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    Clinical Trial Results:
    Phase III Study of D9421-C 9 mg in Patients With Active Crohn's Disease in Japan

    Summary
    EudraCT number
    		 2014-004132-20
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    16 Jan 2015

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

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    D9423C00001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01514240
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Biometrics Department, Science Affairs Division, R&D, AstraZeneca Japan
    Sponsor organisation address
    Grand Front Osaka Tower B, 3-11, Ofukacho, Kitaku, Osaka, Japan, 530-0011
    Public contact
    Masahiro Nii, Biometrics Department, Science Affairs Division, R&D, AstraZeneca Japan, 46 6-7711-4571, Masahiro.Nii@astrazeneca.com
    Scientific contact
    Masahiro Nii, Biometrics Department, Science Affairs Division, R&D, AstraZeneca Japan, 46 6-7711-4571, Masahiro.Nii@astrazeneca.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
    20 Oct 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    20 Oct 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Jan 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this study was to evaluate the clinical efficacy of D9421-C 9 mg once daily compared to Mesalazine 1 g three times a day to patients with mild to moderate active Crohn's disease affecting ileum, ileocecal region and/or ascending colon as defined by a score of 180-400 on the Crohn's Disease Activity Index (CDAI) by assessment of the remission after 8-week treatment defined by a CDAI score of ≤ 150.
    Protection of trial subjects
    If patients had any AE at the end of treatment, the AEs were followed by Investeigators until the investigators judged it was unnecessary to follow the AE.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Feb 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Japan: 112
    Worldwide total number of subjects
    112
    EEA total number of subjects
    0
    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)
    1
    Adults (18-64 years)
    109
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 First patient enrolled on 08 February 2012. Last subject last visit on 08 September 2014.

    Pre-assignment
    Screening details
    		 Out of 123 enrolled subjects, 112 subjects were randomised and 11 subjects were not randomised. The reasons of no randomisation were 'Eligibility criteria not met' (9 subjects) and 'Adverse event' (2 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
    		 Investigator, Monitor, Subject, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 D9421-C 9mg + Mesalazine placebo
    Arm description
    		 Patients randomised to D9421-C 9 mg took 3 capsules of D9421-C capsule 3 mg once daily before breakfast and 4 tablets of Mesalazine tablets placebo three times a day after each meal for 8 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    D9421-C
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    9 mg once daily

    Arm title
    		 Mesalazine 3g + D9421-C placebo
    Arm description
    		 Patients randomised to Mesalazine 3 g took 3 capsules of D9421-C capsule placebo once daily before breakfast and 4 tablets of Mesalazine tablets 250 mg three times a day after each meal for 8 weeks.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Mesalazine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1g three times a day

    Number of subjects in period 1
    		D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Started
    56
    56
    Completed
    50
    45
    Not completed
    6
    11
         Subject Decision
    2
    7
         Adverse event, non-fatal
    4
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    D9421-C 9mg + Mesalazine placebo
    Reporting group description
    		 Patients randomised to D9421-C 9 mg took 3 capsules of D9421-C capsule 3 mg once daily before breakfast and 4 tablets of Mesalazine tablets placebo three times a day after each meal for 8 weeks.

    Reporting group title
    Mesalazine 3g + D9421-C placebo
    Reporting group description
    		 Patients randomised to Mesalazine 3 g took 3 capsules of D9421-C capsule placebo once daily before breakfast and 4 tablets of Mesalazine tablets 250 mg three times a day after each meal for 8 weeks.

    Reporting group values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo Total
    Number of subjects
    		 56 56 112
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 1 0 1
        Adults (18-64 years)
    		 53 56 109
        From 65-84 years
    		 2 0 2
        85 years and over
    		 0 0 0
    Age Continuous |
    Units: Years
        arithmetic mean (standard deviation)
    		 38.1 ± 13.43 35.8 ± 10.71 -
    Gender, Male/Female
    Units: Participants
        Female
    		 19 13 32
        Male
    		 37 43 80
    Age, Customized
    Units: Subjects
        <30 Years
    		 19 20 39
        >=30 Years
    		 37 36 73

    End points

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    End points reporting groups
    Reporting group title
    D9421-C 9mg + Mesalazine placebo
    Reporting group description
    		 Patients randomised to D9421-C 9 mg took 3 capsules of D9421-C capsule 3 mg once daily before breakfast and 4 tablets of Mesalazine tablets placebo three times a day after each meal for 8 weeks.

