A Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (UC)
Sponsor
AbbVie (Industry)
Overall Status
Completed
CT.gov ID
NCT02819635
Collaborator
(none)
1,302
496
8
62.6
2.6
0
Study Details
Study Description
Brief Summary
This study was comprised of three substudies. The objective of Substudy 1 was to characterize the dose-response, efficacy, and safety of upadacitinib compared to placebo in inducing clinical remission to identify the induction dose of upadacitinib for further evaluation in Substudy 2. The objective of Substudy 2 was to evaluate the efficacy and safety of upadacitinib compared to placebo in inducing clinical remission in participants. The objective of Substudy 3 was to evaluate the efficacy and safety of upadacitinib compared to placebo in achieving clinical remission in participants who had a response following induction with upadacitinib.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
Substudy 1 was a Phase 2b dose-ranging study designed to evaluate the efficacy and safety of different oral doses of upadacitinib compared to placebo as 8-week induction therapy in participants with moderately to severely active UC. Approximately 250 participants were planned to be randomized 1:1:1:1:1 to the placebo group and 4 upadacitinib doses (7.5, 15, 30, and 45 mg). Randomization was stratified by previous biologic therapy use (yes/no), Baseline corticosteroid use (yes/no), and Baseline Adapted Mayo score (≤ 7 or > 7). The study duration included a Screening Period of up to 5 weeks and an 8-week double-blind (DB) Induction Period. After all randomized participants completed the 8-week induction, a dose-selection analysis of efficacy and safety (selected laboratory parameters) of upadacitinib versus placebo was performed. Based on this dose-selection analysis, one induction dose (upadacitinib 45 mg) was identified for further evaluation in two Phase 3 induction studies, M14-234 Substudy 2 and M14-675 (NCT03653026). During the analysis period, 132 additional participants were randomized into Groups 3 and 4 of Substudy 1 (upadacitinib 30 mg and 45 mg dose groups; approximately 66 participants per dose group). The objectives of enrolling these additional participants were to avoid interrupting the study activities during the analysis period and to support a sufficient number of participants with clinical response to be re-randomized into the maintenance portion in Substudy 3. Substudy 1 main participants are defined as those first 250 randomized 250, and additional participants are defined as those who were randomized after the main participants.
Substudy 2 was a two-part Phase 3 dose-confirming study designed to evaluate the efficacy and safety of oral administration of upadacitinib 45 mg compared to placebo as induction therapy for up to 16 weeks in participants with moderately to severely active UC. Substudy 2 included a Screening Period of up to 5 weeks, Part 1, and Part 2. Part 1 was a randomized, DB, placebo-controlled 8-week induction period. Part 2 was an open-label, 8-week extended treatment period for clinical non-responders from Part 1 of Substudy 2. Part 1 was planned to enroll 462 subjects; actual enrollment was 474 subjects. Eligible participants were randomized in a 2:1 ratio to one of the two treatment groups (DB upadacitinib 45 mg or matching placebo) for 8 weeks. The randomization was stratified by bio-IR status (Biologic inadequate responders [bio-IR] vs Non-biologic-inadequate responders [non-bio-IR], corticosteroid use (yes or no), and Adapted Mayo score (≤ 7 or > 7) at Baseline. Within bio-IR, the randomization was further stratified by number of prior biologic treatments (≤ 1 or > 1). Within non-bio-IR, the randomization was further stratified by previous biologic use (yes or no). Part 2 was an open label, 8-week Extended Treatment Period for those who did not achieve clinical response per Adapted Mayo score at Week 8 in Part 1. All participants received upadacitinib 45 mg.
Substudy 3 was a Phase 3 maintenance study designed to evaluate the efficacy and safety of upadacitinib 15 and 30 mg once daily (QD) compared to placebo in achieving clinical remission per Adapted Mayo score in participants with moderately to severely active UC who achieved clinical response per Adapted Mayo score following induction therapy from Substudy 1, Substudy 2, or Study M14-675. A total of 1,046 subjects who achieved clinical response per Adapted Mayo score after completion of induction treatment or Extended Treatment Period in Study M14-234 Substudy 1, Substudy 2, or Study M14-675 entered Substudy 3, and 1,044 were treated with a blinded treatment assignment for up to 52 weeks. Substudy 3 included 4 cohorts. Cohort 1: 847 participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at either Week 8 or Week 16, and received upadacitinib 15, 30, or 45 mg QD. The treatment groups in Cohort 1 were Group 1: upadacitinib 15 mg QD; Group 2: upadacitinib 30 mg QD; and Group 3: placebo QD. Those who achieved clinical response and received upadacitinib 15 mg QD in Substudy 1 were re-randomized 1:1 to only receive upadacitinib 15 mg QD or placebo QD (treatment Group 1 or 3). Cohort 2: 104 participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3. Cohort 3: 75 participants who received upadacitinib 45 mg QD in Induction Phase and did not achieve clinical response and received upadacitinib 45 mg QD in Extended Treatment in Substudy 2 Part 2 or in Study M14-675 Part 2 and achieved clinical response at Week 16 were re-randomized 1:1 and received blinded upadacitinib 30 mg QD or upadacitinib 15 mg QD in Substudy 3. Cohort 4: 20 participants who received double-blinded treatment of upadacitinib 7.5 mg QD for 8 weeks during Substudy 1 and achieved clinical response at Week 8 continued to receive blinded treatment of upadacitinib 7.5 mg QD in Substudy 3.
Study Design
Study Type:
Interventional
Actual Enrollment
:
1302 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis
Actual Study Start Date
:
Sep 26, 2016
Actual Primary Completion Date
:
Dec 13, 2021
Actual Study Completion Date
:
Dec 13, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: SS1: Placebo During the 8-week induction phase in Substudy 1, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. |
Drug: Placebo
Film-coated tablet for oral administration
|
| Experimental: SS1: Upadacitinib 7.5 mg During the 8-week induction phase in Substudy 1, participants received 7.5 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. |
Drug: Upadacitinib
Film-coated tablet for oral administration
Other Names:
|
| Experimental: SS1: Upadacitinib 15 mg During the 8-week induction phase in Substudy 1, participants received 15 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. |
Drug: Upadacitinib
Film-coated tablet for oral administration
Other Names:
|
| Experimental: SS1: Upadacitinib 30 mg During the 8-week induction phase in Substudy 1, participants received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. |
Drug: Upadacitinib
Film-coated tablet for oral administration
Other Names:
|
| Experimental: SS1: Upadacitinib 45 mg During the 8-week induction phase in Substudy 1, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. |
Drug: Upadacitinib
Film-coated tablet for oral administration
Other Names:
|
| Experimental: SS2: Placebo/Upadacitinib 45 mg During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Participants who did not achieve clinical response at Week 8 of Part 1 were enrolled in an open-label extended treatment period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for an additional 8 weeks. |
Drug: Placebo
Film-coated tablet for oral administration
Drug: Upadacitinib
Film-coated tablet for oral administration
Other Names:
|
| Experimental: SS2: Upadacitinib 45 mg/Upadacitinib 45 mg During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Participants who did not achieve clinical response at Week 8 of Part 1 were enrolled in an open-label expended treatment period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for an additional 8 weeks. |
Drug: Upadacitinib
Film-coated tablet for oral administration
Other Names:
|
| Experimental: SS3: M14-675 clinical responders Participants in Study M14-675 (NCT03653026) who achieved clinical response defined by Adapted Mayo Score at Week 8 or Week 16 in that study and did not meet any study discontinuation criteria were eligible to enroll into Substudy 3. Participants were re-randomized and treated with a blinded treatment assignment (15 mg upadacitinib film-coated tablets once daily by mouth [QD], or 30 mg upadacitinib film-coated tablets QD, or placebo for upadacitinib film-coated tablets QD) for up to 52 weeks. |
Drug: Placebo
Film-coated tablet for oral administration
Drug: Upadacitinib
Film-coated tablet for oral administration
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Substudy 1: Percentage Of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8 [At Week 8]
The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration) The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. For Substudy 1, clinical remission is defined as SFS ≤ 1, RBS of 0, and endoscopic subscore ≤ 1.
- Substudy 2: Percentage Of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8 [At Week 8]
The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration) The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. For Substudy 2, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In Substudy 2, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2.
- Substudy 3: Percentage Of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 52 [At Week 52]
The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. For Substudy 3, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In addition, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2.
Secondary Outcome Measures
- Substudy 1: Percentage Of Participants With Endoscopic Improvement at Week 8 [At Week 8]
Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
- Substudy 1: Percentage Of Participants Achieving Clinical Remission Per Full Mayo Score at Week 8 [At Week 8]
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Full Mayo score (FMS) ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1.
- Substudy 1: Percentage Of Participants Achieving Clinical Response Per Adapted Mayo Score at Week 8 [At Week 8]
The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. Clinical response is defined as a decrease from baseline in the Adapted Mayo score ≥ 2 points and ≥ 30% from baseline, and a decrease in RBS ≥ 1 or an absolute RBS ≤ 1).
- Substudy 1: Percentage Of Participants Achieving Clinical Response Per Partial Mayo Score at Week 2 [At Week 2]
The Partial Mayo Score is a composite score of UC disease activity based on the following 2 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). The overall Partial Mayo score ranges from 0 to 6 with higher scores representing more severe disease. Clinical response per Partial Mayo Score is defined as a decrease in Partial Adapted Mayo score ≥ 2 points and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.
- Substudy 1: Change in Full Mayo Score From Baseline to Week 8 [Baseline (Week 0), Week 8]
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Full Mayo score (FMS) ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1.
- Substudy 1: Percentage Of Participants With Endoscopic Remission at Week 8 [At Week 8]
Endoscopic remission is defined as an endoscopic subscore of 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
- Substudy 1: Percentage Of Participants Who Achieved Histologic Improvement at Week 8 [At Week 8]
The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration. Histologic improvement was defined as decrease from baseline in Geboes score.
- Substudy 2: Percentage Of Participants With Endoscopic Improvement at Week 8 [At Week 8]
Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
- Substudy 2: Percentage Of Participants With Endoscopic Remission at Week 8 [At Week 8]
Endoscopic remission is defined as an endoscopic subscore of 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
- Substudy 2: Percentage Of Participants Achieving Clinical Response Per Adapted Mayo Score at Week 8 [At Week 8]
The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. Clinical response is defined as a decrease from baseline in the Adapted Mayo score ≥ 2 points and ≥ 30% from baseline, and a decrease in RBS ≥ 1 or an absolute RBS ≤ 1).
- Substudy 2: Percentage Of Participants Achieving Clinical Response Per Partial Mayo Score at Week 2 [At Week 2]
The Partial Mayo Score is a composite score of UC disease activity based on the following 2 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). The overall Partial Mayo score ranges from 0 to 6 with higher scores representing more severe disease. Clinical response per Partial Mayo Score is defined as a decrease from Baseline ≥ 1 point and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.
- Substudy 2: Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement at Week 8 [At Week 8]
Histologic-endoscopic mucosal improvement is defined as an endoscopic subscore of 0 or 1 and a Geboes score ≤ 3.1. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.
- Substudy 2: Percentage Of Participants Who Report No Bowel Urgency at Week 8 [At Week 8]
Bowel urgency was assessed by participants in a subject diary completed once a day.
- Substudy 2: Percentage Of Participants Who Reported No Abdominal Pain at Week 8 [At Week 8]
Abdominal pain was assessed by participants in a subject diary completed once a day.
- Substudy 2: Percentage Of Participants Who Achieved Histologic Improvement at Week 8 [At Week 8]
The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration. Histologic improvement was defined as decrease from baseline in Geboes score.
- Substudy 2: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 8 [Baseline (Week 0), Week 8]
The Inflammatory Bowel Disease Questionnaire (IBDQ) is used to assess health-related quality of life (HRQoL) in patients with ulcerative colitis. It consists of 32 questions evaluating bowel and systemic symptoms, as well as emotional and social functions. Each question is answered on a scale from 1 (worst) to 7 (best). The total score ranges from 32 to 224 with higher scores indicating better health-related quality of life. A positive change from Baseline indicates improvement.
- Substudy 2: Percentage Of Participants With Mucosal Healing at Week 8 [At Week 8]
Mucosal healing is defined as an endoscopic score of 0 and Geboes score < 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.
- Substudy 2: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 8 [Baseline (Week 0), Week 8]
The FACIT fatigue questionnaire was developed to assess fatigue associated with anemia. It consists of 13 fatigue-related questions. Each question is answered on a 5-point Likert scale: 0 (not at all); 1 (a little bit); 2 (somewhat); 3 (quite a bit); and 4 (very much). The total score ranges from 0 to 52, where higher scores represent less fatigue, and a positive change from Baseline indicates improvement.
- Substudy 3: Percentage Of Participants With Endoscopic Improvement at Week 52 [At Week 52]
Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
- Substudy 3: Percentage of Participants With Clinical Remission Per Adapted Mayo Score at Week 52 Among Those Who Achieved Clinical Remission at the End of the Induction Treatment [At Week 52]
The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. For Substudy 3, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In addition, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2.
- Substudy 3: Percentage of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Wk 52 and Were Corticosteroid Free for ≥ 90 Days Immediately Preceding Wk 52 Among Those Who Achieved Clinical Remission at the End of the Induction Treatment [At Week 52]
The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. For Substudy 3, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In addition, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2.
- Substudy 3: Percentage of Participants With Endoscopic Improvement at Wk 52 Among Those Who Achieved Endoscopic Improvement at the End of the Induction Treatment [At Week 52]
Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
- Substudy 3: Percentage Of Participants With Endoscopic Remission At Week 52 [At Week 52]
Endoscopic remission is defined as an endoscopic subscore of 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
- Substudy 3: Percentage Of Participants Who Maintained Clinical Response Per Adapted Mayo Score at Wk 52 Among Those Who Achieved Clinical Response at the End of the Induction Treatment [At Week 52]
The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. Clinical response is defined as a decrease from baseline in the Adapted Mayo score ≥ 2 points and ≥ 30% from baseline, and a decrease in RBS ≥ 1 or an absolute RBS ≤ 1).
- Substudy 3: Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement at Week 52 [At Week 52]
Histologic-endoscopic mucosal improvement is defined as an endoscopic subscore of 0 or 1 and a Geboes score ≤ 3.1. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.
- Substudy 3: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 52 [Baseline (Week 0), Week 52]
The Inflammatory Bowel Disease Questionnaire (IBDQ) is used to assess health-related quality of life (HRQoL) in patients with ulcerative colitis. It consists of 32 questions evaluating bowel and systemic symptoms, as well as emotional and social functions. Each question is answered on a scale from 1 (worst) to 7 (best). The total score ranges from 32 to 224 with higher scores indicating better health-related quality of life. A positive change from Baseline indicates improvement.
- Substudy 3: Percentage Of Participants With Mucosal Healing at Week 52 [At Week 52]
Mucosal healing is defined as an endoscopic score of 0 and Geboes score < 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.
- Substudy 3: Percentage Of Participants Who Reported No Bowel Urgency at Week 52 [At Week 52]
Bowel urgency was assessed by participants in a subject diary completed once a day.
- Substudy 3: Percentage Of Participants Who Reported No Abdominal Pain at Week 52 [At Week 52]
Abdominal pain was assessed by participants in a subject diary completed once a day.
- Substudy 3: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 52 [Baseline (Week 0), Week 52]
The FACIT fatigue questionnaire was developed to assess fatigue associated with anemia. It consists of 13 fatigue-related questions. Each question is answered on a 5-point Likert scale: 0 (not at all); 1 (a little bit); 2 (somewhat); 3 (quite a bit); and 4 (very much). The total score ranges from 0 to 52, where higher scores represent less fatigue, and a positive change from Baseline indicates improvement.
Eligibility Criteria
Criteria
Ages Eligible for Study:
16 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Note: Adolescent participants who are 16 or 17 years old will be eligible to participate if approved by the country or regulatory/health authority. If approval has not been granted, only participants ≥18 years old will be enrolled. Adolescents must weigh ≥ 40 kilograms and meet the definition of Tanner Stage 5 at Screening Visit.
-
Diagnosis of ulcerative colitis for 90 days or greater prior to Baseline, confirmed by colonoscopy during the Screening Period, with exclusion of current infection, colonic dysplasia and/or malignancy. Appropriate documentation of biopsy results consistent with the diagnosis of UC, in the assessment of the Investigator, must be available.
-
Active ulcerative colitis with an Adapted Mayo score of 5 to 9 points and endoscopic sub score of 2 to 3 (confirmed by central reader).
-
Demonstrated an inadequate response to, loss of response to, or intolerance to at least one of the following treatments including: oral aminosalicylates, corticosteroids, immunosuppressants, and/or biologic therapies in the opinion of the investigator.
