Clinical Trial Results:
Phase III Study of D9421C 9 mg in Patients With Active Crohn's Disease in Japan
Summary


EudraCT number 
201400413220 
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
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


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, 311, Ofukacho, Kitaku, Osaka, Japan, 5300011


Public contact 
Masahiro Nii, Biometrics Department, Science Affairs Division, R&D, AstraZeneca Japan, 46 677114571, Masahiro.Nii@astrazeneca.com


Scientific contact 
Masahiro Nii, Biometrics Department, Science Affairs Division, R&D, AstraZeneca Japan, 46 677114571, 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 D9421C 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 180400 on the Crohn's Disease Activity Index (CDAI) by assessment of the remission after 8week 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 followup 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 (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
0


Adolescents (1217 years) 
1


Adults (1864 years) 
109


From 65 to 84 years 
2


85 years and over 
0



Recruitment


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


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 
Carer, Assessor, Subject, Investigator, Monitor, Data analyst  
Arms


Are arms mutually exclusive 
Yes


Arm title

D9421C 9mg + Mesalazine placebo  
Arm description 
Patients randomised to D9421C 9 mg took 3 capsules of D9421C 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 
D9421C


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 + D9421C placebo  
Arm description 
Patients randomised to Mesalazine 3 g took 3 capsules of D9421C 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





Baseline characteristics reporting groups


Reporting group title 
D9421C 9mg + Mesalazine placebo


Reporting group description 
Patients randomised to D9421C 9 mg took 3 capsules of D9421C 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 + D9421C placebo


Reporting group description 
Patients randomised to Mesalazine 3 g took 3 capsules of D9421C capsule placebo once daily before breakfast and 4 tablets of Mesalazine tablets 250 mg three times a day after each meal for 8 weeks.  



End points reporting groups


Reporting group title 
D9421C 9mg + Mesalazine placebo


Reporting group description 
Patients randomised to D9421C 9 mg took 3 capsules of D9421C 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 + D9421C placebo


Reporting group description 
Patients randomised to Mesalazine 3 g took 3 capsules of D9421C capsule placebo once daily before breakfast and 4 tablets of Mesalazine tablets 250 mg three times a day after each meal for 8 weeks. 


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




Statistical analysis title 
Remission rates at Week 8  
Statistical analysis description 
Remission rates at Week 8 for D9421C 9 mg as compared to Mesalazine 3 g.


Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
noninferiority ^{[1]}  
Pvalue 
= 0.526  
Method 
Chisquared  
Parameter type 
Difference of proportion  
Point estimate 
5.4


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
8.49  
upper limit 
18.94  
Notes [1]  A 2sided 90% CI for the observed difference in the remission rates between the D9421C 9mg group and the Mesalazine 3 g group was calculated using the NewcombeWilson score method without continuity correction. Noninferiority was concluded if the lower limit of the 90% CI was higher than –10% in FAS Population. 


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




Statistical analysis title 
Remission rates at Week 2  
Statistical analysis description 
Remission rates at Week 2 for D9421C 9 mg as compared to Mesalazine 3 g.


Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.768  
Method 
Chisquared  
Parameter type 
Difference of proportion  
Point estimate 
1.8


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
8.54  
upper limit 
12.15 


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




Statistical analysis title 
Remission rates at Week 4  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.208  
Method 
Chisquared  
Parameter type 
Difference of proportion  
Point estimate 
8.9


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
2.87  
upper limit 
20.58 


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 wellbeing (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




Statistical analysis title 
Change in CDAI scores from baseline to Weeks 2  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
106


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.058  
Method 
Mixed models analysis  
Parameter type 
LS mean difference between groups  
Point estimate 
22.8


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
42.55  
upper limit 
3.09  
Variability estimate 
Standard error of the mean


Dispersion value 
11.89



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 wellbeing (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




Statistical analysis title 
Change in CDAI scores from baseline to Weeks 4  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
105


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.014  
Method 
Mixed models analysis  
Parameter type 
LS mean difference between group  
Point estimate 
30


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
49.95  
upper limit 
9.96  
Variability estimate 
Standard error of the mean


Dispersion value 
12.05



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 wellbeing (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




Statistical analysis title 
Change in CDAI scores from baseline to Week 8  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
96


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.144  
Method 
Mixed models analysis  
Parameter type 
LS mean difference between group  
Point estimate 
21.4


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
45.47  
upper limit 
2.74  
Variability estimate 
Standard error of the mean


Dispersion value 
14.53



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 KaplanMeier (KM) estimates.


End point type 
Secondary


End point timeframe 
2 Week




No statistical analyses for this end point 


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 KaplanMeier (KM) estimates.


End point type 
Secondary


End point timeframe 
4 Week




No statistical analyses for this end point 


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 KaplanMeier (KM) estimates.


End point type 
Secondary


End point timeframe 
8 Week




No statistical analyses for this end point 


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




Statistical analysis title 
Clinical improvement rates at Weeks 2 (70 points)  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of proportions  
Point estimate 
14.3


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
0.5  
upper limit 
27.4 


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




Statistical analysis title 
Clinical improvement rates at Week 4 (70 points)  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of proportions  
Point estimate 
16.1


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
1.66  
upper limit 
29.61 


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




Statistical analysis title 
Clinical improvement rate at Week 8 (70 points)  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of proportions  
Point estimate 
16.1


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
0.85  
upper limit 
30.29 


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




Statistical analysis title 
Clinical improvement rates at Week 2 (100 points)  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of proportions  
Point estimate 
7.1


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
5.67  
upper limit 
19.71 


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




Statistical analysis title 
Clinical improvement rate at Week 4 (100 points)  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of proportions  
Point estimate 
14.3