    Reporting group title
    Mesalazine 3g + D9421-C placebo
    Reporting group description
    		 Patients randomised to Mesalazine 3 g took 3 capsules of D9421-C capsule placebo once daily before breakfast and 4 tablets of Mesalazine tablets 250 mg three times a day after each meal for 8 weeks.

    Primary: Proportion of patients with remission at Week 8

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    End point title
    		 Proportion of patients with remission at Week 8
    End point description
    For the primary efficacy variable “Remission after 8 weeks of treatment”, Crohn’s Disease Activity Index CDAI scores was used to determine the patient’s response. Remission for this study is defined as a CDAI score of ≤150. A patient who drops out without any remission before week 8 was considered as a nonresponder (no remission) for this analysis. A patient who drops out before Week 8, but was in remission at the time of dropout, was considered in remission after dropout in this analysis.
    End point type
    Primary
    End point timeframe
    8 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    56
    Units: Participants
    17
    14
    Statistical analysis title
    		 Remission rates at Week 8
    Statistical analysis description
    Remission rates at Week 8 for D9421-C 9 mg as compared to Mesalazine 3 g.
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    P-value
    		 = 0.526
    Method
    		 Chi-squared
    Parameter type
    		 Difference of proportion
    Point estimate
    5.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -8.49
         upper limit
    		 18.94
    Notes
    [1] - A 2-sided 90% CI for the observed difference in the remission rates between the D9421-C 9mg group and the Mesalazine 3 g group was calculated using the Newcombe-Wilson score method without continuity correction. Noninferiority was concluded if the lower limit of the 90% CI was higher than –10% in FAS Population.

    Secondary: Proportion of patients with remission at Week 2

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    End point title
    		 Proportion of patients with remission at Week 2
    End point description
    For the secondary efficacy variable “Remission after 2 weeks of treatment”, Crohn’s Disease Activity Index CDAI scores was used to determine the patient’s response. Remission for this study is defined as a CDAI score of ≤150.
    End point type
    Secondary
    End point timeframe
    2 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    56
    Units: Participants
    7
    6
    Statistical analysis title
    		 Remission rates at Week 2
    Statistical analysis description
    Remission rates at Week 2 for D9421-C 9 mg as compared to Mesalazine 3 g.
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.768
    Method
    		 Chi-squared
    Parameter type
    		 Difference of proportion
    Point estimate
    1.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -8.54
         upper limit
    		 12.15

    Secondary: Proportion of patients with remission at Week 4

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    End point title
    		 Proportion of patients with remission at Week 4
    End point description
    For the secondary efficacy variable “Remission after 4 weeks of treatment”, Crohn’s Disease Activity Index CDAI scores was used to determine the patient’s response. Remission for this study is defined as a CDAI score of ≤150.
    End point type
    Secondary
    End point timeframe
    4 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    56
    Units: Participants
    12
    7
    Statistical analysis title
    		 Remission rates at Week 4
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.208
    Method
    		 Chi-squared
    Parameter type
    		 Difference of proportion
    Point estimate
    8.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -2.87
         upper limit
    		 20.58