Note: Participants who have had inadequate response, loss of response to conventional therapy, but have not failed biologic therapy (Non-bio-IR) and have received a prior biologic for up to 1 year may be enrolled, however they must have discontinued the biologic for reasons other than inadequate response or intolerance (e.g., change of insurance, well controlled disease) and must meet criteria for inadequate response, loss of response or intolerance to aminosalicylates, corticosteroids, and/or immunosuppressants as defined above.
-
If female, participant must meet the criteria for Contraception Recommendations
-
Female participants of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit prior to study drug dosing.
Exclusion Criteria:
-
Participant with current diagnosis of Crohn's disease (CD) or diagnosis of indeterminate colitis (IC)
-
Current diagnosis of fulminant colitis and/or toxic megacolon
-
Participant with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy
-
Received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to Baseline
-
Participant on azathioprine or 6-mercaptopurine within 10 days of Baseline
-
Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period.
-
Participant with previous exposure to Janus Activated Kinase (JAK) inhibitor (e.g., tofacitinib, baricitinib, filgotinib, upadacitinib).
-
Screening laboratory and other analyses show any abnormal results meeting the exclusion criteria
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Birmingham Gastroenterology Associates P.C /ID# 151276 | Birmingham | Alabama | United States | 35209 |
| 2 | East View Medical Research, LLC /ID# 171183 | Mobile | Alabama | United States | 36606 |
| 3 | CB Flock Research Corporation /ID# 165980 | Mobile | Alabama | United States | 36608 |
| 4 | Delsol Research Management, Ll /Id# 170131 | Chandler | Arizona | United States | 85224 |
| 5 | Digestive Disease Consultants, A Division of Arizona Digestive Health, P.C /ID# 211885 | Mesa | Arizona | United States | 85206 |
| 6 | Arizona Arthritis & Rheumatology Research, PLLC /ID# 169822 | Sun City | Arizona | United States | 85306 |
| 7 | Adobe Clinical Research LLC /ID# 155250 | Tucson | Arizona | United States | 85712 |
| 8 | University of Arizona /ID# 150553 | Tucson | Arizona | United States | 85724 |
| 9 | Citrus Valley Gastroenterology /ID# 151914 | Covina | California | United States | 91722-3797 |
| 10 | Newport Huntington Medical Group /ID# 217005 | Huntington Beach | California | United States | 92648-5994 |
| 11 | UC San Diego Health System /ID# 155185 | La Jolla | California | United States | 92093 |
| 12 | United Medical Doctors /ID# 207464 | Los Alamitos | California | United States | 90720-3309 |
| 13 | TLC Clinical Research Inc /ID# 216829 | Los Angeles | California | United States | 90048 |
| 14 | Gastrointestinal Biosciences Clinical Trials, LLC /ID# 157080 | Los Angeles | California | United States | 90067-2001 |
| 15 | Facey Medical Foundation /ID# 203133 | Mission Hills | California | United States | 91345 |
| 16 | United Medical Doctors - Murrieta /ID# 151211 | Murrieta | California | United States | 92563 |
| 17 | InSite Digestive Health Care - Oxnard /ID# 163414 | Oxnard | California | United States | 93030 |
| 18 | Inland Empire Clinical Trials, LLC /ID# 216038 | Rialto | California | United States | 92377 |
| 19 | San Diego Clinical Trials /ID# 212120 | San Diego | California | United States | 92120 |
| 20 | Medical Assoc Research Grp /ID# 169148 | San Diego | California | United States | 92123 |
| 21 | Univ of California San Francis /ID# 164581 | San Francisco | California | United States | 94158 |
| 22 | Delta Waves, Inc. /ID# 151721 | Colorado Springs | Colorado | United States | 80918 |
| 23 | South Denver Gastroenterology /ID# 151223 | Lone Tree | Colorado | United States | 80124 |
| 24 | Western States Clinical Res /ID# 158076 | Wheat Ridge | Colorado | United States | 80033-2896 |
| 25 | Western Connecticut Medical Group /ID# 169210 | Danbury | Connecticut | United States | 06810 |
| 26 | Medical Research Center of CT /ID# 150482 | Hamden | Connecticut | United States | 06518 |
| 27 | Gastro Florida /ID# 155245 | Clearwater | Florida | United States | 33756 |
| 28 | Moonshine Research Center, Inc /ID# 152533 | Doral | Florida | United States | 33166 |
| 29 | Universal Axon Clinical Research /ID# 213461 | Doral | Florida | United States | 33166 |
| 30 | Palmetto Research, LLC /ID# 151716 | Hialeah | Florida | United States | 33016 |
| 31 | Nature Coast Clinical Research - Inverness /ID# 154064 | Inverness | Florida | United States | 34452-4717 |
| 32 | Encore Borland-Groover Clinical Research /Id# 170912 | Jacksonville | Florida | United States | 32256 |
| 33 | SIH Research Mumtaz, Inc /ID# 163319 | Kissimmee | Florida | United States | 34741-4161 |
| 34 | Cfagi Llc /Id# 202017 | Maitland | Florida | United States | 32751-6108 |
| 35 | University of Miami /ID# 215441 | Miami | Florida | United States | 33136 |
| 36 | Advanced Pharma /ID# 151719 | Miami | Florida | United States | 33147 |
| 37 | New Horizon Research Center /ID# 152474 | Miami | Florida | United States | 33165-3372 |
| 38 | Crystal Pharmacology Research /ID# 151841 | Miami | Florida | United States | 33165 |
| 39 | Coral Research Clinic /ID# 150444 | Miami | Florida | United States | 33186-4643 |
| 40 | Advanced Research Institute, Inc /ID# 163098 | New Port Richey | Florida | United States | 34653 |
| 41 | Endoscopic Research, Inc. /ID# 151720 | Orlando | Florida | United States | 32803 |
| 42 | Omega Research Maitland, LLC /ID# 200269 | Orlando | Florida | United States | 32808 |
| 43 | Clinical Research Trials of Florida, Inc. /ID# 201790 | Tampa | Florida | United States | 33607 |
| 44 | University of South Florida /ID# 214493 | Tampa | Florida | United States | 33612 |
| 45 | AdventHealth Tampa /ID# 200272 | Tampa | Florida | United States | 33613-4680 |
| 46 | Gastroenterology Associates of Central Georgia, LLC /ID# 165782 | Macon | Georgia | United States | 31201 |
| 47 | Infinite Clinical Trials /ID# 215340 | Riverdale | Georgia | United States | 30274 |
| 48 | Atlanta Gastroenterology Spec /ID# 150548 | Suwanee | Georgia | United States | 30024 |
| 49 | Next Innovative Clinical Research - Chicago /ID# 216060 | Chicago | Illinois | United States | 60605-2168 |
| 50 | The University of Chicago DCAM /ID# 150547 | Chicago | Illinois | United States | 60637 |
| 51 | NorthShore University HealthSystem /ID# 150555 | Evanston | Illinois | United States | 60201 |
| 52 | Northwest Health Care Associates /ID# 151590 | Hoffman Estates | Illinois | United States | 60169 |
| 53 | Carle Foundation Hospital /ID# 151137 | Urbana | Illinois | United States | 61801 |
| 54 | MediSphere Medical Research Center /ID# 152064 | Evansville | Indiana | United States | 47714-8011 |
| 55 | Indianapolis Gastroenterology /ID# 162901 | Indianapolis | Indiana | United States | 46237 |
| 56 | University of Iowa Hospitals and Clinics /ID# 157058 | Iowa City | Iowa | United States | 52242 |
| 57 | Cotton-O'Neil Clinical Res Ctr /ID# 167182 | Topeka | Kansas | United States | 66606 |
| 58 | Tri-State Gastroenterology /ID# 169811 | Crestview Hills | Kentucky | United States | 41017 |
| 59 | Houma Digestive Health Special /ID# 151844 | Houma | Louisiana | United States | 70360 |
| 60 | Nola Research Works, LLC /ID# 153356 | New Orleans | Louisiana | United States | 70115 |
| 61 | Louisana Research Center, LLC /ID# 150446 | Shreveport | Louisiana | United States | 71105-6800 |
| 62 | University of Maryland Med Ctr /ID# 150449 | Baltimore | Maryland | United States | 21201 |
| 63 | Gastro Center of Maryland /ID# 200022 | Columbia | Maryland | United States | 21045 |
| 64 | Massachusetts General Hospital /ID# 165676 | Boston | Massachusetts | United States | 02114 |
| 65 | University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 151140 | Ann Arbor | Michigan | United States | 48109 |
| 66 | Huron Gastroenterology Assoc /ID# 152710 | Ann Arbor | Michigan | United States | 48197 |
| 67 | Clin Res Inst of Michigan, LLC /ID# 153027 | Chesterfield | Michigan | United States | 48047 |
| 68 | Revival Research Institute, LLC /ID# 207280 | Southfield | Michigan | United States | 48034-1659 |
| 69 | Center for Digestive Health /ID# 161984 | Troy | Michigan | United States | 48098-6363 |
| 70 | Gastroenterology Associates of Western Michigan, PLC d.b.a. West Michigan Clinic /ID# 157484 | Wyoming | Michigan | United States | 49519 |
| 71 | Mayo Clinic - Rochester /ID# 151677 | Rochester | Minnesota | United States | 55905-0001 |
| 72 | Minnesota Gastroenterology PA /ID# 151678 | Saint Paul | Minnesota | United States | 55114 |
| 73 | University of Mississippi Medical Center /ID# 213139 | Jackson | Mississippi | United States | 39216-4500 |
| 74 | Southern Therapy and Advanced Research (STAR) LLC /ID# 170712 | Jackson | Mississippi | United States | 39216 |
| 75 | Washington University-School of Medicine /ID# 150485 | Saint Louis | Missouri | United States | 63110 |
| 76 | Las Vegas Medical Research /ID# 153044 | Las Vegas | Nevada | United States | 89113 |
| 77 | Dartmouth-Hitchcock Medical Center /ID# 150549 | Lebanon | New Hampshire | United States | 03756 |
| 78 | AGA Clinical Research Associates, LLC /ID# 153040 | Egg Harbor Township | New Jersey | United States | 08234 |
| 79 | Atlantic Digestive Health Inst /ID# 150447 | Morristown | New Jersey | United States | 07960 |
| 80 | Rutgers Robert Wood Johnson /ID# 155248 | New Brunswick | New Jersey | United States | 08901 |
| 81 | Duplicate_University of New Mexico Department of Internal Medicine /ID# 214396 | Albuquerque | New Mexico | United States | 87131 |
| 82 | Montefiore Medical Center - Moses Campus /ID# 150543 | Bronx | New York | United States | 10467 |
| 83 | Advantage Clinical Trials /ID# 163938 | Bronx | New York | United States | 10468 |
| 84 | NY Scientific /ID# 152707 | Brooklyn | New York | United States | 11235 |
| 85 | NYU Langone Long Island Clinical Research Association /ID# 155272 | Great Neck | New York | United States | 11021 |
| 86 | Columbia Univ Medical Center /ID# 163410 | New York | New York | United States | 10032-3725 |
| 87 | DiGiovanna Institute for Medical Education & Research /ID# 201533 | North Massapequa | New York | United States | 11758 |
| 88 | Premier Medical Group - GI Division /ID# 153357 | Poughkeepsie | New York | United States | 12601 |
| 89 | Gastoenterology Group of Rochester /ID# 151079 | Rochester | New York | United States | 14618-5703 |
| 90 | Richmond University Medical Center /ID# 201859 | Staten Island | New York | United States | 10310-1664 |
| 91 | Digestive Health Partners, P.A /ID# 167237 | Asheville | North Carolina | United States | 28801 |
| 92 | Atrium Health Carolinas Medical Center /ID# 156971 | Charlotte | North Carolina | United States | 28203 |
| 93 | Charlotte Gastroenterology and Hepatology, PLLC /ID# 150545 | Charlotte | North Carolina | United States | 28207 |
| 94 | Atlantic Gastroenterology Clinical Research /ID# 151899 | Greenville | North Carolina | United States | 27834 |
| 95 | Clinical Trials of America /ID# 153448 | Winston-Salem | North Carolina | United States | 27103 |
| 96 | Wake Forest Baptist Medical Center /ID# 150448 | Winston-Salem | North Carolina | United States | 27157-0001 |
| 97 | Plains Clinical Research Center, LLC /ID# 170290 | Fargo | North Dakota | United States | 58104-5925 |
| 98 | Consultants for Clinical Research /ID# 151679 | Cincinnati | Ohio | United States | 45219 |
| 99 | University of Cincinnati /ID# 164582 | Cincinnati | Ohio | United States | 45267-0585 |
| 100 | The Ohio State University /ID# 169416 | Columbus | Ohio | United States | 43210 |
| 101 | Optimed Research, Ltd. /ID# 169696 | Columbus | Ohio | United States | 43235 |
| 102 | Hometown Urgent Care and Resea /ID# 200065 | Dayton | Ohio | United States | 45424 |
| 103 | Dayton Gastroenterology, Inc. /ID# 167631 | Englewood | Ohio | United States | 45415 |
| 104 | Great Lakes Medical Research, LLC /ID# 201772 | Mentor | Ohio | United States | 44060-6211 |
| 105 | Ohio Clinical Research Partner /ID# 154068 | Mentor | Ohio | United States | 44060 |
| 106 | Hightower Clinical /ID# 216337 | Oklahoma City | Oklahoma | United States | 73102 |
| 107 | Digestive Disease Specialists /ID# 201056 | Oklahoma City | Oklahoma | United States | 73112 |
| 108 | Options Health Research, LLC /ID# 150554 | Tulsa | Oklahoma | United States | 74104 |
| 109 | Healthcare Research Consultant /ID# 163100 | Tulsa | Oklahoma | United States | 74135 |
| 110 | Northwest Gastroenterology Clinic /ID# 152527 | Portland | Oregon | United States | 97210 |
| 111 | Guthrie Medical Group, PC /ID# 150481 | Sayre | Pennsylvania | United States | 18840 |
| 112 | Penn State Health Colonnade /ID# 150259 | State College | Pennsylvania | United States | 16803-2309 |
| 113 | Pharmacorp Clinical Trials /ID# 153354 | Charleston | South Carolina | United States | 29412 |
| 114 | Gastroenterology Associates, P.A. of Greenville /ID# 150541 | Greenville | South Carolina | United States | 29615-3593 |
| 115 | Gastro One /ID# 151144 | Germantown | Tennessee | United States | 38138 |
| 116 | East Tennessee Research Institute /ID# 203610 | Johnson City | Tennessee | United States | 37604 |
| 117 | Quality Medical Research /ID# 203426 | Nashville | Tennessee | United States | 37211 |
| 118 | Vanderbilt University Medical Center /ID# 153355 | Nashville | Tennessee | United States | 37232-0011 |
| 119 | TX Clinical Research Institute /ID# 151526 | Arlington | Texas | United States | 76012 |
| 120 | Inquest Clinical Research /ID# 164635 | Baytown | Texas | United States | 77521-2415 |
| 121 | Texas Digestive Disease Consultants /ID# 209947 | Cedar Park | Texas | United States | 78613-5028 |
| 122 | Texas Digestive Disease Consultants /ID# 209804 | Cedar Park | Texas | United States | 78613 |
| 123 | Baylor Scott & White Center for Inflammatory Bowel Diseases /ID# 200770 | Dallas | Texas | United States | 75246 |
| 124 | DHAT Research Institute /ID# 151218 | Garland | Texas | United States | 75044-2208 |
| 125 | Vilo Research Group Inc /ID# 212624 | Houston | Texas | United States | 77017-2337 |
| 126 | CliniCore International, LLC /ID# 152062 | Houston | Texas | United States | 77027-6812 |
| 127 | Baylor College of Medicine - Baylor Medical Center /ID# 150486 | Houston | Texas | United States | 77030-3411 |
| 128 | Centex Studies, Inc. - Houston /ID# 201216 | Houston | Texas | United States | 77058 |
| 129 | GI Specialists of Houston /ID# 202327 | Houston | Texas | United States | 77070-4347 |
| 130 | Caprock Gastro Research, LLC /ID# 214754 | Lubbock | Texas | United States | 79424-3017 |
| 131 | Clinical Associates in Research Therapeutics of America, LLC /ID# 201260 | San Antonio | Texas | United States | 78212 |
| 132 | Southern Star Research Institute, LLC /ID# 169396 | San Antonio | Texas | United States | 78229-5390 |
| 133 | Carl R. Meisner Medical Clinic /ID# 171061 | Sugar Land | Texas | United States | 77478 |
| 134 | Baylor Scott & White Center for Diagnostic Medicine /ID# 204499 | Temple | Texas | United States | 76508 |
| 135 | Tyler Research Institute, LLC /ID# 169146 | Tyler | Texas | United States | 75701-4464 |
| 136 | Gastro Health & Nutrition - Victoria /ID# 167761 | Victoria | Texas | United States | 77904 |
| 137 | HP Clinical Research /ID# 163939 | Bountiful | Utah | United States | 84010 |
| 138 | Advanced Research Institute /ID# 162624 | Ogden | Utah | United States | 84403 |
| 139 | Utah Gastroenternology - St. Mark's Office /ID# 163101 | Salt Lake City | Utah | United States | 84124 |
| 140 | Velocity Clinical Research - Salt Lake City /ID# 163181 | West Jordan | Utah | United States | 84088 |
| 141 | Ctr for Gastrointestinal Healt /ID# 153360 | Franklin | Virginia | United States | 23851 |
| 142 | Emeritas Research Group, LLC /ID# 150258 | Leesburg | Virginia | United States | 20176 |
| 143 | Washington Gastroenterology /ID# 163629 | Bellevue | Washington | United States | 98004 |
| 144 | Virginia Mason Medical Center /ID# 153026 | Seattle | Washington | United States | 98101 |
| 145 | The Polyclinic /ID# 164369 | Seattle | Washington | United States | 98122-4201 |
| 146 | The Vancouver Clinic, INC. PS /ID# 162333 | Vancouver | Washington | United States | 98664 |
| 147 | Aurora Medical Center - Grafto /ID# 151717 | Grafton | Wisconsin | United States | 53024 |
| 148 | Wisconsin Center for Advanced Research, a division of GI Associates, LLC /ID# 151838 | Milwaukee | Wisconsin | United States | 53215 |
| 149 | Medical College of Wisconsin /ID# 151843 | Milwaukee | Wisconsin | United States | 53226-3522 |
| 150 | Cardio Alem /ID# 211280 | San Isidro | Buenos Aires | Argentina | 1642 |
