Efficacy and Safety Study of Apremilast to Treat Active U... | NCT02289417 | Trialant
NCT02289417
Sponsor
Amgen
Status
Completed
Last Update Posted
May 7, 2020Actual
Enrollment
170Actual
Phase
Phase 2
Conditions
Ulcerative Colitis
Interventions
Apremilast
Placebo
Countries
United States
Australia
Bulgaria
Canada
Czechia
France
Germany
Hungary
Italy
Netherlands
New Zealand
Poland
Russia
Ukraine
Protocol Section
Identification Module
NCT ID
NCT02289417
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CC-10004-UC-001
Secondary IDs
ID
Type
Description
Link
2014-002981-64
EudraCT Number
Brief Title
Efficacy and Safety Study of Apremilast to Treat Active Ulcerative Colitis
Official Title
A Phase 2, Randomized, Placebo-controlled, Multicenter Study to Investigate the Efficacy and Safety of Apremilast (CC-10004) for Treatment of Subjects With Active Ulcerative Colitis
Acronym
UC
Organization
AmgenINDUSTRY
Status Module
Record Verification Date
Apr 2020
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
YesNCT03740516No longer available
Start Date
Jan 8, 2015Actual
Primary Completion Date
Sep 25, 2017Actual
Completion Date
Jun 3, 2019Actual
First Submitted Date
Nov 10, 2014
First Submission Date that Met QC Criteria
Nov 10, 2014
First Posted Date
Nov 13, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Sep 25, 2018
Results First Submitted that Met QC Criteria
Sep 25, 2018
Results First Posted Date
Oct 29, 2018Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Feb 28, 2018
Certification/Extension First Submitted that Passed QC Review
Feb 28, 2018
Certification/Extension First Posted Date
Mar 2, 2018Actual
Last Update Submitted Date
Apr 28, 2020
Last Update Posted Date
May 7, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
AmgenINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Conditions Module
Conditions
Ulcerative Colitis
Keywords
Ulcerative Colitis
Inflammatory Bowel Disease
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
170Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Apremilast 30 mg PO BID
Experimental
Apremilast 30 mg by mouth (PO) twice a day (BID) for 12 weeks
After 12 weeks:
Participants who achieve at least a 20% decrease from baseline in the total Mayo score (TMS) will continue to receive apremilast 30 mg BID for an additional 40 weeks. (Wk 52)
Participants who do not achieve at least a 20% decrease from baseline in the TMS will receive apremilast 40 mg BID for an additional 40 weeks (Wk 52)
After 52 weeks, participants who are eligible for the Extension Phase will continue to receive the same dose of apremilast assigned at Wk 12 (30 mg BID or 40 mg BID) for an additional 52 weeks (Wk 104)
Drug: Apremilast
Apremilast 40 mg PO BID
Experimental
Apremilast 40 mg by mouth (PO) twice a day (BID) for 12 weeks
After 12 weeks, participants assigned to the 40 mg BID dose of apremilast at baseline will continue to receive apremilast 40 mg BID for an additional 40 weeks (Wk 52)
After 52 weeks, participants who are eligible for the extension Phase will continue to receive apremilast 40 mg BID for an additional 52 weeks (Wk 104)
Drug: Apremilast
Placebo BID
Placebo Comparator
Identically matching placebo by mouth (PO) twice a day (BID) for 12 weeks. After 12 weeks all participants randomized to placebo at baseline will be re-randomized to receive apremilast 30 mg or 40 mg BID for an additional 40 weeks (Wk 52)
After Wk 52, participants who are eligible for the extension phase will continue to receive the same dose of apremilast assigned at Wk 12 (30 mg BID or 40 mg BID) for an additional 52 weeks (Wk 104)
Drug: Apremilast
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Apremilast
Drug
Apremilast 30 mg PO BID
Apremilast 40 mg PO BID
Placebo BID
CC-10004; Otezla
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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.
Week 12
Secondary Outcomes
Measure
Description
Time Frame
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
= Streaks of blood with stool less than half the time
= Obvious blood with stool
= Blood alone passes Two-sided 95% CI for the within-group percentages are based on the Wilson score method.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
MD
Amgen
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Digestive Health Specialists of The Southeast
Dothan
Alabama
36305
United States
Southern California Research Institute Medical Group, Inc.
