Ulcerative Colitis
Conditions
Keywords
Ulcerative Colitis, Inflammatory Bowel Disease
Brief summary
The purpose of the study is to evaluate the clinical efficacy, safety and tolerability of apremilast (30 mg twice daily \[BID\] and 40 mg BID), compared with placebo, in participants with active Ulcerative Colitis (UC).
Detailed description
Approximately 165 participants (55 subjects per arm) will be randomized in a 1:1:1 ratio to receive oral apremilast (30 mg BID or 40 mg BID), or identically appearing placebo BID for up to 12 weeks, followed by 40 weeks of blinded treatment with apremilast (30 mg BID or 40 mg BID). At the end of the Blinded Active-treatment Phase (Week 52), participants who have a Mayo endoscopy score ≤ 1 will have the opportunity to participate in the Extension Phase. Participants enrolled in the Extension Phase will receive apremilast for an additional 52 weeks (Weeks 52 to 104). With the implementation of Amendment 4, participants entering the Extension Phase will receive apremilast 30 mg BID. Subjects currently in the Extension Phase who are receiving apremilast 40 mg BID will be switched to 30 mg BID at the next scheduled visit.
Interventions
DRUGApremilast
DRUGPlacebo
Sponsors
Amgen
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 No maximum
Healthy volunteers
No
Inclusion criteria
Subjects must satisfy the following criteria to be enrolled in the study: * Male or female aged 18 and over at the time of signing the informed consent. * Must understand and voluntarily sign an informed consent form prior to any study related assessments/procedures being conducted. * Diagnosis of ulcerative colitis (UC) with a duration of at least 3 months prior to the Screening Visit.. * Total Mayo Score (TMS) ≥ 6 to ≤ 11 (range: 0-12) at baseline, prior to randomization in the study. * Endoscopic subscore ≥ 2 (range: 0-3) on the Mayo score prior to randomization in the study. * Subjects must have had a therapeutic failure, been intolerant to, or have a contraindication to, at least one of the following: oral aminosalicylates (ie, 5-aminosalicylic acid \[5-ASA\] compounds or sulfasalazine \[SSZ\]), budesonide, systemic corticosteroids, or immunosuppressants (eg, 6-mercaptopurine \[6-MP\], azathioprine \[AZA\], or methotrexate \[MTX\]).
Exclusion criteria
The presence of any of the following will exclude a subject from enrollment: * Diagnosis of Crohn's disease, indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis. * Ulcerative colitis restricted to the distal 15 cm or less (eg, ulcerative proctitis). * Subjects who have had surgery as a treatment for UC or who, in the opinion of the Investigator, are likely to require surgery for UC during the study. * Clinical signs suggestive of fulminant colitis or toxic megacolon. * Prior use of any tumor necrosing factor (TNF) inhibitor (or any biologic agent). * Prior use of mycophenolic acid, tacrolimus, sirolimus, cyclosporine or thalidomide. * Use of intravenous (IV) corticosteroids within 2 weeks of the Screening Visit. * Use of immunosuppressants (AZA, 6-MP or MTX) within 8 weeks of the Screening Visit. * Use of topical treatment with 5-ASA or corticosteroid enemas or suppositories within 2 weeks of the Screening Visit. * History of any clinically significant neurological, renal, hepatic, gastrointestinal, pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder or disease, or any other medical condition that, in the investigator's opinion, would preclude participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score (TMS) at Week 12 | Week 12 | Clinical remission was defined as a total Mayo score ≤ 2 points, with no individual subscore exceeding 1 point. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. * Stool Frequency Subscore (SFS) * Rectal Bleeding Subscore (RBS) * Endoscopy Subscore * Physician's Global Assessment (PGA). Two-sided 95% confidence intervals (CI) for the within-group percentages are based on the Wilson score method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved an Endoscopic Remission at Week 12 | Week 12 | An endoscopic remission was defined as a Mayo endoscopic subscore (MES) of 0 at Week 12. The MES subscore findings were defined as: 0 = Normal or inactive disease 1. = Mild Disease (erythema, decreased vascular pattern, mild friability) 2. = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) 3. = Severe Disease (spontaneous bleeding, ulceration) The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method. |
| Percentage of Participants Who Achieved an Endoscopic Response at Week 12 | Week 12 | An endoscopic response is defined as a decrease from baseline of at least 1 point in the MES at Week 12. The Mayo endoscopy subscore findings were defined as: 0 = Normal or inactive disease 1. = Mild Disease (erythema, decreased vascular pattern, mild friability) 2. = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) 3 = Severe Disease (spontaneous bleeding, ulceration). The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method. |
