Crohn's Disease
Conditions
Brief summary
The purpose of this study is to verify the safety and efficacy of OPC-6535 and determine the optimal dose by once-daily oral administration of OPC-6535 at 25 or 50 mg or placebo for 8 weeks in combination with base treatment (either a fixed oral dose of 5-aminosalicylic acid \[5-ASA\] or a fixed oral dose of 5-ASA plus enteral nutrition) in 180 patients with active Crohn's disease.
Interventions
DRUGPlacebo
oral administration of placebo once-daily for 8 weeks
DRUGOPC-6535
oral administration of OPC-6535 25 mg once-daily for 8 weeks
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Primary lesion in either small intestine or large intestine * C-reactive protein (CRP) level above the upper limit of the normal range * Patients who have been receiving a 5-ASA formulation (oral mesalazine) at a fixed dose of 2.25 g/day or higher (not exceeding the approved dose) and at a fixed dosing regimen * Patients who have not received enteral nutrition or who have been receiving enteral nutrition at a fixed intake of 1200 kcal/day or less
Exclusion criteria
* Patients with an uncontrolled external fistula (including anal fistula) * Patients with a history of total proctocolectomy or subtotal colectomy * Patients with short bowel syndrome * Patients with an artificial anus * Patients with serious infectious disease (intra-abdominal abscess, etc) * Patients with malignant tumor * Female patients who are pregnant, lactating, or possibly pregnant, or who wish to become pregnant during the trial period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Improvement Rate (Number of Subjects Showing Clinical Improvement / Number of Subjects Evaluated × 100) After 8 Weeks of IMP 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 |
|---|---|---|
| Clinical Improvement Rate After 4 Weeks of IMP Administration | Week 4 | Definition of clinical improvement: CDAI score improved by at least 70 points from the baseline score or to below 150 (CDAI \< 150: remission, CDAI \> 450: severe disease) |
| Remission Rate (Number of Subjects Showing Remission / Number of Subjects Evaluated x 100) After 4 and 8 Weeks of IMP Administration | Weeks 4 and 8 | Definition of remission: Total CDAI score improved to below 150 |
| Mean Change From Baseline in C-reactive Protein (CRP) Level After 4 and 8 Weeks of IMP Administration | Baseline, Weeks 4 and 8 | — |
Countries
Japan, South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OPC-6535 25 mg Oral administration of OPC-6535 25 mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week) | 64 |
| OPC-6535 50 mg Oral administration of OPC-6535 50mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week, with further titration to 50 mg from the third week) | 63 |
| Placebo Oral administration of placebo once daily for 8 weeks | 61 |
| Total | 188 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 12 | 4 |
| Overall Study | Physician Decision | 0 | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 7 | 3 |
Baseline characteristics
| Characteristic | OPC-6535 25 mg | OPC-6535 50 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 32.8 years STANDARD_DEVIATION 10.2 | 30.5 years STANDARD_DEVIATION 10.3 | 32.2 years STANDARD_DEVIATION 9.5 | 31.8 years STANDARD_DEVIATION 10 |
| Region of Enrollment Japan | 40 Participants | 41 Participants | 38 Participants | 119 Participants |
| Region of Enrollment South Korea | 24 Participants | 22 Participants | 23 Participants | 69 Participants |
| Sex: Female, Male Female | 20 Participants | 10 Participants | 23 Participants | 53 Participants |
| Sex: Female, Male Male | 44 Participants | 53 Participants | 38 Participants | 135 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 65 | 0 / 63 | 0 / 63 |
| other Total, other adverse events | 39 / 65 | 35 / 63 | 33 / 63 |
| serious Total, serious adverse events | 8 / 65 | 10 / 63 | 4 / 63 |
Outcome results
Primary
Clinical Improvement Rate (Number of Subjects Showing Clinical Improvement / Number of Subjects Evaluated × 100) After 8 Weeks of IMP 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: Full analysis set comprised all subjects who received at least one dose of IMP and for whom postdosing efficacy data were obtained.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OPC-6535 25 mg | Clinical Improvement Rate (Number of Subjects Showing Clinical Improvement / Number of Subjects Evaluated × 100) After 8 Weeks of IMP Administration | 31.3 percentage of participants |