Danese S, Neurath MF, Kopon A, Zakko SF, Simmons TC, Fogel R, Siegel CA, Panaccione R, Zhan X, Usiskin K, Chitkara D. Effects of Apremilast, an Oral Inhibitor of Phosphodiesterase 4, in a Randomized Trial of Patients With Active Ulcerative Colitis. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2526-2534.e9. doi: 10.1016/j.cgh.2019.12.032. Epub 2020 Jan 8.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Types
Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
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.
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).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo
Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.
= 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.
Week 12
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:
= 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.
Week 12
Percentage of Participants Who Achieved a Rectal Bleeding Subscore (RBS) of ≤ 1 at Week 12
The RBS was measured as:
0 = No blood seen
= Streaks of blood with stool less than half the time
= Obvious blood with stool most of the time
= 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.
Week 12
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.
Week 12
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
= Streaks of blood with stool less than half the time
= Obvious blood with stool most of the time
= 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.
Week 12
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.
Week 8
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.
Week 8
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
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
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.
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
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
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
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
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.
Los Angeles
California
90045
United States
Connecticut Clinical Research Foundation
Bristol
Connecticut
06010
United States
Consultants for Clinical Research of South Florida
Boynton Beach
Florida
33426
United States
Avail Clinical Research, LLC
DeLand
Florida
32720
United States
Precision Clinical Research, LLC
Lauderdale Lakes
Florida
33319
United States
Pharmax Research Clinic, Inc.
Miami
Florida
33126
United States
Gastroenterology Group of Naples
Naples
Florida
34102
United States
Advanced Medical Research Center
Port Orange
Florida
32127
United States
University of Chicago Medical Center
Chicago
Illinois
60637
United States
University of Iowa Hospitals and Clinics
Iowa City
Iowa
52242
United States
University of Louisville
Louisville
Kentucky
40202
United States
UMass Medical Center
Worcester
Massachusetts
01655
United States
Clinical Research Institute of Michigan, LLC
Chesterfield
Michigan
48047
United States
Center for Digestive Health Research
Troy
Michigan
48098
United States
Gastrointestinal Associates PA
Flowood
Mississippi
39232
United States
NYU Langone Long Island Clinical Research Associates
Great Neck
New York
11021
United States
Consultants for Clinical Research
Cincinnati
Ohio
45219
United States
Quality Medical Research
Nashville
Tennessee
37211
United States
Digestive Research Center/ Gastroenterology Consultants of San Antonio
Live Oak
Texas
78233
United States
Digestive Health Specialist of Tyler
Pasadena
Texas
77505
United States
San Antonio Gastroenterology
San Antonio
Texas
78229
United States
University of Utah
Salt Lake City
Utah
84132
United States
Harborview Medical Center
Seattle
Washington
98104
United States
University of Washington Medical Center
Seattle
Washington
98195
United States
Concord Repatriation General Hospital
Concord
New South Wales
2139
Australia
Liverpool Hospital
Liverpool
New South Wales
2170
Australia
Mater Adult Hospital
South Brisbane
Queensland
4101
Australia
Footscray Hospital
Footscray
Victoria
3011
Australia
Royal Melbourne Hospital
Parkville
Victoria
3050
Australia
Multiprofile Hospital for Active Treatment Kaspela
Plovdiv
4002
Bulgaria
Medical Center Asklepion - Humane Medicine Research EOOD
Sofia
1303
Bulgaria
University Multiprofile Hospital for Active Treatment ACIBADEM City Clinic Sofia
Sofia
1407
Bulgaria
University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD
Sofia
1431
Bulgaria
University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna ISUL EAD
Sofia
1527
Bulgaria
Clinic of Gastroenterology
Sofia
1784
Bulgaria
Multiprofile Hospital for Active Treatment Sveta Marina EAD
Varna
9010
Bulgaria
Winnipeg Regional Health Authority - Health Sciences Centre
Winnipeg
Manitoba
R3A 1R9
Canada
Hamilton Health Sciences Corporation, McMaster University Medical Centre
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
Szeged
6720
Hungary
Tolna Megyei Balassa Janos Korhaz
Szekszárd
7100
Hungary
Javorszky Odon Korhaz
Vác
2600
Hungary
Azienda Ospedaliero Universitaria Di Bologna Policlinico Sorsola Malpighi
Bologna
40138
Italy
IRCCS - Istituo Clinico Humanitas - Humanitas Cancer Center
Milan
20089
Italy
Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello
Palermo
90146
Italy
Fondazione PTV Policlinico Tor Vergata
Roma
00133
Italy
Complesso Integrato Columbus
Roma
00168
Italy
Universitair Medisch Centrum Groningen
Groningen
9713 GZ
Netherlands
Ikazia Ziekenhuis
Rotterdam
3083 AN
Netherlands
Auckland City Hospital
Auckland
1023
New Zealand
Christchurch Hospital
Christchurch
8011
New Zealand
Dunedin Hospital
Dunedin
9016
New Zealand
Waikato hospital
Hamilton
3204
New Zealand
Uniwersytecki Szpital Kliniczny w Bialymstoku
Bialystok
15-276
Poland
Osrodek Badan Klinicznych CLINSANTE S.C.