    Secondary: Change in CDAI scores from baseline to Week 2

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    End point title
    		 Change in CDAI scores from baseline to Week 2
    End point description
    Crohn’s Disease Activity Index (CDAI) score is calculated based on the data collected in the diary card. The patients is asked to fill the following items in the diary card (from the morning in preceding day to the morning in current day). (1) Number of liquid or very soft stools (2) Abdominal pain rating (none, mild, moderate, severe) (3) General well-being (generally well, slightly under par, poor, very poor, terrible) (4) Body temperature (if a patient feels fever) (5) Intake of loperamide or other opiates for diarrhoea. The data for the calculation of CDAI score in diary card is then transcribed by the investigator(s) into the eCRFs at each clinical visit. The higher total CDAI score indicates severe condition and total CDAI score 150 less or equal is evaluated as a remission.
    End point type
    Secondary
    End point timeframe
    2 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    53
    53
    Units: Scores on a scale
        least squares mean (standard error)
    -38.5 ± 8.91
    -15.7 ± 7.66
    Statistical analysis title
    		 Change in CDAI scores from baseline to Weeks 2
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.058
    Method
    		 Mixed models analysis
    Parameter type
    		 LS mean difference between groups
    Point estimate
    -22.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -42.55
         upper limit
    		 -3.09
    Variability estimate
    Standard error of the mean
    Dispersion value
    11.89

    Secondary: Change in CDAI scores from baseline to Week 4

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    End point title
    		 Change in CDAI scores from baseline to Week 4
    End point description
    Crohn’s Disease Activity Index (CDAI) score is calculated based on the data collected in the diary card. The patients is asked to fill the following items in the diary card (from the morning in preceding day to the morning in current day). (1) Number of liquid or very soft stools (2) Abdominal pain rating (none, mild, moderate, severe) (3) General well-being (generally well, slightly under par, poor, very poor, terrible) (4) Body temperature (if a patient feels fever) (5) Intake of loperamide or other opiates for diarrhoea. The data for the calculation of CDAI score in diary card is then transcribed by the investigator(s) into the eCRFs at each clinical visit. The higher total CDAI score indicates severe condition and total CDAI score 150 less or equal is evaluated as a remission.
    End point type
    Secondary
    End point timeframe
    4 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    55
    50
    Units: Scores on a scale
        least squares mean (standard error)
    -58.7 ± 9.44
    -28.7 ± 7.29
    Statistical analysis title
    		 Change in CDAI scores from baseline to Weeks 4
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.014
    Method
    		 Mixed models analysis
    Parameter type
    		 LS mean difference between group
    Point estimate
    -30
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -49.95
         upper limit
    		 -9.96
    Variability estimate
    Standard error of the mean
    Dispersion value
    12.05

    Secondary: Change in CDAI scores from baseline to Week 8

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    End point title
    		 Change in CDAI scores from baseline to Week 8
    End point description
    Crohn’s Disease Activity Index (CDAI) score is calculated based on the data collected in the diary card. The patients is asked to fill the following items in the diary card (from the morning in preceding day to the morning in current day). (1) Number of liquid or very soft stools (2) Abdominal pain rating (none, mild, moderate, severe) (3) General well-being (generally well, slightly under par, poor, very poor, terrible) (4) Body temperature (if a patient feels fever) (5) Intake of loperamide or other opiates for diarrhoea. The data for the calculation of CDAI score in diary card is then transcribed by the investigator(s) into the eCRFs at each clinical visit. The higher total CDAI score indicates severe condition and total CDAI score 150 less or equal is evaluated as a remission.
    End point type
    Secondary
    End point timeframe
    8 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    51
    45
    Units: Scores on a scale
        least squares mean (standard error)
    -67 ± 11.17
    -45.7 ± 9.11
    Statistical analysis title
    		 Change in CDAI scores from baseline to Week 8
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.144
    Method
    		 Mixed models analysis
    Parameter type
    		 LS mean difference between group
    Point estimate
    -21.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -45.47
         upper limit
    		 2.74
    Variability estimate
    Standard error of the mean
    Dispersion value
    14.53

    Secondary: Cumulative remission rate at Week 2

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    End point title
    		 Cumulative remission rate at Week 2
    End point description
    Remission rate is defined as CDAI score of less than or equal to 150. Cumulative remission rate at Week 2 is obtained by Kaplan-Meier (KM) estimates.
    End point type
    Secondary
    End point timeframe
    2 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    56
    Units: Percentage of participants
        number (confidence interval)
    12.5 (5.23 to 19.77)
    10.7 (3.92 to 17.51)
    No statistical analyses for this end point

