, MD, Rigel Pharmaceuticals, Inc., +1 650-624-1313, lyan@rigel.com
    Scientific contact
    Lucy Yan, MD, Rigel Pharmaceuticals, Inc., +1 650-624-1313, lyan@rigel.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    16 Dec 2010
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    01 Jun 2009
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Jun 2009
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary efficacy objective of this study is to confirm the efficacy of R788 100 mg PO bid as determined by ACR20 responder rates at 6 months.
    Protection of trial subjects
    The study was conducted in accordance with Good Clinical Practice (GCP) and the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 Placebo tablets were provided to match the appearance of R788-containing 100 and 150 mg tablets. Placebo tablets were administered orally using the same treatment schedule as for R788-containing tablets.
    Actual start date of recruitment
    19 May 2008
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Romania: 25
    Country: Number of subjects enrolled
    United States: 109
    Country: Number of subjects enrolled
    Mexico: 100
    Country: Number of subjects enrolled
    Colombia: 124
    Country: Number of subjects enrolled
    Poland: 80
    Country: Number of subjects enrolled
    Bulgaria: 19
    Worldwide total number of subjects
    457
    EEA total number of subjects
    124
    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)
    376
    From 65 to 84 years
    80
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 Cohort A: 152 subjects were enrolled and 131 completed the study. Cohort B: 152 subjects were enrolled and 126 completed the study. Cohort C: 76 subjects were enrolled and 59 completed the study. Cohort D: 77 subjects were enrolled and 62 completed the study. Subjects were recruited in US, Latin America and Europe

    Pre-assignment
    Screening details
    		 Male and female subjects who had active rheumatoid arthritis (RA) for a minimum of 6 months, and receiving a weekly methotrexate (MTX) dose for a minimum of 3 months were randomly assigned to receive R788 150 mg once daily or 100 mg twice daily, placebo once daily or placebo twice daily. It was planned to randomize approximately 420 subjects.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    In order to enhance the blinded scoring of subjective efficacy-related measurements, a trained and qualified IJA at each site was responsible for performing the tender and swollen joint counts and completing the global assessment of disease activity.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort A R788 100 mg bid
    Arm description
    		 R788 100 mg, oral tablets, twice daily, double-blind
    Arm type
    		 Experimental

    Investigational medicinal product name
    R935788
    Investigational medicinal product code
    R935788 sodium hexahydrate
    Other name
    R788 Sodium, R788 Na, R788
    Pharmaceutical forms
    Coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    R788 100 mg, oral tablets, twice daily, double-blind

    Arm title
    		 Cohort B R788 150 mg qd
    Arm description
    		 R788 150 mg, oral tablets, once daily, double-blind
    Arm type
    		 Experimental

    Investigational medicinal product name
    R935788
    Investigational medicinal product code
    R935788 sodium hexahydrate
    Other name
    R788 Sodium, R788 Na, R788
    Pharmaceutical forms
    Coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    R788 150 mg, oral tablets, once daily, double-blind

    Arm title
    		 Cohort C Placebo 100 mg bid
    Arm description
    		 Placebo 100 mg, oral tablets, twice daily, double-blind
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo 100 mg, oral tablets, twice daily, double-blind

    Arm title
    		 Cohort D Placebo 150 mg qd
    Arm description
    		 Placebo 150 mg, oral tablets, once daily, double-blind
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo 150 mg, oral tablets, once daily, double-blind

    Number of subjects in period 1
    		Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Started
    152
    152
    76
    77
    Completed
    131
    126
    59
    62
    Not completed
    21
    26
    17
    15
         Consent withdrawn by subject
    2
    3
    2
    2
         Physician decision
    2
    1
    -
    -
         Adverse event, non-fatal
    5
    10
    5
    1
         Due to exclusion criteria
    -
    -
    -
    1
         Enrolled by mistake
    1
    -
    -
    -
         Lost to follow-up
    2
    2
    2
    1
         Lack of efficacy
    8
    9
    8
    10
         Protocol deviation
    1
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort A R788 100 mg bid
    Reporting group description
    		 R788 100 mg, oral tablets, twice daily, double-blind

    Reporting group title
    Cohort B R788 150 mg qd
    Reporting group description
    		 R788 150 mg, oral tablets, once daily, double-blind

    Reporting group title
    Cohort C Placebo 100 mg bid
    Reporting group description
    		 Placebo 100 mg, oral tablets, twice daily, double-blind

    Reporting group title
    Cohort D Placebo 150 mg qd
    Reporting group description
    		 Placebo 150 mg, oral tablets, once daily, double-blind

    Reporting group values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd Total
    Number of subjects
    		 152 152 76 77 457
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Please note, baseline data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses.
    Units: years
        arithmetic mean (standard deviation)
    		 52.5 ( 12.97 ) 52.6 ( 12.31 ) 53.4 ( 12.66 ) 51.3 ( 13.68 ) -
    Gender categorical
    Please note, baseline data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses.
    Units: Subjects
        Female
    		 131 128 64 67 390
        Male
    		 21 24 12 10 67
    Race
    Units: Subjects
        Asian
    		 1 0 0 0 1
        Black
    		 4 2 3 4 13
        Caucasian
    		 58 75 32 39 204
        Hispanic
    		 88 74 41 34 237
        Other
    		 1 1 0 0 2
    Height
    Units: cm
        arithmetic mean (standard deviation)
    		 160.13 ( 8.156 ) 161.35 ( 9.618 ) 161.08 ( 9.913 ) 160.93 ( 9.279 ) -
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    		 70.67 ( 15.673 ) 72.25 ( 16.213 ) 70.95 ( 19.475 ) 69.60 ( 18.862 ) -

    End points

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    End points reporting groups
    Reporting group title
    Cohort A R788 100 mg bid
    Reporting group description
    		 R788 100 mg, oral tablets, twice daily, double-blind

    Reporting group title
    Cohort B R788 150 mg qd
    Reporting group description
    		 R788 150 mg, oral tablets, once daily, double-blind

    Reporting group title
    Cohort C Placebo 100 mg bid
    Reporting group description
    		 Placebo 100 mg, oral tablets, twice daily, double-blind

    Reporting group title
    Cohort D Placebo 150 mg qd
    Reporting group description
    		 Placebo 150 mg, oral tablets, once daily, double-blind

    Subject analysis set title
    Placebo Pooled
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    For analysis purposes, both Placebo groups (150 mg qd and 100 mg bid) have been pooled into one group.