Bydgoszcz
85-794
Poland
Centrum Medyczne sw. Lukasza
Częstochowa
42 202
Poland
Economicus - NZOZ ALL-MEDICUS
Katowice
40 659
Poland
Endoskopia Sp. z o.o.
Sopot
81-756
Poland
Sonomed Sp. z o.o.
Szczecin
71-685
Poland
Gastromed Kopon Zmudzinski i Wspolnicy Sp. j. Specjalistyczne Centrum Gastrologii i Endoskopii Spec. Gabinety Lekarskie
Torun
40 659
Poland
Centrum Zdrowia Matki, Dziecka i Mlodziezy
Warsaw
00-632
Poland
Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED
Warsaw
03-563
Poland
Lexmedica Drubajlo Hanna
Wroclaw
03-580
Poland
Ars Medica
Wroclaw
53-333
Poland
Republican Clinical Hospital
Kazan'
420064
Russia
Stolitsa-Medikl, LLC
Moscow
115088
Russia
SEIHPE Rostov State Medical University of MoH of RF
Rostov-on-Don
344022
Russia
Russian Medical Military Academy na SMKirov
Saint Petersburg
129329
Russia
Regional Clinical Hospital
Saratov
410053
Russia
Regional Clinical Hospital, Gastroenterology department, State Higher Education Institute Ivano-Frankivsk National Medical University
Ivano-Frankivsk
58001
Ukraine
Ivano-Frankivsk Regional Clinical Hospital
Ivano-Frankivsk
76008
Ukraine
Ivano-Frankivsk Central City Clinical Hospital
Ivano-Frankivsk
76018
Ukraine
Kharkiv City Clinical Hospital 2
Kharkiv
61037
Ukraine
Private Enterprise Private Manufacture Company Acinus
Kirovograd
25006
Ukraine
Kremenchuk City Hospital # 1 n.a O.T.Bohaievskyi
Kremenchuk
39617
Ukraine
Lviv Emergency Clinical Hospital, Therapeutics Department No. 1
Lviv
79059
Ukraine
Municipal Institution Odesa Regional Clinical Hospital
Odesa
65025
Ukraine
Central City Clinical Hospital
Uzhhorod
88000
Ukraine
Vinnytsia Regional Clinical Hospital n a M I Pyrohov
Vinnytsia
21018
Ukraine
Municipal Institution Zaporizhzhia
Zaporizhzhia
69600
Ukraine
Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
At week 12, participants who achieved at least a 20% decrease from baseline in the total Mayo score (TMS) continued to receive 30 mg apremilast capsules BID for an additional 40 weeks during the active treatment phase.
FG002
Apremilast 40 mg
Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. At week 12, participants who achieved at least a 20% decrease from baseline in the TMS continued to receive 40 mg apremilast capsules BID for an additional 40 weeks during the active treatment phase.
FG003
Placebo/Apremilast 30 mg
Participants initially randomized to placebo capsules in the placebo-controlled period were re-randomized at week 12 to receive 30 mg apremilast capsules BID for 40 weeks during the active treatment phase.
FG004
Placebo/Apremilast 40 mg
Participants initially randomized to placebo in the placebo-controlled period were re-randomized at week 12 to receive 40 mg apremilast capsules BID for 40 weeks during the active treatment phase.
FG005
Apremilast 30 mg/Apremilast 40 mg
Participants initially randomized to 30 mg apremilast capsules BID in the placebo-controlled phase who did not achieve at least a 20% decrease from baseline in the TMS were re-assigned to 40 mg apremilast capsules BID for 40 weeks during the active treatment phase.