    Secondary: Cumulative remission rate at Week 4

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    End point title
    		 Cumulative remission rate at Week 4
    End point description
    Remission rate is defined as CDAI score of less than or equal to 150. Cumulative remission rate at Week 4 is obtained by Kaplan-Meier (KM) estimates.
    End point type
    Secondary
    End point timeframe
    4 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    56
    Units: Percentage of participants
        number (confidence interval)
    25 (15.48 to 34.52)
    17.9 (9.44 to 26.28)
    No statistical analyses for this end point

    Secondary: Cumulative remission rate at Week 8

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    End point title
    		 Cumulative remission rate at Week 8
    End point description
    Remission rate is defined as CDAI score of less than or equal to 150. Cumulative remission rate at Week 8 is obtained by Kaplan-Meier (KM) estimates.
    End point type
    Secondary
    End point timeframe
    8 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    56
    Units: Percentage of participants
        number (confidence interval)
    37.5 (26.86 to 48.14)
    30.4 (20.25 to 40.46)
    No statistical analyses for this end point

    Secondary: Clinical improvement rates at Week 2 (70 points)

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    End point title
    		 Clinical improvement rates at Week 2 (70 points)
    End point description
    Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 70 points.
    End point type
    Secondary
    End point timeframe
    2 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    56
    Units: Participants
    19
    11
    Statistical analysis title
    		 Clinical improvement rates at Weeks 2 (70 points)
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference of proportions
    Point estimate
    14.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 27.4

    Secondary: Clinical improvement rates at Week 4 (70 points)

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    End point title
    		 Clinical improvement rates at Week 4 (70 points)
    End point description
    Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 70 points.
    End point type
    Secondary
    End point timeframe
    4 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    56
    Units: Participants
    22
    13
    Statistical analysis title
    		 Clinical improvement rates at Week 4 (70 points)
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference of proportions
    Point estimate
    16.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.66
         upper limit
    		 29.61

    Secondary: Clinical improvement rates at Week 8 (70 points)

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    End point title
    		 Clinical improvement rates at Week 8 (70 points)
    End point description
    Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 70 points.
    End point type
    Secondary
    End point timeframe
    8 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    56
    Units: Participants
    27
    18
    Statistical analysis title
    		 Clinical improvement rate at Week 8 (70 points)
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference of proportions
    Point estimate
    16.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 30.29

    Secondary: Clinical improvement rates at Week 2 (100 points)

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    End point title
    		 Clinical improvement rates at Week 2 (100 points)
    End point description
    Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 100 points.
    End point type
    Secondary
    End point timeframe
    2 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    56
    Units: Participants
    14
    10
    Statistical analysis title
    		 Clinical improvement rates at Week 2 (100 points)
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference of proportions
    Point estimate
    7.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -5.67
         upper limit
    		 19.71

    Secondary: Clinical improvement rates at Week 4 (100 points)

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    End point title
    		 Clinical improvement rates at Week 4 (100 points)
    End point description
    Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 100 points.
    End point type
    Secondary
    End point timeframe
    4 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    56
    Units: Participants
    19
    11
    Statistical analysis title
    		 Clinical improvement rate at Week 4 (100 points)
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference of proportions
    Point estimate
    14.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 27.4

    Secondary: Clinical improvement rates at Week 8

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    End point title
    		 Clinical improvement rates at Week 8
    End point description
    Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 100 points.
    End point type
    Secondary
    End point timeframe
    8 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    56
    Units: Participants
    24
    17
    Statistical analysis title
    		 Clinical improvement rate at Week 8 (100 points)
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference of proportions
    Point estimate
    12.5
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -2.44
         upper limit
    		 26.68