    Primary: American College of Rheumatology 20 (ACR20) Response at 6 Months

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    End point title
    		 American College of Rheumatology 20 (ACR20) Response at 6 Months [1] [2]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Primary
    End point timeframe
    after 6 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis performed for primary endpoint. At Month 6, the ACR20 response was achieved by significantly more patients in both the R788 150 mg qd (57%) and 100 mg bid (67%) groups and in the combined R788 group (62%) versus the total placebo group (35%, p <0.001).
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    151
    152
    153
    Units: subjects
        Subjects achieving ACR20 criteria
    101
    87
    53
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 20 (ACR20) Response at 1 week

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    End point title
    		 American College of Rheumatology 20 (ACR20) Response at 1 week [3]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 1 week
    Notes
    [3] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    146
    151
    153 [4]
    Units: subjects
        Subjects achieving ACR20 criteria
    53
    34
    21
    Notes
    [4] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 70 (ACR70) Response at 1 week

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    End point title
    		 American College of Rheumatology 70 (ACR70) Response at 1 week [5]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    after 1 week
    Notes
    [5] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    146
    151
    153 [6]
    Units: subjects
        Subjects achieving ACR70 criteria
    2
    1
    1
    Notes
    [6] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology Index of Improvement (ACRn) at 1 week

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    End point title
    		 American College of Rheumatology Index of Improvement (ACRn) at 1 week [7]
    End point description
    The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA
    End point type
    Secondary
    End point timeframe
    After 1 week
    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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    145
    151
    153 [8]
    Units: Score
        arithmetic mean (standard deviation)
    16.22 ( 19.564 )
    10.75 ( 15.788 )
    7.07 ( 13.677 )
    Notes
    [8] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 1 month

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    End point title
    		 Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 1 month [9]
    End point description
    Number of intent-to-treat subjects with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms
    End point type
    Secondary
    End point timeframe
    After 1 month
    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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    86
    93
    85 [10]
    Units: subjects
        Subjects achieving DAS28-CRP criteria
    4
    10
    2
    Notes
    [10] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 1 month

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    End point title
    		 Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 1 month [11]
    End point description
    Number of intent-to-treat subjects with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity
    End point type
    Secondary
    End point timeframe
    After 1 month
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    86
    93
    85 [12]
    Units: subjects
        Subjects achieving DAS28-CRP criteria
    15
    15
    6
    Notes
    [12] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 1 month

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    End point title
    		 Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 1 month [13]
    End point description
    Number of intent-to-treat subjects with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms
    End point type
    Secondary
    End point timeframe
    At 1 month
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    61
    53
    64 [14]
    Units: subjects
        Subjects achieving DAS28-ESR criteria
    12
    3
    2
    Notes
    [14] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 1 month

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    End point title
    		 Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 1 month [15]
    End point description
    Number of intent-to-treat subjects with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity
    End point type
    Secondary
    End point timeframe
    After 1 month
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    61
    53
    64 [16]
    Units: subjects
        Subjects achieving DAS28-ESR criteria
    18
    6
    3
    Notes
    [16] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at 6 months

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    End point title
    		 Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at 6 months [17]
    End point description
    Change from baseline in FACIT-F, which is a subject-reported 13-item questionnaire that assesses fatigue, calculated as the score at 6 months minus the score at baseline. The FACIT-F runs from 0 to 52 with lower scores indicating higher fatigue. A positive change from baseline indicates an improvement in fatigue after treatment.
    End point type
    Secondary
    End point timeframe
    After 6 months
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    117
    107
    109 [18]
    Units: Score
    arithmetic mean (standard deviation)
        After 6 months
    7.4 ( 10.87 )
    5.7 ( 10.28 )
    4.5 ( 9.79 )
    Notes
    [18] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Short Form Health Survey (SF-36) Physical Component Summary (PCS) at 6 Months

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    End point title
    		 Short Form Health Survey (SF-36) Physical Component Summary (PCS) at 6 Months [19]
    End point description
    Change from baseline in the PCS of the SF-36 (which assesses health and wellbeing), calculated as the score at 6 months minus the score at baseline. The PCS ranges from 0 to 100 with 100 indicating the highest level of functioning possible. A positive change indicates an improvement in PCS after treatment
    End point type
    Secondary
    End point timeframe
    After 6 months
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    129
    124
    118
    Units: Score
    arithmetic mean (standard deviation)
        After 6 months
    8.524 ( 8.7068 )
    5.903 ( 8.9541 )
    4.902 ( 8.4808 )
    No statistical analyses for this end point

    Secondary: Short Form Health Survey (SF-36) Mental Component Summary (MCS) at 6 Months

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    End point title
    		 Short Form Health Survey (SF-36) Mental Component Summary (MCS) at 6 Months [20]
    End point description
    Change from baseline in the MCS of the SF-36 (which assesses health and wellbeing), calculated as the score at 6 months minus the score at baseline. The MCS ranges from 0 to 100 with 100 indicating the highest level of functioning possible. A positive change indicates an improvement in MCS after treatment
    End point type
    Secondary
    End point timeframe
    After 6 months
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    129
    125
    118 [21]
    Units: Score
    arithmetic mean (standard deviation)
        After 6 months
    3.990 ( 10.5129 )
    2.033 ( 10.7089 )
    3.711 ( 10.7098 )
    Notes
    [21] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Number of subjects with ALT values greater than 1.5 times the ULN