| Percentage of Participants Who Achieved a Rectal Bleeding Subscore (RBS) of ≤ 1 at Week 12 | Week 12 | The RBS was measured as: 0 = No blood seen 1. = Streaks of blood with stool less than half the time 2. = Obvious blood with stool most of the time 3. = Blood alone passes The daily bleeding score represents the most severe bleeding of the day. Two-sided 95% CI for the within-group proportions are based on the Wilson score method. |
| Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Subscore (MMS) at Week 12 | Week 12 | Clinical remission was defined as a modified Mayo score of ≤ 2, with no individual subscore \> 1, at Week 12. The MMS was based on a modification of the total Mayo score (TMS) which included the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the Physician's Global Assessment (PGA) subscore, since this was a global measure that is subjective in nature. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method. |
| Percentage of Participants Who Achieved Clinical Response in the Modified Mayo Subscore (MMS) at Week 12 | Week 12 | Clinical response in the MMS was defined as a decrease from baseline in the MMS of at least 2 points and at least 25%, along with a reduction in the RBS of at least 1 point or an absolute RBS ≤ 1. The MMS was based on the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the PGA subscore. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The RBS was measured as: 0 = No blood seen 1. = Streaks of blood with stool less than half the time 2. = Obvious blood with stool most of the time 3. = Blood alone passes The daily bleeding score represents the most severe bleeding of the day. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method. |
| Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score and the Reduction in the Rectal Bleeding Subscore at Week 12 | Week 12 | Clinical response was defined as a decrease from baseline in the TMS of at least 3 points and at least 30%, along with a reduction in the rectal bleeding subscore (RBS) of at least 1 point or an absolute RBS of ≤ 1. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. * Stool Frequency Subscore (SFS) * Rectal Bleeding Subscore * Endoscopy Subscore * Physician's Global Assessment (PGA) Rectal bleeding (subscore 0-3) was defined as: 0 = No blood seen 1. = Streaks of blood with stool less than half the time 2. = Obvious blood with stool 3. = Blood alone passes Two-sided 95% CI for the within-group percentages are based on the Wilson score method. |
| Percentage of Participants Who Achieved Clinical Response in the Partial Mayo Subscore at Week 8 | Week 8 | Clinical response in the PMS was defined as a decrease from baseline in PMS of at least 2 points and at least 25%, with an accompanying decrease in the RBS of at least 1 point or an absolute RBS of 0 or 1. The PMS score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Two-sided 95% CI for the within-group proportions are based on the Wilson score method. |
| The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | From the first dose of investigational product (IP) and no later than 28 days after the last dose of IP for those who had completed the study or discontinued (D/C) early; maximum duration of exposure to treatment was 12.00 weeks | A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain |
| The Number of Participants Who Discontinued Apremilast Due to Treatment Emergent Adverse Events During the Placebo-Controlled Period | From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early; median duration of exposure to treatment was 12.00 weeks | A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain. |
| The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | From first dose of IP and no later than 28 days after last dose of IP for those who completed the active treatment phase or D/C early; median duration of exposure = 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms | A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain |
| The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) | From the first dose of IP at Week 52 and no later than 28 days after the last dose of IP for those who completed the study or had discontinued early; median exposure of apremilast for the total apremilast group was 52 weeks. | A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain |
| Percentage of Participants Who Achieved Clinical Remission in the Partial Mayo Subscore (PMS) With no Individual Subscore >1 at Week 8 | Week 8 | Clinical remission in the partial Mayo subscore was defined as a PMS of 2 points or lower, with no individual subscore \>1. The PMS is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Two-sided 95% CI for the within-group proportions are based on the Wilson score method. |
Countries
Australia, Bulgaria, Canada, Czechia, France, Germany, Hungary, Italy, Netherlands, New Zealand, Poland, Russia, Ukraine, United States
Participant flow
Recruitment details
The study was conducted at 61 sites in Australia (3 sites) and New Zealand (1 site); Bulgaria (6 sites), Czech Republic (2 sites), Hungary (3 sites), Poland (9 sites), Russia (1 site), and Ukraine (10 sites); Canada (2 sites) and United States (13 sites); and France (4 sites), Germany (1 site), Italy (4 sites), and the Netherlands (2 sites).
