Crohn Disease
Conditions
Keywords
OPC-6535, Crohn's disease
Brief summary
The purpose of this study to examine the safety and efficacy of OPC-6535 and determine its optimal dose by once-daily oral administration at 0, 25, or 50 mg for 8 weeks in combination with a fixed oral dose of 5-aminosalicylic acid (5-ASA) or in combination with a fixed oral dose of 5-ASA and enteral nutrition in patients with active Crohn's disease.
Interventions
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
16 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients with active Crohn's disease * Patients who have a primary lesion in either the small intestine or the large intestine * Patients who have been receiving an oral 5-ASA formulation at a fixed regimen and at a fixed dose * Patients who have either never received enteral nutrition or have been receiving enteral nutrition at a fixed intake of 1200 kcal/day or less * Either inpatient or outpatient
Exclusion criteria
* Patients who have an external fistula (including anal fistula) in which persistent drainage is observed (and who require treatment with antibiotics or synthetic antibacterial agents) * Patients with short bowel syndrome (and who require intravenous nutritional support due to insufficient intestinal nutrient uptake) * Patients with an artificial anus * Patients who have a complication of serious infectious disease (intra-abdominal abscess, etc.) * Patients who have a complication of malignant tumor * Female patients who are pregnant, lactating, or possibly pregnant, or who wish to become pregnant during the study period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Improvement Rate (Number of Subjects Showing Clinical Improvement/Number of Subjects Evaluated x 100) After 8 Weeks of Study Drug Administration | Week 8 | Definition of clinical improvement: Total Crohn's Disease Activity Index (CDAI) score improved by at least 70 points from the baseline score or to below 150 (CDAI \< 150: Remission, CDAI \> 450: severe disease) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Remission Rate (Number of Patients Showing Remission/Number of Patients Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 2, Week 4，Week 8 | Definition of remission: Total CDAI score improved to below 150 |
| Clinical Improvement Rate (50) by Change in Total CDAI Score (Number of Subjects for Each Change/Number of Subjects Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Baseline, Weeks 2, 4, and 8 | Definition of clinical improvement (50) : Total CDAI score improved by at least 50 points from the baseline score or to below 150 (CDAI \< 150: Remission, CDAI \> 450: severe disease) |
| Mean Change From Baseline in Total CDAI Score After 2, 4, and 8 Weeks of Study Drug Administration | Baseline, Weeks 2, 4, and 8 | CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity (CDAI \< 150: Remission, CDAI \> 450: Very severe). A negative change in mean score indicates improvement. |
| Clinical Improvement Rate After 2 and 4 Weeks of Study Drug Administration | Week 2, Week 4 | Definition of clinical improvement: Total CDAI score improved by at least 70 points from the baseline score or to below 150 (CDAI \< 150: Remission, CDAI \> 450: severe disease) |
| Mean Change From the Baseline in Crohn's Disease Endoscopic Index of Severity (CDEIS) Score After 8 Weeks of Study Drug Administration | Baseline, Week 8 | Large bowel endoscopic findings were assessed based on the CDEIS. The CDEIS considers deep ulcer, superficial ulcer, lesion ratio of , and ulcer ratio of the 5 pre-defined segments of the colon (small intestine, right colon, transverse colon, left colon, and rectum). The score ranges from 0 to 44 where higher scores indicate more severe disease. |
| Mean Change in C-reactive Protein (CRP) Level From the Baseline After 4 and 8 Weeks of Study Drug Administration | Baseline, Weeks 4 and 8 | — |
| Mean Change From the Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score After 8 Weeks of Study Drug Administration | Baseline, Week 8 | The IBDQ has been frequently adopted in Japanese and overseas clinical assessments as a scale for evaluating the quality of life (QOL) of patients with inflammatory bowel disease. The IBDQ score was calculated as the sum of the responses (each ranging from 1 to 7) to all 32 questions that address symptoms as a result of Crohn's disease: bowel symptoms, systemic symptoms, emotional function, and social function. Total IBDQ score ranges from 32 to 224 with a higher score indicating a better QOL. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OPC-6535 25 mg 25 mg OPC-6535 orally administered once daily in the morning for 8 weeks. | 10 |
| OPC-6535 50 mg 25 mg OPC-6535 orally administered once daily in the morning for the first week, and the dose was increased to 50 mg for the remaining 7 weeks. | 9 |
| Placebo 0 mg OPC-6535 orally administered once daily in the morning for 8 weeks. | 10 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | OPC-6535 25 mg | OPC-6535 50 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 9 Participants | 10 Participants | 29 Participants |
| Age, Continuous | 35.5 years STANDARD_DEVIATION 9.9 | 36.7 years STANDARD_DEVIATION 15 | 33.4 years STANDARD_DEVIATION 6.3 | 35.1 years STANDARD_DEVIATION 10.5 |
| Race/Ethnicity, Customized Japanese | 10 Participants | 9 Participants | 10 Participants | 29 Participants |
| Region of Enrollment Japan | 10 Participants | 9 Participants | 10 Participants | 29 Participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 0 Participants | 5 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 10 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 9 | 0 / 10 |
| other Total, other adverse events | 9 / 10 | 9 / 9 | 8 / 10 |
| serious Total, serious adverse events | 1 / 10 | 2 / 9 | 0 / 10 |
Outcome results
Primary
Clinical Improvement Rate (Number of Subjects Showing Clinical Improvement/Number of Subjects Evaluated x 100) After 8 Weeks of Study Drug Administration
