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    Clinical Trial Results:
    An Open-Label Extension Study to Assess the Safety of GSK1605786A in Subjects with Crohn’s Disease

    Summary
    EudraCT number
    2010-022384-35
    Trial protocol
    DE   BE   SE   GB   CZ   DK   HU   GR   AT   PL   ES   PT   EE   IT   SK   BG  
    Global end of trial date
    29 Oct 2013

    Results information
    Results version number
    v2(current)
    This version publication date
    10 Mar 2016
    First version publication date
    05 Jun 2015
    Other versions
    v1
    Version creation reason
    • Correction of full data set
    Correction of full data set

    Trial information

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    Trial identification
    Sponsor protocol code
    CCX114644
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01318993
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, +1 8664357343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, +1 8664357343,
    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
    05 Mar 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Oct 2013
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To assess the safety and tolerability of long-term treatment with GSK1605786A in subjects with Crohn’s disease.
    Protection of trial subjects
    Women of child-bearing potential were excluded unless they agreed to take adequate contraceptive measures. Subjects with known hepatic disease and / or biliary dysfunction were excluded. Liver chemistry stopping criteria were implemented in alignment with premarketing clinical liver safety guidance. Withdrawal criteria were implemented for those developing prolongation of the QTc interval. Background medications to manage Crohn’s Disease were permitted.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    05 Apr 2011
    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
    Slovakia: 4
    Country: Number of subjects enrolled
    South Africa: 4
    Country: Number of subjects enrolled
    Spain: 3
    Country: Number of subjects enrolled
    Sweden: 5
    Country: Number of subjects enrolled
    Switzerland: 2
    Country: Number of subjects enrolled
    Ukraine: 1
    Country: Number of subjects enrolled
    United Kingdom: 16
    Country: Number of subjects enrolled
    United States: 107
    Country: Number of subjects enrolled
    Australia: 23
    Country: Number of subjects enrolled
    Austria: 4
    Country: Number of subjects enrolled
    Belgium: 24
    Country: Number of subjects enrolled
    Canada: 53
    Country: Number of subjects enrolled
    Czech Republic: 29
    Country: Number of subjects enrolled
    Denmark: 13
    Country: Number of subjects enrolled
    Estonia: 1
    Country: Number of subjects enrolled
    France: 22
    Country: Number of subjects enrolled
    Germany: 32
    Country: Number of subjects enrolled
    Hong Kong: 1
    Country: Number of subjects enrolled
    Hungary: 5
    Country: Number of subjects enrolled
    Israel: 6
    Country: Number of subjects enrolled
    Japan: 23
    Country: Number of subjects enrolled
    Korea, Republic of: 9
    Country: Number of subjects enrolled
    New Zealand: 3
    Country: Number of subjects enrolled
    Poland: 8
    Worldwide total number of subjects
    398
    EEA total number of subjects
    166
    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)
    391
    From 65 to 84 years
    7
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Participants were eligible to enter the study if they completed the placebo-controlled induction study CCX114151; completed the maintenance study CCX114157 at Week 52; or withdrew from the maintenance study CCX114157.

    Pre-assignment
    Screening details
    All participants entered the study at a Baseline visit, Week 0, and received GSK1605786A 500 milligrams (mg), twice daily (BID) for 216 weeks.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    GSK1605786A 500 mg BID
    Arm description
    Participants received two GSK1605786A 250 milligram (mg), oral capsules twice daily (BID), once in the morning and once in the evening, for 216 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK1605786A
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    500 mg twice daily, oral administration

    Number of subjects in period 1
    GSK1605786A 500 mg BID
    Started
    398
    Completed
    174
    Not completed
    224
         Protocol Defined Stopping Criteria
    6
         Protocol deviation
    3
         Physician decision
    13
         Lack of efficacy
    121
         Adverse event, non-fatal
    53
         Consent withdrawn by subject
    24
         Lost to follow-up
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    -

    Reporting group values
    Overall Study Total
    Number of subjects
    398 398
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    36.5 ± 11.99 -
    Gender categorical
    Units: Subjects
        Female
    213 213
        Male
    185 185
    Race, Customized
    Units: Subjects
        White- Caucasian/European
    341 341
        White- Arabic/North African
    10 10
        Black
    7 7
        Asian- Central/South
    4 4
        Asian- East
    9 9
        Asian- South East
    1 1
        Asian- Japanese
    24 24
        American Indian/native Alaskan
    1 1
        Multiple Race
    1 1

    End points

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    End points reporting groups
    Reporting group title
    GSK1605786A 500 mg BID
    Reporting group description
    Participants received two GSK1605786A 250 milligram (mg), oral capsules twice daily (BID), once in the morning and once in the evening, for 216 weeks.