Pre-assignment details
A total of 170 participants were randomized in a 1:1:1 ratio and received apremilast (30 mg BID or 40 mg BID), or identically appearing placebo and stratified based on concomitant use of oral corticosteroids and previous exposure to immunosuppressants.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth PO BID for 12 weeks during the double-blind placebo-controlled phase. | 58 |
| Apremilast 30 mg Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. | 57 |
| Apremilast 40 mg Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. | 55 |
| Total | 170 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Active Treatment Phase Weeks 12-52 | Adverse Event | 0 | 1 | 4 | 2 | 2 | 1 | 0 | 0 | 0 |
| Active Treatment Phase Weeks 12-52 | Lack of Efficacy | 0 | 1 | 4 | 6 | 2 | 3 | 0 | 0 | 0 |
| Active Treatment Phase Weeks 12-52 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Active Treatment Phase Weeks 12-52 | Miscellaneous | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
| Active Treatment Phase Weeks 12-52 | Pregnancy | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Active Treatment Phase Weeks 12-52 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0 |
| Extension Phase Weeks 52-104 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 3 |
| Extension Phase Weeks 52-104 | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 |
| Extension Phase Weeks 52-104 | Miscellaneous | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Extension Phase Weeks 52-104 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 |
| Placebo-Controlled Phase Weeks 0-12 | Adverse Event | 3 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo-Controlled Phase Weeks 0-12 | Lack of Efficacy | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo-Controlled Phase Weeks 0-12 | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Placebo-Controlled Phase Weeks 0-12 | Withdrawal by Subject | 1 | 3 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Apremilast 30 mg | Apremilast 40 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 42.9 Years STANDARD_DEVIATION 14.04 | 40.1 Years STANDARD_DEVIATION 13.5 | 43.4 Years STANDARD_DEVIATION 14.92 | 42.1 Years STANDARD_DEVIATION 14.15 |
| Baseline Total Mayo Score (TMS) | 8.2 units on a scale STANDARD_DEVIATION 1.68 | 8.5 units on a scale STANDARD_DEVIATION 1.62 | 8.1 units on a scale STANDARD_DEVIATION 1.67 | 8.3 units on a scale STANDARD_DEVIATION 1.65 |
| Baseline Use of Oral Corticosteroids | 17 Participants | 14 Participants | 12 Participants | 43 Participants |
| Duration of Ulcerative Colitis | 6.85 Years STANDARD_DEVIATION 7.043 | 6.15 Years STANDARD_DEVIATION 5.432 | 8.63 Years STANDARD_DEVIATION 10.278 | 7.19 Years STANDARD_DEVIATION 7.832 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants | 54 Participants | 46 Participants | 155 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 4 Participants | 7 Participants |
| Mayo Endoscopic Subscore (MES) | 2.6 units on a scale STANDARD_DEVIATION 0.49 | 2.7 units on a scale STANDARD_DEVIATION 0.45 | 2.6 units on a scale STANDARD_DEVIATION 0.49 | 2.6 units on a scale STANDARD_DEVIATION 0.48 |
| Modified Mayo Score (MMS) | 6.1 units on a scale STANDARD_DEVIATION 1.51 | 6.4 units on a scale STANDARD_DEVIATION 1.48 | 6.0 units on a scale STANDARD_DEVIATION 1.47 | 6.2 units on a scale STANDARD_DEVIATION 1.49 |
| Partial Mayo Score (PMS) | 5.6 units on a scale STANDARD_DEVIATION 1.46 | 5.8 units on a scale STANDARD_DEVIATION 1.44 | 5.5 units on a scale STANDARD_DEVIATION 1.57 | 5.6 units on a scale STANDARD_DEVIATION 1.49 |