Definition of clinical improvement: Total Crohn's Disease Activity Index (CDAI) score improved by at least 70 points from the baseline score or to below 150 (CDAI \< 150: Remission, CDAI \> 450: severe disease)
Time frame: Week 8
Population: Efficacy was evaluated in the subjects who took at least one dose of the study drug and provided postdosing data concerning the efficacy endpoints. Subjects with GCP violations (noncompliance of obtaining informed consent, start of the trial before obtaining informed consent, trial conducted outside the contract period) were to be excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OPC-6535 25 mg | Clinical Improvement Rate (Number of Subjects Showing Clinical Improvement/Number of Subjects Evaluated x 100) After 8 Weeks of Study Drug Administration | 20.0 percentage of participants |
| OPC-6535 50 mg | Clinical Improvement Rate (Number of Subjects Showing Clinical Improvement/Number of Subjects Evaluated x 100) After 8 Weeks of Study Drug Administration | 33.3 percentage of participants |
| Placebo | Clinical Improvement Rate (Number of Subjects Showing Clinical Improvement/Number of Subjects Evaluated x 100) After 8 Weeks of Study Drug Administration | 10.0 percentage of participants |
Secondary
Clinical Improvement Rate (50) by Change in Total CDAI Score (Number of Subjects for Each Change/Number of Subjects Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration
Definition of clinical improvement (50) : Total CDAI score improved by at least 50 points from the baseline score or to below 150 (CDAI \< 150: Remission, CDAI \> 450: severe disease)
Time frame: Baseline, Weeks 2, 4, and 8
Population: Efficacy was evaluated in the subjects who took at least one dose of the study drug and provided postdosing data concerning the efficacy endpoints.~Subjects with GCP violations (noncompliance of obtaining informed consent, start of the trial before obtaining informed consent, trial conducted outside the contract period) were to be excluded from the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OPC-6535 25 mg | Clinical Improvement Rate (50) by Change in Total CDAI Score (Number of Subjects for Each Change/Number of Subjects Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 4 | 30.0 percentage of participants |
| OPC-6535 25 mg | Clinical Improvement Rate (50) by Change in Total CDAI Score (Number of Subjects for Each Change/Number of Subjects Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 2 | 30.0 percentage of participants |
| OPC-6535 25 mg | Clinical Improvement Rate (50) by Change in Total CDAI Score (Number of Subjects for Each Change/Number of Subjects Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 8 | 30.0 percentage of participants |
| OPC-6535 50 mg | Clinical Improvement Rate (50) by Change in Total CDAI Score (Number of Subjects for Each Change/Number of Subjects Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 4 | 22.2 percentage of participants |
| OPC-6535 50 mg | Clinical Improvement Rate (50) by Change in Total CDAI Score (Number of Subjects for Each Change/Number of Subjects Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 2 | 22.2 percentage of participants |
| OPC-6535 50 mg | Clinical Improvement Rate (50) by Change in Total CDAI Score (Number of Subjects for Each Change/Number of Subjects Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 8 | 33.3 percentage of participants |
| Placebo | Clinical Improvement Rate (50) by Change in Total CDAI Score (Number of Subjects for Each Change/Number of Subjects Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 2 | 10.0 percentage of participants |
| Placebo | Clinical Improvement Rate (50) by Change in Total CDAI Score (Number of Subjects for Each Change/Number of Subjects Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 8 | 20.0 percentage of participants |
| Placebo | Clinical Improvement Rate (50) by Change in Total CDAI Score (Number of Subjects for Each Change/Number of Subjects Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 4 | 30.0 percentage of participants |
Secondary
Clinical Improvement Rate After 2 and 4 Weeks of Study Drug Administration
Definition of clinical improvement: Total CDAI score improved by at least 70 points from the baseline score or to below 150 (CDAI \< 150: Remission, CDAI \> 450: severe disease)
Time frame: Week 2, Week 4
Population: Efficacy was evaluated in the subjects who took at least one dose of the study drug and provided postdosing data concerning the efficacy endpoints. Subjects with GCP violations (noncompliance of obtaining informed consent, start of the trial before obtaining informed consent, trial conducted outside the contract period) were to be excluded from the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OPC-6535 25 mg | Clinical Improvement Rate After 2 and 4 Weeks of Study Drug Administration | Week 2 | 20.0 percentage of participants |
| OPC-6535 25 mg | Clinical Improvement Rate After 2 and 4 Weeks of Study Drug Administration | Week 4 | 20.0 percentage of participants |
| OPC-6535 50 mg | Clinical Improvement Rate After 2 and 4 Weeks of Study Drug Administration | Week 2 | 22.2 percentage of participants |
| OPC-6535 50 mg | Clinical Improvement Rate After 2 and 4 Weeks of Study Drug Administration | Week 4 | 22.2 percentage of participants |
| Placebo | Clinical Improvement Rate After 2 and 4 Weeks of Study Drug Administration | Week 2 | 0.0 percentage of participants |
| Placebo | Clinical Improvement Rate After 2 and 4 Weeks of Study Drug Administration | Week 4 | 10.0 percentage of participants |
Secondary
Mean Change From Baseline in Total CDAI Score After 2, 4, and 8 Weeks of Study Drug Administration
CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity (CDAI \< 150: Remission, CDAI \> 450: Very severe). A negative change in mean score indicates improvement.