    Primary: Number of participants with any adverse event (AE) and any serious adverse event (SAE)

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    End point title
    Number of participants with any adverse event (AE) and any serious adverse event (SAE) [1]
    End point description
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death; was life threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; was a congenital anomaly/birth defect. The Safety population consisted of all participants who enrolled in the study except those who did not take >=1 dose of investigational product.
    End point type
    Primary
    End point timeframe
    From the start of study medication until the follow-up visit (up to Week 112).
    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: There are no statistics for this endpoint.
    End point values
    GSK1605786A 500 mg BID
    Number of subjects analysed
    398 [2]
    Units: Participants
    number (not applicable)
        Any AE
    303
        Any SAE
    41
    Notes
    [2] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP)

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    End point title
    Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP)
    End point description
    Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) values were obtained as part of vital sign monitoring and measured after the participant was at rest in the supine position for at least 5 minutes. Change from Baseline measurements in SBP and DBP were assessed at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 4 weeks post-treatment. The Baseline value is defined as the value at Week 0. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 112
    End point values
    GSK1605786A 500 mg BID
    Number of subjects analysed
    398 [3]
    Units: millimeters of mercury (mmHg)
    arithmetic mean (standard deviation)
        SBP, Week 4, n=390
    -0.4 ± 11.39
        SBP, Week 8, n=337
    -0.4 ± 11.46
        SBP, Week 12, n=291
    -0.9 ± 13.12
        SBP, Week 24, n=197
    1 ± 12.69
        SBP, Week 36, n=132
    1.3 ± 12.64
        SBP, Week 48, n=91
    -0.5 ± 13.22
        SBP, Week 60, n=56
    1.5 ± 13
        SBP, Week 72, n=36
    -0.1 ± 13.15
        SBP, Week 84, n=19
    5.4 ± 18.65
        SBP, Week 96, n=13
    -5.4 ± 10.72
        SBP, Week 108, n=6
    2.2 ± 13.44
        SBP, 4 week post treatment, n=298
    0.5 ± 13.56
        DBP, Week 4, n=390
    0.1 ± 8.58
        DBP, Week 8, n=337
    0.1 ± 8.18
        DBP, Week 12, n=291
    0.2 ± 9.21
        DBP, Week 24, n=197
    0.1 ± 10.17
        DBP, Week 36, n=132
    1 ± 9.8
        DBP, Week 48, n=91
    0 ± 9.02
        DBP, Week 60, n=56
    1.2 ± 10.59
        DBP, Week 72, n=36
    0 ± 10.03
        DBP, Week 84, n=19
    4.4 ± 11
        DBP, Week 96, n=13
    -1.8 ± 9.33
        DBP, Week 108, n=6
    1.3 ± 9.52
        DBP, 4 week post treatment, n=298
    0.1 ± 9.91
    Notes
    [3] - Safety Population. Only participants available at the specified time points were analyzed (n=X).
    No statistical analyses for this end point

    Secondary: Change from Baseline in heart rate (HR)

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    End point title
    Change from Baseline in heart rate (HR)
    End point description
    Heart Rate (HR) values were obtained as part of vital sign monitoring and measured after the participant was at rest in the supine position for at least 5 minutes. Change from Baseline in HR was assessed at Week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 4 weeks post-treatment. The Baseline value is defined as the value at Week 0. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 112
    End point values
    GSK1605786A 500 mg BID
    Number of subjects analysed
    398 [4]
    Units: beats per minute
    arithmetic mean (standard deviation)
        HR, Week 4, n=390
    1.3 ± 10.92
        HR, Week 8, n=337
    0.1 ± 11.41
        HR, Week 12, n=291
    0.8 ± 11.93
        HR, Week 24, n=197
    -0.5 ± 12.56
        HR, Week 36, n=132
    2.1 ± 12.35
        HR, Week 48, n=91
    -1.2 ± 13.16
        HR, Week 60, n=56
    0.4 ± 12.85
        HR, Week 72, n=36
    -1.2 ± 12.39
        HR, Week 84, n=19
    -0.7 ± 15.44
        HR, Week 96, n=13
    -4.9 ± 17.01
        HR, Week 108, n=6
    -7.7 ± 12.83
        HR, 4 week post treatment, n=298
    -0.8 ± 12.89
    Notes
    [4] - Safety Population. Only participants available at the specified time points were analyzed (n=X).
    No statistical analyses for this end point

    Secondary: Number of participants with shifts from Baseline for the indicated hematology parameters