| 151 | Gedyt /ID# 210015 | Ciudad Autonoma de Buenos Aire | Ciuadad Autonoma De Buenos Aires | Argentina | 1115 |
| 152 | Mautalen Salud e Investigacion /ID# 171173 | Ciudad Autonoma de Buenos Aire | Ciuadad Autonoma De Buenos Aires | Argentina | 1128 |
| 153 | Hospital Britanico de Buenos Aires /ID# 209495 | Ciudad Autonoma de Buenos Aire | Ciuadad Autonoma De Buenos Aires | Argentina | 1280 |
| 154 | Sanatorio 9 de Julio /ID# 150189 | San Miguel de Tucuman | Tucuman | Argentina | 4000 |
| 155 | Hospital Privado Univesitario /ID# 164185 | Cordoba | Argentina | 5016 | |
| 156 | Macquarie University Hospital /ID# 211951 | Macquarie University | New South Wales | Australia | 2109 |
| 157 | Mater Misericordiae Limited /ID# 212685 | South Brisbane | Queensland | Australia | 4101 |
| 158 | Griffith University /ID# 211952 | Southport | Queensland | Australia | 4222 |
| 159 | Monash Medical Centre /ID# 150206 | Clayton | Victoria | Australia | 3168 |
| 160 | St Vincent's Hospital Melbourne /ID# 152472 | Fitzroy Melbourne | Victoria | Australia | 3065 |
| 161 | Fiona Stanley Hospital /ID# 211640 | Murdoch | Western Australia | Australia | 6150 |
| 162 | Ordensklinikum Linz GmbH Barmherzige Schwestern /ID# 150305 | Linz | Oberoesterreich | Austria | 4010 |
| 163 | Klinik Landstrasse /ID# 162866 | Vienna | Wien | Austria | 1030 |
| 164 | Medizinische Universitaet Wien /ID# 150614 | Vienna | Wien | Austria | 1090 |
| 165 | Landeskrankenhaus Salzburg-Universitätsklinikum der PMU (LKH) /ID# 150306 | Salzburg | Austria | 5020 | |
| 166 | Vitebsk Regional Advanced Clin /ID# 169612 | Витебск | Belarus | 210001 | |
| 167 | Universitair Ziekenhuis Leuven /ID# 150332 | Leuven | Vlaams-Brabant | Belgium | 3000 |
| 168 | AZ Maria Middelares /ID# 150331 | Gent | Belgium | 9000 | |
| 169 | AZ-Delta /ID# 150330 | Roeselare | Belgium | 8800 | |
| 170 | University Clinical Centre of the Republic of Srpska /ID# 150209 | Banja Luka | Republika Srpska | Bosnia and Herzegovina | 78000 |
| 171 | University Clinical Centre of the Republic of Srpska /ID# 150706 | Banja Luka | Republika Srpska | Bosnia and Herzegovina | 78000 |
| 172 | University Clinical Center Tuzla /ID# 150211 | Tuzla | Tuzlanski | Bosnia and Herzegovina | 75000 |
| 173 | University Clinical Hospital Mostar /ID# 150705 | Mostar | Bosnia and Herzegovina | 88000 | |
| 174 | Clinical Center University of Sarajevo /ID# 150208 | Sarajevo | Bosnia and Herzegovina | 71000 | |
| 175 | Instituto Goiano de Gastroenterologia e Endoscopia Digestiva /ID# 153742 | Goiânia | Goias | Brazil | 74535-170 |
| 176 | Hospital Nossa Senhora das Graças /ID# 152480 | Curitiba | Parana | Brazil | 80810-040 |
| 177 | Hospital de Clinicas de Porto Alegre /ID# 153743 | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-903 |
| 178 | Upeclin Fmb - Unesp /Id# 152485 | Botucatu | Sao Paulo | Brazil | 18618-686 |
| 179 | Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto - USP /ID# 152484 | Ribeirão Preto | Sao Paulo | Brazil | 14051-140 |
| 180 | Faculdade de Medicina do ABC /ID# 152481 | Santo André | Sao Paulo | Brazil | 09060-870 |
| 181 | Kaiser Clinica e Hospital Dia /ID# 152483 | Sao Jose Do Rio Preto | Sao Paulo | Brazil | 15015-110 |
| 182 | University of Calgary /ID# 151821 | Calgary | Alberta | Canada | T2N 4Z6 |
| 183 | Allen Whey Khye Lim Professional Corporation /ID# 211168 | Edmonton | Alberta | Canada | T5R 1W2 |
| 184 | University of Alberta - Zeidler Ledcor Centre /ID# 151100 | Edmonton | Alberta | Canada | T6G 2X8 |
| 185 | Covenant Health /ID# 158930 | Edmonton | Alberta | Canada | T6K 4B2 |
| 186 | Okanagan Clinical Trials /ID# 153178 | Kelowna | British Columbia | Canada | V1Y 1Z9 |
| 187 | Percuro Clinical Research, Ltd /ID# 150367 | Victoria | British Columbia | Canada | V8V 3M9 |
| 188 | Hamilton Health Sciences - McMaster University Medical Centre /ID# 150365 | Hamilton | Ontario | Canada | L8S 4K1 |
| 189 | Ottawa Hospital Research Institute /ID# 151820 | Ottawa | Ontario | Canada | K1H 8L6 |
| 190 | Medicor Research Inc /ID# 151101 | Sudbury | Ontario | Canada | P3A 1W8 |
| 191 | Toronto Digestive Disease Asso /ID# 150363 | Vaughan | Ontario | Canada | L4L 4Y7 |
| 192 | CISSS de la Monteregie /ID# 159215 | Greenfield Park | Quebec | Canada | J4V 2H1 |
| 193 | CISSS de Chaudière-Appalaches, Hôpital Hotel-Dieu de Lévis /ID# 150361 | Levis | Quebec | Canada | G6V 3Z1 |
| 194 | Recherche GCP Research /ID# 151822 | Montreal | Quebec | Canada | H1M 1B1 |
| 195 | Centre Hospitalier de l'Universite de Montreal - CRCHUM /ID# 167169 | Montreal | Quebec | Canada | H2X 0A9 |
| 196 | Montreal General Hospital - McGill University Health Centre /ID# 170012 | Montréal | Quebec | Canada | H3G 1A4 |
| 197 | CIUSSS de l'Estrie - CHUS /ID# 150366 | Sherbrooke | Quebec | Canada | J1G 2E8 |
| 198 | Research Group /ID# 203176 | Santiago | Region Metropolitana De Santiago | Chile | 2540364 |
| 199 | M y F Estudios Clínicos /ID# 200107 | Santiago | Region Metropolitana Santiago | Chile | 7750495 |
| 200 | Centro de Investigaciones Clínicas Viña del Mar /ID# 150212 | Viña del Mar | Valparaíso | Chile | 2540488 |
| 201 | Hospital Guillermo Grant Benavente de Concepción /ID# 212424 | Concepción | Chile | 4070038 | |
| 202 | CTR Estudios Clinicos /ID# 200110 | Providencia | Chile | 7500571 | |
| 203 | Hospital Clinico Universidad De Los Andes /ID# 207422 | Santiago | Chile | 7501504 | |
| 204 | The First Affiliated Hospital, Sun Yat-sen University /ID# 150455 | Guangzhou | Guangdong | China | 510080 |
| 205 | The Sixth Affiliated Hosp Sun /ID# 150456 | Guangzhou | Guangdong | China | 510655 |
| 206 | Affiliated Taihe Hospital of Hubei University of Medicine /ID# 216405 | Shiyan | Hubei | China | 442700 |
| 207 | Tongji Hospital Tongji Medical College Huazhong University of Science and Techno /ID# 167088 | Wuhan | Hubei | China | 430022 |
| 208 | Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 167078 | Wuhan | Hubei | China | 430022 |
| 209 | The First Affiliated Hospital of Nanchang University /ID# 211750 | Nanchang | Jiangxi | China | 330006 |
| 210 | The First Hospital of Jilin University /ID# 209986 | Changchun | Jilin | China | 130021 |
| 211 | Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 150461 | Shanghai | Shanghai | China | 200065 |
| 212 | Shanghai Tenth People's Hospital /ID# 150460 | Shanghai | Shanghai | China | 200072 |
| 213 | Renji Hospital, Shanghai Jiaotong University School of Medicine /ID# 165815 | Shanghai | Shanghai | China | 200127 |
| 214 | The second Affiliated hospital of Zhejiang University school of Medicine /ID# 165807 | Hangzhou | Zhejiang | China | 310009 |
| 215 | Sir Run Run Shaw Hospital,Meical School Zhejiang University /ID# 150454 | Hangzhou | Zhejiang | China | 310018 |
| 216 | Xiangya Hospital Central South University /ID# 167229 | Changsha | China | 410008 | |
| 217 | West China Hospital, Sichuan University /ID# 167040 | Chengdu | China | 610041 | |
| 218 | Shengjing Hospital of China Medical University /ID# 166920 | Shenyang | China | 110022 | |
| 219 | Tianjin Medical University General Hospital /ID# 170604 | Tianjin | China | 300052 | |
| 220 | Instituto Medico de Alta Tecnologia Oncomédica S.A /ID# 207042 | Monteria | Cordoba | Colombia | 230002 |
| 221 | Corporacion Hospitalaria Juan Cuidad Sede Denominada Hospital Universitario Mayo /ID# 151564 | Bogota DC | Cundinamarca | Colombia | 111221 |
| 222 | Hospital Universitario de San /ID# 155387 | Medellin | Colombia | ||
| 223 | Clinical Hospital Dubrava /ID# 150213 | Zagreb | Grad Zagreb | Croatia | 10000 |
| 224 | Klinicki bolnicki centar Zagreb /ID# 150225 | Zagreb | Grad Zagreb | Croatia | 10000 |
| 225 | Klinicki bolnicki centar Zagreb /ID# 150709 | Zagreb | Grad Zagreb | Croatia | 10000 |
| 226 | Poliklinika Solmed /ID# 211483 | Zagreb | Grad Zagreb | Croatia | 10000 |
| 227 | Duplicate_Klinicki bolnicki centar Osijek /ID# 150216 | Osijek | Osjecko-baranjska Zupanija | Croatia | 31000 |
| 228 | Klinicki bolnicki centar Rijeka /ID# 150708 | Rijeka | Primorsko-goranska Zupanija | Croatia | 51000 |
| 229 | Klinicki bolnicki centar Split /ID# 213988 | Split | Splitsko-dalmatinska Zupanija | Croatia | 21000 |
| 230 | Zadar General Hospital /ID# 150221 | Zadar | Croatia | 23000 | |
| 231 | Hepato-Gastroenterologie HK, s.r.o. /ID# 150912 | Hradec Kralove | Czechia | 500 12 | |
| 232 | CTCenter MaVe s.r.o. /ID# 150904 | Olomouc | Czechia | 779 00 | |
| 233 | ARTROSCAN s.r.o. /ID# 150401 | Ostrava | Czechia | 722 00 | |
| 234 | Nemocnice Pardubickeho kraje, a.s. /ID# 213539 | Pardubice | Czechia | 530 03 | |
| 235 | Nemocnice Milosrdnych sester sv. Karla Boromejskeho v Praze /ID# 216221 | Praha | Czechia | 118 33 | |
| 236 | Axon Clinical, s.r.o. /ID# 152479 | Praha | Czechia | 140 00 | |
| 237 | ISCARE a.s. /ID# 209278 | Praha | Czechia | 190 00 | |
| 238 | East Tallinn Central Hospital /ID# 150417 | Kesklinna Linnaosa | Harjumaa | Estonia | 10138 |
| 239 | North Estonia Medical Centre /ID# 160870 | Mustamäe Linnaosa | Harjumaa | Estonia | 13419 |
| 240 | Tartu University Hospital /ID# 150418 | Tartu Linn | Tartumaa | Estonia | 50406 |
| 241 | West Tallinn Central Hospital /ID# 150419 | Tallinn | Estonia | 10617 | |
| 242 | Tampere University Hospital /ID# 150114 | Tampere | Pirkanmaa | Finland | 33520 |
| 243 | Duplicate_Helsinki Univ Central Hospital /ID# 150407 | Helsinki | Finland | 00290 | |
| 244 | Keski-Suomen Sairaala Nova /ID# 155666 | Jyvaskyla | Finland | 40620 | |
| 245 | Laakarikeskus Ikioma /ID# 150121 | Mikkeli | Finland | 50100 | |
| 246 | Turku University Hospital /ID# 168301 | Turku | Finland | 20520 | |
| 247 | Chu de Nice-Hopital L'Archet Ii /Id# 152606 | Nice | Alpes-Maritimes | France | 06200 |
| 248 | HCL - Hôpital Lyon Sud /ID# 152539 | Pierre Benite CEDEX | Auvergne-Rhone-Alpes | France | 69495 |
| 249 | CHU Hopital Nord /ID# 163508 | Marseille | Bouches-du-Rhone | France | 13915 |
| 250 | CHRU Lille - Hopital Claude Huriez /ID# 152607 | Lille | Hauts-de-France | France | 59037 |
| 251 | CHU Montpellier - Hôpital Saint Eloi /ID# 200006 | Montpellier Cedex 5 | Herault | France | 34295 |
| 252 | CHU Amiens-Picardie Site Sud /ID# 163456 | Amiens CEDEX 1 | Somme | France | 80054 |
| 253 | CHD Vendée- La Roche-sur-Yon - Les Oudairies /ID# 154452 | La Roche Sur Yon | France | 85000 | |
| 254 | CHU de Saint-Etienne, Hopital Nord /ID# 154453 | SAINT-ETIENNE Cedex 1 | France | 42270 | |
| 255 | Universitatsklinikum Mannheim /ID# 150173 | Mannheim | Baden-Wuerttemberg | Germany | 68167 |
| 256 | Universitaetsklinimum Tuebingen /ID# 150767 | Tubingen | Baden-Wuerttemberg | Germany | 72076 |
| 257 | Universitatsklinikum Munster /ID# 150158 | Munster | Niedersachsen | Germany | 48149 |
| 258 | Gastroenterologische Gemeinschaftspraxis Herne /ID# 214574 | Herne | Nordrhein-Westfalen | Germany | 44623 |
| 259 | Zentrum für Gastroenterologie Saar MVZ GmbH /ID# 215811 | Saarbrücken | Saarland | Germany | 66111 |
| 260 | Universitaetsklinikum Schleswig-Holstein Campus Kiel /ID# 161981 | Kiel | Schleswig-Holstein | Germany | 24105 |
| 261 | MVZ fuer Gastroenterlogie am Bayerischen Platz /ID# 150766 | Berlin | Germany | 10825 | |
| 262 | Agaplesion Markus Krankenhaus /ID# 161982 | Frankfurt am Main | Germany | 60431 | |
| 263 | Medizinisches Versorgungszentrum Portal 10 /ID# 207135 | Muenster | Germany | 48155 | |
| 264 | Praxis medicum /ID# 150166 | Wiesbaden | Germany | 65189 | |
| 265 | General Hospital of Athens Laiko /ID# 208669 | Athens | Attiki | Greece | 11527 |
| 266 | General Hospital of Chest Diseases of Athens SOTIRIA /ID# 202100 | Athens | Attiki | Greece | 11527 |
| 267 | University General Hospital of Heraklion PA.G.N.I /ID# 150250 | Heraklion | Kriti | Greece | 71500 |
| 268 | General Hospital of Athens Evaggelismos and Ophthalmiatrio of Athens Polyclinic /ID# 150309 | Athens | Greece | 10676 | |
| 269 | University General Hospital of Ioannina /ID# 164248 | Ioannina | Greece | 45500 | |
| 270 | Theageneio Anticancer Hospital /ID# 163896 | Thessaloniki | Greece | 54639 | |
| 271 | General Hospital of Thessaloniki Hippokrateio /ID# 209521 | Thessaloniki | Greece | 54642 | |
| 272 | Markusovszky Egyetemi Oktatokorhaz /ID# 150313 | Szombathely | Vas | Hungary | 9700 |
| 273 | Bekes Megyei Kozponti Korhaz /ID# 151572 | Bekescsaba | Hungary | 5600 | |
| 274 | Semmelweis Egyetem /ID# 150312 | Budapest | Hungary | 1085 | |
| 275 | Meditres Kft. /ID# 151521 | Kecskemet | Hungary | 6000 | |
| 276 | Soproni Erzsebet Oktato Korhaz es Rehabilitacios Intezet /ID# 151523 | Sopron | Hungary | 9400 | |
| 277 | Mentahaz Maganorvosi Kozpont /ID# 205884 | Szekesfehervar | Hungary | 8000 | |
| 278 | Beaumont Hospital /ID# 150321 | Beaumont | Dublin | Ireland | D09 XR63 |
| 279 | St James Hospital /ID# 150320 | Dublin 8 | Dublin | Ireland | D08 NHY1 |
| 280 | St Vincent's University Hospital /ID# 150318 | Elm Park | Dublin | Ireland | D04 T6F4 |
| 281 | Mercy University Hospital /ID# 151529 | Cork | Ireland | T12 WE28 | |
| 282 | University Hospital Galway /ID# 150319 | Galway | Ireland | H91 YR71 | |
| 283 | Soroka University Medical Center /ID# 156561 | Be'er Sheva | HaDarom | Israel | 8443901 |
| 284 | Rambam Health Care Campus /ID# 150325 | Haifa | Israel | 3109601 | |
| 285 | Shaare Zedek Medical Center /ID# 161677 | Jerusalem | Israel | 91031 | |
| 286 | Hadassah Medical Center-Hebrew University /ID# 165118 | Jerusalem | Israel | 91120 | |
| 287 | Azienda Ospedaliera San Camillo Forlanini /ID# 151360 | Rome | Lazio | Italy | 00152 |
| 288 | ASST Rhodense/Presidio Ospedaliero di Rho /ID# 216610 | Rho | Milano | Italy | 20017 |
| 289 | Istituto Clinico Humanitas /ID# 151361 | Rozzano | Milano | Italy | 20089 |
| 290 | Fondazione PTV Policlinico Tor Vergata /ID# 150338 | Rome | Roma | Italy | 00133 |
| 291 | Presidio Columbus-Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Un /ID# 150333 | Rome | Roma | Italy | 00168 |
| 292 | IRCCS Ospedale Sacro Cuore Don Calabria /ID# 201725 | Negrar | Verona | Italy | 37024 |
| 293 | IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 150337 | Bologna | Italy | 40138 | |
| 294 | ASST Fatebenefratelli Sacco - Ospedale Fatebenefratelli e Oftalmico /ID# 150602 | Milano | Italy | 20121 | |
| 295 | Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 150334 | Milan | Italy | 20122 | |
| 296 | A.O. Ospedali Riuniti Villa Sofia - Cervello /ID# 150253 | Palermo | Italy | 90146 | |
| 297 | Aichi Medical University Hospital /ID# 151993 | Nagakute-shi | Aichi | Japan | 480-1195 |
| 298 | Nagoya City University Hospital /ID# 151950 | Nagoya shi | Aichi | Japan | 467-8602 |
| 299 | Nagoya University Hospital /ID# 152709 | Nagoyashi | Aichi | Japan | 4668560 |
| 300 | Toyohashi Municipal Hospital /ID# 171457 | Toyohashi-shi | Aichi | Japan | 441-8570 |
| 301 | Ieda Hospital /ID# 157781 | Toyota-shi | Aichi | Japan | 470-1219 |
| 302 | Hirosaki National Hospital /ID# 152763 | Hirosaki-shi | Aomori | Japan | 036-8545 |
| 303 | Tokatsu Tsujinaka Hospital /ID# 214962 | Abiko-shi | Chiba | Japan | 270-1168 |
| 304 | Tsujinaka Hospital Kashiwanoha /ID# 209130 | Kashiwa-shi | Chiba | Japan | 277-0871 |
| 305 | Toho University Sakura Medical Center /ID# 151936 | Sakura-shi | Chiba | Japan | 285-8741 |
| 306 | Juntendo University Urayasu Hospital /ID# 208781 | Urayasu-shi | Chiba | Japan | 279-0021 |
| 307 | Fukui Prefectural Hospital /ID# 210448 | Fukui-shi | Fukui | Japan | 910-8526 |
| 308 | Fukuoka University Chikushi Hospital /ID# 152628 | Chikushino-shi | Fukuoka | Japan | 818-8502 |
| 309 | Saiseikai Fukuoka Genaral Hospital /ID# 209479 | Fukuoka-shi | Fukuoka | Japan | 810-0001 |
| 310 | Kyushu University Hospital /ID# 152526 | Fukuoka-shi | Fukuoka | Japan | 812-8582 |
| 311 | Kitakyushu Municipal Med Ctr /ID# 152588 | Kitakyushu | Fukuoka | Japan | 8020077 |
| 312 | Kurume University Hospital /ID# 151976 | Kurume-shi | Fukuoka | Japan | 830-0011 |
| 313 | Ogaki Municipal Hospital /ID# 208225 | Ogaki-shi | Gifu | Japan | 503-8502 |
| 314 | NHO Fukuyama Medical Center /ID# 206293 | Fukuyama-shi | Hiroshima | Japan | 720-8520 |
| 315 | Hiroshima University Hospital /ID# 151951 | Hiroshima-shi | Hiroshima | Japan | 734-8551 |
| 316 | Asahikawa Medical University Hospital /ID# 170289 | Asahikawa-shi | Hokkaido | Japan | 078-8510 |
| 317 | Obihiro kosei Hospital /ID# 210412 | Obihiro-shi | Hokkaido | Japan | 080-0024 |
| 318 | Sapporo Tokushukai Hospital /ID# 209397 | Sapporo-shi | Hokkaido | Japan | 004-0041 |
| 319 | Hokkaido P.W.F.A.C. Sapporo-Kosei General Hospital /ID# 151506 | Sapporo-shi | Hokkaido | Japan | 060-0033 |
| 320 | Sapporo Medical University Hospital /ID# 206492 | Sapporo-shi | Hokkaido | Japan | 060-8543 |
| 321 | Sapporo Higashi Tokushukai Hospital /ID# 208487 | Sapporo-shi | Hokkaido | Japan | 065-0033 |