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
0.5  
upper limit 
27.4 


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




Statistical analysis title 
Clinical improvement rate at Week 8 (100 points)  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
112


Analysis specification 
Prespecified


Analysis type 

Method 

Parameter type 
Difference of proportions  
Point estimate 
12.5


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
2.44  
upper limit 
26.68 


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




Statistical analysis title 
Change in total IBDQ scores at Week 2  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
110


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
10.5


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
4.86  
upper limit 
16.14  
Variability estimate 
Standard error of the mean


Dispersion value 
3.4



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




Statistical analysis title 
Change in total IBDQ scores at Week 4  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
105


Analysis specification 
Prespecified


Analysis type 

Method 

Parameter type 
LS mean difference between group  
Point estimate 
12.6


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
6.07  
upper limit 
19.11  
Variability estimate 
Standard error of the mean


Dispersion value 
3.93



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




Statistical analysis title 
Change in total IBDQ scores at Week 8  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
96


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
12.6


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
5.4  
upper limit 
19.72  
Variability estimate 
Standard error of the mean


Dispersion value 
4.31



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




Statistical analysis title 
Change in total IBDQ scores at Week 10  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
95


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
14.1


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
6.9  
upper limit 
21.23  
Variability estimate 
Standard error of the mean


Dispersion value 
4.32



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




Statistical analysis title 
Change in IBDQ scores at W2  Bowel function  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
110


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
3.4


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
1.49  
upper limit 
5.29  
Variability estimate 
Standard error of the mean


Dispersion value 
1.14



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




Statistical analysis title 
Change in IBDQ scores at W4  Bowel function  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
105


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
3.8


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
1.64  
upper limit 
5.97  
Variability estimate 
Standard error of the mean


Dispersion value 
1.31



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




Statistical analysis title 
Change in IBDQ scores at W8  Bowel function  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
96


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
4.1


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
1.58  
upper limit 
6.64  
Variability estimate 
Standard error of the mean


Dispersion value 
1.53



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




Statistical analysis title 
Change in IBDQ scores at W10  Bowel function  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
95


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
3.3


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
0.9  
upper limit 
5.76  
Variability estimate 
Standard error of the mean


Dispersion value 
1.47



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




Statistical analysis title 
Change in IBDQ scores at W2  Systemic symptom  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
110


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
2


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
0.89  
upper limit 
3.17  
Variability estimate 
Standard error of the mean


Dispersion value 
0.69



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




Statistical analysis title 
Change in IBDQ scores at W4  Systemic symptom  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
105


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
2


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
0.73  
upper limit 
3.19  
Variability estimate 
Standard error of the mean


Dispersion value 
0.74



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




Statistical analysis title 
Change in IBDQ scores at W8  Systemic symptom  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
96


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
2.4


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
0.96  
upper limit 
3.76  
Variability estimate 
Standard error of the mean


Dispersion value 
0.84



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




Statistical analysis title 
Change in IBDQ scores at W10  Systemic symptom  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
95


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
2.6


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
1.15  
upper limit 
4.09  
Variability estimate 
Standard error of the mean


Dispersion value 
0.89



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




Statistical analysis title 
Change in IBDQ scores at W2  Emotional function  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
110


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
3.8


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
1.44  
upper limit 
6.19  
Variability estimate 
Standard error of the mean


Dispersion value 
1.43



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




Statistical analysis title 
Change in IBDQ scores at W4  Emotional function  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
105


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
4.9


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
2.14  
upper limit 
7.65  
Variability estimate 
Standard error of the mean


Dispersion value 
1.66



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




Statistical analysis title 
Change in IBDQ scores at W8  Emotional function  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
96


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
4.3


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
1.4  
upper limit 
7.25  
Variability estimate 
Standard error of the mean


Dispersion value 
1.76



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




Statistical analysis title 
Change in IBDQ scores at W10  Emotional function  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
95


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
6.6


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
3.56  
upper limit 
9.72  
Variability estimate 
Standard error of the mean


Dispersion value 
1.86



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




Statistical analysis title 
Change in IBDQ scores at W2  Social function  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
110


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
1.2


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
0.01  
upper limit 
2.43  
Variability estimate 
Standard error of the mean


Dispersion value 
0.73



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




Statistical analysis title 
Change in IBDQ scores at W4  Social function  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
105


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
1.8


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
0.42  
upper limit 
3.12  
Variability estimate 
Standard error of the mean


Dispersion value 
0.81



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




Statistical analysis title 
Change in IBDQ scores at W8  Social function  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
96


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
1.6


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
0.19  
upper limit 
3.04  
Variability estimate 
Standard error of the mean


Dispersion value 
0.86



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




Statistical analysis title 
Change in IBDQ scores at W10  Social function  
Comparison groups 
D9421C 9mg + Mesalazine placebo v Mesalazine 3g + D9421C placebo


Number of subjects included in analysis 
95


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
LS mean difference between group  
Point estimate 
1.3


Confidence interval 

level 
90%  
sides 
2sided


lower limit 
0.15  
upper limit 
2.76  
Variability estimate 
Standard error of the mean


Dispersion value 
0.85



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 
D9421C 9mg + Mesalazine placebo


Reporting group description 
Patients randomised to D9421C 9 mg took 3 capsules of D9421C 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 + D9421C placebo


Reporting group description 
Patients randomised to Mesalazine 3 g took 3 capsules of D9421C capsule placebo once daily before breakfast and 4 tablets of Mesalazine tablets 250 mg three times a day after each meal for 8 weeks.  


Frequency threshold for reporting nonserious adverse events: 5%  



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 