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    End point title
    Number of participants with shifts from Baseline for the indicated hematology parameters
    End point description
    Hematology parameters measured included platelets, neutrophils (NL), lymphocytes, monocytes, eosinophils, basophils, hematocrit, band cells, red blood cell (RBC) count, hemoglobin, white blood cell (WBC) count, and segmented (seg) NL. The Baseline value is defined as the value obtained at Week 0. The number of participants with the indicated hematology parameters data reference range shifts from Baseline (defined as shift to low, shift to normal or no change, shift to high) until 4 weeks post treatment are presented. A value of 99999 is used where no participants were analyzed for the indicated category therefore there is no data to present.
    End point type
    Secondary
    End point timeframe
    From Baseline until Week 112
    End point values
    GSK1605786A 500 mg BID
    Number of subjects analysed
    398 [5]
    Units: Participants
    number (not applicable)
        Platelets, shift to low, n=393
    2
        Platelets, shift to normal or no change, n=394
    325
        Platelets, shift to high, n=295
    67
        NL, shift to low, n=393
    5
        NL, shift to normal or no change, n=395
    284
        NL, shift to high, n=214
    106
        Lymphocytes, shift to low, n=239
    99
        Lymphocytes, shift to normal or no change, n=395
    292
        Lymphocytes, shift to high, n=392
    4
        Monocytes, shift to low, n=395
    0
        Monocytes, shift to normal or no change, n=395
    372
        Monocytes, shift to high, n=383
    23
        Eosinophils, shift to low, n=0
    99999
        Eosinophils, shift to normal or no change, n=395
    366
        Eosinophils, shift to high, n=382
    29
        Basophils, shift to low, n=0
    99999
        Basophils, shift to normal or no change, n=395
    395
        Basophils, shift to high, n=394
    0
        Hematocrit, shift to low, n=249
    75
        Hematocrit, shift to normal or no change, n=395
    312
        Hematocrit, shift to high, n=392
    8
        Band cells, shift to low, n=0
    99999
        Band cells, shift to normal or no change, n=6
    5
        Band cells, shift to high, n=2
    1
        RBC Count, shift to low, n=293
    62
        RBC Count, shift to normal or no change, n=395
    322
        RBC Count, shift to high, n=393
    11
        Hemoglobin, shift to low, n=191
    74
        Hemoglobin, shift to normal or no change, n=395
    320
        Hemoglobin, shift to high, n=395
    1
        WBC Count, shift to low, n=388
    23
        WBC Count, shift to normal or no change, n=395
    289
        WBC Count, shift to high, n=313
    83
        Segmented (Seg) NL, shift to low, n=393
    5
        Seg NL, shift to normal or no change, n=395
    283
        Seg NL, shift to high, n=215
    107
    Notes
    [5] - Safety Population. Only participants available at the specified time points were analyzed (n=X).
    No statistical analyses for this end point

    Secondary: Number of participants with shifts from Baseline for the indicated clinical chemistry parameters

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    End point title
    Number of participants with shifts from Baseline for the indicated clinical chemistry parameters
    End point description
    Clinical chemistry parameters included platelets, total protein, phosphorous, albumin, sodium, potassium, chloride, calcium, glucose, gamma-glutamyl transferase, total bilirubin (TB), direct bilirubin (DB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN)/urea, creatinine, uric acid, bicarbonate, lactate dehydrogenase, cholesterol, and creatine kinase. The Baseline value is defined as the value obtained at Week 0. The number of participants with the indicated clinical chemistry parameters' data refernce range shifts from Baseline (defined as shift to low, shift to normal or no change, or shift to high) until 4 weeks post-treatment are presented. A value of 99999 is used where no participants were analyzed for the indicated category therefore there is no data to present.
    End point type
    Secondary
    End point timeframe
    From Baseline until Week 112
    End point values
    GSK1605786A 500 mg BID
    Number of subjects analysed
    398 [6]
    Units: Participants
    number (not applicable)
        Total Protein, shift to low, n=370
    27
        Total Protein, shift to normal or no change, n=395
    367
        Total Protein, shift to high, n=395
    1
        Phosphorous, shift to low, n=369
    85
        Phosphorous, shift to normal or no change, n=395
    283
        Phosphorous, shift to high, n=385
    30
        Albumin, shift to low, n=372
    19
        Albumin, shift to normal or no change, n=395
    373
        Albumin, shift to high, n=395
    3
        Sodium, shift to low, n=392
    18
        Sodium, shift to normal or no change, n=395
    376
        Sodium, shift to high, n=395
    1
        Potassium, shift to low, n=379
    25
        Potassium, shift to normal or no change, n=395
    360
        Potassium, shift to high, n=393
    10
        Chloride, shift to low, n=395
    3
        Chloride, shift to normal or no change, n=395
    361
        Chloride, shift to high, n=381
    31
        Calcium, shift to low, n=363
    43
        Calcium, shift to normal or no change, n=395
    340
        Calcium, shift to high, n=394
    12
        Glucose, shift to low, n=370
    54
        Glucose, shift to normal or no change, n=395
    279
        Glucose, shift to high, n=361
    66
        GGT, shift to low, n=0
    99999
        GGT, shift to normal or no change, n=397
    330
        GGT, shift to high, n=355
    67
        TB, shift to low, n=0
    99999
        TB, shift to normal or no change, n=397
    391
        TB, shift to high, n=393
    6
        DB, shift to low, n=0
    99999
        DB, shift to normal or no change, n=397
    397
        DB, shift to high, n=397
    0
        ALP, shift to low, n=395
    0
        ALP, shift to normal or no change, n=397
    357
        ALP, shift to high, n=370
    40
        ALT, shift to low, n=0
    99999
        ALT, shift to normal or no change, n=397
    349
        ALT, shift to high, n=390
    48
        AST, shift to low, n=0
    99999
        AST, shift to normal or no change, n=397
    362
        AST, shift to high, n=390
    35
        BUN/Urea, shift to low, n=367
    44
        BUN/Urea, shift to normal or no change, n=395
    345
        BUN/Urea, shift to high, n=393
    6
        Creatinine, shift to low, n=326
    50
        Creatinine, shift to normal or no change, n=395
    335
        Creatinine, shift to high, n=392
    10
        Uric Acid, shift to low, n=382
    21
        Uric Acid, shift to normal or no change, n=395
    350
        Uric Acid, shift to high, n=390
    24
        Bicarbonate, shift to low, n=355
    92
        Bicarbonate, shift to normal or no change, n=395
    303
        Bicarbonate, shift to high, n=394
    0
        LDH, shift to low, n=0
    99999
        LDH, shift to normal or no change, n=395
    386
        LDH, shift to high, n=392
    9
        Cholesterol, shift to low, n=0
    99999
        Cholesterol, shift to normal or no change, n=395
    330
        Cholesterol, shift to high, n=335
    65
        CK, shift to low, n=0
    99999
        CK, shift to normal or no change, n=395
    357
        CK, shift to high, n=335
    38
    Notes
    [6] - Safety Population. Only participants available at the specified time points were analyzed (n=X).
    No statistical analyses for this end point