FG006
Apremilast 40 mg/ Apremilast 40 mg
Participants initially randomized to 40 mg apremilast capsules BID in the placebo-controlled phase who did not achieve at least a 20% decrease from baseline in the TMS continued to receive 40 mg apremilast capsules BID for an additional 40 weeks during the active treatment phase.
FG007
Extension Phase: Apremilast 30 mg
Participants who completed 52 weeks of treatment and had a Mayo endoscopy score ≤ 1 at week 52 were eligible to participate in the 52-week extension phase and receive 30 mg apremilast BID for an additional 52 weeks. This includes participants assigned to 30 mg apremilast BID at week 12, and participants who entered the extension phase after implementation of Protocol Amendment 4.
FG008
Extension Phase Apremilast 40 mg
Participants who completed 52 weeks of treatment and had a Mayo endoscopy score ≤ 1 at week 52 were eligible to participate in the 52-week extension phase and receive 40 mg apremilast BID for an additional 52 weeks. After implementation of Protocol Amendment 4 participants were switched to 30 mg apremilast BID for the remainder of the extension phase.
FG00058 subjects
FG00157 subjects
FG00255 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
COMPLETED
FG00051 subjects
FG00153 subjects
FG00252 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
NOT COMPLETED
FG0007 subjects
FG0014 subjects
FG0023 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
Type
Comment
Reasons
Adverse Event
FG0003 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
Withdrawal by Subject
FG0001 subjects
FG0013 subjects
FG0022 subjects
FG0030 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Lack of Efficacy
FG0003 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Active Treatment Phase Weeks 12-52
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG00141 subjects
FG00242 subjects
FG00326 subjects
FG00425 subjects
FG00512 subjects1 participant went only to Week 20
FG0067 subjectsWeek 12 TMS were missing for 3 participants
FG0070 subjects
FG0080 subjects
COMPLETED
FG0000 subjects
FG00139 subjects
FG00232 subjects
FG00317 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0012 subjects
FG00210 subjects
FG0039 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0011 subjects
FG0024 subjects
FG003
Extension Phase Weeks 52-104
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG00745 subjects
FG00854 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
The intent to treat (ITT) population consisted of all participants who were randomized and received at least 1 dose of investigational product (IP).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
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.
BG001
Apremilast 30 mg
Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
BG002
Apremilast 40 mg
Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00058
BG00157
BG00255
BG003170
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00042.9± 14.04
BG00140.1± 13.50
BG00243.4± 14.92
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00025
BG00118
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0002
BG0011
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Asian
BG0000
BG0010
BG002
Duration of Ulcerative Colitis
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG0006.85± 7.043
BG0016.15± 5.432
BG002
Baseline Total Mayo Score (TMS)
The TMS is an instrument designed to measure disease activity of Ulcerative Colitis (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)
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG0008.2± 1.68
BG001
Modified Mayo Score (MMS)
The MMS was based on the stool frequency, rectal bleeding and endoscopy subscores of the total Mayo score, and excluded the Physician's Global subscore, since this was a global measure that is subjective in nature. The MMS range from 0 to 9 points with zero indicating no symptoms of active ulcerative colitis and 9 indicating the most severe symptoms.
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG0006.1± 1.51
BG001
Partial Mayo Score (PMS)
The partial Mayo score is the sum of the rectal bleeding score, the stool frequency score and the physician's global assessment. The partial Mayo score range is from 0 to 9 points with zero indicating no symptoms of active ulcerative colitis and 9 indicating the most severe symptoms and assessment.
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG0005.6± 1.46
BG001
Mayo Endoscopic Subscore (MES)
The Mayo endoscopy subscore findings are defined as:
= Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) 3 = Severe Disease (spontaneous bleeding, ulceration).
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG0002.6± 0.49
BG001
Baseline Use of Oral Corticosteroids
Participants were stratified based on concomitant use of oral corticosteroids and previous exposure to immunosuppressants.
Number
Participants
Title
Denominators
Categories
Title
Measurements
BG00017
BG00114
Previous Exposure to Use of Immunosuppressants
Participants were stratified based on concomitant use of oral corticosteroids and previous exposure to immunosuppressants.