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    End point title
    		 Number of subjects with ALT values greater than 1.5 times the ULN
    End point description
    The number of intent-to-treat subjects with ALT (Alanine Aminotransferase) (a test of liver function) values greater than 1.5 times the ULN (Upper Limit of Normal)
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
        Subjects
    31
    28
    11
    3
    No statistical analyses for this end point

    Secondary: The number of subjects with AST values greater than 1.5 times the ULN

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    End point title
    		 The number of subjects with AST values greater than 1.5 times the ULN
    End point description
    The number of participants with AST (Aspartate Aminotransferase) (a test of liver function) values greater than 1.5 times the ULN (Upper Limit of Normal)
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
    11
    19
    4
    1
    No statistical analyses for this end point

    Secondary: The number of subjects with Alkaline Phosphatase >1.5 x Upper Limit of Normal (ULN) and >1.5 Times Baseline

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    End point title
    		 The number of subjects with Alkaline Phosphatase >1.5 x Upper Limit of Normal (ULN) and >1.5 Times Baseline
    End point description
    The number of intent-to-treat subjects with alkaline phosphatase (a test of liver function) values greater than 1.5 times the ULN and greater than 1.5 times baseline
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
        >1.5x ULN and baseline
    6
    1
    1
    0
    No statistical analyses for this end point

    Secondary: Number of subjects with Bilirubin 1.5 times the Upper Limit of Normal (ULN)

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    End point title
    		 Number of subjects with Bilirubin 1.5 times the Upper Limit of Normal (ULN)
    End point description
    The number of intent-to-treat subjects with bilirubin (a test of liver function) values greater than 1.5 times the ULN
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
        >1.5 times
    4
    4
    2
    0
    No statistical analyses for this end point

    Secondary: Number of subjects with Absolute Neutrophil Count (ANC) <1500/mm3

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    End point title
    		 Number of subjects with Absolute Neutrophil Count (ANC) <1500/mm3
    End point description
    The number of intent-to-treat subjecs with ANC values lower than 1500/mm3
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
    9
    10
    0
    1
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 20 (ACR20) Response at 2 weeks

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    End point title
    		 American College of Rheumatology 20 (ACR20) Response at 2 weeks [22]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 2 weeks
    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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    148
    152
    153 [23]
    Units: subjects
        Subjects achieving ACR20 criteria
    67
    47
    29
    Notes
    [23] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 20 (ACR20) Response at 1 month

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    End point title
    		 American College of Rheumatology 20 (ACR20) Response at 1 month [24]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 1 month
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    150
    152
    151 [25]
    Units: subjects
        Subjects achieving ACR20 criteria
    89
    72
    48
    Notes
    [25] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 20 (ACR20) Response at 2 months

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    End point title
    		 American College of Rheumatology 20 (ACR20) Response at 2 months [26]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 2 months
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    149
    151
    151 [27]
    Units: subjects
        Subjects achieving ACR20 criteria
    95
    81
    58
    Notes
    [27] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 20 (ACR20) Response at 3 months

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    End point title
    		 American College of Rheumatology 20 (ACR20) Response at 3 months [28]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 3 months
    Notes
    [28] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    150
    152
    152 [29]
    Units: subjects
        Subjects achieving ACR20 criteria
    97
    79
    64
    Notes
    [29] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 20 (ACR20) Response at 4 months

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    End point title
    		 American College of Rheumatology 20 (ACR20) Response at 4 months [30]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 4 months
    Notes
    [30] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    147
    151
    152 [31]
    Units: subjects
        Subjects achieving ACR20 criteria
    100
    71
    57
    Notes
    [31] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 20 (ACR20) Response at 5 months

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    End point title
    		 American College of Rheumatology 20 (ACR20) Response at 5 months [32]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 5 months
    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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    150
    152
    151 [33]
    Units: subjects
        Subjects achieving ACR20 criteria
    97
    84
    61
    Notes
    [33] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 50 (ACR50) Response at 1 Week

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    End point title
    		 American College of Rheumatology 50 (ACR50) Response at 1 Week [34]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 1 week
    Notes
    [34] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    146
    151
    153 [35]
    Units: subjects
        Subjects achieving ACR50 criteria
    10
    7
    4
    Notes
    [35] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 50 (ACR50) Response at 2 weeks

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    End point title
    		 American College of Rheumatology 50 (ACR50) Response at 2 weeks [36]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 2 weeks
    Notes
    [36] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    148
    152
    153 [37]
    Units: subjects
        Subjects achieving ACR50 criteria
    21
    15
    7
    Notes
    [37] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 50 (ACR50) Response at 1 month

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    End point title
    		 American College of Rheumatology 50 (ACR50) Response at 1 month [38]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 1 month
    Notes
    [38] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    150
    152
    151 [39]
    Units: subjects
        Subjects achieving ACR50 criteria
    45
    24
    11
    Notes
    [39] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 50 (ACR50) Response at 6 weeks

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    End point title
    		 American College of Rheumatology 50 (ACR50) Response at 6 weeks [40]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 6 weeks
    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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    150
    151
    148 [41]
    Units: subjects
        Subjects achieving ACR50 criteria
    43
    30
    19
    Notes
    [41] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 50 (ACR50) Response at 2 months

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    End point title
    		 American College of Rheumatology 50 (ACR50) Response at 2 months [42]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 2 months
    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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    149
    151
    151 [43]
    Units: subjects
        Subjects achieving ACR50 criteria
    51
    34
    22
    Notes
    [43] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 50 (ACR50) Response at 3 months