| Previous Exposure to Use of Immunosuppressants | 17 Participants | 18 Participants | 16 Participants | 51 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Reported or Collected | 3 Participants | 4 Participants | 8 Participants | 15 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 54 Participants | 52 Participants | 45 Participants | 151 Participants |
| Sex: Female, Male Female | 25 Participants | 18 Participants | 21 Participants | 64 Participants |
| Sex: Female, Male Male | 33 Participants | 39 Participants | 34 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 58 | 0 / 57 | 0 / 55 | 0 / 83 | 0 / 80 | 0 / 11 |
| other Total, other adverse events | 20 / 58 | 26 / 57 | 25 / 55 | 49 / 83 | 53 / 80 | 11 / 11 |
| serious Total, serious adverse events | 2 / 58 | 0 / 57 | 1 / 55 | 9 / 83 | 11 / 80 | 1 / 11 |
Outcome results
Primary
Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score (TMS) at Week 12
Clinical remission was defined as a total Mayo score ≤ 2 points, with no individual subscore exceeding 1 point. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. * Stool Frequency Subscore (SFS) * Rectal Bleeding Subscore (RBS) * Endoscopy Subscore * Physician's Global Assessment (PGA). Two-sided 95% confidence intervals (CI) for the within-group percentages are based on the Wilson score method.
Time frame: Week 12
Population: The intent to treat (ITT) population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score (TMS) at Week 12 | 12.1 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score (TMS) at Week 12 | 31.6 Percentage of Participants |
| Apremilast 40 mg | Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score (TMS) at Week 12 | 21.8 Percentage of Participants |
p-value: 0.014295% CI: [3.4, 33.6]Cochran-Mantel-Haenszel
p-value: 0.268995% CI: [-6.9, 22]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score and the Reduction in the Rectal Bleeding Subscore at Week 12
Clinical response was defined as a decrease from baseline in the TMS of at least 3 points and at least 30%, along with a reduction in the rectal bleeding subscore (RBS) of at least 1 point or an absolute RBS of ≤ 1. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. * Stool Frequency Subscore (SFS) * Rectal Bleeding Subscore * Endoscopy Subscore * Physician's Global Assessment (PGA) Rectal bleeding (subscore 0-3) was defined as: 0 = No blood seen 1. = Streaks of blood with stool less than half the time 2. = Obvious blood with stool 3. = Blood alone passes Two-sided 95% CI for the within-group percentages are based on the Wilson score method.
Time frame: Week 12
Population: The intent to treat (ITT) population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score and the Reduction in the Rectal Bleeding Subscore at Week 12 | 46.6 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score and the Reduction in the Rectal Bleeding Subscore at Week 12 | 61.4 Percentage of Participants |
| Apremilast 40 mg | Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score and the Reduction in the Rectal Bleeding Subscore at Week 12 | 67.3 Percentage of Participants |
p-value: 0.122495% CI: [-3.6, 31.5]Cochran-Mantel-Haenszel
p-value: 0.040195% CI: [1.1, 36]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved an Endoscopic Remission at Week 12
An endoscopic remission was defined as a Mayo endoscopic subscore (MES) of 0 at Week 12. The MES subscore findings were defined as: 0 = Normal or inactive disease 1. = Mild Disease (erythema, decreased vascular pattern, mild friability) 2. = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) 3. = Severe Disease (spontaneous bleeding, ulceration) The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.
