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

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT01514240

Collaborator

(none)

123

Enrollment

Locations

Arms

Duration (Months)

4.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is 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.

Condition or Disease	Intervention/Treatment	Phase
Crohn's Disease	Drug: D9421-C capsule 3 mg Drug: Mesalazine tablets	Phase 3

Detailed Description

A multicentre, double-blind, randomised, parallel-group, Phase III study to assess efficacy and safety of D9421-C 9 mg versus Mesalazine 3 g in patients with active Crohn's Disease (CD) in Japan

Study Design

Study Type:

Interventional

Actual Enrollment :

123 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Multicentre, Double-blind, Randomised, Parallel-group, Phase III Study to Assess Efficacy and Safety of D9421-C 9 mg Versus Mesalazine 3 g in Patients With Active Crohn's Disease (CD) in Japan

Study Start Date :

Feb 1, 2012

Actual Primary Completion Date :

Sep 1, 2014

Actual Study Completion Date :

Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: D9421-C D9421-C 9 mg once daily	Drug: D9421-C capsule 3 mg Patients randomised to D9421-C 9 mg will take 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.
Active Comparator: Mesalazine Mesalazine 1 g three times a day	Drug: Mesalazine tablets Patients randomised to Mesalazine 3 g will take 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

Intervention/Treatment

Experimental: D9421-C

D9421-C 9 mg once daily

Drug: D9421-C capsule 3 mg

Patients randomised to D9421-C 9 mg will take 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.

Active Comparator: Mesalazine

Mesalazine 1 g three times a day

Drug: Mesalazine tablets

Patients randomised to Mesalazine 3 g will take 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.

Outcome Measures

Primary Outcome Measures

Remission After 8-week of Treatment [8 Week]
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.

Secondary Outcome Measures

Remission After 2-week of Treatment [2 Week]
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.
Remission After 4-week of Treatment [4 Week]
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.
Change in Observed CDAI Scores From Baseline to Weeks 2 [2 Week]
Crohn's Disease Activity Index (CDAI) score is calculated based on the data collected in the diary card. The total CDAI score ranges from 0 to approximately 600, a higher scores indicating more severe disease. The target population of total CDAI score 180 to 400 is defined mild to modarate active Crohn's disease. Total CDAI score 150 less or equal is evaluated as a remission. Patients are 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.
Change in Observed CDAI Scores From Baseline to Weeks 4 [4 Week]
Crohn's Disease Activity Index (CDAI) score is calculated based on the data collected in the diary card. The total CDAI score ranges from 0 to approximately 600, a higher scores indicating more severe disease. The target population of total CDAI score 180 to 400 is defined mild to modarate active Crohn's disease. Total CDAI score 150 less or equal is evaluated as a remission. Patients are 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.
Change in Observed CDAI Scores From Baseline to Weeks 8 [8 Week]
Crohn's Disease Activity Index (CDAI) score is calculated based on the data collected in the diary card. The total CDAI score ranges from 0 to approximately 600, a higher scores indicating more severe disease. The target population of total CDAI score 180 to 400 is defined mild to modarate active Crohn's disease. Total CDAI score 150 less or equal is evaluated as a remission. Patients are 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.
Cumulative Remission Rate at Week 2 [2 Week]
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.
Cumulative Remission Rate at Week 4 [4 Week]
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.
Cumulative Remission Rate at Week 8 [8 Week]
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.
Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 70 Points) at Weeks 2 [2 Week]
Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 70 points.
Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 70 Points) at Weeks 4 [4 Week]
Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 70 points.
Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 70 Points) at Weeks 8 [8 Week]
Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 70 points.
Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 100 Points) at Weeks 2 [2 Week]
Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 100 points.
Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 100 Points) at Weeks 4 [4 Week]
Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 100 points.
Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 100 Points) at Weeks 8 [8 Week]
Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 100 points.
Change in Total IBDQ Scores From Baseline to Weeks 2 [2 Week]
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.
Change in Total IBDQ Scores From Baseline to Weeks 4 [4 Week]
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.
Change in Total IBDQ Scores From Baseline to Weeks 8 [8 Week]
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.
Change in Total IBDQ Scores From Baseline to Weeks 10 [10 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 2 - Bowel Function [2 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 4 - Bowel Function [4 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 8 - Bowel Function [8 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 10 - Bowel Function [10 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 2 - Systemic Symptom [2 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 4 - Systemic Symptom [4 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 8 - Systemic Symptom [8 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 10 - Systemic Symptom [10 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 2 - Emotional Function [2 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 4 - Emotional Function [4 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 8 - Emotional Function [8 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 10 - Emotional Function [10 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 2 - Social Function [2 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 4 - Social Function [4 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 8 - Social Function [8 Week]
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.
Change in IBDQ Scores From Baseline to Weeks 10 - Social Function [10 Week]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 130 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