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    End point title
    		 American College of Rheumatology 50 (ACR50) Response at 3 months [44]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 3 months
    Notes
    [44] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    150
    152
    152 [45]
    Units: subjects
        Subjects achieving ACR50 criteria
    58
    43
    23
    Notes
    [45] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 50 (ACR50) Response at 4 months

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    End point title
    		 American College of Rheumatology 50 (ACR50) Response at 4 months [46]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 4 months
    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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    147
    151
    152 [47]
    Units: subjects
        Subjects achieving ACR50 criteria
    62
    34
    25
    Notes
    [47] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 50 (ACR50) Response at 5 months

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    End point title
    		 American College of Rheumatology 50 (ACR50) Response at 5 months [48]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 5 months
    Notes
    [48] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    150
    152
    151 [49]
    Units: subjects
        Subjects achieving ACR50 criteria
    62
    41
    25
    Notes
    [49] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 50 (ACR50) Response at 6 months

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    End point title
    		 American College of Rheumatology 50 (ACR50) Response at 6 months [50]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 6 months
    Notes
    [50] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    151
    152
    153 [51]
    Units: subjects
        Subjects achieving ACR50 criteria
    65
    49
    29
    Notes
    [51] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 70 (ACR70) Response at 2 weeks

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    End point title
    		 American College of Rheumatology 70 (ACR70) Response at 2 weeks [52]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 2 weeks
    Notes
    [52] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    148
    152
    153 [53]
    Units: subjects
        Subjects achieving ACR70 criteria
    7
    5
    1
    Notes
    [53] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 70 (ACR70) Response at 1 month

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    End point title
    		 American College of Rheumatology 70 (ACR70) Response at 1 month [54]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 1 month
    Notes
    [54] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    150
    152
    151 [55]
    Units: subjects
        Subjects achieving ACR70 criteria
    14
    13
    7
    Notes
    [55] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 70 (ACR70) Response at 6 weeks

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    End point title
    		 American College of Rheumatology 70 (ACR70) Response at 6 weeks [56]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 6 weeks
    Notes
    [56] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    150
    151
    148 [57]
    Units: subjects
        Subjects achieving ACR70 criteria
    16
    13
    5
    Notes
    [57] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 70 (ACR70) Response at 2 months

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    End point title
    		 American College of Rheumatology 70 (ACR70) Response at 2 months [58]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 2 months
    Notes
    [58] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    149
    151
    151 [59]
    Units: subjects
        Subjects achieving ACR70 criteria
    20
    15
    4
    Notes
    [59] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 70 (ACR70) Response at 3 months

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    End point title
    		 American College of Rheumatology 70 (ACR70) Response at 3 months [60]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 3 months
    Notes
    [60] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    150
    152
    152 [61]
    Units: subjects
        Subjects achieving ACR70 criteria
    30
    19
    10
    Notes
    [61] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 70 (ACR70) Response at 4 months

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    End point title
    		 American College of Rheumatology 70 (ACR70) Response at 4 months [62]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 4 months
    Notes
    [62] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    147
    151
    152 [63]
    Units: subjects
        Subjects achieving ACR70 criteria
    32
    17
    8
    Notes
    [63] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 70 (ACR70) Response at 5 months

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    End point title
    		 American College of Rheumatology 70 (ACR70) Response at 5 months [64]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 5 months
    Notes
    [64] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    150
    152
    151 [65]
    Units: subjects
        Subjects achieving ACR70 criteria
    33
    20
    8
    Notes
    [65] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 70 (ACR70) Response at 6 months

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    End point title
    		 American College of Rheumatology 70 (ACR70) Response at 6 months [66]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 6 months
    Notes
    [66] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    151
    152
    153 [67]
    Units: subjects
        Subjects achieving ACR70 criteria
    43
    21
    16
    Notes
    [67] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology Index of Improvement (ACRn) at 2 weeks

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    End point title
    		 American College of Rheumatology Index of Improvement (ACRn) at 2 weeks [68]
    End point description
    The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA
    End point type
    Secondary
    End point timeframe
    After 2 weeks
    Notes
    [68] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    145
    150
    151 [69]
    Units: score
    arithmetic mean (standard deviation)
        Score
    21.62 ( 23.491 )
    16.27 ( 20.899 )
    9.74 ( 16.987 )
    Notes
    [69] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology Index of Improvement (ACRn) at 1 month

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    End point title
    		 American College of Rheumatology Index of Improvement (ACRn) at 1 month [70]
    End point description
    The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA
    End point type
    Secondary
    End point timeframe
    After 1 month
    Notes
    [70] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    146
    148
    149 [71]
    Units: score
    arithmetic mean (standard deviation)
        Score
    32.23 ( 26.304 )
    24.14 ( 25.428 )
    14.65 ( 20.537 )
    Notes
    [71] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology Index of Improvement (ACRn) at 6 weeks

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    End point title
    		 American College of Rheumatology Index of Improvement (ACRn) at 6 weeks [72]
    End point description
    The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA
    End point type
    Secondary
    End point timeframe
    After 6 weeks
    Notes
    [72] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    146
    146
    145 [73]
    Units: score
    arithmetic mean (standard deviation)
        Score
    31.08 ( 27.789 )
    26.87 ( 26.893 )
    18.05 ( 22.904 )
    Notes
    [73] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology Index of Improvement (ACRn) at 2 months

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    End point title
    		 American College of Rheumatology Index of Improvement (ACRn) at 2 months [74]
    End point description
    The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA
    End point type
    Secondary
    End point timeframe
    After 2 months
    Notes
    [74] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    143
    145
    148 [75]
    Units: score
    arithmetic mean (standard deviation)
        Score
    36.73 ( 28.254 )
    29.11 ( 26.827 )
    20.12 ( 23.179 )
    Notes
    [75] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology Index of Improvement (ACRn) at 3 months