Number
Participants
Title
Denominators
Categories
Title
Measurements
BG00017
BG00118
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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.
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.
Posted
Number
95% Confidence Interval
Percentage of Participants
Week 12
ID
Title
Description
OG000
Placebo
Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.
OG001
Apremilast 30 mg
Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
OG002
Apremilast 40 mg
Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Units
Counts
Participants
OG00058
OG00157
OG00255
Title
Denominators
Categories
Title
Measurements
OG00012.1(6.0 to 22.9)
OG00131.6(21.0 to 44.5)
OG00221.8(12.9 to 34.4)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Cochran-Mantel-Haenszel
Stratification was based on baseline use of oral (PO) corticosteroids and previously used immunosuppressants (yes/no).
0.0142
Stratified Difference
19.2
2-Sided
95
3.4
33.6
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
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
= Streaks of blood with stool less than half the time
= Obvious blood with stool
= Blood alone passes Two-sided 95% CI for the within-group percentages are based on the Wilson score method.
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.
Posted
Number
95% Confidence Interval
Percentage of Participants
Week 12
ID
Title
Description
OG000
Placebo
Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.
OG001
Apremilast 30 mg
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.
= 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.
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.
Posted
Number
95% Confidence Interval
Percentage of Participants
Week 12
ID
Title
Description
OG000
Placebo
Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.
OG001
Apremilast 30 mg
Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
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:
= 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.
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.
Posted
Number
95% Confidence Interval
Percentage of Participants
Week 12
ID
Title
Description
OG000
Placebo
Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.
OG001
Apremilast 30 mg
Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
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
= Streaks of blood with stool less than half the time
= Obvious blood with stool most of the time
= 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.
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.
Posted
Number
95% Confidence Interval
Percentage of Participants
Week 12
ID
Title
Description
OG000
Placebo
Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.
OG001
Apremilast 30 mg
Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
OG002
Apremilast 40 mg
Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
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.
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.
Posted
Number
95% Confidence Interval
Percentage of Participants
Week 12
ID
Title
Description
OG000
Placebo
Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.
OG001
Apremilast 30 mg
Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
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
= Streaks of blood with stool less than half the time
= Obvious blood with stool most of the time
= 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.
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.
Posted
Number
95% Confidence Interval
Percentage of Participants
Week 12
ID
Title
Description
OG000
Placebo
Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.
OG001
Apremilast 30 mg
Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
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.
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.
Posted
Number
95% Confidence Interval
Percentage of Participants
Week 8
ID
Title
Description
OG000
Placebo
Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.
OG001
Apremilast 30 mg
Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
OG002
Apremilast 40 mg
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.
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.
Posted
Number
95% Confidence Interval
Percentage of Participants
Week 8
ID
Title
Description
OG000
Placebo
Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.
OG001
Apremilast 30 mg
Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
OG002
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
Safety population included all participants who were enrolled and received at least 1 dose of investigational product.
Posted
Count of Participants
Participants
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
ID
Title
Description
OG000
Placebo
Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.
OG001
Apremilast 30 mg
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.
Safety population included all participants who were enrolled and received at least 1 dose of investigational product.
Posted
Count of Participants
Participants
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
ID
Title
Description
OG000
Placebo
Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.
OG001
Apremilast 30 mg
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
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.
Posted
Count of Participants
Participants
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
ID
Title
Description
OG000
Apremilast 30 mg
TEAEs during the apremilast 30 mg BID treatment for participants who received 30 mg apremilast capsules BID only and participants who initially received 30 mg apremilast capsules BID and switched to 40 mg apremilast capsules BID at Week 12, and participants who initially received placebo capsules BID and switched to 30 mg apremilast capsules BID at Week 12.
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
Participants who received at least 1 dose of apremilast after week 52.
Posted
Count of Participants
Participants
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.
ID
Title
Description
OG000
Extension Phase: Apremilast 30 mg
Participants who completed 52 weeks of treatment and had a Mayo endoscopy score ≤ 1 at week 52 were eligible to participate in the 52-week extension phase and received 30 mg apremilast BID for an additional 52 weeks. Includes participants assigned to 30 mg apremilast BID at week 12, and participants who entered the extension phase after implementation of Protocol Amendment 4.
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. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104.
Description
Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo (Placebo Controlled Period)
TEAEs for participants who were randomized to identically matching placebo capsules twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.