| 322 | Aoyama Clinic /ID# 152049 | Kobe-shi | Hyogo | Japan | 650-0015 |
| 323 | Hyogo College of Medicine College Hospital /Id# 152434 | Nishinomiya-shi | Hyogo | Japan | 663-8501 |
| 324 | National Hospital Organization Mito Medical Center /ID# 152631 | Higashi Ibaraki-gun | Ibaraki | Japan | 311-3193 |
| 325 | Kanazawa University Hospital /ID# 205099 | Kanazawa-shi | Ishikawa | Japan | 920-8641 |
| 326 | Iwate Medical University Uchimaru Medical Center /ID# 203411 | Morioka-shi | Iwate | Japan | 020-8505 |
| 327 | Imamura General Hospital /ID# 227134 | Kagoshima-shi | Kagoshima | Japan | 890-0064 |
| 328 | Idzuro Imamura Hospital /ID# 206024 | Kagoshima-shi | Kagoshima | Japan | 892-0824 |
| 329 | Sameshima Hospital /ID# 206672 | Kagoshima-shi | Kagoshima | Japan | 892-0846 |
| 330 | St. Marianna University School of Medicine Hospital /ID# 208654 | Kawasaki-shi | Kanagawa | Japan | 216-8511 |
| 331 | Yokohama City University Medical Center /ID# 169899 | Yokohama shi | Kanagawa | Japan | 232-0024 |
| 332 | Showa University Fujigaoka Hospital /ID# 208222 | Yokohama-shi | Kanagawa | Japan | 227-8501 |
| 333 | Japanese Red Cross Kyoto Daiichi Hosital /ID# 152359 | Kyoto-shi | Kyoto | Japan | 605-0981 |
| 334 | Kyoto University Hospital /ID# 211758 | Kyoto-shi | Kyoto | Japan | 606-8507 |
| 335 | Mie University Hospital /ID# 205362 | Tsu-shi | Mie | Japan | 514-8507 |
| 336 | Yokkaichi Hazu Medical Center /ID# 214347 | Yokkaichi-shi | Mie | Japan | 510-0016 |
| 337 | National Hospital Organization Sendai Medical Center /ID# 209527 | Sendai-shi | Miyagi | Japan | 983-8520 |
| 338 | NHO Nagasaki Medical Center /ID# 209531 | Omura-shi | Nagasaki | Japan | 856-8562 |
| 339 | Kenseikai Dongo Hospital /ID# 208100 | Yamatotakada-shi | Nara | Japan | 635-0022 |
| 340 | Saiseikai Niigata Hospital /ID# 209916 | Niigata-shi | Niigata | Japan | 950-1104 |
| 341 | Niigata University Medical & Dental Hospital /ID# 218048 | Niigata-shi | Niigata | Japan | 951-8520 |
| 342 | Ishida Clinic of IBD and Gastroenterology /ID# 210117 | Oita-shi | Oita | Japan | 870-0823 |
| 343 | Chikuba Hospital for Proctological and Gastrointestinal Diseases /ID# 157821 | Kurashiki-shi | Okayama | Japan | 710-0142 |
| 344 | Okayama University Hospital /ID# 217923 | Okayama-shi | Okayama | Japan | 700-8558 |
| 345 | Kinshukai Infusion Clinic /ID# 207864 | Osaka-shi | Osaka | Japan | 530-0011 |
| 346 | Kitano Hospital /ID# 210395 | Osaka-shi | Osaka | Japan | 530-8480 |
| 347 | Osaka City General Hospital /ID# 152704 | Osaka-shi | Osaka | Japan | 534-0021 |
| 348 | Japanese Red Cross Osaka Hospital /ID# 209476 | Osaka-shi | Osaka | Japan | 543-8555 |
| 349 | Osaka City University Hospital /ID# 152682 | Osaka-shi | Osaka | Japan | 545-8586 |
| 350 | Toyonaka Municipal Hospital /ID# 217079 | Toyonaka-shi | Osaka | Japan | 560-0055 |
| 351 | Saga University Hospital /ID# 209268 | Saga-shi | Saga | Japan | 849-8501 |
| 352 | Saitama Medical Center /ID# 152031 | Kawagoe-shi | Saitama | Japan | 350-8550 |
| 353 | Tokitokai Tokito clinic /ID# 152677 | Saitama-shi | Saitama | Japan | 336-0963 |
| 354 | National Hospital Organization Higashi-Ohmi General Medical Center /ID# 210709 | Higashi-ohmi-shi | Shiga | Japan | 527-8505 |
| 355 | Shimane University Hospital /ID# 208899 | Izumo-shi | Shimane | Japan | 693-8501 |
| 356 | Hamamatsu University Hospital /ID# 205708 | Hamamatsu-shi | Shizuoka | Japan | 431-3192 |
| 357 | NHO Shizuoka Medical Center /ID# 163572 | Sunto-gun | Shizuoka | Japan | 411-8611 |
| 358 | Tokyo Medical And Dental University Hospital /ID# 152016 | Bunkyo-ku | Tokyo | Japan | 113-8519 |
| 359 | St.Luke's International Hospital /ID# 208074 | Chuo-ku | Tokyo | Japan | 104-8560 |
| 360 | Tokai University Hachioji Hospital /ID# 152587 | Hachioji-shi | Tokyo | Japan | 192-0032 |
| 361 | Teikyo University Hospital /ID# 208897 | Itabashi-ku | Tokyo | Japan | 173-8606 |
| 362 | Kitasato University Kitasato Institute Hospital /ID# 152686 | Minato-ku | Tokyo | Japan | 108-8642 |
| 363 | Kyorin University Hospital /ID# 153194 | Mitaka-shi | Tokyo | Japan | 181-8611 |
| 364 | Center Hospital of the National Center for Global Health and Medicine /ID# 209267 | Shinjuku-ku | Tokyo | Japan | 162-8655 |
| 365 | Tokyo Women's Medical University Hospital /ID# 205977 | Shinjuku-ku | Tokyo | Japan | 162-8666 |
| 366 | Yamagata University Hospital /ID# 171454 | Yamagata-shi | Yamagata | Japan | 990-9585 |
| 367 | Tokuyama Central Hospital /ID# 216993 | Shunan-shi | Yamaguchi | Japan | 745-8522 |
| 368 | Yamanashi Prefectural Central Hospital /ID# 151908 | Kofu-shi | Yamanashi | Japan | 400-8506 |
| 369 | Shoyukai Fujita Gastroenterological Hospital /ID# 216492 | Takatsuki-shi | Japan | 569-0086 | |
| 370 | Hayang University GuriHospital /ID# 150344 | Guri | Gyeonggido | Korea, Republic of | 11923 |
| 371 | CHA University Bundang Medical Center /ID# 159479 | Seongnam si | Gyeonggido | Korea, Republic of | 13496 |
| 372 | The Catholic University of Korea, ST. Vincent's Hospital /ID# 150347 | Suwon | Gyeonggido | Korea, Republic of | 16247 |
| 373 | Kangbuk Samsung Hospital /ID# 150348 | Seoul | Seoul Teugbyeolsi | Korea, Republic of | 03181 |
| 374 | Yonsei University Health System Severance Hospital /ID# 159478 | Seoul | Seoul Teugbyeolsi | Korea, Republic of | 03722 |
| 375 | Dong-A University Hospital /ID# 159480 | Busan | Korea, Republic of | 49201 | |
| 376 | Pusan National University Hospital /ID# 159481 | Busan | Korea, Republic of | 49241 | |
| 377 | Yeungnam University Medical Center /ID# 150345 | Daegu | Korea, Republic of | 42415 | |
| 378 | Asan Medical Center /ID# 150900 | Seoul | Korea, Republic of | 05505 | |
| 379 | Samsung Medical Center /ID# 150346 | Seoul | Korea, Republic of | 06351 | |
| 380 | Pauls Stradins Clinical University Hospital /ID# 151409 | Riga | Latvia | 1002 | |
| 381 | Riga East Clinical University Hospital /ID# 150354 | Riga | Latvia | LV-1079 | |
| 382 | Hospital of Lithuanian University of Health Sciences Kaunas Clinics /ID# 150357 | Kaunas | Lithuania | 50161 | |
| 383 | Klaipeda Seamens Hospital /ID# 154319 | Klaipeda | Lithuania | 92288 | |
| 384 | Klaipeda University Hospital /ID# 158862 | Klaipeda | Lithuania | 92288 | |
| 385 | Vilnius University Hospital /ID# 154318 | Vilnius | Lithuania | LT-08661 | |
| 386 | Hospital Sultanah Bahiyah /ID# 151687 | Alor Setar | Kedah | Malaysia | 05460 |
| 387 | Universiti Kebangsaan Malaysia (UKM) Medical Centre /ID# 151689 | Kuala Lumpur | Selangor | Malaysia | 56000 |
| 388 | Hospital Ampang /ID# 151298 | Ampang | Malaysia | 68000 | |
| 389 | Uni Malaya MC /ID# 150359 | Kuala Lumpur | Malaysia | 59100 | |
| 390 | Morales Vargas Centro de Investigacion S.C. /ID# 211325 | Leon | Guanajuato | Mexico | 37000 |
| 391 | Clinica de Investigacion en Reumatologia y Obesidad S.C. /ID# 150710 | Guadalajara | Jalisco | Mexico | 44650 |
| 392 | Centro Regiomontano de Estudios Clínicos ROMA S.C /ID# 150256 | Monterrey | Nuevo Leon | Mexico | 64610 |
| 393 | Radboud Universitair Medisch Centrum /ID# 151700 | Nijmegen | Gelderland | Netherlands | 6525 GA |
| 394 | Erasmus Medisch Centrum /ID# 150308 | Rotterdam | Zuid-Holland | Netherlands | 3015 GD |
| 395 | Academisch Medisch Centrum /ID# 150647 | Amsterdam | Netherlands | 1105 AZ | |
| 396 | Leids Universitair Medisch Centrum /ID# 152624 | Leiden | Netherlands | 2333 ZA | |
| 397 | Universitair Medisch Centrum Utrecht /ID# 152775 | Utrecht | Netherlands | 3584 CX | |
| 398 | Akershus universitetssykehus /ID# 150317 | Nordbyhagen | Akershus | Norway | 1474 |
| 399 | Universitetssykehuset Nord-Norge /ID# 152835 | Tromsø | Troms | Norway | 9019 |
| 400 | Gastromed /Id# 216197 | Torun | Kujawsko-pomorskie | Poland | 87-100 |
| 401 | Centrum Zdrowia MDM /ID# 150351 | Warszawa | Mazowieckie | Poland | 00-635 |
| 402 | Centralny Szpital Kliniczny MSWiA w Warszawie /ID# 150580 | Warszawa | Mazowieckie | Poland | 02-507 |
| 403 | Centrum Medyczne Reuma Park /ID# 150349 | Warszawa | Mazowieckie | Poland | 02-665 |
| 404 | NZOZ Vivamed /ID# 216742 | Warszawa | Mazowieckie | Poland | 03-580 |
| 405 | Instytut Pomnik - Centrum Zdrowia Dziecka /ID# 215732 | Warszawa | Mazowieckie | Poland | 04-730 |
| 406 | Endoskopia Sp. z o.o. /ID# 150765 | Sopot | Pomorskie | Poland | 81-756 |
| 407 | Hospital da Senhora da Oliveira Guimaraes, EPE /ID# 151607 | Guimaraes | Braga | Portugal | 4835-044 |
| 408 | Centro Hospitalar de Entre Douro e Vouga /ID# 152335 | Santa Maria Da Feira | Porto | Portugal | 4520-211 |
| 409 | Unidade Local de Saúde do Alto Minho, EPE - Hospital Conde de Bertiandos /ID# 151609 | Ponte de Lima | Viana Do Castelo | Portugal | 4990-041 |
| 410 | Hospital Garcia de Orta, EPE /ID# 151613 | Almada | Portugal | 2805-267 | |
| 411 | CCA Braga - Hospital de Braga /ID# 151608 | Braga | Portugal | 4710-243 | |
| 412 | Centro Hospitalar Universitario Lisboa Central, EPE - Hospital dos Capuchos /ID# 151611 | Lisboa | Portugal | 1169-050 | |
| 413 | Centro Hospitalar Universitário de Lisboa Norte, EPE - Hospital de Santa Maria /ID# 151606 | Lisboa | Portugal | 1649-035 | |
| 414 | Centro Hospitalar Universitario de Sao Joao, EPE /ID# 151610 | Porto | Portugal | 4200-319 | |
| 415 | School of Medicine University of Puerto Rico-Medical Science Campus /ID# 150358 | San Juan | Puerto Rico | 00935 | |
| 416 | Immanuel Kant Baltic Federal University /ID# 200719 | Kaliningrad | Kaliningradskaya Oblast | Russian Federation | 236016 |
| 417 | NW State Medical Univ na Mechn /ID# 169322 | St. Petersburg | Leningradskaya Oblast | Russian Federation | 191015 |
| 418 | Perm Clinical Center of the Federal Medical and Biological Agency /ID# 150386 | Perm | Permskiy Kray | Russian Federation | 614109 |
| 419 | Medical Company Hepatolog /ID# 200197 | Samara | Samarskaya Oblast | Russian Federation | 443063 |
| 420 | LLC Novaya Klinika /ID# 208107 | Pyatigorsk | Stavropol Skiy Kray | Russian Federation | 357500 |
| 421 | Kazan State Medical University /ID# 166042 | Kazan | Tatarstan, Respublika | Russian Federation | 420012 |
| 422 | Olla-Med Clinic /ID# 215332 | Moscow | Russian Federation | 105554 | |
| 423 | City Clinical Hospital #24 /ID# 150395 | Moscow | Russian Federation | 127015 | |
| 424 | Republican hospital named after V.A. Baranov /ID# 206506 | Petrozavodsk | Russian Federation | 185019 | |
| 425 | Euromedservice /ID# 203800 | Pushkin | Russian Federation | 196603 | |
| 426 | Duplicate_Stavropol State Medical Univ /ID# 150387 | Stavropol | Russian Federation | 355017 | |
| 427 | Clinical Hosp Center Zvezdara /ID# 150427 | Belgrade | Beograd | Serbia | 11000 |
| 428 | Military Medical Academy /ID# 150429 | Belgrade | Beograd | Serbia | 11000 |
| 429 | University Clinical Center Serbia /ID# 150428 | Belgrade | Beograd | Serbia | 11000 |
| 430 | Clin Hosp Ctr Bezanijska Kosa /ID# 150426 | Belgrade | Beograd | Serbia | 11080 |
| 431 | University Clinical Center of Nis /ID# 151903 | NIS | Nisavski Okrug | Serbia | 18000 |
| 432 | University Clinical Center Kragujevac /ID# 150430 | Kragujevac | Sumadijski Okrug | Serbia | 34000 |
| 433 | Clinical Center Vojvodina /ID# 150764 | Novi Sad | Vojvodina | Serbia | 21000 |
| 434 | General Hospital Leskovac /ID# 217880 | Leskovac | Serbia | 16000 | |
| 435 | National University Hospital /ID# 150453 | Singapore | Singapore | 119074 | |
| 436 | Gleneagles Medical Centre /ID# 206018 | Singapore | Singapore | 258499 | |
| 437 | Tan Tock Seng Hospital /ID# 150443 | Singapore | Singapore | 308433 | |
| 438 | Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica /ID# 150868 | Banska Bystrica | Slovakia | 975 17 | |
| 439 | Medak s.r.o. /ID# 150480 | Bratislava | Slovakia | 851 01 | |
| 440 | Slovak Research Center Team Me /ID# 150257 | Ilava | Slovakia | 019 01 | |
| 441 | B+B MED, s.r.o. /ID# 150471 | Kosice | Slovakia | 040 01 | |
| 442 | Fakultna nemocnica s poliklinikou Nove Zamky /ID# 211370 | Nove Zamky | Slovakia | 940 34 | |
| 443 | GASTRO I., s.r.o. /ID# 150472 | Presov | Slovakia | 080 01 | |
| 444 | MD Search /ID# 167293 | Boksburg North | Gauteng | South Africa | 1460 |
| 445 | Clinresco Centers /ID# 163622 | Johannesburg | Gauteng | South Africa | 1619 |
| 446 | Lenasia Clinical Trial Centre /ID# 214344 | Johannesburg | Gauteng | South Africa | 1820 |
| 447 | Wits Clinical Research , Wits Health Consortium (PTY) Ltd /ID# 150785 | Johannesburg | Gauteng | South Africa | 2193 |
| 448 | Wits Clinical Research Site /ID# 150496 | Johannesburg | Gauteng | South Africa | 2193 |
| 449 | Spoke Research Inc /ID# 162202 | CAPE TOWN Milnerton | Western Cape | South Africa | 7441 |
| 450 | Kingsbury Hospital /ID# 150497 | Cape Town | Western Cape | South Africa | 7708 |
| 451 | Private Practice Dr MN Rajabally /ID# 155144 | Cape Town | Western Cape | South Africa | 7800 |
| 452 | Hospital Clínico Universitario de Santiago-CHUS /ID# 151065 | Santiago de Compostela | A Coruna | Spain | 15706 |
| 453 | Hospital Unversitario Marques de Valdecilla /ID# 216620 | Santander | Cantabria | Spain | 39008 |
| 454 | Hospital Universitario Dr. Negrin /ID# 203937 | Las Palmas de Gran Canaria | Las Palmas | Spain | 35019 |
| 455 | Hospital Universitario A Coruna - CHUAC /ID# 203911 | A Coruna | Spain | 15006 | |
| 456 | Hospital Clinic de Barcelona /ID# 150612 | Barcelona | Spain | 08036 | |
| 457 | Hospital Universitario Reina Sofia /ID# 151066 | Cordoba | Spain | 14004 | |
| 458 | Hospital Universitario Ramon y Cajal /ID# 151067 | Madrid | Spain | 28034 | |
| 459 | Hospital Universitario La Paz /ID# 214539 | Madrid | Spain | 28046 | |
| 460 | Hospital Universitario de Salamanca /ID# 150509 | Salamanca | Spain | 37711 | |
| 461 | Hospital Universitario y Politecnico La Fe /ID# 150611 | Valencia | Spain | 46026 | |
| 462 | Sahlgrenska University Hospital /ID# 151496 | Gothenburg | Vastra Gotalands Lan | Sweden | 413 45 |
| 463 | Universitätsspital Basel /ID# 161731 | Basel | Basel-Stadt | Switzerland | 4031 |
| 464 | Kantonsspital St. Gallen /ID# 152599 | St. Gallen | Sankt Gallen | Switzerland | 9007 |
| 465 | Universitätsspital Zürich /ID# 152591 | Zürich | Zuerich | Switzerland | 8091 |
| 466 | Inselspital, Universitätsspital Bern /ID# 152590 | Bern | Switzerland | 3010 | |
| 467 | Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 150575 | Kaohsiung | Taiwan | 807 | |
| 468 | China Medical University Hospital /ID# 150571 | Taichung City | Taiwan | 40447 | |
| 469 | Chung Shan Medical University Hospital /ID# 150573 | Taichung | Taiwan | 40201 | |
| 470 | National Cheng Kung University Hospital /ID# 151749 | Tainan | Taiwan | 704 | |
| 471 | National Taiwan University Hospital /ID# 150574 | Taipei City | Taiwan | 100 | |
| 472 | Taipei Veterans General Hosp /ID# 151748 | Taipei City | Taiwan | 11217 | |
| 473 | Erciyes University Medical Fac /ID# 150129 | Melikgazi | Kayseri | Turkey | 38030 |
| 474 | Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty /ID# 150125 | Istanbul | Turkey | 34098 | |
| 475 | Umraniye Training and Res Hosp /ID# 162659 | Istanbul | Turkey | 34764 | |
| 476 | Marmara University Medical Fac /ID# 213969 | Istanbul | Turkey | 34899 | |
| 477 | Mersin University Medical /ID# 157849 | Mersin | Turkey | 33343 | |
| 478 | Gazi Universitesi Tip Fakultes /ID# 150127 | Yenimahalle | Turkey | 06560 | |
| 479 | Medical Center of the "Health /ID# 151274 | Vinnytsya | Vinnytska Oblast | Ukraine | 21009 |
| 480 | Municipal Enterprise "I.I. Mechnikov Dnipropetrovsk Regional Clinical Hospital" /ID# 207723 | Dnipro | Ukraine | 49005 | |
| 481 | CNCE of Kharkiv Regional Council Regional Clinical Hospital /ID# 206940 | Kharkiv | Ukraine | 61058 | |
| 482 | PE PMC Acinus, Medical and Diagnostic Center /ID# 217216 | Kropyvnytskyi | Ukraine | 25006 | |
| 483 | Kyiv Municipal Clinical Hospital #18 /ID# 150372 | Kyiv | Ukraine | 01030 | |
| 484 | Medical Center CONSILIUM MEDICAL /ID# 217446 | Kyiv | Ukraine | 04050 | |
| 485 | CNPE of Kyiv Regional Council Kyiv Regional Hospital /ID# 217372 | Kyiv | Ukraine | 04073 | |
| 486 | Lviv Regional Clinical Hospital /ID# 150375 | Lviv | Ukraine | 79010 | |
| 487 | Municipal Non-Commercial Enterprise Odesa Regional Clinical Hospital of the Od /ID# 151275 | Odesa | Ukraine | 65025 | |
| 488 | CNE Vinnytsya Regional Clinical Hospital named after N.I.Pirogov /ID# 216297 | Vinnytsia | Ukraine | 21028 | |
| 489 | Royal Devon and Exeter NHS Trust Hospital /ID# 150379 | Exeter | Devon | United Kingdom | EX2 5DW |
| 490 | Hampshire Hospitals NHS Foundation Trust /ID# 150380 | Basingstoke | Essex | United Kingdom | RG24 9NA |
| 491 | Barts Health NHS Trust /ID# 150384 | London | London, City Of | United Kingdom | E1 2ES |
| 492 | NHS Greater Glasgow and Clyde /ID# 163787 | Glasgow | Scotland | United Kingdom | G12 0XH |
| 493 | Royal United Hospitals Bath /ID# 151532 | Bath | United Kingdom | BA1 3NG | |