    Secondary: Change in total IBDQ scores from baseline to Week 2

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    End point title
    		 Change in total IBDQ scores from baseline to Week 2
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    2 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    54
    Units: Scores on a scale
        least squares mean (standard error)
    16.2 ± 2.3
    5.7 ± 2.41
    Statistical analysis title
    		 Change in total IBDQ scores at Week 2
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    10.5
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 4.86
         upper limit
    		 16.14
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.4

    Secondary: Change in total IBDQ scores from baseline to Week 4

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    End point title
    		 Change in total IBDQ scores from baseline to Week 4
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    4 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    55
    50
    Units: Scores on a scale
        least squares mean (standard error)
    19.4 ± 3.03
    6.8 ± 2.44
    Statistical analysis title
    		 Change in total IBDQ scores at Week 4
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    12.6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 6.07
         upper limit
    		 19.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.93

    Secondary: Change in total IBDQ scores from baseline to Week 8

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    End point title
    		 Change in total IBDQ scores from baseline to Week 8
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    8 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    51
    45
    Units: Scores on a scale
        least squares mean (standard error)
    18.3 ± 2.93
    5.8 ± 3.16
    Statistical analysis title
    		 Change in total IBDQ scores at Week 8
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    12.6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 5.4
         upper limit
    		 19.72
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.31

    Secondary: Change in total IBDQ scores from baseline to Week 10

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    End point title
    		 Change in total IBDQ scores from baseline to Week 10
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    10 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    50
    45
    Units: Scores on a scale
        least squares mean (standard error)
    21.1 ± 3.11
    7.1 ± 2.96
    Statistical analysis title
    		 Change in total IBDQ scores at Week 10
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    14.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 6.9
         upper limit
    		 21.23
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.32

    Secondary: Change in IBDQ scores from baseline to Week 2 - Bowel function

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    End point title
    		 Change in IBDQ scores from baseline to Week 2 - Bowel function
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    2 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    54
    Units: Scores on a scale
        least squares mean (standard error)
    6.1 ± 0.77
    2.7 ± 0.82
    Statistical analysis title
    		 Change in IBDQ scores at W2 - Bowel function
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    3.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.49
         upper limit
    		 5.29
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.14

    Secondary: Change in IBDQ scores from baseline to Week 4 - Bowel function

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    End point title
    		 Change in IBDQ scores from baseline to Week 4 - Bowel function
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    4 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    55
    50
    Units: Scores on a scale
        least squares mean (standard error)
    6.6 ± 0.99
    2.8 ± 0.84
    Statistical analysis title
    		 Change in IBDQ scores at W4 - Bowel function
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    3.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.64
         upper limit
    		 5.97
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.31

    Secondary: Change in IBDQ scores from baseline to Week 8 - Bowel function

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    End point title
    		 Change in IBDQ scores from baseline to Week 8 - Bowel function
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    8 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    51
    45
    Units: Scores on a scale
        least squares mean (standard error)
    6.5 ± 1.04
    2.4 ± 1.11
    Statistical analysis title
    		 Change in IBDQ scores at W8 - Bowel function
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    4.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.58
         upper limit
    		 6.64
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.53

    Secondary: Change in IBDQ scores from baseline to Week 10 - Bowel function

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    End point title
    		 Change in IBDQ scores from baseline to Week 10 - Bowel function
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    10 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    50
    45
    Units: Scores on a scale
        least squares mean (standard error)
    6.9 ± 1.08
    3.6 ± 0.98
    Statistical analysis title
    		 Change in IBDQ scores at W10 - Bowel function
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    3.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 5.76
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.47

    Secondary: Change in IBDQ scores from baseline to Week 2 - Systemic symptom

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    End point title
    		 Change in IBDQ scores from baseline to Week 2 - Systemic symptom
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    2 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    54
    Units: Scores on a scale
        least squares mean (standard error)
    3 ± 0.49
    1 ± 0.48
    Statistical analysis title
    		 Change in IBDQ scores at W2 - Systemic symptom
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 3.17
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.69