0
58
2
58
20
58
EG001
Apremilast 30 mg (Placebo Controlled Period)
TEAEs for participants who were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
0
57
0
57
26
57
EG002
Apremilast 40 mg BID (Placebo Controlled Period)
TEAEs for participants who were randomized to apremilast 40 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
0
55
1
55
25
55
EG003
Apremilast 30 mg (Apremilast Exposure Period)
TEAEs during the apremilast 30 mg BID treatment for participants who received 30 mg apremilast capsules BID only and participants who initially received 30 mg apremilast capsules BID and switched to 40 mg apremilast capsules BID at Week 12, and participants who initially received placebo capsules BID and switched to 30 mg apremilast capsules BID at Week 12.
0
83
9
83
49
83
EG004
Apremilast 40 mg (Apremilast Exposure Period)
TEAEs during the apremilast 40 mg BID treatment for participants who received 40 mg apremilast capsules BID only, and participants who initially received placebo BID and switched to 40 mg apremilast capsules BID at Week 12.
0
80
11
80
53
80
EG005
Apremilast 30/40 mg (Apremilast Exposure Period)
TEAEs during the apremilast 40 mg BID treatment for participants who initially received 30 mg apremilast BID and switched to apremilast 40 mg BID at Week 12. for participants who initially received 30 mg apremilast dosage and switched to 40 mg apremilast capsules BID at Week 12.
0
11
1
11
11
11
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Acute myocardial infarction
Cardiac disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG0031 affected83 at risk
EG0040 affected80 at risk
EG0050 affected11 at risk
Congestive cardiomyopathy
Cardiac disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Abdominal hernia
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Colitis ulcerative
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0002 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Crohn's disease
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Inguinal hernia
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0021 affected55 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Clostridium difficile infection
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Epididymitis tuberculous
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Pilonidal cyst
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Rectal abscess
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Epididymal neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Renal colic
Renal and urinary disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Menorrhagia
Reproductive system and breast disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected58 at risk
EG0011 affected57 at risk
EG0020 affected55 at risk
EG0034 affected83 at risk
EG0044 affected80 at risk
EG0050 affected11 at risk
Dyspepsia
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected58 at risk
EG0011 affected57 at risk
EG0020 affected55 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0005 affected58 at risk
EG0013 affected57 at risk
EG0026 affected55 at risk
EG003
Asthenia
General disorders
MedDRA 22.0
Systematic Assessment
EG0002 affected58 at risk
EG0013 affected57 at risk
EG0021 affected55 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0002 affected58 at risk
EG0011 affected57 at risk
EG0020 affected55 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected58 at risk
EG0012 affected57 at risk
EG0021 affected55 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected58 at risk
EG0013 affected57 at risk
EG0020 affected55 at risk
EG003
Anorectal discomfort
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Colitis ulcerative
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0002 affected58 at risk
EG0011 affected57 at risk
EG0020 affected55 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Inguinal hernia
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Swollen tongue
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected58 at risk
EG0012 affected57 at risk
EG0022 affected55 at risk
EG003
Influenza like illness
General disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0011 affected57 at risk
EG0021 affected55 at risk
EG003
Pyrexia
General disorders
MedDRA 22.0
Systematic Assessment
EG0002 affected58 at risk
EG0011 affected57 at risk
EG0021 affected55 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0001 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Influenza
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0001 affected58 at risk
EG0010 affected57 at risk
EG0021 affected55 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0001 affected58 at risk
EG0014 affected57 at risk
EG0022 affected55 at risk
EG003
Periodontitis
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0011 affected57 at risk
EG0020 affected55 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0021 affected55 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0011 affected57 at risk
EG0020 affected55 at risk
EG003
Blood lactate dehydrogenase increased
Investigations
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Faecal calprotectin increased
Investigations
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0011 affected57 at risk
EG0021 affected55 at risk