| 494 | University Hospitals Birmingham NHS Foundation Trust /ID# 150382 | Birmingham | United Kingdom | B15 2TH | |
| 495 | Calderdale and Huddersfield NHS Foundation Trust /ID# 217658 | Huddersfield | United Kingdom | HX3 0PW | |
| 496 | St George's University Hospitals NHS Foundation Trust /ID# 208374 | Tooting | United Kingdom | SW17 0QT |
Sponsors and Collaborators
- AbbVie
Investigators
- Study Director: ABBVIE INC., AbbVie
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
AbbVie
ClinicalTrials.gov Identifier:
NCT02819635
Other Study ID Numbers:
- M14-234
- 2016-000641-31
First Posted:
Jun 30, 2016
Last Update Posted:
Jun 30, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by AbbVie
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Intent-to-treat (ITT) analysis set: Substudy 1 (all randomized participants who received at least one dose of study drug in Substudy 1); Substudy 2 (all randomized participants who received at least one dose of doubleblinded study drug in Part 1 and all participants who received at least one dose of upadacitinib 45 mg in Part 2); Substudy 3 (all participants who received at least one dose of study drug in Substudy 3) |
| Arm/Group Title | SS1: Placebo | SS1: Upadacitinib 7.5 mg | SS1: Upadacitinib 15 mg | SS1: Upadacitinib 30 mg | SS1: Upadacitinib 45 mg | SS2: Placebo/Upadacitinib 45 mg | SS2: Upadacitinib 45 mg/Upadacitinib 45 mg | SS3: M14-675 Clinical Responders | SS3: Placebo | SS3: UPA 7.5 mg | SS3: UPA 15 mg | SS3: UPA 30 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | During the 8-week induction phase in Substudy 1, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 7.5 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 15 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. | During the 8-week induction phase in Substudy 1, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Participants who did not achieve clinical response at Week 8 of Part 1 were enrolled in an open-label extended treatment period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for an additional 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Participants who did not achieve clinical response at Week 8 of Part 1 were enrolled in an open-label expended treatment period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for an additional 8 weeks. | Participants in Study M14-675 (NCT03653026) who achieved clinical response defined by Adapted Mayo Score at Week 8 or Week 16 in that study and did not meet any study discontinuation criteria were eligible to enroll into Substudy 3. Participants were treated with a blinded treatment assignment (15 mg upadacitinib film-coated tablets once daily by mouth [QD], or 30 mg upadacitinib film-coated tablets QD, or placebo for upadacitinib film-coated tablets QD) for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at either Week 8 or Week 16, while receiving upadacitinib 15, 30, or 45 mg QD and those who achieved clinical response while receiving upadacitinib 15 mg QD in Substudy 1 and were randomized to placebo QD in Substudy 3 for up to 52 weeks. In addition, participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3 for up to 52 weeks. | Participants who received double-blinded treatment of upadacitinib 7.5 mg QD for 8 weeks during Substudy 1 and achieved clinical response at Week 8 continued to receive blinded treatment of upadacitinib 7.5 mg QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at either Week 8 or Week 16, while receiving upadacitinib 15, 30, or 45 mg QD and those who achieved clinical response while receiving upadacitinib 15 mg QD in Substudy 1 and were randomized to upadacitinib 15 mg QD in Substudy 3 for up to 52 weeks. In addition, participants who received upadacitinib 45 mg QD in Induction Phase and did not achieve clinical response and received upadacitinib 45 mg QD in Extended Treatment in Substudy 2 Part 2 or in Study M14-675 Part 2 and achieved clinical response at Week 16 and were randomized to upadacitinib 15 mg QD in Substudy 3. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at either Week 8 or Week 16, while receiving upadacitinib 15, 30, or 45 mg QD and those who achieved clinical response while receiving upadacitinib 15 mg QD in Substudy 1 and were randomized to upadacitinib 30 mg QD in Substudy 3 for up to 52 weeks. In addition, participants who received upadacitinib 45 mg QD in Induction Phase and did not achieve clinical response and received upadacitinib 45 mg QD in Extended Treatment in Substudy 2 Part 2 or in Study M14-675 Part 2 and achieved clinical response at Week 16 and were randomized to upadacitinib 30 mg QD in Substudy 3. |
| Period Title: Substudy 1 and Substudy 2, Part 1 | ||||||||||||
| STARTED | 46 | 47 | 49 | 117 | 123 | 155 | 319 | 446 | 0 | 0 | 0 | 0 |
| COMPLETED | 41 | 45 | 45 | 105 | 113 | 135 | 306 | 446 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 5 | 2 | 4 | 12 | 10 | 20 | 13 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Substudy 1 and Substudy 2, Part 1 | ||||||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 85 | 59 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 74 | 47 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 11 | 12 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Substudy 1 and Substudy 2, Part 1 | ||||||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 386 | 20 | 324 | 316 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 140 | 11 | 218 | 248 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 246 | 9 | 106 | 68 |
Baseline Characteristics
| Arm/Group Title | SS1: Placebo | SS1: Upadacitinib 7.5 mg | SS1: Upadacitinib 15 mg | SS1: Upadacitinib 30 mg | SS1: Upadacitinib 45 mg | SS2: Placebo/Upadacitinib 45 mg | SS2: Upadacitinib 45 mg/Upadacitinib 45 mg | SS3: M14-675 Clinical Responders | Total |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | During the 8-week induction phase in Substudy 1, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 7.5 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 15 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. | During the 8-week induction phase in Substudy 1, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Participants who did not achieve clinical response at Week 8 of Part 1 were enrolled in an open-label extended treatment period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for an additional 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Participants who did not achieve clinical response at Week 8 of Part 1 were enrolled in an open-label expended treatment period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for an additional 8 weeks. | Participants in Study M14-675 (NCT03653026) who achieved clinical response defined by Adapted Mayo Score at Week 8 or Week 16 in that study and did not meet any study discontinuation criteria were eligible to enroll into Substudy 3. Participants were treated with a blinded treatment assignment (15 mg upadacitinib film-coated tablets once daily by mouth [QD], or 30 mg upadacitinib film-coated tablets QD, or placebo for upadacitinib film-coated tablets QD) for up to 52 weeks. | Total of all reporting groups |
| Overall Participants | 46 | 47 | 49 | 117 | 123 | 155 | 319 | 446 | 1302 |
| Age (years) [Mean (Standard Deviation) ] | |||||||||
| Mean (Standard Deviation) [years] |
42.3
(13.29)
|
41.7
(14.58)
|
46.0
(13.58)
|
42.9
(14.44)
|
41.6
(14.19)
|
44.3
(14.64)
|
43.6
(14.04)
|
42.1
(14.42)
|
42.9
(14.27)
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
17
37%
|
24
51.1%
|
19
38.8%
|
47
40.2%
|
44
35.8%
|
58
37.4%
|
121
37.9%
|
170
38.1%
|
500
38.4%
|
| Male |
29
63%
|
23
48.9%
|
30
61.2%
|
70
59.8%
|
79
64.2%
|
97
62.6%
|
198
62.1%
|
276
61.9%
|
802
61.6%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||||||
| White |
37
80.4%
|
36
76.6%
|
38
77.6%
|
88
75.2%
|
90
73.2%
|
101
65.2%
|
206
64.6%
|
302
67.7%
|
898
69%
|
| Black or African American |
0
0%
|
3
6.4%
|
1
2%
|
3
2.6%
|
2
1.6%
|
4
2.6%
|
12
3.8%
|
15
3.4%
|
40
3.1%
|
| Asian |
8
17.4%
|
7
14.9%
|
10
20.4%
|
23
19.7%
|
28
22.8%
|
46
29.7%
|
95
29.8%
|
124
27.8%
|
341
26.2%
|
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
1
0.9%
|
0
0%
|
2
1.3%
|
0
0%
|
1
0.2%
|
4
0.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.3%
|
1
0.2%
|
2
0.2%
|
| Multiple |
1
2.2%
|
1
2.1%
|
0
0%
|
2
1.7%
|
3
2.4%
|
2
1.3%
|
5
1.6%
|
3
0.7%
|
17
1.3%
|
| Average Stool Frequency Subscore (units on a scale) [Mean (Standard Deviation) ] | |||||||||
| Mean (Standard Deviation) [units on a scale] |
2.56
(0.667)
|
2.62
(0.600)
|
2.68
(0.565)
|
2.61
(0.613)
|
2.58
(0.648)
|
2.52
(0.668)
|
2.60
(0.624)
|
2.55
(0.623)
|
2.58
(0.628)
|
| Average Rectal Bleeding Subscore (units on a scale) [Mean (Standard Deviation) ] | |||||||||
| Mean (Standard Deviation) [units on a scale] |
1.66
(1.034)
|
1.61
(1.027)
|
1.55
(0.915)
|
1.51
(0.975)
|
1.49
(0.960)
|
1.76
(0.994)
|
1.71
(1.046)
|
1.77
(0.990)
|
1.68
(1.003)
|
| Average Endoscopy Subscore (units on a scale) [Mean (Standard Deviation) ] | |||||||||
| Mean (Standard Deviation) [units on a scale] |
2.8
(0.43)
|
2.8
(0.40)
|
2.8
(0.39)
|
2.7
(0.47)
|
2.7
(0.48)
|
2.7
(0.47)
|
2.7
(0.46)
|
2.7
(0.47)
|
2.7
(0.46)
|
| Previous Biologic Use (Count of Participants) | |||||||||
| Yes |
35
76.1%
|
36
76.6%
|
38
77.6%
|
87
74.4%
|
92
74.8%
|
288
185.8%
|
|||
| No |
11
23.9%
|
11
23.4%
|
11
22.4%
|
30
25.6%
|
31
25.2%
|
94
60.6%
|
|||
| Biologic-inadequate Responder (Bio-IR) Status (Count of Participants) | |||||||||
| Bio-IR |
79
171.7%
|
168
357.4%
|
221
451%
|
468
400%
|
|||||
| Non-Bio-IR |
76
165.2%
|
151
321.3%
|
225
459.2%
|
452
386.3%
|
|||||
| Baseline Corticosteroid Use (Count of Participants) | |||||||||
| Yes |
26
56.5%
|
24
51.1%
|
27
55.1%
|
51
43.6%
|
53
43.1%
|
62
40%
|
124
38.9%
|
173
38.8%
|
540
41.5%
|
| No |
20
43.5%
|
23
48.9%
|
22
44.9%
|
66
56.4%
|
70
56.9%
|
93
60%
|
195
61.1%
|
273
61.2%
|
762
58.5%
|
Outcome Measures
| Title | Substudy 1: Percentage Of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8 |
|---|---|
| Description | The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration) The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. For Substudy 1, clinical remission is defined as SFS ≤ 1, RBS of 0, and endoscopic subscore ≤ 1. |
| Time Frame | At Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| SS1 main population (ITT1A): those randomized to ≥1 dose of study drug during the initial part of SS1. Non-responder imputation (NRI) was used to impute missing values. |
| Arm/Group Title | SS1: Placebo | SS1: Upadacitinib 7.5 mg | SS1: Upadacitinib 15 mg | SS1: Upadacitinib 30 mg | SS1: Upadacitinib 45 mg |
|---|---|---|---|---|---|
| Arm/Group Description | During the 8-week induction phase in Substudy 1, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 7.5 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 15 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. | During the 8-week induction phase in Substudy 1, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. |
| Measure Participants | 46 | 47 | 49 | 52 | 56 |
| Number [percentage of participants] |
0
0%
|
8.5
18.1%
|
14.3
29.2%
|
13.5
11.5%
|
21.4
17.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 7.5 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.049 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 8.4 | |
| Confidence Interval |
(2-Sided) 95% 0.0 to 16.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 7.5 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.010 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 13.5 | |
| Confidence Interval |
(2-Sided) 95% 3.3 to 23.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 30 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.007 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 13.8 | |
| Confidence Interval |
(2-Sided) 95% 3.8 to 23.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 45 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 21.1 | |
| Confidence Interval |
(2-Sided) 95% 8.6 to 33.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 2: Percentage Of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8 |
|---|---|
| Description | The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal) Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed) Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration) The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. For Substudy 2, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In Substudy 2, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2. |
| Time Frame | At Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| SS2, Part 1 population (ITT1): all randomized participants in the 8-week double-blind induction period who received ≥1 dose of study drug. NRI incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used for SS2, with participants analyzed according to treatment groups to which they were randomized. |
| Arm/Group Title | SS2: Placebo | SS2: Upadacitinib 45 mg |
|---|---|---|
| Arm/Group Description | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. |
| Measure Participants | 154 | 319 |
| Number [percentage of participants] |
4.8
10.4%
|
26.1
55.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 2: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by bio-IR status (bio-IR vs. non-bio-IR), Baseline corticosteroid use (yes vs. no) and Baseline Adapted Mayo score (≤ 7 vs. > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 21.6 | |
| Confidence Interval |
(2-Sided) 95% 15.8 to 27.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 3: Percentage Of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 52 |
|---|---|
| Description | The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. For Substudy 3, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In addition, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2. |
| Time Frame | At Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Substudy 3 ITT_A population: the first 451 upadacitinib 45 mg 8-week induction responders who were enrolled under the protocol for 52-week maintenance treatment period in Cohort 1. Non-responder imputation incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used to handle missing data. |
| Arm/Group Title | SS3: Placebo | SS3: UPA 15 mg | SS3: UPA 30 mg |
|---|---|---|---|
| Arm/Group Description | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8, while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to placebo QD in Substudy 3 for up to 52 weeks. In addition, participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 15 mg QD in Substudy 3 for up to 52 weeks | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 30 mg QD in Substudy 3 for up to 52 weeks |
| Measure Participants | 149 | 148 | 154 |
| Number (95% Confidence Interval) [percentage of participants] |
12.1
26.3%
|
42.3
90%
|
51.7
105.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Baseline of Induction Study; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 30.7 | |
| Confidence Interval |
(2-Sided) 95% 21.7 to 39.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Baseline of Induction Study; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 39.0 | |
| Confidence Interval |
(2-Sided) 95% 29.7 to 48.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
| Title | Substudy 1: Percentage Of Participants With Endoscopic Improvement at Week 8 |
|---|---|
| Description | Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). |
| Time Frame | At Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 1 main population (ITT1A) includes participants who were randomized to at least one dose (placebo or upadacitinib 7.5 mg, 15 mg, 30 mg, 45 mg) during the main (initial) part of Substudy 1. Non-responder imputation (NRI) was used to impute missing values for the ITT1A population. |
| Arm/Group Title | SS1: Placebo | SS1: Upadacitinib 7.5 mg | SS1: Upadacitinib 15 mg | SS1: Upadacitinib 30 mg | SS1: Upadacitinib 45 mg |
|---|---|---|---|---|---|
| Arm/Group Description | During the 8-week induction phase in Substudy 1, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 7.5 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 15 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. | During the 8-week induction phase in Substudy 1, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. |
| Measure Participants | 46 | 47 | 49 | 52 | 56 |
| Number [percentage of participants] |
2.2
4.8%
|
14.9
31.7%
|
30.6
62.4%
|
26.9
23%
|
35.7
29%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 7.5 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.030 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 13.1 | |
| Confidence Interval |
(2-Sided) 95% 1.2 to 25.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 7.5 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 27.6 | |