Time frame: Week 12
Population: The intent to treat population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved an Endoscopic Remission at Week 12 | 3.4 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved an Endoscopic Remission at Week 12 | 8.8 Percentage of Participants |
| Apremilast 40 mg | Percentage of Participants Who Achieved an Endoscopic Remission at Week 12 | 7.3 Percentage of Participants |
p-value: 0.247295% CI: [-5.7, 16.7]Cochran-Mantel-Haenszel
p-value: 0.462895% CI: [-7.5, 14.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved an Endoscopic Response at Week 12
An endoscopic response is defined as a decrease from baseline of at least 1 point in the MES at Week 12. The Mayo endoscopy subscore findings were defined as: 0 = Normal or inactive disease 1. = Mild Disease (erythema, decreased vascular pattern, mild friability) 2. = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) 3 = Severe Disease (spontaneous bleeding, ulceration). The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.
Time frame: Week 12
Population: The intent to treat population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved an Endoscopic Response at Week 12 | 41.4 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved an Endoscopic Response at Week 12 | 73.7 Percentage of Participants |
| Apremilast 40 mg | Percentage of Participants Who Achieved an Endoscopic Response at Week 12 | 47.3 Percentage of Participants |
p-value: 0.000595% CI: [13.8, 47.4]Cochran-Mantel-Haenszel
p-value: 0.687895% CI: [-14.4, 21.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved a Rectal Bleeding Subscore (RBS) of ≤ 1 at Week 12
The RBS was measured as: 0 = No blood seen 1. = Streaks of blood with stool less than half the time 2. = Obvious blood with stool most of the time 3. = Blood alone passes The daily bleeding score represents the most severe bleeding of the day. Two-sided 95% CI for the within-group proportions are based on the Wilson score method.
Time frame: Week 12
Population: The intent to treat population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a Rectal Bleeding Subscore (RBS) of ≤ 1 at Week 12 | 72.4 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved a Rectal Bleeding Subscore (RBS) of ≤ 1 at Week 12 | 84.2 Percentage of Participants |
| Apremilast 40 mg | Percentage of Participants Who Achieved a Rectal Bleeding Subscore (RBS) of ≤ 1 at Week 12 | 87.3 Percentage of Participants |
p-value: 0.138895% CI: [-4.1, 26.1]Cochran-Mantel-Haenszel
p-value: 0.078895% CI: [-1.6, 27.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Subscore (MMS) at Week 12
Clinical remission was defined as a modified Mayo score of ≤ 2, with no individual subscore \> 1, at Week 12. The MMS was based on a modification of the total Mayo score (TMS) which included the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the Physician's Global Assessment (PGA) subscore, since this was a global measure that is subjective in nature. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.
Time frame: Week 12
Population: The intent to treat population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Subscore (MMS) at Week 12 | 19.0 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Subscore (MMS) at Week 12 | 43.9 Percentage of Participants |
| Apremilast 40 mg | Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Subscore (MMS) at Week 12 | 27.3 Percentage of Participants |
p-value: 0.004695% CI: [7.5, 40.1]Cochran-Mantel-Haenszel
p-value: 0.447695% CI: [-9.8, 21.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved Clinical Remission in the Partial Mayo Subscore (PMS) With no Individual Subscore >1 at Week 8
Clinical remission in the partial Mayo subscore was defined as a PMS of 2 points or lower, with no individual subscore \>1. The PMS is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Two-sided 95% CI for the within-group proportions are based on the Wilson score method.