Time frame: Baseline, Weeks 2, 4, and 8
Population: Efficacy was evaluated in the subjects who took at least one dose of the study drug and provided postdosing data concerning the efficacy endpoints. Subjects with GCP violations (noncompliance of obtaining informed consent, start of the trial before obtaining informed consent, trial conducted outside the contract period) were to be excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OPC-6535 25 mg | Mean Change From Baseline in Total CDAI Score After 2, 4, and 8 Weeks of Study Drug Administration | Week 4 | -17.1 score on a scale | Standard Deviation 77.6 |
| OPC-6535 25 mg | Mean Change From Baseline in Total CDAI Score After 2, 4, and 8 Weeks of Study Drug Administration | Week 2 | -19.4 score on a scale | Standard Deviation 46.5 |
| OPC-6535 25 mg | Mean Change From Baseline in Total CDAI Score After 2, 4, and 8 Weeks of Study Drug Administration | Week 8 | -30.3 score on a scale | Standard Deviation 60.3 |
| OPC-6535 50 mg | Mean Change From Baseline in Total CDAI Score After 2, 4, and 8 Weeks of Study Drug Administration | Week 4 | -22.1 score on a scale | Standard Deviation 78.2 |
| OPC-6535 50 mg | Mean Change From Baseline in Total CDAI Score After 2, 4, and 8 Weeks of Study Drug Administration | Week 2 | -4.1 score on a scale | Standard Deviation 57.9 |
| OPC-6535 50 mg | Mean Change From Baseline in Total CDAI Score After 2, 4, and 8 Weeks of Study Drug Administration | Week 8 | -32.3 score on a scale | Standard Deviation 80.4 |
| Placebo | Mean Change From Baseline in Total CDAI Score After 2, 4, and 8 Weeks of Study Drug Administration | Week 2 | -8.8 score on a scale | Standard Deviation 25.9 |
| Placebo | Mean Change From Baseline in Total CDAI Score After 2, 4, and 8 Weeks of Study Drug Administration | Week 8 | -31.2 score on a scale | Standard Deviation 51.4 |
| Placebo | Mean Change From Baseline in Total CDAI Score After 2, 4, and 8 Weeks of Study Drug Administration | Week 4 | -23.5 score on a scale | Standard Deviation 32 |
Secondary
Mean Change From the Baseline in Crohn's Disease Endoscopic Index of Severity (CDEIS) Score After 8 Weeks of Study Drug Administration
Large bowel endoscopic findings were assessed based on the CDEIS. The CDEIS considers deep ulcer, superficial ulcer, lesion ratio of , and ulcer ratio of the 5 pre-defined segments of the colon (small intestine, right colon, transverse colon, left colon, and rectum). The score ranges from 0 to 44 where higher scores indicate more severe disease.
Time frame: Baseline, Week 8
Population: Efficacy was evaluated in the subjects who took at least one dose of the study drug and provided postdosing data concerning the efficacy endpoints. Subjects with GCP violations (noncompliance of obtaining informed consent, start of the trial before obtaining informed consent, trial conducted outside the contract period) were to be excluded from the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Mean Change From the Baseline in Crohn's Disease Endoscopic Index of Severity (CDEIS) Score After 8 Weeks of Study Drug Administration | -4.0 score on a scale |
Secondary
Mean Change From the Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score After 8 Weeks of Study Drug Administration
The IBDQ has been frequently adopted in Japanese and overseas clinical assessments as a scale for evaluating the quality of life (QOL) of patients with inflammatory bowel disease. The IBDQ score was calculated as the sum of the responses (each ranging from 1 to 7) to all 32 questions that address symptoms as a result of Crohn's disease: bowel symptoms, systemic symptoms, emotional function, and social function. Total IBDQ score ranges from 32 to 224 with a higher score indicating a better QOL.