EG003
Iron deficiency
Metabolism and nutrition disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0002 affected58 at risk
EG0010 affected57 at risk
EG0021 affected55 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected58 at risk
EG0010 affected57 at risk
EG0023 affected55 at risk
EG003
Osteochondrosis
Musculoskeletal and connective tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0011 affected57 at risk
EG0020 affected55 at risk
EG003
Angiomyolipoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0011 affected57 at risk
EG0020 affected55 at risk
EG003
Headache
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0004 affected58 at risk
EG00112 affected57 at risk
EG00214 affected55 at risk
EG003
Migraine
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0011 affected57 at risk
EG0021 affected55 at risk
EG003
Sciatica
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0011 affected57 at risk
EG0020 affected55 at risk
EG003
Sinus headache
Nervous system disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0011 affected57 at risk
EG0020 affected55 at risk
EG003
Depressed mood
Psychiatric disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0021 affected55 at risk
EG003
Depression
Psychiatric disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected58 at risk
EG0010 affected57 at risk
EG0021 affected55 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0012 affected57 at risk
EG0021 affected55 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0001 affected58 at risk
EG0010 affected57 at risk
EG0021 affected55 at risk
EG003
Dysphonia
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0011 affected57 at risk
EG0020 affected55 at risk
EG003
Respiratory tract congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0011 affected57 at risk
EG0020 affected55 at risk
EG003
Rhinitis allergic
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0011 affected57 at risk
EG0020 affected55 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0021 affected55 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0010 affected57 at risk
EG0020 affected55 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0011 affected57 at risk
EG0020 affected55 at risk
EG003
Angiopathy
Vascular disorders
MedDRA 22.0
Systematic Assessment
EG0000 affected58 at risk
EG0011 affected57 at risk
EG0020 affected55 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Results from a center cannot be submitted for publication before results of multicenter study are published unless it is > 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.
Point of Contact
Title
Organization
Phone
Extension
Email
Anne McClain, Senior Manager, Clinical Trial Disclosure
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.2689
Stratified Difference
7.7
2-Sided
95
-6.9
22.0
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method
Superiority
Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
OG002
Apremilast 40 mg
Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Units
Counts
Participants
OG00058
OG00157
OG00255
Title
Denominators
Categories
Title
Measurements
OG00046.6(34.3 to 59.2)
OG00161.4(48.4 to 72.9)
OG00267.3(54.1 to 78.2)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Cochran-Mantel-Haenszel
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.1224
Stratified Difference
14.6
2-Sided
95
-3.6
31.5
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
OG000
OG002
Cochran-Mantel-Haenszel
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.0401
Stratified Difference
19.4
2-Sided
95
1.1
36.0
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
OG002
Apremilast 40 mg
Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Units
Counts
Participants
OG00058
OG00157
OG00255
Title
Denominators
Categories
Title
Measurements
OG0003.4(1.0 to 11.7)
OG0018.8(3.8 to 18.9)
OG0027.3(2.9 to 17.3)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Cochran-Mantel-Haenszel
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.2472
Stratified Difference
5.2
2-Sided
95
-5.7
16.7
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
OG000
OG002
Cochran-Mantel-Haenszel
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.4628
Stratified Difference
3.1
2-Sided
95
-7.5
14.6
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
OG002
Apremilast 40 mg
Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Units
Counts
Participants
OG00058
OG00157
OG00255
Title
Denominators
Categories
Title
Measurements
OG00041.4(29.6 to 54.2)
OG00173.7(61.0 to 83.4)
OG00247.3(34.7 to 60.2)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Cochran-Mantel-Haenszel
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.0005
Stratified Difference
32.0
2-Sided
95
13.8
47.4
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
OG000
OG002
Cochran-Mantel-Haenszel
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.6878
Stratified Difference
3.7
2-Sided
95
-14.4
21.5
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
Units
Counts
Participants
OG00058
OG00157
OG00255
Title
Denominators
Categories
Title
Measurements
OG00072.4(59.8 to 82.2)
OG00184.2(72.6 to 91.5)
OG00287.3(76.0 to 93.7)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Cochran-Mantel-Haenszel
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.1388