Time frame: Week 8
Population: The intent to treat population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved Clinical Remission in the Partial Mayo Subscore (PMS) With no Individual Subscore >1 at Week 8 | 32.8 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved Clinical Remission in the Partial Mayo Subscore (PMS) With no Individual Subscore >1 at Week 8 | 47.4 Percentage of Participants |
| Apremilast 40 mg | Percentage of Participants Who Achieved Clinical Remission in the Partial Mayo Subscore (PMS) With no Individual Subscore >1 at Week 8 | 52.7 Percentage of Participants |
p-value: 0.116795% CI: [-3.3, 31.4]Cochran-Mantel-Haenszel
p-value: 0.053495% CI: [-0.3, 34.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved Clinical Response in the Modified Mayo Subscore (MMS) at Week 12
Clinical response in the MMS was defined as a decrease from baseline in the MMS of at least 2 points and at least 25%, along with a reduction in the RBS of at least 1 point or an absolute RBS ≤ 1. The MMS was based on the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the PGA subscore. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The RBS was measured as: 0 = No blood seen 1. = Streaks of blood with stool less than half the time 2. = Obvious blood with stool most of the time 3. = Blood alone passes The daily bleeding score represents the most severe bleeding of the day. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.
Time frame: Week 12
Population: The intent to treat population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved Clinical Response in the Modified Mayo Subscore (MMS) at Week 12 | 46.6 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved Clinical Response in the Modified Mayo Subscore (MMS) at Week 12 | 63.2 Percentage of Participants |
| Apremilast 40 mg | Percentage of Participants Who Achieved Clinical Response in the Modified Mayo Subscore (MMS) at Week 12 | 67.3 Percentage of Participants |
p-value: 0.075595% CI: [-1.4, 33.5]Cochran-Mantel-Haenszel
p-value: 0.03795% CI: [1.5, 36.4]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved Clinical Response in the Partial Mayo Subscore at Week 8
Clinical response in the PMS was defined as a decrease from baseline in PMS of at least 2 points and at least 25%, with an accompanying decrease in the RBS of at least 1 point or an absolute RBS of 0 or 1. The PMS score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Two-sided 95% CI for the within-group proportions are based on the Wilson score method.
Time frame: Week 8
Population: The intent to treat population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved Clinical Response in the Partial Mayo Subscore at Week 8 | 48.3 Percentage of Participants |
| Apremilast 30 mg | Percentage of Participants Who Achieved Clinical Response in the Partial Mayo Subscore at Week 8 | 64.9 Percentage of Participants |
| Apremilast 40 mg | Percentage of Participants Who Achieved Clinical Response in the Partial Mayo Subscore at Week 8 | 81.8 Percentage of Participants |
p-value: 0.075895% CI: [-1.5, 33.3]Cochran-Mantel-Haenszel
p-value: 0.000495% CI: [14.9, 47.5]Cochran-Mantel-Haenszel
Secondary
The Number of Participants Who Discontinued Apremilast Due to Treatment Emergent Adverse Events During the Placebo-Controlled Period
A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain.