15 years of age or older
Main active disease of the ileal, ileocecal region, and/or ascending colon - - If treated with partial nutrition treatment (≤1200 kcal/day) or if treated with azathioprine (≤2.0 mg/kg/day) or 6-mercaptopurine (≤1.2 mg/kg/day), prior to randomisation until the study completion or discontinuation
Ability to read, write and to fill a diary card and HRQL questionnaire Having mild to moderate active Crohn's disease, defined as CDAI score of 180-400 at baseline

Exclusion Criteria:

Patient with CD lesion or status which may affect the evaluation of the efficacy (e.g. lesion only in the upper G-I, active anorectal lesion, abscess formation, stenosis, fistulae, ostomy, short bowel or other uncontrolled concomitant disease)
Patient who need any concomitant treatment for CD that may affect the assessment for efficacy of the study drug
Patient who need any medication which is prohibited due to suspected influence to metabolism of the study drug
Patient who is judged to be inadequate to participate in this study from the safety point of view Patient with well-founded doubt about protocol violation

Contacts and Locations

Locations

	Site	City	Country
1	Research Site	Chikushino-shi	Japan
2	Research Site	Fukuoka-shi	Japan
3	Research Site	Fukuyama-shi	Japan
4	Research Site	Hirosaki-shi	Japan
5	Research Site	Hiroshima-shi	Japan
6	Research Site	Kagoshima-shi	Japan
7	Research Site	Kitakyushu-shi	Japan
8	Research Site	Koshigaya-shi	Japan
9	Research Site	Kurume-shi	Japan
10	Research Site	Kyoto-shi	Japan
11	Research Site	Nagakute-shi	Japan
12	Research Site	Nagoya-shi	Japan
13	Research Site	Nishinomiya-shi	Japan
14	Research Site	Oita-shi	Japan
15	Research Site	Okayama-shi	Japan
16	Research Site	Omura-shi	Japan
17	Research Site	Osaka-shi	Japan
18	Research Site	Osaka	Japan
19	Research Site	Sakura	Japan
20	Research Site	Sapporo-shi	Japan
21	Research Site	Sendai-shi	Japan
22	Research Site	Shinjyuku-ku	Japan
23	Research Site	Suginami-ku	Japan
24	Research Site	Suita-shi	Japan
25	Research Site	Toyoake-shi	Japan
26	Research Site	Toyota-shi	Japan

Sponsors and Collaborators

AstraZeneca

Investigators

Principal Investigator: Toshifumi Hibi, Professor, Chairman, Department of Internal Medicine, Keio University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

AstraZeneca

ClinicalTrials.gov Identifier:

NCT01514240

Other Study ID Numbers:

D9423C00001

First Posted:

Jan 23, 2012

Last Update Posted:

Oct 31, 2016

Last Verified:

Sep 1, 2016

Keywords provided by AstraZeneca

mild to moderate active Crohn's disease

affecting ileum

ileocecal region

ascending colon

score of 180-400 on the CDAI

Additional relevant MeSH terms:

Crohn Disease

Mesalamine

Study Results

Participant Flow

Recruitment Details	First patient enrolled on 08 February 2012. Last subject last visit on 08 September 2014.
Pre-assignment Detail	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).