    Secondary: Change from Baseline in ALT, AST, ALP, and gamma-glutamyl transferase (GGT)

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    End point title
    Change from Baseline in ALT, AST, ALP, and gamma-glutamyl transferase (GGT)
    End point description
    Changes in Baseline in Alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) were assessed to monitor liver function. Blood samples were taken at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 4 Weeks post-treatment. The last value on or prior to the treatment start date was considered the Baseline value. Change from Baseline was calculated as the post-Baseline value at the timepoint indicated minus the value at Baseline.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 112
    End point values
    GSK1605786A 500 mg BID
    Number of subjects analysed
    398 [7]
    Units: International Unit per Liter (IU/L)
    arithmetic mean (standard deviation)
        ALT, Week 2, n=374
    -0.4 ± 9.18
        ALT, Week 4, n=365
    4.1 ± 42.63
        ALT, Week 6, n=348
    2 ± 16.12
        ALT, Week 8, n=322
    2.3 ± 22.27
        ALT, Week 10, n=297
    1.1 ± 13.96
        ALT, Week 12, n=281
    1.6 ± 16.03
        ALT, Week 16, n=229
    0.7 ± 12.99
        ALT, Week 20, n=203
    2.5 ± 33.03
        ALT, Week 24, n=182
    -0.4 ± 10.36
        ALT, Week 28, n=158
    1.9 ± 19.93
        ALT, Week 32, n=141
    0.4 ± 12.19
        ALT, Week 36, n=121
    0.9 ± 9.95
        ALT, Week 40, n=102
    1.9 ± 9.29
        ALT, Week 44, n=95
    2.9 ± 12.13
        ALT, Week 48, n=89
    0.1 ± 7.99
        ALT, Week 52, n=77
    0.7 ± 8.75
        ALT, Week 60, n=55
    1.1 ± 9.49
        ALT, Week 72, n=36
    0.9 ± 4.73
        ALT, Week 84, n=18
    1.5 ± 5.81
        ALT, Week 96, n=13
    1.5 ± 9.63
        ALT, Week 108, n=6
    2.2 ± 6.74
        ALT, 4 week post treatment, n=299
    3 ± 24.12
        AST, Week 2, n=373
    -0.1 ± 4.7
        AST, Week 4, n=365
    1.8 ± 18.11
        AST, Week 6, n=348
    0.9 ± 8.29
        AST, Week 8, n=322
    1.1 ± 13.49
        AST, Week 10, n=296
    0.5 ± 8.12
        AST, Week 12, n=280
    2.2 ± 25.34
        AST, Week 16, n=228
    0.5 ± 8.59
        AST, Week 20, n=202
    1.9 ± 21.69
        AST, Week 24, n=182
    0.3 ± 6.82
        AST, Week 28, n=158
    1.1 ± 13.05
        AST, Week 32, n=141
    0.6 ± 7.96
        AST, Week 36, n=120
    1.5 ± 7.84
        AST, Week 40, n=102
    1.4 ± 6.94
        AST, Week 44, n=95
    2 ± 8.63
        AST, Week 48, n=89
    0.2 ± 6.2
        AST, Week 52, n=77
    -0.1 ± 6.4
        AST, Week 60, n=55
    0.6 ± 6.83
        AST, Week 72, n=36
    0.6 ± 4.2
        AST, Week 84, n=18
    0.8 ± 4.37
        AST, Week 96, n=13
    2 ± 9.17
        AST, Week 108, n=6
    1 ± 5.93
        AST, 4 week post treatment, n=298
    2.5 ± 12.91
        ALP, Week 2, n=374
    -0.5 ± 11.23
        ALP, Week 4, n=365
    0.7 ± 14.35
        ALP, Week 6, n=348
    0.3 ± 15.25
        ALP, Week 8, n=322
    0.2 ± 14.66
        ALP, Week 10, n=297
    0.7 ± 14.72
        ALP, Week 12, n=281
    0.6 ± 16.16
        ALP, Week 16, n=229
    1 ± 14.35
        ALP, Week 20, n=203
    0.8 ± 15.57
        ALP, Week 24, n=182
    3.1 ± 16.41
        ALP, Week 28, n=158
    3.6 ± 19.19
        ALP, Week 32, n=141
    3.7 ± 17.16
        ALP, Week 36, n=121
    5 ± 19.31
        ALP, Week 40, n=102
    5.5 ± 17.36
        ALP, Week 44, n=95
    3.5 ± 15.21
        ALP, Week 48, n=89
    3.8 ± 19.78
        ALP, Week 52, n=77
    1.8 ± 16.41
        ALP, Week 60, n=55
    2.1 ± 16.62
        ALP, Week 72, n=36
    3.5 ± 14.34
        ALP, Week 84, n=18
    4.6 ± 15.53
        ALP, Week 96, n=13
    2.9 ± 10.51
        ALP, Week 108, n=6
    0.8 ± 11.94
        ALP, 4 week post treatment, n=299
    1.3 ± 23.34
        GGT, Week 2, n=374
    1.8 ± 12.47
        GGT, Week 4, n=365
    4.6 ± 18.39
        GGT, Week 6, n=347
    3.2 ± 17.48
        GGT, Week 8, n=322
    3 ± 14.4
        GGT, Week 10, n=297
    2.6 ± 15.39
        GGT, Week 12, n=281
    3.2 ± 18.24
        GGT, Week 16, n=229
    2.1 ± 16.99
        GGT, Week 20, n=203
    2.4 ± 17.5
        GGT, Week 24, n=182
    3 ± 23.22
        GGT, Week 28, n=158
    4.7 ± 27.54
        GGT, Week 32, n=141
    4.2 ± 23.18
        GGT, Week 36, n=121
    4.1 ± 22.19
        GGT, Week 40, n=102
    6.1 ± 23.2
        GGT, Week 44, n=95
    3 ± 19.38
        GGT, Week 48, n=89
    3.6 ± 28.93
        GGT, Week 52, n=77
    2 ± 13.83
        GGT, Week 60, n=55
    4.3 ± 11.66
        GGT, Week 72, n=36
    2.4 ± 9.84
        GGT, Week 84, n=18
    1.7 ± 12.16
        GGT, Week 96, n=13
    -3.6 ± 14.18
        GGT, Week 108, n=6
    -8.5 ± 15.25
        GGT, 4 week post treatment, n=297
    1.3 ± 24.77
    Notes
    [7] - Safety Population. Only participants available at the specified time points were analyzed (n=X).
    No statistical analyses for this end point