| OPC-6535 50 mg | Clinical Improvement Rate (Number of Subjects Showing Clinical Improvement / Number of Subjects Evaluated × 100) After 8 Weeks of IMP Administration | 21.0 percentage of participants |
| Placebo | Clinical Improvement Rate (Number of Subjects Showing Clinical Improvement / Number of Subjects Evaluated × 100) After 8 Weeks of IMP Administration | 29.5 percentage of participants |
Secondary
Clinical Improvement Rate After 4 Weeks of IMP Administration
Definition of clinical improvement: 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 4
Population: Full analysis set comprised all subjects who received at least one dose of IMP and for whom postdosing efficacy data were obtained.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OPC-6535 25 mg | Clinical Improvement Rate After 4 Weeks of IMP Administration | 30.2 percentage of participants |
| OPC-6535 50 mg | Clinical Improvement Rate After 4 Weeks of IMP Administration | 16.1 percentage of participants |
| Placebo | Clinical Improvement Rate After 4 Weeks of IMP Administration | 28.3 percentage of participants |
Secondary
Mean Change From Baseline in C-reactive Protein (CRP) Level After 4 and 8 Weeks of IMP Administration
Time frame: Baseline, Weeks 4 and 8
Population: Full analysis set comprised all subjects who received at least one dose of IMP and for whom postdosing efficacy data were obtained.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OPC-6535 25 mg | Mean Change From Baseline in C-reactive Protein (CRP) Level After 4 and 8 Weeks of IMP Administration | Week 4 | -0.19 mg/dL | Standard Deviation 1.25 |
| OPC-6535 25 mg | Mean Change From Baseline in C-reactive Protein (CRP) Level After 4 and 8 Weeks of IMP Administration | Week 8 | -0.03 mg/dL | Standard Deviation 1.92 |
| OPC-6535 50 mg | Mean Change From Baseline in C-reactive Protein (CRP) Level After 4 and 8 Weeks of IMP Administration | Week 4 | -0.16 mg/dL | Standard Deviation 2.35 |
| OPC-6535 50 mg | Mean Change From Baseline in C-reactive Protein (CRP) Level After 4 and 8 Weeks of IMP Administration | Week 8 | -0.36 mg/dL | Standard Deviation 2.19 |
| Placebo | Mean Change From Baseline in C-reactive Protein (CRP) Level After 4 and 8 Weeks of IMP Administration | Week 4 | 0.24 mg/dL | Standard Deviation 1.58 |
| Placebo | Mean Change From Baseline in C-reactive Protein (CRP) Level After 4 and 8 Weeks of IMP Administration | Week 8 | 0.34 mg/dL | Standard Deviation 1.54 |
Secondary
Remission Rate (Number of Subjects Showing Remission / Number of Subjects Evaluated x 100) After 4 and 8 Weeks of IMP Administration
Definition of remission: Total CDAI score improved to below 150
Time frame: Weeks 4 and 8
Population: Full analysis set comprised all subjects who received at least one dose of IMP and for whom postdosing efficacy data were obtained.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OPC-6535 25 mg | Remission Rate (Number of Subjects Showing Remission / Number of Subjects Evaluated x 100) After 4 and 8 Weeks of IMP Administration | Week 4 | 15.9 percentage of participants |
| OPC-6535 25 mg | Remission Rate (Number of Subjects Showing Remission / Number of Subjects Evaluated x 100) After 4 and 8 Weeks of IMP Administration | Week 8 | 20.3 percentage of participants |
| OPC-6535 50 mg | Remission Rate (Number of Subjects Showing Remission / Number of Subjects Evaluated x 100) After 4 and 8 Weeks of IMP Administration | Week 4 | 6.5 percentage of participants |
| OPC-6535 50 mg | Remission Rate (Number of Subjects Showing Remission / Number of Subjects Evaluated x 100) After 4 and 8 Weeks of IMP Administration | Week 8 | 11.3 percentage of participants |
| Placebo | Remission Rate (Number of Subjects Showing Remission / Number of Subjects Evaluated x 100) After 4 and 8 Weeks of IMP Administration | Week 4 | 10.0 percentage of participants |
| Placebo | Remission Rate (Number of Subjects Showing Remission / Number of Subjects Evaluated x 100) After 4 and 8 Weeks of IMP Administration | Week 8 | 18.0 percentage of participants |