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Period Title: Overall Study
STARTED	56	56
COMPLETED	50	45
NOT COMPLETED	6	11

Baseline Characteristics

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo	Total
Arm/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.	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.	Total of all reporting groups
Overall Participants	56	56	112
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	38.1 (13.43)	35.8 (10.71)	36.9 (12.15)
Age, Customized (Number) [Number]
<30 Years	19 33.9%	20 35.7%	39 34.8%
>=30 Years	37 66.1%	36 64.3%	73 65.2%
Sex: Female, Male (Count of Participants)
Female	19 33.9%	13 23.2%	32 28.6%
Male	37 66.1%	43 76.8%	80 71.4%
Race/Ethnicity, Customized (Number) [Number]
Asian	56 100%	55 98.2%	111 99.1%
Black/African American	0 0%	1 1.8%	1 0.9%

Outcome Measures

1. Primary Outcome

Title	Remission After 8-week of Treatment
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.
Time Frame	8 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	56
Number [Participants]	17 30.4%	14 25%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments	The primary objective of this study was to determine non-inferiority in the differences in remission rates at Week 8 for D9421-C 9 mg as compared to Mesalazine 3 g.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A 2-sided 90% CI for the observed difference in the primary outcome measure (remission rate) between the D9421-C 9mg group and the Mesalazine 3 g group was calculated at week 8 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.

Statistical Test of Hypothesis	p-Value	0.526
	Comments
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Difference of proportion
	Estimated Value	5.4
	Confidence Interval	(2-Sided) 90% -8.49 to 18.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Remission After 2-week of Treatment
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.
Time Frame	2 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	56
Number [Participants]	7 12.5%	6 10.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.768
	Comments
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Difference of proportion
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 90% -8.54 to 12.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	Differences in remission rate at Week 2 between D9421-C 9 mg and Mesalazine 3 g along with their 2-sided 90% CIs calculated by the Newcombe-Wilson score method without continuity correction

3. Secondary Outcome

Title	Remission After 4-week of Treatment
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.
Time Frame	4 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	56
Number [Participants]	12 21.4%	7 12.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.208
	Comments
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Difference of proportion
	Estimated Value	8.9
	Confidence Interval	(2-Sided) 90% -2.87 to 20.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	Differences in remission rate at Week 4 between D9421-C 9 mg and Mesalazine 3 g along with their 2-sided 90% CIs calculated by the Newcombe-Wilson score method without continuity correction

4. Secondary Outcome

Title	Change in Observed CDAI Scores From Baseline to Weeks 2
Description	Crohn's Disease Activity Index (CDAI) score is calculated based on the data collected in the diary card. The total CDAI score ranges from 0 to approximately 600, a higher scores indicating more severe disease. The target population of total CDAI score 180 to 400 is defined mild to modarate active Crohn's disease. Total CDAI score 150 less or equal is evaluated as a remission. Patients are 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.
Time Frame	2 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 2 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	53	53
Least Squares Mean (Standard Error) [Scores on a scale]	-38.5 (8.91)	-15.7 (7.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.058
	Comments
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	-22.8
	Confidence Interval	(2-Sided) 90% -42.55 to -3.09
	Parameter Dispersion	Type: Standard Error of the Mean Value: 11.89
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

5. Secondary Outcome

Title	Change in Observed CDAI Scores From Baseline to Weeks 4
Description	Crohn's Disease Activity Index (CDAI) score is calculated based on the data collected in the diary card. The total CDAI score ranges from 0 to approximately 600, a higher scores indicating more severe disease. The target population of total CDAI score 180 to 400 is defined mild to modarate active Crohn's disease. Total CDAI score 150 less or equal is evaluated as a remission. Patients are 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.
Time Frame	4 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 4 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	55	50
Least Squares Mean (Standard Error) [Scores on a scale]	-58.7 (9.44)	-28.7 (7.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	-30.0
	Confidence Interval	(2-Sided) 90% -49.95 to -9.96
	Parameter Dispersion	Type: Standard Error of the Mean Value: 12.05
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

6. Secondary Outcome

Title	Change in Observed CDAI Scores From Baseline to Weeks 8
Description	Crohn's Disease Activity Index (CDAI) score is calculated based on the data collected in the diary card. The total CDAI score ranges from 0 to approximately 600, a higher scores indicating more severe disease. The target population of total CDAI score 180 to 400 is defined mild to modarate active Crohn's disease. Total CDAI score 150 less or equal is evaluated as a remission. Patients are 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.
Time Frame	8 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 8 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	51	45
Least Squares Mean (Standard Error) [Scores on a scale]	-67.0 (11.17)	-45.7 (9.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.144
	Comments
	Method	Mixed Models Analysis
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	-21.4
	Confidence Interval	(2-Sided) 90% -45.47 to 2.74
	Parameter Dispersion	Type: Standard Error of the Mean Value: 14.53
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