    Secondary: Change from Baseline in total bilirubin

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    End point title
    Change from Baseline in total bilirubin
    End point description
    Changes from Baseline in total bilirubin (TB) was assessed to monitor liver function. Blood samples were taken at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 4 Weeks post-treatment. The last value on or prior to the treatment start date was considered the Baseline value. Change from Baseline was calculated as the post-Baseline value at the timepoint indicated minus the value at Baseline.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 112
    End point values
    GSK1605786A 500 mg BID
    Number of subjects analysed
    398 [8]
    Units: micromole/Liter (umol/L)
    arithmetic mean (standard deviation)
        TB, Week 2, n=374
    -0.2 ± 2.44
        TB, Week 4, n=365
    0.1 ± 2.75
        TB, Week 6, n=348
    -0.2 ± 2.44
        TB, Week 8, n=322
    -0.2 ± 2.51
        TB, Week 10, n=297
    0.1 ± 2.7
        TB, Week 12, n=281
    -0.2 ± 2.31
        TB, Week 16, n=229
    -0.1 ± 2.37
        TB, Week 20, n=203
    -0.2 ± 2.31
        TB, Week 24, n=182
    0.3 ± 2.15
        TB, Week 28, n=158
    0.2 ± 2.48
        TB, Week 32, n=141
    0 ± 2.48
        TB, Week 36, n=121
    0.1 ± 2.4
        TB, Week 40, n=102
    0.5 ± 2.84
        TB, Week 44, n=95
    0.4 ± 2.56
        TB, Week 48, n=89
    0.2 ± 2.16
        TB, Week 52, n=77
    0.3 ± 2.58
        TB, Week 60, n=55
    0.3 ± 2.44
        TB, Week 72, n=36
    0.2 ± 3.05
        TB, Week 84, n=18
    0.4 ± 2.15
        TB, Week 96, n=13
    1.2 ± 2.28
        TB, Week 108, n=6
    0.7 ± 1.51
        TB, 4 week post treatment, n=299
    1 ± 3.25
    Notes
    [8] - Safety Population. Only participants available at the specified time points were analyzed (n=X).
    No statistical analyses for this end point