Stratified Difference
11.5
2-Sided
95
-4.1
26.1
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
OG000
OG002
Cochran-Mantel-Haenszel
0.0788
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
Stratified Difference
13.5
2-Sided
95
-1.6
27.7
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
OG002
Apremilast 40 mg
Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Units
Counts
Participants
OG00058
OG00157
OG00255
Title
Denominators
Categories
Title
Measurements
OG00019.0(10.9 to 30.9)
OG00143.9(31.8 to 56.7)
OG00227.3(17.3 to 40.2)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Cochran-Mantel-Haenszel
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.0046
Stratified Difference
24.8
2-Sided
95
7.5
40.1
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
OG000
OG002
Cochran-Mantel-Haenszel
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.4476
Stratified Difference
6.0
95
-9.8
21.6
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
OG002
Apremilast 40 mg
Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Units
Counts
Participants
OG00058
OG00157
OG00255
Title
Denominators
Categories
Title
Measurements
OG00046.6(34.3 to 59.2)
OG00163.2(50.2 to 74.5)
OG00267.3(54.1 to 78.2)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Cochran-Mantel-Haenszel
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.0755
Stratified Difference
16.7
2-Sided
95
-1.4
33.5
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
OG000
OG002
Cochran-Mantel-Haenszel
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.0370
Stratified Difference
19.8
2-Sided
95
1.5
36.4
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Units
Counts
Participants
OG00058
OG00157
OG00255
Title
Denominators
Categories
Title
Measurements
OG00032.8(22.1 to 45.6)
OG00147.4(35.0 to 60.1)
OG00252.7(39.8 to 65.3)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Cochran-Mantel-Haenszel
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.1167
Stratified Difference
14.6
2-Sided
95
-3.3
31.4
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
OG000
OG002
Cochran-Mantel-Haenszel
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.0534
Stratified Difference
18.1
2-Sided
95
-0.3
34.9
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
Apremilast 40 mg
Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Units
Counts
Participants
OG00058
OG00157
OG00255
Title
Denominators
Categories
Title
Measurements
OG00048.3(35.9 to 60.8)
OG00164.9(51.9 to 76.0)
OG00281.8(69.7 to 89.8)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Cochran-Mantel-Haenszel
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.0758
Stratified Difference
16.6
2-Sided
95
-1.5
33.3
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
OG000
OG002
Cochran-Mantel-Haenszel
Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
0.0004
Stratified Difference
32.5
2-Sided
95
14.9
47.5
Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
Superiority
Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
OG002
Apremilast 40 mg
Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Units
Counts
Participants
OG00058
OG00157
OG00255
Title
Denominators
Categories
Any TEAE
Title
Measurements
OG00031
OG00128
OG00236
Any IP-related TEAE
Title
Measurements
OG00012
OG00113
OG00220
Any Severe TEAE
Title
Measurements
OG0004
OG0010
OG0021
Any Serious TEAE
Title
Measurements
OG0002
OG0010
OG0021
Any Serious IP-related TEAE
Title
Measurements
OG0000
OG0010
OG0020
Any TEAE Leading to IP Withdrawal
Title
Measurements
OG0005
OG0010
OG0021
Any TEAE Leading to IP Interruption
Title
Measurements
OG0001
OG0010
OG0020
Any TEAE Leading to Death
Title
Measurements
OG0000
OG0010
OG0020
Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
OG002
Apremilast 40 mg
Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Units
Counts
Participants
OG00058
OG00157
OG00255
Title
Denominators
Categories
Title
Measurements
OG0005
OG0010
OG0021
OG001
Apremilast 40 mg
TEAEs during the apremilast 40 mg BID treatment for participants who received 40 mg apremilast capsules BID only, and participants who initially received placebo BID and switched to 40 mg apremilast capsules BID at Week 12.
OG002
Apremilast 30 mg/Apremilast 40 mg
TEAEs during the apremilast 40 mg BID treatment for participants who initially received 30 mg apremilast BID and switched to apremilast 40 mg BID at Week 12.
Units
Counts
Participants
OG00083
OG00180
OG00211
Title
Denominators
Categories
Any TEAE
Title
Measurements
OG00060
OG00167
OG0028
Any Severe TEAE
Title
Measurements
OG0005
OG0016
OG0020
Any Serious TEAE
Title
Measurements
OG0006
OG0018
OG0021
Any TEAE Leading to Drug Withdrawal
Title
Measurements
OG0003
OG0019
OG0021
Any TEAE Leading to Drug Interruption
Title
Measurements
OG0001
OG0014
OG0020
Any TEAE Leading to Death
Title
Measurements
OG0000
OG0010
OG0020
OG001
Extension Phase: Apremilast 40 mg
Participants who completed 52 weeks of treatment and had a Mayo endoscopy score ≤ 1 at week 52 were eligible to participate in the 52-week extension phase and received 40 mg apremilast BID for an additional 52 weeks. After implementation of Protocol Amendment 4, participants were switched to 30 mg apremilast BID for the remainder of the extension phase.