| Confidence Interval |
(2-Sided) 95% 13.1 to 42.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 30 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 26.6 | |
| Confidence Interval |
(2-Sided) 95% 12.3 to 40.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 45 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 35.4 | |
| Confidence Interval |
(2-Sided) 95% 19.2 to 51.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 1: Percentage Of Participants Achieving Clinical Remission Per Full Mayo Score at Week 8 |
|---|---|
| Description | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Full Mayo score (FMS) ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1. |
| Time Frame | At Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 1 main population (ITT1A) includes participants who were randomized to at least one dose (placebo or upadacitinib 7.5 mg, 15 mg, 30 mg, 45 mg) during the main (initial) part of Substudy 1. Non-responder imputation (NRI) was used to impute missing values for the ITT1A population. |
| Arm/Group Title | SS1: Placebo | SS1: Upadacitinib 7.5 mg | SS1: Upadacitinib 15 mg | SS1: Upadacitinib 30 mg | SS1: Upadacitinib 45 mg |
|---|---|---|---|---|---|
| Arm/Group Description | During the 8-week induction phase in Substudy 1, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 7.5 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 15 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. | During the 8-week induction phase in Substudy 1, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. |
| Measure Participants | 46 | 47 | 49 | 52 | 56 |
| Number [percentage of participants] |
0
0%
|
10.6
22.6%
|
10.2
20.8%
|
11.5
9.8%
|
19.6
15.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 7.5 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.021 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 11.0 | |
| Confidence Interval |
(2-Sided) 95% 1.7 to 20.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 7.5 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.024 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 9.6 | |
| Confidence Interval |
(2-Sided) 95% 1.3 to 18.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 30 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.015 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 12.2 | |
| Confidence Interval |
(2-Sided) 95% 2.3 to 22.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 45 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 20.1 | |
| Confidence Interval |
(2-Sided) 95% 8.0 to 32.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 1: Percentage Of Participants Achieving Clinical Response Per Adapted Mayo Score at Week 8 |
|---|---|
| Description | The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. Clinical response is defined as a decrease from baseline in the Adapted Mayo score ≥ 2 points and ≥ 30% from baseline, and a decrease in RBS ≥ 1 or an absolute RBS ≤ 1). |
| Time Frame | At Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 1 main population (ITT1A) includes participants who were randomized to at least one dose (placebo or upadacitinib 7.5 mg, 15 mg, 30 mg, 45 mg) during the main (initial) part of Substudy 1. Non-responder imputation (NRI) was used to impute missing values for the ITT1A population. |
| Arm/Group Title | SS1: Placebo | SS1: Upadacitinib 7.5 mg | SS1: Upadacitinib 15 mg | SS1: Upadacitinib 30 mg | SS1: Upadacitinib 45 mg |
|---|---|---|---|---|---|
| Arm/Group Description | During the 8-week induction phase in Substudy 1, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 7.5 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 15 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. | During the 8-week induction phase in Substudy 1, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. |
| Measure Participants | 46 | 47 | 49 | 52 | 56 |
| Number [percentage of participants] |
13.0
28.3%
|
29.8
63.4%
|
49.0
100%
|
46.2
39.5%
|
55.4
45%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 7.5 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.038 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 16.7 | |
| Confidence Interval |
(2-Sided) 95% 0.9 to 32.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 7.5 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 35.2 | |
| Confidence Interval |
(2-Sided) 95% 17.5 to 52.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 30 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 33.6 | |
| Confidence Interval |
(2-Sided) 95% 16.3 to 50.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 45 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 45.1 | |
| Confidence Interval |
(2-Sided) 95% 26.2 to 63.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 1: Percentage Of Participants Achieving Clinical Response Per Partial Mayo Score at Week 2 |
|---|---|
| Description | The Partial Mayo Score is a composite score of UC disease activity based on the following 2 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). The overall Partial Mayo score ranges from 0 to 6 with higher scores representing more severe disease. Clinical response per Partial Mayo Score is defined as a decrease in Partial Adapted Mayo score ≥ 2 points and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1. |
| Time Frame | At Week 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 1 main population (ITT1A) includes participants who were randomized to at least one dose (placebo or upadacitinib 7.5 mg, 15 mg, 30 mg, 45 mg) during the main (initial) part of Substudy 1. Non-responder imputation (NRI) was used to impute missing values for the ITT1A population. |
| Arm/Group Title | SS1: Placebo | SS1: Upadacitinib 7.5 mg | SS1: Upadacitinib 15 mg | SS1: Upadacitinib 30 mg | SS1: Upadacitinib 45 mg |
|---|---|---|---|---|---|
| Arm/Group Description | During the 8-week induction phase in Substudy 1, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 7.5 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 15 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. | During the 8-week induction phase in Substudy 1, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. |
| Measure Participants | 46 | 47 | 49 | 52 | 56 |
| Number [percentage of participants] |
17.4
37.8%
|
23.4
49.8%
|
34.7
70.8%
|
36.5
31.2%
|
55.4
45%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 7.5 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.495 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 5.9 | |
| Confidence Interval |
(2-Sided) 95% -11.1 to 22.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 7.5 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.074 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 15.9 | |
| Confidence Interval |
(2-Sided) 95% -1.6 to 33.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 30 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.033 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 19.2 | |
| Confidence Interval |
(2-Sided) 95% 1.6 to 36.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 45 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 40.1 | |
| Confidence Interval |
(2-Sided) 95% 20.5 to 59.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 1: Change in Full Mayo Score From Baseline to Week 8 |
|---|---|
| Description | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Full Mayo score (FMS) ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1. |
| Time Frame | Baseline (Week 0), Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 1 main population (ITT1A) includes participants who were randomized to at least one dose (placebo or upadacitinib 7.5 mg, 15 mg, 30 mg, 45 mg) during the main (initial) part of Substudy 1. Last observation carried forward (LOCF) was used for missing data. |
| Arm/Group Title | SS1: Placebo | SS1: Upadacitinib 7.5 mg | SS1: Upadacitinib 15 mg | SS1: Upadacitinib 30 mg | SS1: Upadacitinib 45 mg |
|---|---|---|---|---|---|
| Arm/Group Description | During the 8-week induction phase in Substudy 1, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 7.5 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 15 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. | During the 8-week induction phase in Substudy 1, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. |
| Measure Participants | 41 | 43 | 44 | 44 | 48 |
| Mean (Standard Deviation) [units on a scale] |
-0.741
(2.3302)
|
-2.870
(2.9685)
|
-3.589
(2.4984)
|
-4.211
(3.0886)
|
-4.606
(2.8976)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 7.5 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | ANCOVA | |
| Comments | Stratified by previous biologic use, Baseline corticosteroid use, Baseline Adapted Mayo score (<= 7 and > 7)), and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -2.142 | |
| Confidence Interval |
(2-Sided) 95% -3.2323 to -1.0520 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 7.5 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | ANCOVA | |
| Comments | Stratified by previous biologic use, Baseline corticosteroid use, Baseline Adapted Mayo score (<= 7 and > 7)), and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -2.938 | |
| Confidence Interval |
(2-Sided) 95% -4.0284 to -1.8478 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 30 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | ANCOVA | |
| Comments | Stratified by previous biologic use, Baseline corticosteroid use, Baseline Adapted Mayo score (<= 7 and > 7)), and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -3.736 | |
| Confidence Interval |
(2-Sided) 95% -4.8247 to -2.6470 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 45 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | ANCOVA | |
| Comments | Stratified by previous biologic use, Baseline corticosteroid use, Baseline Adapted Mayo score (<= 7 and > 7)), and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -4.061 | |
| Confidence Interval |
(2-Sided) 95% -5.1252 to -2.9974 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 1: Percentage Of Participants With Endoscopic Remission at Week 8 |
|---|---|
| Description | Endoscopic remission is defined as an endoscopic subscore of 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). |
| Time Frame | At Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 1 main population (ITT1A) includes participants who were randomized to at least one dose (placebo or upadacitinib 7.5 mg, 15 mg, 30 mg, 45 mg) during the main (initial) part of Substudy 1. Non-responder imputation (NRI) was used to impute missing values for the ITT1A population. |
| Arm/Group Title | SS1: Placebo | SS1: Upadacitinib 7.5 mg | SS1: Upadacitinib 15 mg | SS1: Upadacitinib 30 mg | SS1: Upadacitinib 45 mg |
|---|---|---|---|---|---|
| Arm/Group Description | During the 8-week induction phase in Substudy 1, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 7.5 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 15 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. | During the 8-week induction phase in Substudy 1, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. |
| Measure Participants | 46 | 47 | 49 | 52 | 56 |
| Number [percentage of participants] |
0
0%
|
6.4
13.6%
|
4.1
8.4%
|
9.6
8.2%
|
17.9
14.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 7.5 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.075 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 6.6 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 13.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 7.5 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.199 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 3.8 | |
| Confidence Interval |
(2-Sided) 95% -2.0 to 9.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 30 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.015 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 11.1 | |
| Confidence Interval |
(2-Sided) 95% 2.2 to 20.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 45 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 17.8 | |
| Confidence Interval |
(2-Sided) 95% 5.8 to 29.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 1: Percentage Of Participants Who Achieved Histologic Improvement at Week 8 |
|---|---|
| Description | The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration. Histologic improvement was defined as decrease from baseline in Geboes score. |
| Time Frame | At Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 1 main population (ITT1A) includes participants who were randomized to at least one dose (placebo or upadacitinib 7.5 mg, 15 mg, 30 mg, 45 mg) during the main (initial) part of Substudy 1. Non-responder imputation (NRI) was used to impute missing values for the ITT1A population. |
| Arm/Group Title | SS1: Placebo | SS1: Upadacitinib 7.5 mg | SS1: Upadacitinib 15 mg | SS1: Upadacitinib 30 mg | SS1: Upadacitinib 45 mg |
|---|---|---|---|---|---|
| Arm/Group Description | During the 8-week induction phase in Substudy 1, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 7.5 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 15 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. | During the 8-week induction phase in Substudy 1, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. |
| Measure Participants | 46 | 47 | 49 | 52 | 56 |
| Number [percentage of participants] |
6.5
14.1%
|
31.9
67.9%
|
51.0
104.1%
|
44.2
37.8%
|
48.2
39.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 7.5 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 25.6 | |
| Confidence Interval |
(2-Sided) 95% 8.9 to 42.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 7.5 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 43.6 | |
| Confidence Interval |
(2-Sided) 95% 25.4 to 61.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 30 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 39.4 | |
| Confidence Interval |
(2-Sided) 95% 21.3 to 57.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 45 mg |
|---|---|---|
| Comments | Substudy 1: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by previous biologic use, baseline corticosteroid use and baseline Adapted Mayo score (≤ 7 and > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 43.1 | |
| Confidence Interval |
(2-Sided) 95% 24.4 to 61.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 2: Percentage Of Participants With Endoscopic Improvement at Week 8 |
|---|---|
| Description | Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). |
| Time Frame | At Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 2, Part 1 population (ITT1) includes all randomized participants in the 8-week double-blind induction period who received at least one dose of double-blinded study drug in Part 1; NRI incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used with participants analyzed according to treatment groups to which they were randomized. |
| Arm/Group Title | SS2: Placebo | SS2: Upadacitinib 45 mg |
|---|---|---|
| Arm/Group Description | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. |
| Measure Participants | 154 | 319 |
| Number (95% Confidence Interval) [percentage of participants] |
7.4
16.1%
|
36.3
77.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 2: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by bio-IR status (bio-IR vs. non-bio-IR), Baseline corticosteroid use (yes or no) and Baseline Adapted Mayo score (≤ 7 vs. > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 29.3 | |
| Confidence Interval |
(2-Sided) 95% 22.6 to 35.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 2: Percentage Of Participants With Endoscopic Remission at Week 8 |
|---|---|
| Description | Endoscopic remission is defined as an endoscopic subscore of 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). |
| Time Frame | At Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 2, Part 1 population (ITT1) includes all randomized participants in the 8-week double-blind induction period who received at least one dose of double-blinded study drug in Part 1; NRI incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used with participants analyzed according to treatment groups to which they were randomized. |
| Arm/Group Title | SS2: Placebo | SS2: Upadacitinib 45 mg |
|---|---|---|
| Arm/Group Description | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. |
| Measure Participants | 154 | 319 |
| Number (95% Confidence Interval) [percentage of participants] |
1.3
2.8%
|
13.7
29.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 2: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by bio-IR status (bio-IR vs. non-bio-IR), Baseline corticosteroid use (yes or no) and Baseline Adapted Mayo score (≤ 7 vs. > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 12.7 | |
| Confidence Interval |