    Secondary: Change from Baseline in albumin

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    End point title
    Change from Baseline in albumin
    End point description
    Change from Baseline in albumin was assessed to monitor liver function. Blood samples were taken at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 4 Weeks post-treatment. The last value on or prior to the treatment start date was considered the Baseline value. Change from Baseline was calculated as the post-Baseline value at the timepoint indicated minus the value at Baseline. A value of 99999 is used to indicate too few participants were analyzed to determine a standard deviation therefore there is no data to present.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 112
    End point values
    GSK1605786A 500 mg BID
    Number of subjects analysed
    398 [9]
    Units: Gram/Liter (G/L)
    arithmetic mean (standard deviation)
        Albumin, Week 2, n=20
    -0.5 ± 3.97
        Albumin, Week 4, n=356
    0.2 ± 2.52
        Albumin, Week 6, n=31
    0.1 ± 2.36
        Albumin, Week 8, n=317
    0.3 ± 2.72
        Albumin, Week 10, n=19
    -0.2 ± 2.79
        Albumin, Week 12, n=277
    0.4 ± 2.7
        Albumin, Week 16, n=22
    -1 ± 3.88
        Albumin, Week 20, n=19
    0.2 ± 2.52
        Albumin, Week 24, n=181
    0.9 ± 3.36
        Albumin, Week 28, n=8
    -0.4 ± 6.21
        Albumin, Week 32, n=8
    -1 ± 3.51
        Albumin, Week 36, n=121
    1.2 ± 3.42
        Albumin, Week 40, n=6
    0.5 ± 4.23
        Albumin, Week 44, n=1
    -2 ± 99999
        Albumin, Week 48, n=88
    1.1 ± 3.09
        Albumin, Week 52, n=6
    1 ± 3.58
        Albumin, Week 60, n=55
    0.8 ± 3.54
        Albumin, Week 72, n=36
    1.4 ± 3.54
        Albumin, Week 84, n=18
    1.6 ± 3.29
        Albumin, Week 96, n=13
    1.5 ± 3.95
        Albumin, Week 108, n=6
    0.8 ± 1.17
        Albumin, 4 week post treatment, n=295
    0.5 ± 3.3
    Notes
    [9] - Safety Population. Only participants available at the specified time points were analyzed (n=X).
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated change from Baseline in corrected QT interval (QTc) value

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    End point title
    Number of participants with the indicated change from Baseline in corrected QT interval (QTc) value
    End point description
    QTc is the corrected QT interval as measured by the electrocardiogram (ECG). ECG parameters including the change from Baseline in the QTc interval values QTcF and QTcB were summarised. The QTcF is Fridericia’s formula and defined as the QT interval/cubed root of the R-R interval. The QTcB is the Bazett’s formula defined as the QT/squared root of the R-R interval. The number of participants with change from Baseline in the QTcF and QTcB intervals of >30, 30-<60 and >=60 milliseconds were assesed at Week 24, 48, 72 and Week 108. The last value on or prior to the treatment start date was considered the Baseline value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 24, 48, 72 and Week 108
    End point values
    GSK1605786A 500 mg BID
    Number of subjects analysed
    398 [10]
    Units: Participants
    number (not applicable)
        QTcB, Week 24,<30, n=70
    66
        QTcB, Week 24, 30-<60, n=70
    3
        QTcB, Week 24, >=60, n=70
    1
        QTcB, Week 48,<30, n=35
    34
        QTcB, Week 48, 30-<60, n=35
    0
        QTcB, Week 48, >=60, n=35
    1
        QTcB, Week 72,<30, n=17
    15
        QTcB, Week 72, 30-<60, n=17
    1
        QTcB, Week 72, >=60, n=17
    1
        QTcB, Week 108,<30, n=3
    3
        QTcB, Week 108, 30-<60, n=3
    0
        QTcB, Week 108, >=60, n=3
    0
        QTcB, 4 Weeks Post Treatment, <30, n=96
    89
        QTcB, 4 Weeks Post Treatment, 30-<60, n=96
    6
        QTcB, 4 Weeks Post Treatment, >=60, n=96
    1
        QTcF, Week 24,<30, n=23
    22
        QTcF, Week 24, 30-<60, n=23
    1
        QTcF, Week 24, >=60, n=23
    0
        QTcF, Week 48,<30, n=13
    13
        QTcF, Week 48, 30-<60, n=13
    0
        QTcB, Week 48, >=60, n=13
    0
        QTcF, Week 72,<30, n=7
    7
        QTcF, Week 72, 30-<60, n=7
    0
        QTcF, Week 72, >=60, n=7
    0
        QTcF, Week 108,<30, n=2
    1
        QTcF, Week 108, 30-<60, n=2
    1
        QTcF, Week 108, >=60, n=2
    0
        QTcF, 4 Weeks Post Treatment, <30, n=32
    32
        QTcF, 4 Weeks Post Treatment, 30-<60, n=32
    0
        QTcF, 4 Weeks Post Treatment, >=60, n=32
    0
    Notes
    [10] - Safety Population. Only participants available at the specified time points were analyzed (n=X).
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks).
    Adverse event reporting additional description
    On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    GSK1605786A 500 mg BID
    Reporting group description
    Participants received two GSK1605786A 250 milligram (mg), oral capsules twice daily (BID), once in the morning and once in the evening, for 216 weeks.