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    End point title
    		 American College of Rheumatology Index of Improvement (ACRn) at 3 months [76]
    End point description
    The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA
    End point type
    Secondary
    End point timeframe
    After 3 months
    Notes
    [76] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    142
    141
    147
    Units: score
    arithmetic mean (standard deviation)
        Score
    39.04 ( 30.059 )
    31.79 ( 27.959 )
    22.11 ( 25.904 )
    No statistical analyses for this end point

    Secondary: American College of Rheumatology Index of Improvement (ACRn) at 4 months

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    End point title
    		 American College of Rheumatology Index of Improvement (ACRn) at 4 months [77]
    End point description
    The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA
    End point type
    Secondary
    End point timeframe
    After 4 months
    Notes
    [77] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    132
    130
    130 [78]
    Units: score
    arithmetic mean (standard deviation)
        Score
    44.70 ( 29.789 )
    30.24 ( 28.347 )
    22.61 ( 25.661 )
    Notes
    [78] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology Index of Improvement (ACRn) at 5 months

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    End point title
    		 American College of Rheumatology Index of Improvement (ACRn) at 5 months [79]
    End point description
    The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA
    End point type
    Secondary
    End point timeframe
    After 5 months
    Notes
    [79] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    130
    126
    123 [80]
    Units: score
    arithmetic mean (standard deviation)
        Score
    44.76 ( 29.972 )
    35.35 ( 27.683 )
    25.66 ( 25.734 )
    Notes
    [80] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: American College of Rheumatology Index of Improvement (ACRn) at 6 months

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    End point title
    		 American College of Rheumatology Index of Improvement (ACRn) at 6 months [81]
    End point description
    The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA
    End point type
    Secondary
    End point timeframe
    After 6 months
    Notes
    [81] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    130
    126
    121 [82]
    Units: score
    arithmetic mean (standard deviation)
        Score
    49.55 ( 30.189 )
    38.45 ( 29.108 )
    26.00 ( 29.402 )
    Notes
    [82] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 2 months

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    End point title
    		 Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 2 months [83]
    End point description
    Number of intent-to-treat subjects with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms
    End point type
    Secondary
    End point timeframe
    After 2 months
    Notes
    [83] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    82
    94
    83 [84]
    Units: subjects
        Subjects achieving DAS28-CRP criteria
    8
    8
    3
    Notes
    [84] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 3 months

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    End point title
    		 Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 3 months [85]
    End point description
    Number of intent-to-treat subjects with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms
    End point type
    Secondary
    End point timeframe
    After 3 months
    Notes
    [85] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    84
    92
    83 [86]
    Units: subjects
        Subjects achieving DAS28-CRP criteria
    11
    7
    5
    Notes
    [86] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 4 months

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    End point title
    		 Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 4 months [87]
    End point description
    Number of intent-to-treat subjects with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms
    End point type
    Secondary
    End point timeframe
    After 4 months
    Notes
    [87] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    80
    84
    73 [88]
    Units: subjects
        Subjects achieving DAS28-CRP criteria
    15
    10
    4
    Notes
    [88] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 5 months

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    End point title
    		 Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 5 months [89]
    End point description
    Number of intent-to-treat subjects with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms
    End point type
    Secondary
    End point timeframe
    After 5 months
    Notes
    [89] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    76
    81
    71 [90]
    Units: subjects
        Subjects achieving DAS28-CRP criteria
    24
    8
    5
    Notes
    [90] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 6 months

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    End point title
    		 Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 6 months [91]
    End point description
    Number of intent-to-treat subjects with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms
    End point type
    Secondary
    End point timeframe
    After 6 months
    Notes
    [91] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    77
    81
    70 [92]
    Units: subjects
        Subjects achieving DAS28-CRP criteria
    20
    17
    6
    Notes
    [92] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 2 months

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    End point title
    		 Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 2 months [93]
    End point description
    Number of intent-to-treat subjects with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity
    End point type
    Secondary
    End point timeframe
    After 2 months
    Notes
    [93] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    82
    94
    83 [94]
    Units: subjects
        Subjects achieving DAS28-CRP criteria
    21
    19
    9
    Notes
    [94] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 3 months

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    End point title
    		 Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 3 months [95]
    End point description
    Number of intent-to-treat subjects with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity
    End point type
    Secondary
    End point timeframe
    After 3 months
    Notes
    [95] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    84
    92
    83 [96]
    Units: subjects
        Subjects achieving DAS28-CRP criteria
    21
    25
    8
    Notes
    [96] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 4 months

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    End point title
    		 Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 4 months [97]
    End point description
    Number of intent-to-treat subjects with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity
    End point type
    Secondary
    End point timeframe
    After 4 months
    Notes
    [97] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    80
    84
    73 [98]
    Units: subjects
        Subjects achieving DAS28-CRP criteria
    28
    20
    9
    Notes
    [98] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 5 months

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    End point title
    		 Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 5 months [99]
    End point description
    Number of intent-to-treat subjects with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity
    End point type
    Secondary
    End point timeframe
    After 5 months
    Notes
    [99] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    76
    81
    71 [100]
    Units: subjects
        Subjects achieving DAS28-CRP criteria
    34
    21
    8
    Notes
    [100] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 6 months

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    End point title
    		 Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 6 months [101]
    End point description
    Number of intent-to-treat subjects with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity
    End point type
    Secondary
    End point timeframe
    After 6 months
    Notes
    [101] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    77
    81
    70 [102]
    Units: subjects
        Subjects achieving DAS28-CRP criteria
    30
    26
    7
    Notes
    [102] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 2 months