Time frame: Baseline, Week 8
Population: Efficacy was evaluated in the subjects who took at least one dose of the study drug and provided postdosing data concerning the efficacy endpoints. Subjects with GCP violations (noncompliance of obtaining informed consent, start of the trial before obtaining informed consent, trial conducted outside the contract period) were to be excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-6535 25 mg | Mean Change From the Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score After 8 Weeks of Study Drug Administration | 11.6 score on a scale | Standard Deviation 19.7 |
| OPC-6535 50 mg | Mean Change From the Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score After 8 Weeks of Study Drug Administration | 1.4 score on a scale | Standard Deviation 14.6 |
| Placebo | Mean Change From the Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score After 8 Weeks of Study Drug Administration | 5.0 score on a scale | Standard Deviation 17 |
Secondary
Mean Change in C-reactive Protein (CRP) Level From the Baseline After 4 and 8 Weeks of Study Drug Administration
Time frame: Baseline, Weeks 4 and 8
Population: Efficacy was evaluated in the subjects who took at least one dose of the study drug and provided postdosing data concerning the efficacy endpoints. Subjects with GCP violations (noncompliance of obtaining informed consent, start of the trial before obtaining informed consent, trial conducted outside the contract period) were to be excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OPC-6535 25 mg | Mean Change in C-reactive Protein (CRP) Level From the Baseline After 4 and 8 Weeks of Study Drug Administration | Week 4 | -0.65 mg/dL | Standard Deviation 0.72 |
| OPC-6535 25 mg | Mean Change in C-reactive Protein (CRP) Level From the Baseline After 4 and 8 Weeks of Study Drug Administration | Week 8 | -0.63 mg/dL | Standard Deviation 0.99 |
| OPC-6535 50 mg | Mean Change in C-reactive Protein (CRP) Level From the Baseline After 4 and 8 Weeks of Study Drug Administration | Week 4 | -1.49 mg/dL | Standard Deviation 2.06 |
| OPC-6535 50 mg | Mean Change in C-reactive Protein (CRP) Level From the Baseline After 4 and 8 Weeks of Study Drug Administration | Week 8 | -1.21 mg/dL | Standard Deviation 1.9 |
| Placebo | Mean Change in C-reactive Protein (CRP) Level From the Baseline After 4 and 8 Weeks of Study Drug Administration | Week 4 | 0.52 mg/dL | Standard Deviation 1.19 |
| Placebo | Mean Change in C-reactive Protein (CRP) Level From the Baseline After 4 and 8 Weeks of Study Drug Administration | Week 8 | 1.26 mg/dL | Standard Deviation 2.05 |
Secondary
Remission Rate (Number of Patients Showing Remission/Number of Patients Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration
Definition of remission: Total CDAI score improved to below 150
Time frame: Week 2, Week 4，Week 8
Population: Efficacy was evaluated in the subjects who took at least one dose of the study drug and provided postdosing data concerning the efficacy endpoints. Subjects with GCP violations (noncompliance of obtaining informed consent, start of the trial before obtaining informed consent, trial conducted outside the contract period) were to be excluded from the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OPC-6535 25 mg | Remission Rate (Number of Patients Showing Remission/Number of Patients Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 8 | 20.0 percentage of participants |
| OPC-6535 25 mg | Remission Rate (Number of Patients Showing Remission/Number of Patients Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 4 | 20.0 percentage of participants |
| OPC-6535 25 mg | Remission Rate (Number of Patients Showing Remission/Number of Patients Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 2 | 10.0 percentage of participants |
| OPC-6535 50 mg | Remission Rate (Number of Patients Showing Remission/Number of Patients Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 8 | 11.1 percentage of participants |
| OPC-6535 50 mg | Remission Rate (Number of Patients Showing Remission/Number of Patients Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 2 | 11.1 percentage of participants |
| OPC-6535 50 mg | Remission Rate (Number of Patients Showing Remission/Number of Patients Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 4 | 11.1 percentage of participants |
| Placebo | Remission Rate (Number of Patients Showing Remission/Number of Patients Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 8 | 0.0 percentage of participants |
| Placebo | Remission Rate (Number of Patients Showing Remission/Number of Patients Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 4 | 0.0 percentage of participants |
| Placebo | Remission Rate (Number of Patients Showing Remission/Number of Patients Evaluated x 100) After 2, 4, and 8 Weeks of Study Drug Administration | Week 2 | 0.0 percentage of participants |