    Serious adverse events
    GSK1605786A 500 mg BID
    Total subjects affected by serious adverse events
         subjects affected / exposed
    41 / 398 (10.30%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Intermittent Claudication
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon Neoplasm
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Drug Ineffective
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    Bartholinitis
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Incisional Hernia
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Postoperative Ileus
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Liver Function Test Abnormal
         subjects affected / exposed
    2 / 398 (0.50%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Iron Deficiency Anemia
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Multiple Sclerosis
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Myoclonus
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Crohn’s Disease
         subjects affected / exposed
    8 / 398 (2.01%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Anal Fistula
         subjects affected / exposed
    2 / 398 (0.50%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Small Intestine Obstruction
         subjects affected / exposed
    2 / 398 (0.50%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Abdominal Pain
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Abdominal Pain Upper
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal Stenosis
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intestinal Obstruction
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intestinal Perforation
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Large Intestinal Stenosis
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancreatitis Acute
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Subilieus
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fistula
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Endocrine disorders
    Adrenal Insufficiency
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypokalemia
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypomagnesemia
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Malnutrition
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Anal Abscess
         subjects affected / exposed
    2 / 398 (0.50%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    2 / 398 (0.50%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Abdominal Abscess
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Campylobacter Gastroenteritis
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cellulits
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis Viral
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Lobar Pneumonia
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Shigella Infection
         subjects affected / exposed
    1 / 398 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    GSK1605786A 500 mg BID
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    295 / 398 (74.12%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    42 / 398 (10.55%)
         occurrences all number
    78
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    49 / 398 (12.31%)
         occurrences all number
    64
    Crohn’s Disease
         subjects affected / exposed
    49 / 398 (12.31%)
         occurrences all number
    56
    Nausea
         subjects affected / exposed
    26 / 398 (6.53%)
         occurrences all number
    36
    Diarrhea
         subjects affected / exposed
    24 / 398 (6.03%)
         occurrences all number
    29
    Dyspepsia
         subjects affected / exposed
    20 / 398 (5.03%)
         occurrences all number
    28
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    20 / 398 (5.03%)
         occurrences all number
    26
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    66 / 398 (16.58%)
         occurrences all number
    95