Time frame: From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early; median duration of exposure to treatment was 12.00 weeks
Population: Safety population included all participants who were enrolled and received at least 1 dose of investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | The Number of Participants Who Discontinued Apremilast Due to Treatment Emergent Adverse Events During the Placebo-Controlled Period | 5 Participants |
| Apremilast 30 mg | The Number of Participants Who Discontinued Apremilast Due to Treatment Emergent Adverse Events During the Placebo-Controlled Period | 0 Participants |
| Apremilast 40 mg | The Number of Participants Who Discontinued Apremilast Due to Treatment Emergent Adverse Events During the Placebo-Controlled Period | 1 Participants |
Secondary
The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52
A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain
Time frame: From first dose of IP and no later than 28 days after last dose of IP for those who completed the active treatment phase or D/C early; median duration of exposure = 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms
Population: Apremilast exposure population included all participants who were randomized at Week 0 or assigned at Week 12 to an apremilast group and received at least 1 dose of apremilast.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any TEAE | 60 Participants |
| Placebo | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any Severe TEAE | 5 Participants |
| Placebo | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any Serious TEAE | 6 Participants |
| Placebo | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any TEAE Leading to Drug Withdrawal | 3 Participants |
| Placebo | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any TEAE Leading to Drug Interruption | 1 Participants |
| Placebo | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any TEAE Leading to Death | 0 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any TEAE Leading to Death | 0 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any TEAE | 67 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any TEAE Leading to Drug Withdrawal | 9 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any TEAE Leading to Drug Interruption | 4 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any Severe TEAE | 6 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any Serious TEAE | 8 Participants |
| Apremilast 40 mg | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any Severe TEAE | 0 Participants |
| Apremilast 40 mg | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any Serious TEAE | 1 Participants |
| Apremilast 40 mg | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any TEAE Leading to Death | 0 Participants |
| Apremilast 40 mg | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any TEAE Leading to Drug Withdrawal | 1 Participants |
| Apremilast 40 mg | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any TEAE | 8 Participants |
| Apremilast 40 mg | The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 | Any TEAE Leading to Drug Interruption | 0 Participants |
Secondary
The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase)
A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain
Time frame: From the first dose of IP at Week 52 and no later than 28 days after the last dose of IP for those who completed the study or had discontinued early; median exposure of apremilast for the total apremilast group was 52 weeks.
Population: Participants who received at least 1 dose of apremilast after week 52.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) | Any Severe TEAE | 1 Participants |
| Placebo | The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) | Any Serious IP-related TEAE | 0 Participants |
| Placebo | The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) | Any TEAE | 16 Participants |
| Placebo | The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) | Any TEAE Leading to IP Withdrawal | 2 Participants |
| Placebo | The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) | Any Serious TEAE | 4 Participants |
| Placebo | The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) | Any TEAE Leading to Death | 0 Participants |
| Placebo | The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) | Any TEAE Leading to IP Interruption | 1 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) | Any TEAE Leading to Death | 0 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) | Any TEAE Leading to IP Interruption | 0 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) | Any TEAE | 27 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) | Any Severe TEAE | 0 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) | Any Serious TEAE | 3 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) | Any Serious IP-related TEAE | 1 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) | Any TEAE Leading to IP Withdrawal | 1 Participants |
Secondary
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase
A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain
Time frame: From the first dose of investigational product (IP) and no later than 28 days after the last dose of IP for those who had completed the study or discontinued (D/C) early; maximum duration of exposure to treatment was 12.00 weeks
Population: Safety population included all participants who were enrolled and received at least 1 dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any TEAE Leading to Death | 0 Participants |
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any TEAE | 31 Participants |
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any Serious TEAE | 2 Participants |
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any TEAE Leading to IP Interruption | 1 Participants |
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any IP-related TEAE | 12 Participants |
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any Serious IP-related TEAE | 0 Participants |
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any Severe TEAE | 4 Participants |
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any TEAE Leading to IP Withdrawal | 5 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any Severe TEAE | 0 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any TEAE | 28 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any TEAE Leading to IP Interruption | 0 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any TEAE Leading to Death | 0 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any Serious IP-related TEAE | 0 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any TEAE Leading to IP Withdrawal | 0 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any Serious TEAE | 0 Participants |
| Apremilast 30 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any IP-related TEAE | 13 Participants |
| Apremilast 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any TEAE Leading to Death | 0 Participants |
| Apremilast 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any TEAE | 36 Participants |
| Apremilast 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any IP-related TEAE | 20 Participants |
| Apremilast 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any Severe TEAE | 1 Participants |
| Apremilast 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any Serious TEAE | 1 Participants |
| Apremilast 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any Serious IP-related TEAE | 0 Participants |
| Apremilast 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any TEAE Leading to IP Withdrawal | 1 Participants |
| Apremilast 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase | Any TEAE Leading to IP Interruption | 0 Participants |