7. Secondary Outcome

Title	Cumulative Remission Rate at Week 2
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.
Time Frame	2 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	56
Number (90% Confidence Interval) [Percentage of participants]	12.5 22.3%	10.7 19.1%

8. Secondary Outcome

Title	Cumulative Remission Rate at Week 4
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.
Time Frame	4 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	56
Number (90% Confidence Interval) [Percentage of participants]	25.0 44.6%	17.9 32%

9. Secondary Outcome

Title	Cumulative Remission Rate at Week 8
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.
Time Frame	8 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	56
Number (90% Confidence Interval) [Percentage of participants]	37.5 67%	30.4 54.3%

10. Secondary Outcome

Title	Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 70 Points) at Weeks 2
Description	Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 70 points.
Time Frame	2 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	56
Number [Participants]	19 (9.07) 33.9%	11 (7.46) 19.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference of proportions
	Estimated Value	14.3
	Confidence Interval	(2-Sided) 90% 0.50 to 27.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	90% CI calculated using the Newcombe-Wilson score method without continuity corrections.

11. Secondary Outcome

Title	Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 70 Points) at Weeks 4
Description	Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 70 points.
Time Frame	4 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	56
Number [Participants]	22 (9.07) 39.3%	13 (7.46) 23.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference of proportions
	Estimated Value	16.1
	Confidence Interval	(2-Sided) 90% 1.66 to 29.61
	Parameter Dispersion	Type: Value:
	Estimation Comments	90% CI calculated using the Newcombe-Wilson score method without continuity corrections.

12. Secondary Outcome

Title	Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 70 Points) at Weeks 8
Description	Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 70 points.
Time Frame	8 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	56
Number [Participants]	27 (9.07) 48.2%	18 (7.46) 32.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference of proportions
	Estimated Value	16.1
	Confidence Interval	(2-Sided) 90% 0.85 to 30.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	90% CI calculated using the Newcombe-Wilson score method without continuity corrections.

13. Secondary Outcome

Title	Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 100 Points) at Weeks 2
Description	Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 100 points.
Time Frame	2 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	56
Number [Participants]	14 (9.07) 25%	10 (7.46) 17.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference of proportions
	Estimated Value	7.1
	Confidence Interval	(2-Sided) 90% -5.67 to 19.71
	Parameter Dispersion	Type: Value:
	Estimation Comments	90% CI calculated using the Newcombe-Wilson score method without continuity corrections.

14. Secondary Outcome

Title	Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 100 Points) at Weeks 4
Description	Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 100 points.
Time Frame	4 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	56
Number [Participants]	19 (9.07) 33.9%	11 (7.46) 19.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference of proportions
	Estimated Value	14.3
	Confidence Interval	(2-Sided) 90% 0.50 to 27.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	90% CI calculated using the Newcombe-Wilson score method without continuity corrections.

15. Secondary Outcome

Title	Clinical Improvement Rates (Decrease in CDAI Score From Baseline of at Least 100 Points) at Weeks 8
Description	Clinical improvement is defined as CDAI score of <=150 or a decrease in CDAI score from baseline of at least 100 points.
Time Frame	8 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	56
Number [Participants]	24 (9.07) 42.9%	17 (7.46) 30.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference of proportions
	Estimated Value	12.5
	Confidence Interval	(2-Sided) 90% -2.44 to 26.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	90% CI calculated using the Newcombe-Wilson score method without continuity corrections.