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Feb 2011
    To clarify in study description that subjects who withdraw early from the placebo-controlled maintenance study, CCX114157, due to worsening of Crohn’s disease requiring a treatment change, may also be eligible for the open-label extension study. Addition of a new author, Jatin Patel, To add contact details for David J Chang as Medical Monitor, To delete abbreviations not referenced in the protocol, to clarify that subjects can enter Study CCX114644 if they complete Study CCX114151 and do not achieve clinical response (CDAI >=100 point decrease) or remission (CDAI < 150) or they complete any other GSK-sponsored induction study of GSK1605786A as designated by the sponsor. To specify that study will be conducted for 108 weeks with amendment of study duration to be considered following results of Study CCX114151, to amend wording for CDAI assessments every 3 months to every 12 weeks for consistency within the protocol To amend other endpoints for assessment of effectiveness to include the key outcome measures of proportion of subjects in remission(CDAI < 150), proportion of subjects in remission for subjects in remission at baseline, proportion of subjects in remission for subjects not in remission at baseline, and to remove endpoints of remission and response by previous study and include as subgroup analyses; to clarify that response will be measured relative to baseline of previous study, to correct typographical errors to specify 108 weeks rather than 104 weeks or Week 108 rather than Week 104, to amend wording of exclusion criterion #2 to clarify testing requirement for anti-tTG antibodies. To amend wording of exclusion criterion #3 to clarify fixed symptomatic stenoses or strictures of small bowel or colon, to include new exclusion criterion #7 to exclude subjects who have demonstrated safety or tolerability issues which were possibly related to study treatment(in the investigator’s opinion) during participation in a previous clinical study with GSK1605786A.
    10 Feb 2011
    To clarify that subjects may be enrolled in the study prior to receiving baseline results for LFTs and anti-tTG antibodies (if applicable). Subjects who fulfill these exclusion criteria should be withdrawn due to inability to meet continuation criteria and recorded as screen failures, To include a withdrawal criterion at Week 12 based on investigator assessment that subject is not receiving clinical benefit , to remove reference to randomised subjects, randomisation code or treatment groups made as typographical errors, to clarify text on procedures for an Early Withdrawal visit, to include wording to direct investigators to the Study Procedures Manual for details on Investigational Product, to include immunisation with live vaccines as prohibited therapy To clarify requirements for permitted medications, including allowance for steroid taper and additional use of corticosteroids, 5-ASAs, opioid analgesics and paracetamol/acetaminophen (including correction of daily allowed dose to <=2 g/day) and inclusion of treatment for fistulae under permitted medications section, to make the following corrections or amendments to the Time and Events schedule: Correction of visit numbers, as Visit 12 had been replicated in error,Expansion of footnote to clarify only LFTs are assessed at certain visits,Addition of 12 lead ECG at Week 72 and deletion at Weeks 12, 60 and 84, Addition of haematology assessment at Week 96, Deletion of pregnancy testing at Weeks 16, 24, 32, 40 and 48, consistent with initial testing every 4 weeks, and then every 8 weeks after Week 20 and every 12 weeks after Week 60; Amendment of footnote to specify home pregnancy testing every 4 weeks after Week 60
    10 Feb 2011
    Addition of CRP assessment at Weeks 8, 72 and 96 and at Early Withdrawal and Follow-up visits to align with CDAI assessments Deletion of assessment of fistula closure at Weeks 12, 60 and 84 and addition of assessment of fistula closure at Week 0 (this is not a repeated assessment but carry over from Study CCX114151 Week 12 assessment or end of study visit from any other preceding study of GSK1605786A), Weeks 72 and 108, Addition of * to pregnancy test at Week 0, indicating that the test is not repeated but the result is carried over from the preceding study of GSK1605786A, Inclusion of test for coeliac disease at baseline if indicated and corresponding footnote to specify that testing should be performed upon suspicion of coeliac disease Inclusion of Week 12 investigator assessment of clinical benefit, Amendment of timepoints for assessment of IBDQ, SF-36, EQ5D, WPAI-CD, disability and resource utilisation from Weeks 60 and 84 to Weeks 48 and 72 in Time and Events schedule; Inclusion in footnote that Week 0 disability assessment will not be available for subjects entering from a prior induction study and is not required, To amend timepoints for efficacy, safety and health outcomes assessments in protocol text to correspond with timepoints and changes in timepoints in the Time and Events schedule detailed above, To clarify that the treatment allocation from the previous study will not be available prior to enrolment, To remove the requirement for locally determined haematocrit values for CDAI calculation, To clarify timings for adverse event reporting and wording regarding serious adverse events as reported, To clarify wording for frequency of assessment of LFTs, To include assessment of concomitant medications and CRP in Follow Up visit, To include response and remission status at end of previous induction study as a subgroup analysis with clarification that response will be measured relative to baseline of previous study
    10 Feb 2011
    To incorporate revisions into description of efficacy analyses to correspond with changes to endpoints To amend CDAI in Appendix 4 to reflect that investigator assessments should be performed based on findings on day of examination To include correct version of IBDQ in Appendix 5 To correct other minor typographical errors in the protocol
    02 Aug 2011
    To update information on sponsor departmental information To update abbreviations to include revised information To clarify that subjects who completed Study CCX114643 are not eligible to participate in this study To include additional secondary objectives of assessment of activity impairment, unemployment and disability rates and biomarkers of inflammation to clarify that these evaluations are secondary objectives of this study To include exploratory objective of assessment of fistula closure to clarify that this will be an exploratory objective of this study. To clarify for secondary endpoints that changes in body weight and temperature will be performed only in relation to CDAI scoring and not as separate assessments To clarify that changes in CRP concentrations as a biomarker of inflammation will be assessed as an endpoint To amend Inclusion Criteria to include updated criteria for acceptable contraceptive methods of birth control according to sponsor standards To amend Exclusion Criteria • To clarify criteria for fixed symptomatic stenoses and stricture • To include use of prohibited medications at baseline and throughout the study to ensure subject safety. To update withdrawal and stopping criteria and testing procedures for liver chemistry abnormalities and ECG findings to be consistent with revisions to GSK standard withdrawal criteria To clarify that the Investigator should conduct a Follow-up visit in addition to an Early Withdrawal visit for safety follow up To clarify that prohibited medications should not be taken throughout the study and that use of stable doses of Crohn’s disease medications ongoing from a previous study are permissible To include use of digoxin or related cardiac glycosides (e.g digitoxin, deslanoside, lanatoside C, metildigoxin) as a prohibited medication To correct typographical errors in Time and Events table and to amend assessments to be consistent with protocol content.
    02 Aug 2011
    To extend visit windows with longer intervals between visits to allow flexibility in scheduling To clarify that subjects should initiate study drug administration the evening of the day of the baseline (Week 0) visit To provide additional clarification regarding reporting of worsening of Crohn’s disease as an AE To include information on reporting and analyses of Disease-related events common in Crohn’s disease for consistency with new FDA safety reporting guidance. Protocol-specified events related to worsening of Crohn’s disease will not be reported as SAEs To delete concomitant medications as a safety outcome To provide additional clarification on data handling To include additional information on analyses of components of SF-36v2 and disability benefit data To provide additional clarification on IDMC purpose and safety review To amend CDAI to clarify that Investigator should assess symptoms/findings for subject based on current conditions and fever should be documented if present over the past week
    19 Mar 2013
    To amend the study duration to 216 weeks, to revise the list of authors, to revise sponsor address and medical monitor contact information, to correct typographical errors, to consistently define draining fistulae as “open.” To indicate that in 2012, GSK1605786A received approval for the generic name vercirnon, to remove information concerning the method of confirming male partner sterilization from the protocol to the Study Procedure Manual, to remove the exclusion prohibiting subjects with fistulae likely to require surgery from entering the study, to clarify that subjects who have been withdrawn early from study CCX114157 due to disease worsening and have received, or are receiving, certain rescue treatments shall be excluded from entry into study CCX114644, to clarify that enteral or parenteral nutritional supplementation to treat malnutrition is permitted, to clarify that any biologic or investigational agent, including – but not limited to - janus kinase inhibitors, vedolizumab and ustekinumab are prohibited medications, to revise the Time & Events table to provide for ongoing assessments from week 108 to week 216, to extend the visit window for visits from week 16 onward, to clarify the definition of the safety population, to clarify the analysis of data by subgroups, to clarify the purpose of the interim analyses that will be performed, to clarify the definition of baseline for statistical analysis purposes, to clarify how the extent of treatment exposure will be defined and summarized. To clarify that the incidence rate of adverse events will be summarized by overall duration of exposure as well as by 6-month intervals of exposure. To clarify that ECG data will be summarized separately for data calculated manually and by machine. To clarify the efficacy analyses that will be performed based on CDAI score and fistulae closure. To clarify how the CRP concentration data will be summarized and analyzed for statistical purposes.

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    23 Aug 2013
    Discontinued investigational product and discontinued enrollment of new subjects. Study termination occurred on 04Sep2013
    -

    Limitations and caveats

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