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    End point title
    		 Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 2 months [103]
    End point description
    Number of intent-to-treat subjects with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms
    End point type
    Secondary
    End point timeframe
    After 2 months
    Notes
    [103] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    60
    50
    64 [104]
    Units: subjects
        Subjects achieving DAS28-ESR criteria
    13
    4
    4
    Notes
    [104] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 3 months

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    End point title
    		 Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 3 months [105]
    End point description
    Number of intent-to-treat subjects with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms
    End point type
    Secondary
    End point timeframe
    After 3 months
    Notes
    [105] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    58
    49
    64 [106]
    Units: subjects
        Subjects achieving DAS28-ESR criteria
    19
    3
    4
    Notes
    [106] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 4 months

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    End point title
    		 Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 4 months [107]
    End point description
    Number of intent-to-treat subjects with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms
    End point type
    Secondary
    End point timeframe
    After 4 months
    Notes
    [107] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    53
    46
    57 [108]
    Units: subjects
        Subjects achieving DAS28-ESR criteria
    15
    3
    5
    Notes
    [108] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 5 months

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    End point title
    		 Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 5 months [109]
    End point description
    Number of intent-to-treat subjects with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms
    End point type
    Secondary
    End point timeframe
    After 5 months
    Notes
    [109] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    54
    45
    52 [110]
    Units: subjects
        Subjects achieving DAS28-ESR criteria
    12
    7
    3
    Notes
    [110] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 6 months

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    End point title
    		 Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 6 months [111]
    End point description
    Number of intent-to-treat subjects with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms
    End point type
    Secondary
    End point timeframe
    After 6 months
    Notes
    [111] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    54
    44
    51 [112]
    Units: subjects
        Subjects achieving DAS28-ESR criteria
    21
    9
    3
    Notes
    [112] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 2 months

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    End point title
    		 Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 2 months [113]
    End point description
    Number of intent-to-treat subjects with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity
    End point type
    Secondary
    End point timeframe
    After 2 months
    Notes
    [113] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    60
    50
    64 [114]
    Units: subjects
        Subjects achieving DAS28-ESR criteria
    23
    7
    9
    Notes
    [114] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 3 months

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    End point title
    		 Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 3 months [115]
    End point description
    Number of intent-to-treat subjects with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity
    End point type
    Secondary
    End point timeframe
    After 3 months
    Notes
    [115] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    58
    49
    64 [116]
    Units: subjects
        Subjects achieving DAS28-ESR criteria
    22
    8
    7
    Notes
    [116] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 4 months

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    End point title
    		 Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 4 months [117]
    End point description
    Number of intent-to-treat subjects with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity
    End point type
    Secondary
    End point timeframe
    After 4 months
    Notes
    [117] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    53
    46
    57 [118]
    Units: subjects
        Subjects achieving DAS28-ESR criteria
    23
    6
    8
    Notes
    [118] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 5 months

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    End point title
    		 Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 5 months [119]
    End point description
    Number of intent-to-treat subjects with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity
    End point type
    Secondary
    End point timeframe
    After 5 months
    Notes
    [119] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    54
    45
    52 [120]
    Units: subjects
        Subjects achieving DAS28-ESR criteria
    24
    8
    7
    Notes
    [120] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 6 months

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    End point title
    		 Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 6 months [121]
    End point description
    Number of intent-to-treat subjects with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity
    End point type
    Secondary
    End point timeframe
    After 6 months
    Notes
    [121] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    54
    44
    51 [122]
    Units: subjects
        Subjects achieving DAS28-ESR criteria
    29
    11
    8
    Notes
    [122] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Secondary: Number of subjects with ALT values greater than 1.5 to 2 times the ULN

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    End point title
    		 Number of subjects with ALT values greater than 1.5 to 2 times the ULN
    End point description
    The number of intent-to-treat subjects with ALT (Alanine Aminotransferase) (a test of liver function) values greater than 1.5 to 2 times the ULN (Upper Limit of Normal)
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
        >1.5 to 2 times
    15
    14
    5
    1
    No statistical analyses for this end point

    Secondary: Number of subjects with ALT values greater than 2 to 3 times the ULN

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    End point title
    		 Number of subjects with ALT values greater than 2 to 3 times the ULN
    End point description
    The number of intent-to-treat subjects with ALT (Alanine Aminotransferase) (a test of liver function) values greater than 2 to 3 times the ULN (Upper Limit of Normal)
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
        >2 to 3 times
    10
    8
    4
    1
    No statistical analyses for this end point

    Secondary: Number of subjects with ALT values greater than 3 times the ULN

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    End point title
    		 Number of subjects with ALT values greater than 3 times the ULN
    End point description
    The number of intent-to-treat subjects with ALT (Alanine Aminotransferase) (a test of liver function) values greater than 3 times the ULN (Upper Limit of Normal)
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
        >3 times
    6
    6
    2
    1
    No statistical analyses for this end point

    Secondary: Number of subjects with ALT values greater than 3 to 5 times the ULN

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    End point title
    		 Number of subjects with ALT values greater than 3 to 5 times the ULN
    End point description
    The number of intent-to-treat subjects with ALT (Alanine Aminotransferase) (a test of liver function) values greater than 3 to 5 times the ULN (Upper Limit of Normal)
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
        >3 to 5 times
    3
    3
    1
    1
    No statistical analyses for this end point

    Secondary: Number of subjects with ALT values greater than 5 to 10 times the ULN

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    End point title
    		 Number of subjects with ALT values greater than 5 to 10 times the ULN
    End point description
    The number of intent-to-treat subjects with ALT (Alanine Aminotransferase) (a test of liver function) values greater than 5 to 10 times the ULN (Upper Limit of Normal)
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
        >5 to 10 times
    3
    3
    1
    0
    No statistical analyses for this end point