    Secondary: Change in IBDQ scores from baseline to Week 4 - Systemic symptom

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    End point title
    		 Change in IBDQ scores from baseline to Week 4 - Systemic symptom
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    4 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    55
    50
    Units: Scores on a scale
        least squares mean (standard error)
    3.3 ± 0.57
    1.3 ± 0.47
    Statistical analysis title
    		 Change in IBDQ scores at W4 - Systemic symptom
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 3.19
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.74

    Secondary: Change in IBDQ scores from baseline to Week 8 - Systemic symptom

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    End point title
    		 Change in IBDQ scores from baseline to Week 8 - Systemic symptom
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    8 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    51
    45
    Units: Scores on a scale
        least squares mean (standard error)
    3.5 ± 0.58
    1.2 ± 0.61
    Statistical analysis title
    		 Change in IBDQ scores at W8 - Systemic symptom
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    2.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 3.76
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.84

    Secondary: Change in IBDQ scores from baseline to Week 10 - Systemic symptom

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    End point title
    		 Change in IBDQ scores from baseline to Week 10 - Systemic symptom
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    10 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    50
    45
    Units: Scores on a scale
        least squares mean (standard error)
    3.8 ± 0.64
    1.2 ± 0.62
    Statistical analysis title
    		 Change in IBDQ scores at W10 - Systemic symptom
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    2.6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.15
         upper limit
    		 4.09
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.89

    Secondary: Change in IBDQ scores from baseline to Week 2 - Emotional function

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    End point title
    		 Change in IBDQ scores from baseline to Week 2 - Emotional function
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    2 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    54
    Units: Scores on a scale
        least squares mean (standard error)
    5.1 ± 1
    1.3 ± 1
    Statistical analysis title
    		 Change in IBDQ scores at W2 - Emotional function
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    3.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.44
         upper limit
    		 6.19
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.43

    Secondary: Change in IBDQ scores from baseline to Week 4 - Emotional function

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    End point title
    		 Change in IBDQ scores from baseline to Week 4 - Emotional function
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    4 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    55
    50
    Units: Scores on a scale
        least squares mean (standard error)
    7 ± 1.25
    2.1 ± 1.08
    Statistical analysis title
    		 Change in IBDQ scores at W4 - Emotional function
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    4.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 2.14
         upper limit
    		 7.65
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.66

    Secondary: Change in IBDQ scores from baseline to Week 8 - Emotional function

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    End point title
    		 Change in IBDQ scores from baseline to Week 8 - Emotional function
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    8 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    51
    45
    Units: Scores on a scale
        least squares mean (standard error)
    5.9 ± 1.18
    1.6 ± 1.31
    Statistical analysis title
    		 Change in IBDQ scores at W8 - Emotional function
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    4.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.4
         upper limit
    		 7.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.76

    Secondary: Change in IBDQ scores from baseline to Week 10 - Emotional function

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    End point title
    		 Change in IBDQ scores from baseline to Week 10 - Emotional function
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    10 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    50
    45
    Units: Scores on a scale
        least squares mean (standard error)
    8 ± 1.28
    1.3 ± 1.34
    Statistical analysis title
    		 Change in IBDQ scores at W10 - Emotional function
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    6.6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 3.56
         upper limit
    		 9.72
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.86

    Secondary: Change in IBDQ scores from baseline to Week 2 - Social function

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    End point title
    		 Change in IBDQ scores from baseline to Week 2 - Social function
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    2 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    56
    54
    Units: Scores on a scale
        least squares mean (standard error)
    1.9 ± 0.45
    0.6 ± 0.55
    Statistical analysis title
    		 Change in IBDQ scores at W2 - Social function
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    1.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.01
         upper limit
    		 2.43
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.73

    Secondary: Change in IBDQ scores from baseline to Week 4 - Social function

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    End point title
    		 Change in IBDQ scores from baseline to Week 4 - Social function
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    4 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    55
    50
    Units: Scores on a scale
        least squares mean (standard error)
    2.5 ± 0.58
    0.7 ± 0.56
    Statistical analysis title
    		 Change in IBDQ scores at W4 - Social function
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    1.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 3.12
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.81