(2-Sided) 95% 8.4 to 17.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 2: Percentage Of Participants Achieving Clinical Response Per Adapted Mayo Score at Week 8 |
|---|---|
| Description | The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. Clinical response is defined as a decrease from baseline in the Adapted Mayo score ≥ 2 points and ≥ 30% from baseline, and a decrease in RBS ≥ 1 or an absolute RBS ≤ 1). |
| Time Frame | At Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 2, Part 1 population (ITT1) includes all randomized participants in the 8-week double-blind induction period who received at least one dose of double-blinded study drug in Part 1; NRI incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used with participants analyzed according to treatment groups to which they were randomized. |
| Arm/Group Title | SS2: Placebo | SS2: Upadacitinib 45 mg |
|---|---|---|
| Arm/Group Description | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. |
| Measure Participants | 154 | 319 |
| Number (95% Confidence Interval) [percentage of participants] |
27.3
59.3%
|
72.6
154.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 2: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by bio-IR status (bio-IR vs. non-bio-IR), Baseline corticosteroid use (yes or no) and Baseline Adapted Mayo score (≤ 7 vs. > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 46.3 | |
| Confidence Interval |
(2-Sided) 95% 38.4 to 54.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 2: Percentage Of Participants Achieving Clinical Response Per Partial Mayo Score at Week 2 |
|---|---|
| Description | The Partial Mayo Score is a composite score of UC disease activity based on the following 2 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). The overall Partial Mayo score ranges from 0 to 6 with higher scores representing more severe disease. Clinical response per Partial Mayo Score is defined as a decrease from Baseline ≥ 1 point and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1. |
| Time Frame | At Week 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 2, Part 1 population (ITT1) includes all randomized participants in the 8-week double-blind induction period who received at least one dose of double-blinded study drug in Part 1; NRI incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used with participants analyzed according to treatment groups to which they were randomized. |
| Arm/Group Title | SS2: Placebo | SS2: Upadacitinib 45 mg |
|---|---|---|
| Arm/Group Description | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. |
| Measure Participants | 154 | 319 |
| Number (95% Confidence Interval) [percentage of participants] |
27.3
59.3%
|
60.1
127.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 2: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by bio-IR status (bio-IR vs. non-bio-IR), Baseline corticosteroid use (yes or no) and Baseline Adapted Mayo score (≤ 7 vs. > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 33.3 | |
| Confidence Interval |
(2-Sided) 95% 24.8 to 41.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 2: Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement at Week 8 |
|---|---|
| Description | Histologic-endoscopic mucosal improvement is defined as an endoscopic subscore of 0 or 1 and a Geboes score ≤ 3.1. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration. |
| Time Frame | At Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 2, Part 1 population (ITT1) includes all randomized participants in the 8-week double-blind induction period who received at least one dose of double-blinded study drug in Part 1; NRI incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used with participants analyzed according to treatment groups to which they were randomized. |
| Arm/Group Title | SS2: Placebo | SS2: Upadacitinib 45 mg |
|---|---|---|
| Arm/Group Description | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. |
| Measure Participants | 154 | 319 |
| Number (95% Confidence Interval) [percentage of participants] |
6.6
14.3%
|
30.1
64%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 2: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by bio-IR status (bio-IR vs. non-bio-IR), Baseline corticosteroid use (yes or no) and Baseline Adapted Mayo score (≤ 7 vs. > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 23.7 | |
| Confidence Interval |
(2-Sided) 95% 17.5 to 30.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 2: Percentage Of Participants Who Report No Bowel Urgency at Week 8 |
|---|---|
| Description | Bowel urgency was assessed by participants in a subject diary completed once a day. |
| Time Frame | At Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 2, Part 1 population (ITT1) includes all randomized participants in the 8-week double-blind induction period who received at least one dose of double-blinded study drug in Part 1; NRI incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used with participants analyzed according to treatment groups to which they were randomized. |
| Arm/Group Title | SS2: Placebo | SS2: Upadacitinib 45 mg |
|---|---|---|
| Arm/Group Description | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. |
| Measure Participants | 154 | 319 |
| Number (95% Confidence Interval) [percentage of participants] |
21.4
46.5%
|
48.4
103%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 2: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by bio-IR status (bio-IR vs. non-bio-IR), Baseline corticosteroid use (yes or no) and Baseline Adapted Mayo score (≤ 7 vs. > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 27.4 | |
| Confidence Interval |
(2-Sided) 95% 19.2 to 35.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 2: Percentage Of Participants Who Reported No Abdominal Pain at Week 8 |
|---|---|
| Description | Abdominal pain was assessed by participants in a subject diary completed once a day. |
| Time Frame | At Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 2, Part 1 population (ITT1) includes all randomized participants in the 8-week double-blind induction period who received at least one dose of double-blinded study drug in Part 1; NRI incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used with participants analyzed according to treatment groups to which they were randomized. |
| Arm/Group Title | SS2: Placebo | SS2: Upadacitinib 45 mg |
|---|---|---|
| Arm/Group Description | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. |
| Measure Participants | 154 | 319 |
| Number (95% Confidence Interval) [percentage of participants] |
23.4
50.9%
|
46.6
99.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 2: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by bio-IR status (bio-IR vs. non-bio-IR), Baseline corticosteroid use (yes or no) and Baseline Adapted Mayo score (≤ 7 vs. > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 23.6 | |
| Confidence Interval |
(2-Sided) 95% 15.1 to 32.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 2: Percentage Of Participants Who Achieved Histologic Improvement at Week 8 |
|---|---|
| Description | The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration. Histologic improvement was defined as decrease from baseline in Geboes score. |
| Time Frame | At Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 2, Part 1 population (ITT1) includes all randomized participants in the 8-week double-blind induction period who received at least one dose of double-blinded study drug in Part 1; NRI incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used with participants analyzed according to treatment groups to which they were randomized. |
| Arm/Group Title | SS2: Placebo | SS2: Upadacitinib 45 mg |
|---|---|---|
| Arm/Group Description | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. |
| Measure Participants | 154 | 319 |
| Number (95% Confidence Interval) [percentage of participants] |
22.5
48.9%
|
55.0
117%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 2: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by bio-IR status (bio-IR vs. non-bio-IR), Baseline corticosteroid use (yes or no) and Baseline Adapted Mayo score (≤ 7 vs. > 7) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 32.2 | |
| Confidence Interval |
(2-Sided) 95% 23.8 to 40.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 2: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 8 |
|---|---|
| Description | The Inflammatory Bowel Disease Questionnaire (IBDQ) is used to assess health-related quality of life (HRQoL) in patients with ulcerative colitis. It consists of 32 questions evaluating bowel and systemic symptoms, as well as emotional and social functions. Each question is answered on a scale from 1 (worst) to 7 (best). The total score ranges from 32 to 224 with higher scores indicating better health-related quality of life. A positive change from Baseline indicates improvement. |
| Time Frame | Baseline (Week 0), Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 2, Part 1 ITT1 population with available data; a mixed effect model repeat measurement (MMRM) analysis with data from observed cases up to Week 8 was used except for measurements at or after the occurrence of UC-related corticosteroids intercurrent event were excluded |
| Arm/Group Title | SS2: Placebo | SS2: Upadacitinib 45 mg |
|---|---|---|
| Arm/Group Description | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. |
| Measure Participants | 125 | 292 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
21.7
|
55.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 2: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Mixed-effect model repeated measurement | |
| Comments | MMRM with Baseline, treatment, visit, treatment-by-visit interaction, and strata (Baseline Adapted Mayo score, corticosteroid use, and bio-IR status). | |
| Method of Estimation | Estimation Parameter | Least Squares (LS) Mean Difference |
| Estimated Value | 33.7 | |
| Confidence Interval |
(2-Sided) 95% 27.02 to 40.36 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.39 |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 2: Percentage Of Participants With Mucosal Healing at Week 8 |
|---|---|
| Description | Mucosal healing is defined as an endoscopic score of 0 and Geboes score < 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration. |
| Time Frame | At Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 2, Part 1 population (ITT1) includes all randomized participants in the 8-week double-blind induction period who received at least one dose of double-blinded study drug in Part 1; NRI incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used with participants analyzed according to treatment groups to which they were randomized. |
| Arm/Group Title | SS2: Placebo | SS2: Upadacitinib 45 mg |
|---|---|---|
| Arm/Group Description | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. |
| Measure Participants | 154 | 319 |
| Number (95% Confidence Interval) [percentage of participants] |
1.3
2.8%
|
10.7
22.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 2: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 9.7 | |
| Confidence Interval |
(2-Sided) 95% 5.7 to 13.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 2: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 8 |
|---|---|
| Description | The FACIT fatigue questionnaire was developed to assess fatigue associated with anemia. It consists of 13 fatigue-related questions. Each question is answered on a 5-point Likert scale: 0 (not at all); 1 (a little bit); 2 (somewhat); 3 (quite a bit); and 4 (very much). The total score ranges from 0 to 52, where higher scores represent less fatigue, and a positive change from Baseline indicates improvement. |
| Time Frame | Baseline (Week 0), Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Substudy 2, Part 1 ITT1 population with available data; a mixed effect model repeat measurement (MMRM) analysis with data from observed cases up to Week 8 was used except for measurements at or after the occurrence of UC-related corticosteroids intercurrent event were excluded |
| Arm/Group Title | SS2: Placebo | SS2: Upadacitinib 45 mg |
|---|---|---|
| Arm/Group Description | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. |
| Measure Participants | 125 | 291 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
2.8
|
9.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 2: Upadacitinib 45 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided). | |
| Method | Mixed-effect model repeated measurement | |
| Comments | MMRM with Baseline, treatment, visit, treatment-by-visit interaction, and strata (Baseline Adapted Mayo score, corticosteroid use, and bio-IR status) | |
| Method of Estimation | Estimation Parameter | Least Squares (LS) Mean Difference |
| Estimated Value | 6.7 | |
| Confidence Interval |
(2-Sided) 95% 4.79 to 8.59 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.97 |
|
| Estimation Comments | Difference = Upadacitinib 45 mg - Placebo | |
| Title | Substudy 3: Percentage Of Participants With Endoscopic Improvement at Week 52 |
|---|---|
| Description | Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). |
| Time Frame | At Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Substudy 3 ITT_A population: the first 451 upadacitinib 45 mg 8-week induction responders who were enrolled under the protocol for 52-week maintenance treatment period in Cohort 1. Non-responder imputation incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used to handle missing data. |
| Arm/Group Title | SS3: Placebo | SS3: UPA 15 mg | SS3: UPA 30 mg |
|---|---|---|---|
| Arm/Group Description | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8, while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to placebo QD in Substudy 3 for up to 52 weeks. In addition, participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 15 mg QD in Substudy 3 for up to 52 weeks | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 30 mg QD in Substudy 3 for up to 52 weeks |
| Measure Participants | 149 | 148 | 154 |
| Number (95% Confidence Interval) [percentage of participants] |
14.5
31.5%
|
48.7
103.6%
|
61.6
125.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 34.4 | |
| Confidence Interval |
(2-Sided) 95% 25.1 to 43.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 46.3 | |
| Confidence Interval |
(2-Sided) 95% 36.7 to 55.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
| Title | Substudy 3: Percentage of Participants With Clinical Remission Per Adapted Mayo Score at Week 52 Among Those Who Achieved Clinical Remission at the End of the Induction Treatment |
|---|---|
| Description | The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. For Substudy 3, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In addition, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2. |
| Time Frame | At Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Substudy 3 ITT_A population: the first 451 upadacitinib 45 mg 8-week induction responders who were enrolled under the protocol for 52-week maintenance treatment period in Cohort 1 and who achieved clinical remission per Adapted Mayo Score in Substudy 1, 2, or M14-675. Non-responder imputation incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used to handle missing data. |
| Arm/Group Title | SS3: Placebo | SS3: UPA 15 mg | SS3: UPA 30 mg |
|---|---|---|---|
| Arm/Group Description | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8, while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to placebo QD in Substudy 3 for up to 52 weeks. In addition, participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 15 mg QD in Substudy 3 for up to 52 weeks | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 30 mg QD in Substudy 3 for up to 52 weeks |
| Measure Participants | 54 | 47 | 58 |
| Number (95% Confidence Interval) [percentage of participants] |
22.2
48.3%
|
59.2
126%
|
69.7
142.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 37.4 | |
| Confidence Interval |
(2-Sided) 95% 20.3 to 54.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 47.0 | |
| Confidence Interval |
(2-Sided) 95% 30.7 to 63.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
| Title | Substudy 3: Percentage of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Wk 52 and Were Corticosteroid Free for ≥ 90 Days Immediately Preceding Wk 52 Among Those Who Achieved Clinical Remission at the End of the Induction Treatment |
|---|---|
| Description | The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. For Substudy 3, clinical remission is defined as SFS ≤ 1 and not greater than Baseline, RBS of 0, and endoscopic subscore ≤ 1. In addition, evidence of friability during endoscopy in participants with otherwise "mild" endoscopic activity conferred an endoscopic subscore of 2. |