    Secondary: Number of subjects with ALT values greater than 10 times the ULN

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    End point title
    		 Number of subjects with ALT values greater than 10 times the ULN
    End point description
    The number of intent-to-treat subjects with ALT (Alanine Aminotransferase) (a test of liver function) values greater than 10 times the ULN (Upper Limit of Normal)
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
        >10 times
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: The number of subjects with AST values greater than 1.5 to 2 times the ULN

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    End point title
    		 The number of subjects with AST values greater than 1.5 to 2 times the ULN
    End point description
    The number of participants with AST (Aspartate Aminotransferase) (a test of liver function) values greater than 1.5 to 2 times the ULN (Upper Limit of Normal)
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
    5
    13
    1
    0
    No statistical analyses for this end point

    Secondary: The number of subjects with AST values greater than 2 to 3 times the ULN

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    End point title
    		 The number of subjects with AST values greater than 2 to 3 times the ULN
    End point description
    The number of participants with AST (Aspartate Aminotransferase) (a test of liver function) values greater than 2 to 3 times the ULN (Upper Limit of Normal)
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
        >2 to 3 times
    1
    4
    2
    0
    No statistical analyses for this end point

    Secondary: The number of subjects with AST values greater than 3 times the ULN

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    End point title
    		 The number of subjects with AST values greater than 3 times the ULN
    End point description
    The number of participants with AST (Aspartate Aminotransferase) (a test of liver function) values greater than 3 times the ULN (Upper Limit of Normal)
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
        >3 times
    5
    2
    1
    1
    No statistical analyses for this end point

    Secondary: The number of subjects with AST values greater than 3 to 5 times the ULN

    		 Close Top of page
    End point title
    		 The number of subjects with AST values greater than 3 to 5 times the ULN
    End point description
    The number of participants with AST (Aspartate Aminotransferase) (a test of liver function) values greater than 3 to 5 times the ULN (Upper Limit of Normal)
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
        >3 to 5 times
    5
    2
    1
    0
    No statistical analyses for this end point

    Secondary: The number of subjects with AST values greater than 5 to 10 times the ULN

    		 Close Top of page
    End point title
    		 The number of subjects with AST values greater than 5 to 10 times the ULN
    End point description
    The number of participants with AST (Aspartate Aminotransferase) (a test of liver function) values greater than 5 to 10 times the ULN (Upper Limit of Normal)
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
        >5 to 10 times
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: The number of subjects with AST values greater than 10 times the ULN

    		 Close Top of page
    End point title
    		 The number of subjects with AST values greater than 10 times the ULN
    End point description
    The number of participants with AST (Aspartate Aminotransferase) (a test of liver function) values greater than 10 times the ULN (Upper Limit of Normal)
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
        >10 times
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of subjects with Bilirubin 2 times the Upper Limit of Normal (ULN)

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    End point title
    		 Number of subjects with Bilirubin 2 times the Upper Limit of Normal (ULN)
    End point description
    The number of intent-to-treat subjects with bilirubin (a test of liver function) values greater than 2 times the ULN
    End point type
    Secondary
    End point timeframe
    Any time between baseline and 6 months
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Number of subjects analysed
    152
    152
    76
    77
    Units: subjects
        >2 times
    3
    0
    0
    0
    No statistical analyses for this end point

    Secondary: American College of Rheumatology 20 (ACR20) Response at 6 weeks

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    End point title
    		 American College of Rheumatology 20 (ACR20) Response at 6 weeks [123]
    End point description
    The number of intent-to-treat subjects with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR)
    End point type
    Secondary
    End point timeframe
    After 6 weeks
    Notes
    [123] - 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: The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis.
    End point values
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Placebo Pooled
    Number of subjects analysed
    150
    151
    148 [124]
    Units: subjects
        Subjects achieving ACR20 criteria
    84
    75
    55
    Notes
    [124] - Pooled placebo subjects from Cohorts C and D
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From ICF signature until visit 11 (Month 6) for AEs and until 30 days after the last dose of of study drug for SAEs.
    Adverse event reporting additional description
    Please note, safety data were only calculated for the placebo qd and placebo bid groups. Data from the placebo groups were only pooled for the efficacy analyses
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    9.0
    Reporting groups
    Reporting group title
    Cohort A R788 100 mg bid
    Reporting group description
    		 R788 100 mg, oral tablets, twice daily, double-blind

    Reporting group title
    Cohort B R788 150 mg qd
    Reporting group description
    		 R788 150 mg, oral tablets, once daily, double-blind

    Reporting group title
    Cohort C Placebo 100 mg bid
    Reporting group description
    		 Placebo 100 mg, oral tablets, twice daily, double-blind

    Reporting group title
    Cohort D Placebo 150 mg qd
    Reporting group description
    		 Placebo 150 mg, oral tablets, once daily, double-blind