    Secondary: Change in IBDQ scores from baseline to Week 8 - Social function

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    End point title
    		 Change in IBDQ scores from baseline to Week 8 - Social function
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    8 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    51
    45
    Units: Scores on a scale
        least squares mean (standard error)
    2.3 ± 0.57
    0.7 ± 0.63
    Statistical analysis title
    		 Change in IBDQ scores at W8 - Social function
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    1.6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.19
         upper limit
    		 3.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.86

    Secondary: Change in IBDQ scores from baseline to Week 10 - Social function

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    End point title
    		 Change in IBDQ scores from baseline to Week 10 - Social function
    End point description
    The Inflammatory Bowel Disease Questionnaire (IBDQ) is a standard measure of HRQL in Crohn's disease patients (Guyatt G et al 1989). The validated Japanese version of the IBDQ was used in this study (Hashimoto H et al 2003). The IBDQ contains 32 questions; each with seven possible answers ranging from 1 to 7, where 7 is the most favourable. Ten questions are related to bowel symptoms, five to systemic symptoms, twelve to emotional function, and five to social function. The corresponding answers will be added to form four subscores and a total score: bowel function score (10 – 70), systemic symptom score (5 – 35), emotional function score (12 – 84), social function score (5 – 35) and the total score (32 – 224), with higher scores indicating more favorable outcome.
    End point type
    Secondary
    End point timeframe
    10 Week
    End point values
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Number of subjects analysed
    50
    45
    Units: Scores on a scale
        least squares mean (standard error)
    2.4 ± 0.63
    1.2 ± 0.56
    Statistical analysis title
    		 Change in IBDQ scores at W10 - Social function
    Comparison groups
    D9421-C 9mg + Mesalazine placebo v Mesalazine 3g + D9421-C placebo
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS mean difference between group
    Point estimate
    1.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 2.76
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.85

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events collected from the date of signing of informed consent to Visit 6 or withdrawal visit (including the tapering period)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    D9421-C 9mg + Mesalazine placebo
    Reporting group description
    		 Patients randomised to D9421-C 9 mg took 3 capsules of D9421-C capsule 3 mg once daily before breakfast and 4 tablets of Mesalazine tablets placebo three times a day after each meal for 8 weeks.

    Reporting group title
    Mesalazine 3g + D9421-C placebo
    Reporting group description
    		 Patients randomised to Mesalazine 3 g took 3 capsules of D9421-C capsule placebo once daily before breakfast and 4 tablets of Mesalazine tablets 250 mg three times a day after each meal for 8 weeks.

    Serious adverse events
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 56 (5.36%)
    1 / 56 (1.79%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Gastrointestinal disorders
    Ileus
         subjects affected / exposed
    1 / 56 (1.79%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumatosis intestinalis
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 D9421-C 9mg + Mesalazine placebo Mesalazine 3g + D9421-C placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 56 (19.64%)
    16 / 56 (28.57%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 56 (5.36%)
    0 / 56 (0.00%)
         occurrences all number
    4
    0
    Gastrointestinal disorders
    Crohn's disease
         subjects affected / exposed
    1 / 56 (1.79%)
    3 / 56 (5.36%)
         occurrences all number
    1
    3
    Vomiting
         subjects affected / exposed
    3 / 56 (5.36%)
    0 / 56 (0.00%)
         occurrences all number
    3
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    6 / 56 (10.71%)
    10 / 56 (17.86%)
         occurrences all number
    6
    10
    Pharyngitis
         subjects affected / exposed
    0 / 56 (0.00%)
    3 / 56 (5.36%)
         occurrences all number
    0
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Dec 2011
    Amendment 1
    04 Apr 2012
    Amendment 2
    01 Mar 2013
    Amendment 3
    25 Sep 2013
    Amendment 4

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

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