16. Secondary Outcome

Title	Change in Total IBDQ Scores From Baseline to Weeks 2
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.
Time Frame	2 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 2 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	54
Least Squares Mean (Standard Error) [Scores on a scale]	16.2 (2.30)	5.7 (2.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	10.5
	Confidence Interval	(2-Sided) 90% 4.86 to 16.14
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.40
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

17. Secondary Outcome

Title	Change in Total IBDQ Scores From Baseline to Weeks 4
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.
Time Frame	4 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 4 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	55	50
Least Squares Mean (Standard Error) [Scores on a scale]	19.4 (3.03)	6.8 (2.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	12.6
	Confidence Interval	(2-Sided) 90% 6.07 to 19.11
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.93
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

18. Secondary Outcome

Title	Change in Total IBDQ Scores From Baseline to Weeks 8
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.
Time Frame	8 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 8 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	51	45
Least Squares Mean (Standard Error) [Scores on a scale]	18.3 (2.93)	5.8 (3.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	12.6
	Confidence Interval	(2-Sided) 90% 5.40 to 19.72
	Parameter Dispersion	Type: Standard Error of the Mean Value: 4.31
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

19. Secondary Outcome

Title	Change in Total IBDQ Scores From Baseline to Weeks 10
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.
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 10 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	50	45
Least Squares Mean (Standard Error) [Scores on a scale]	21.1 (3.11)	7.1 (2.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	14.1
	Confidence Interval	(2-Sided) 90% 6.90 to 21.23
	Parameter Dispersion	Type: Standard Error of the Mean Value: 4.32
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

20. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 2 - Bowel Function
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.
Time Frame	2 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 2 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	54
Least Squares Mean (Standard Error) [Scores on a scale]	6.1 (0.77)	2.7 (0.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 90% 1.49 to 5.29
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.14
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

21. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 4 - Bowel Function
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.
Time Frame	4 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 4 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	55	50
Least Squares Mean (Standard Error) [Scores on a scale]	6.6 (0.99)	2.8 (0.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	3.8
	Confidence Interval	(2-Sided) 90% 1.64 to 5.97
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.31
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

22. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 8 - Bowel Function
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.
Time Frame	8 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 8 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	51	45
Least Squares Mean (Standard Error) [Scores on a scale]	6.5 (1.04)	2.4 (1.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	4.1
	Confidence Interval	(2-Sided) 90% 1.58 to 6.64
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.53
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

23. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 10 - Bowel Function
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.
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 10 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	50	45
Least Squares Mean (Standard Error) [Scores on a scale]	6.9 (1.08)	3.6 (0.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	3.3
	Confidence Interval	(2-Sided) 90% 0.90 to 5.76
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.47
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

24. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 2 - Systemic Symptom
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.
Time Frame	2 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 2 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	54
Least Squares Mean (Standard Error) [Scores on a scale]	3.0 (0.49)	1.0 (0.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 90% 0.89 to 3.17
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.69
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

25. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 4 - Systemic Symptom
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.
Time Frame	4 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 4 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	55	50
Least Squares Mean (Standard Error) [Scores on a scale]	3.3 (0.57)	1.3 (0.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 90% 0.73 to 3.19
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.74
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

26. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 8 - Systemic Symptom
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.
Time Frame	8 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 8 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	51	45
Least Squares Mean (Standard Error) [Scores on a scale]	3.5 (0.58)	1.2 (0.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	2.4
	Confidence Interval	(2-Sided) 90% 0.96 to 3.76
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.84
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

27. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 10 - Systemic Symptom
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.
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 10 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	50	45
Least Squares Mean (Standard Error) [Scores on a scale]	3.8 (0.64)	1.2 (0.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	2.6
	Confidence Interval	(2-Sided) 90% 1.15 to 4.09
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.89
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

28. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 2 - Emotional Function
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.
Time Frame	2 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 2 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	54
Least Squares Mean (Standard Error) [Scores on a scale]	5.1 (1.00)	1.3 (1.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	3.8
	Confidence Interval	(2-Sided) 90% 1.44 to 6.19
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.43
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

29. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 4 - Emotional Function
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.
Time Frame	4 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 4 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	55	50
Least Squares Mean (Standard Error) [Scores on a scale]	7.0 (1.25)	2.1 (1.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	4.9
	Confidence Interval	(2-Sided) 90% 2.14 to 7.65
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.66
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

30. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 8 - Emotional Function
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.
Time Frame	8 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 8 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	51	45
Least Squares Mean (Standard Error) [Scores on a scale]	5.9 (1.18)	1.6 (1.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	4.3
	Confidence Interval	(2-Sided) 90% 1.40 to 7.25
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.76
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

31. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 10 - Emotional Function
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.
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 10 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	50	45
Least Squares Mean (Standard Error) [Scores on a scale]	8.0 (1.28)	1.3 (1.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	6.6
	Confidence Interval	(2-Sided) 90% 3.56 to 9.72
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.86
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

32. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 2 - Social Function
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.
Time Frame	2 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 2 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	56	54
Least Squares Mean (Standard Error) [Scores on a scale]	1.9 (0.45)	0.6 (0.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 90% 0.01 to 2.43
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.73
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

33. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 4 - Social Function
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.
Time Frame	4 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 4 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	55	50
Least Squares Mean (Standard Error) [Scores on a scale]	2.5 (0.58)	0.7 (0.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 90% 0.42 to 3.12
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.81
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

34. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 8 - Social Function
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.
Time Frame	8 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 8 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	51	45
Least Squares Mean (Standard Error) [Scores on a scale]	2.3 (0.57)	0.7 (0.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 90% 0.19 to 3.04
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.86
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

35. Secondary Outcome

Title	Change in IBDQ Scores From Baseline to Weeks 10 - Social Function
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.
Time Frame	10 Week

Outcome Measure Data

Analysis Population Description
All randomised patients who take the investigational products at least once and have data in the treatment period. However, the patients with both baseline and week 10 data were analyzed.

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo	Mesalazine 3g + D9421-C Placebo
Arm/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.	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.
Measure Participants	50	45
Least Squares Mean (Standard Error) [Scores on a scale]	2.4 (0.63)	1.2 (0.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D9421-C 9mg + Mesalazine Placebo, Mesalazine 3g + D9421-C Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	LS mean difference between group
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 90% -0.15 to 2.76
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.85
	Estimation Comments	The analysis using a MMRM analysis including a covariate of the corresponding score at baseline,fixed effects of time (as a categorical factor) and treatment and interaction between time and treatment group.

Adverse Events

	D9421-C 9mg + Mesalazine Placebo		Mesalazine 3g + D9421-C Placebo
Time Frame	Adverse events collected from the date of signing of informed consent to Visit 6 or withdrawal visit (including the tapering period)
Adverse Event Reporting Description

Arm/Group Title	D9421-C 9mg + Mesalazine Placebo		Mesalazine 3g + D9421-C Placebo
Arm/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.		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.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	D9421-C 9mg + Mesalazine Placebo		Mesalazine 3g + D9421-C Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/56 (5.4%)		1/56 (1.8%)
Gastrointestinal disorders
Ileus	1/56 (1.8%)	1	1/56 (1.8%)	1
Lower gastrointestinal haemorrhage	1/56 (1.8%)	1	0/56 (0%)	0
Pneumatosis intestinalis	1/56 (1.8%)	1	0/56 (0%)	0
Other (Not Including Serious) Adverse Events
	D9421-C 9mg + Mesalazine Placebo		Mesalazine 3g + D9421-C Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/56 (19.6%)		16/56 (28.6%)
Gastrointestinal disorders
Crohn's disease	1/56 (1.8%)	1	3/56 (5.4%)	3
Vomiting	3/56 (5.4%)	3	0/56 (0%)	0
Infections and infestations
Nasopharyngitis	6/56 (10.7%)	6	10/56 (17.9%)	10
Pharyngitis	0/56 (0%)	0	3/56 (5.4%)	3
Nervous system disorders
Headache	3/56 (5.4%)	4	0/56 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

All PIs were prohibited to disclose all information related to this study without AZ approval before this study was completed.

Results Point of Contact

Name/Title	Masahiro Nii
Organization	Biometrics Department, Science Affairs Division, R&D, AstraZeneca Japan
Phone
Email	Masahiro.Nii@astrazeneca.com

Responsible Party:

AstraZeneca

ClinicalTrials.gov Identifier:

NCT01514240

Other Study ID Numbers:

D9423C00001

First Posted:

Jan 23, 2012

Last Update Posted:

Oct 31, 2016

Last Verified:

Sep 1, 2016