    Serious adverse events
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 152 (8.55%)
    5 / 152 (3.29%)
    4 / 76 (5.26%)
    2 / 77 (2.60%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Renal cell carcinoma stage unspecified
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 152 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (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
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 152 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (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
    Carcinoma in situ of penis
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 152 (0.66%)
    0 / 76 (0.00%)
    0 / 77 (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
    Injury, poisoning and procedural complications
    Subdural haematoma
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 152 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (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
    Angina unstable
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 152 (0.66%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Stillbirth
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 152 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (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
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    0 / 152 (0.00%)
    0 / 152 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (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
    Duodenal ulcer
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 152 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (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
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 152 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 152 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 152 (0.66%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthmatic crisis
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 152 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (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
    Renal and urinary disorders
    Hydronephrosis
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 152 (0.66%)
    0 / 76 (0.00%)
    0 / 77 (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
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 152 (0.00%)
    0 / 152 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (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
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 152 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gallbladder empyema
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 152 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (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
    Herpes zoster ophthalmic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 152 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 152 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 152 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (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
    Erysipelas
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 152 (0.66%)
    0 / 76 (0.00%)
    0 / 77 (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
    Pyelonephritis
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 152 (0.66%)
    0 / 76 (0.00%)
    0 / 77 (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
    Arthritis infective
         subjects affected / exposed
    0 / 152 (0.00%)
    0 / 152 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (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
    Soft tissue infection
         subjects affected / exposed
    0 / 152 (0.00%)
    0 / 152 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (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
    Bursitis infective
         subjects affected / exposed
    0 / 152 (0.00%)
    0 / 152 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort A R788 100 mg bid Cohort B R788 150 mg qd Cohort C Placebo 100 mg bid Cohort D Placebo 150 mg qd
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    73 / 152 (48.03%)
    62 / 152 (40.79%)
    20 / 76 (26.32%)
    26 / 77 (33.77%)
    Investigations
    Transaminases increased
    Additional description: Data was entered only for affected subjects, not occurrences.
         subjects affected / exposed
    8 / 152 (5.26%)
    7 / 152 (4.61%)
    2 / 76 (2.63%)
    3 / 77 (3.90%)
         occurrences all number
    9
    7
    2
    3
    Vascular disorders
    Hypertension
    Additional description: Data was entered only for affected subjects, not occurrences.
         subjects affected / exposed
    21 / 152 (13.82%)
    18 / 152 (11.84%)
    3 / 76 (3.95%)
    4 / 77 (5.19%)
         occurrences all number
    21
    18
    3
    4
    Nervous system disorders
    Headache
    Additional description: Data was entered only for affected subjects, not occurrences.
         subjects affected / exposed
    9 / 152 (5.92%)
    10 / 152 (6.58%)
    6 / 76 (7.89%)
    3 / 77 (3.90%)
         occurrences all number
    9
    11
    6
    4
    Gastrointestinal disorders
    Diarrhoea
    Additional description: Data was entered only for affected subjects, not occurrences.
         subjects affected / exposed
    29 / 152 (19.08%)
    19 / 152 (12.50%)
    1 / 76 (1.32%)
    4 / 77 (5.19%)
         occurrences all number
    41
    23
    1
    4
    Nausea
    Additional description: Data was entered only for affected subjects, not occurrences.
         subjects affected / exposed
    7 / 152 (4.61%)
    9 / 152 (5.92%)
    6 / 76 (7.89%)
    1 / 77 (1.30%)
         occurrences all number
    8
    10
    6
    1
    Skin and subcutaneous tissue disorders
    Rash
    Additional description: Data was entered only for affected subjects, not occurrences.
         subjects affected / exposed
    3 / 152 (1.97%)
    2 / 152 (1.32%)
    0 / 76 (0.00%)
    5 / 77 (6.49%)
         occurrences all number
    3
    3
    0
    5
    Musculoskeletal and connective tissue disorders
    Back pain
    Additional description: Data was entered only for affected subjects, not occurrences.
         subjects affected / exposed
    1 / 152 (0.66%)
    1 / 152 (0.66%)
    1 / 76 (1.32%)
    5 / 77 (6.49%)
         occurrences all number
    1
    1
    1
    6
    Infections and infestations
    Urinary tract infection
    Additional description: Data was entered only for affected subjects, not occurrences.
         subjects affected / exposed
    11 / 152 (7.24%)
    6 / 152 (3.95%)
    6 / 76 (7.89%)
    2 / 77 (2.60%)
         occurrences all number
    12
    7
    6
    2
    Upper respiratory tract infection
    Additional description: Data was entered only for affected subjects, not occurrences.
         subjects affected / exposed
    10 / 152 (6.58%)
    3 / 152 (1.97%)
    2 / 76 (2.63%)
    3 / 77 (3.90%)
         occurrences all number
    13
    3
    2
    3
    Influenza
    Additional description: Data was entered only for affected subjects, not occurrences.
         subjects affected / exposed
    5 / 152 (3.29%)
    3 / 152 (1.97%)
    4 / 76 (5.26%)
    2 / 77 (2.60%)
         occurrences all number
    5
    3
    5
    2
    Metabolism and nutrition disorders
    Dyslipidaemia
    Additional description: Data was entered only for affected subjects, not occurrences.
         subjects affected / exposed
    5 / 152 (3.29%)
    9 / 152 (5.92%)
    2 / 76 (2.63%)
    4 / 77 (5.19%)
         occurrences all number
    6
    10
    2
    4

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Mar 2008
    Amendment 1 (Version 2), dated 19 March 2008, implemented prior to the first patient’s first dose (19 May 2008). original protocol (Version 1), issued on 29 February 2008. This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of Directive 2001/20EC of the European Parliament and the Council of the European Union. Changed the central laboratory, allowed sites to confirm ALT/ANC results that met dose adjustment/stopping guidelines using their local laboratory; and provided an updated version of the SF-36.
    11 Nov 2008
    Amendment 2 (Version 3), dated 19 March 2008, implemented after to the first patient’s first dose (19 May 2008), original protocol (Version 1), issued on 29 February 2008, amendment 1 (version 2) issued on 19 March 2008 This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of Directive 2001/20EC of the European Parliament and the Council of the European Union. Clarified the inclusion criteria (ESR should be >ULN for the local laboratory rather than a set parameter given differences in local laboratory reference ranges), added serum pregnancy testing at Screening and Baseline in addition to a urine pregnancy test, specified that total and direct bilirubin should be reported, and clarified terms for non-SAEs, reporting requirements for hepatotoxicity, and that only SAEs identified within 30 days of the last dose of study drug administration were to be reported (not all AEs).

    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.
    The 2 placebo groups (bid and qd) were pooled for all efficacy data summaries and analysis since the observed ACR20 response rate difference between the placebo groups was <15 percentage points (prospectively defined in protocol).
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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