| Time Frame | At Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Substudy 3 ITT_A population: the first 451 upadacitinib 45 mg 8-week induction responders who were enrolled under the protocol for 52-week maintenance treatment period in Cohort 1 and who achieved clinical remission per Adapted Mayo Score in Substudy 1, 2, or M14-675. Non-responder imputation incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used to handle missing data. |
| Arm/Group Title | SS3: Placebo | SS3: UPA 15 mg | SS3: UPA 30 mg |
|---|---|---|---|
| Arm/Group Description | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8, while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to placebo QD in Substudy 3 for up to 52 weeks. In addition, participants who received double-blind placebo QD treatment for 8 weeks during Substudy1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 15 mg QD in Substudy 3 for up to 52 weeks | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 30 mg QD in Substudy 3 for up to 52 weeks. |
| Measure Participants | 54 | 47 | 58 |
| Number (95% Confidence Interval) [percentage of participants] |
22.2
48.3%
|
57.1
121.5%
|
68.0
138.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 35.4 | |
| Confidence Interval |
(2-Sided) 95% 18.2 to 52.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 45.1 | |
| Confidence Interval |
(2-Sided) 95% 28.7 to 61.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
| Title | Substudy 3: Percentage of Participants With Endoscopic Improvement at Wk 52 Among Those Who Achieved Endoscopic Improvement at the End of the Induction Treatment |
|---|---|
| Description | Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). |
| Time Frame | At Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Substudy 3 ITT_A population: the first 451 upadacitinib 45 mg 8-week induction responders who were enrolled under the protocol for 52-week maintenance treatment period in Cohort 1 and who achieved endoscopic improvement in Substudy 1, 2, or M14-675. Non-responder imputation incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used to handle missing data. |
| Arm/Group Title | SS3: Placebo | SS3: UPA 15 mg | SS3: UPA 30 mg |
|---|---|---|---|
| Arm/Group Description | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8, while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to placebo QD in Substudy 3 for up to 52 weeks. In addition, participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 15 mg QD in Substudy 3 for up to 52 weeks | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 30 mg QD in Substudy 3 for up to 52 weeks |
| Measure Participants | 73 | 63 | 79 |
| Number (95% Confidence Interval) [percentage of participants] |
19.2
41.7%
|
61.6
131.1%
|
69.5
141.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 42.0 | |
| Confidence Interval |
(2-Sided) 95% 27.8 to 56.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 48.6 | |
| Confidence Interval |
(2-Sided) 95% 35.5 to 61.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
| Title | Substudy 3: Percentage Of Participants With Endoscopic Remission At Week 52 |
|---|---|
| Description | Endoscopic remission is defined as an endoscopic subscore of 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). |
| Time Frame | At Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Substudy 3 ITT_A population: the first 451 upadacitinib 45 mg 8-week induction responders who were enrolled under the protocol for 52-week maintenance treatment period in Cohort 1. Non-responder imputation incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used to handle missing data. |
| Arm/Group Title | SS3: Placebo | SS3: UPA 15 mg | SS3: UPA 30 mg |
|---|---|---|---|
| Arm/Group Description | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8, while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to placebo QD in Substudy 3 for up to 52 weeks. In addition, participants who received double-blind placebo QD treatment for 8 weeks during Substudy1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 15 mg QD in Substudy 3 for up to 52 weeks | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 30 mg QD in Substudy 3 for up to 52 weeks |
| Measure Participants | 149 | 148 | 154 |
| Number (95% Confidence Interval) [percentage of participants] |
5.6
12.2%
|
24.2
51.5%
|
25.9
52.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 18.7 | |
| Confidence Interval |
(2-Sided) 95% 11.0 to 26.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 19.4 | |
| Confidence Interval |
(2-Sided) 95% 11.7 to 27.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
| Title | Substudy 3: Percentage Of Participants Who Maintained Clinical Response Per Adapted Mayo Score at Wk 52 Among Those Who Achieved Clinical Response at the End of the Induction Treatment |
|---|---|
| Description | The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. Clinical response is defined as a decrease from baseline in the Adapted Mayo score ≥ 2 points and ≥ 30% from baseline, and a decrease in RBS ≥ 1 or an absolute RBS ≤ 1). |
| Time Frame | At Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Substudy 3 ITT_A population: the first 451 upadacitinib 45 mg 8-week induction responders who were enrolled under the protocol for 52-week maintenance treatment period in Cohort 1 and who achieved clinical response per Adapted Mayo Score in Substudy 1, 2, or M14-675. Non-responder imputation incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used to handle missing data. |
| Arm/Group Title | SS3: Placebo | SS3: UPA 15 mg | SS3: UPA 30 mg |
|---|---|---|---|
| Arm/Group Description | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8, while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to placebo QD in Substudy 3 for up to 52 weeks. In addition, participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 15 mg QD in Substudy 3 for up to 52 weeks | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 30 mg QD in Substudy 3 for up to 52 weeks |
| Measure Participants | 134 | 135 | 144 |
| Number (95% Confidence Interval) [percentage of participants] |
18.8
40.9%
|
63.0
134%
|
76.6
156.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 44.6 | |
| Confidence Interval |
(2-Sided) 95% 34.5 to 54.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 56.6 | |
| Confidence Interval |
(2-Sided) 95% 47.2 to 66.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
| Title | Substudy 3: Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement at Week 52 |
|---|---|
| Description | Histologic-endoscopic mucosal improvement is defined as an endoscopic subscore of 0 or 1 and a Geboes score ≤ 3.1. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration. |
| Time Frame | At Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Substudy 3 ITT_A population: the first 451 upadacitinib 45 mg 8-week induction responders who were enrolled under the protocol for 52-week maintenance treatment period in Cohort 1. Non-responder imputation incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used to handle missing data. |
| Arm/Group Title | SS3: Placebo | SS3: UPA 15 mg | SS3: UPA 30 mg |
|---|---|---|---|
| Arm/Group Description | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8, while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to placebo QD in Substudy 3 for up to 52 weeks. In addition, participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 15 mg QD in Substudy 3 for up to 52 weeks | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 30 mg QD in Substudy 3 for up to 52 weeks |
| Measure Participants | 149 | 148 | 154 |
| Number (95% Confidence Interval) [percentage of participants] |
11.9
25.9%
|
35.0
74.5%
|
49.8
101.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 23.8 | |
| Confidence Interval |
(2-Sided) 95% 14.8 to 32.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 37.3 | |
| Confidence Interval |
(2-Sided) 95% 27.8 to 46.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
| Title | Substudy 3: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 52 |
|---|---|
| Description | The Inflammatory Bowel Disease Questionnaire (IBDQ) is used to assess health-related quality of life (HRQoL) in patients with ulcerative colitis. It consists of 32 questions evaluating bowel and systemic symptoms, as well as emotional and social functions. Each question is answered on a scale from 1 (worst) to 7 (best). The total score ranges from 32 to 224 with higher scores indicating better health-related quality of life. A positive change from Baseline indicates improvement. |
| Time Frame | Baseline (Week 0), Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Substudy 3 ITT_A population with available data: Baseline is defined as the last non-missing value prior to the first dose in Phase 2b Induction or Induction Studies. Multiple Imputation Incorporating Return-to-Baseline (RTB-MI) was used to handle missing data. |
| Arm/Group Title | SS3: Placebo | SS3: UPA 15 mg | SS3: UPA 30 mg |
|---|---|---|---|
| Arm/Group Description | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8, while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to placebo QD in Substudy 3 for up to 52 weeks. In addition, participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 15 mg QD in Substudy 3 for up to 52 weeks | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 30 mg QD in Substudy 3 for up to 52 weeks |
| Measure Participants | 149 | 148 | 154 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
17.9
|
49.2
|
58.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | ANCOVA | |
| Comments | Stratified by corticosteroid use at Week 0 (yes/no); clinical remission status at Week 0 (yes/ no); Bio-IR status at Baseline (Bio-IR or Non-Bio-IR) | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 31.3 | |
| Confidence Interval |
(2-Sided) 95% 21.98 to 40.70 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.77 |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | ANCOVA | |
| Comments | Stratified by corticosteroid use at Week 0 (yes/no); clinical remission status at Week 0 (yes/ no); Bio-IR status at Baseline (Bio-IR or Non-Bio-IR) | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 41.0 | |
| Confidence Interval |
(2-Sided) 95% 31.39 to 50.55 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.88 |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
| Title | Substudy 3: Percentage Of Participants With Mucosal Healing at Week 52 |
|---|---|
| Description | Mucosal healing is defined as an endoscopic score of 0 and Geboes score < 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration. |
| Time Frame | At Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Substudy 3 ITT_A population: the first 451 upadacitinib 45 mg 8-week induction responders who were enrolled under the protocol for 52-week maintenance treatment period in Cohort 1. Non-responder imputation incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used to handle missing data. |
| Arm/Group Title | SS3: Placebo | SS3: UPA 15 mg | SS3: UPA 30 mg |
|---|---|---|---|
| Arm/Group Description | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8, while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to placebo QD in Substudy 3 for up to 52 weeks. In addition, participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 15 mg QD in Substudy 3 for up to 52 weeks | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 30 mg QD in Substudy 3 for up to 52 weeks |
| Measure Participants | 149 | 148 | 154 |
| Number (95% Confidence Interval) [percentage of participants] |
4.7
10.2%
|
17.6
37.4%
|
19.0
38.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 13.0 | |
| Confidence Interval |
(2-Sided) 95% 6.0 to 20.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 13.6 | |
| Confidence Interval |
(2-Sided) 95% 6.6 to 20.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
| Title | Substudy 3: Percentage Of Participants Who Reported No Bowel Urgency at Week 52 |
|---|---|
| Description | Bowel urgency was assessed by participants in a subject diary completed once a day. |
| Time Frame | At Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Substudy 3 ITT_A population: the first 451 upadacitinib 45 mg 8-week induction responders who were enrolled under the protocol for 52-week maintenance treatment period in Cohort 1. Non-responder imputation incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used to handle missing data. |
| Arm/Group Title | SS3: Placebo | SS3: UPA 15 mg | SS3: UPA 30 mg |
|---|---|---|---|
| Arm/Group Description | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8, while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to placebo QD in Substudy 3 for up to 52 weeks. In addition, participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 15 mg QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 30 mg QD in Substudy 3 for up to 52 weeks |
| Measure Participants | 149 | 148 | 154 |
| Number (95% Confidence Interval) [percentage of participants] |
17.4
37.8%
|
56.1
119.4%
|
63.6
129.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 38.7 | |
| Confidence Interval |
(2-Sided) 95% 28.9 to 48.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 45.1 | |
| Confidence Interval |
(2-Sided) 95% 35.5 to 54.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
| Title | Substudy 3: Percentage Of Participants Who Reported No Abdominal Pain at Week 52 |
|---|---|
| Description | Abdominal pain was assessed by participants in a subject diary completed once a day. |
| Time Frame | At Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Substudy 3 ITT_A population: the first 451 upadacitinib 45 mg 8-week induction responders who were enrolled under the protocol for 52-week maintenance treatment period in Cohort 1. Non-responder imputation incorporating multiple imputation (MI) to handle missing data due to COVID-19 (NRI-C) was used to handle missing data. |
| Arm/Group Title | SS3: Placebo | SS3: UPA 15 mg | SS3: UPA 30 mg |
|---|---|---|---|
| Arm/Group Description | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8, while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to placebo QD in Substudy 3 for up to 52 weeks. In addition, participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 15 mg QD in Substudy 3 for up to 52 weeks | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 30 mg QD in Substudy 3 for up to 52 weeks |
| Measure Participants | 149 | 148 | 154 |
| Number (95% Confidence Interval) [percentage of participants] |
20.8
45.2%
|
45.9
97.7%
|
55.3
112.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 24.3 | |
| Confidence Interval |
(2-Sided) 95% 14.2 to 34.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by Bio-IR (Bio-IR/Non-Bio-IR) at Induction Study Baseline; clinical remission at Week 0 (yes/no); corticosteroid use at Week 0 (yes/no) | |
| Method of Estimation | Estimation Parameter | Adjusted risk difference (%) |
| Estimated Value | 33.7 | |
| Confidence Interval |
(2-Sided) 95% 23.6 to 43.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
| Title | Substudy 3: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 52 |
|---|---|
| Description | The FACIT fatigue questionnaire was developed to assess fatigue associated with anemia. It consists of 13 fatigue-related questions. Each question is answered on a 5-point Likert scale: 0 (not at all); 1 (a little bit); 2 (somewhat); 3 (quite a bit); and 4 (very much). The total score ranges from 0 to 52, where higher scores represent less fatigue, and a positive change from Baseline indicates improvement. |
| Time Frame | Baseline (Week 0), Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Substudy 3 ITT_A population with available data: Baseline is defined as the last non-missing value prior to the first dose in Phase 2b Induction or Induction Studies. Multiple Imputation Incorporating Return-to-Baseline (RTB-MI) was used to handle missing data. |
| Arm/Group Title | SS3: Placebo | SS3: UPA 15 mg | SS3: UPA 30 mg |
|---|---|---|---|
| Arm/Group Description | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8, while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to placebo QD in Substudy 3 for up to 52 weeks. In addition, participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 15 mg QD in Substudy 3 for up to 52 weeks | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at Week 8 while receiving upadacitinib 15, 30, or 45 mg QD and were randomized to upadacitinib 30 mg QD in Substudy 3 for up to 52 weeks |
| Measure Participants | 149 | 148 | 154 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
3.7
|
8.7
|
9.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 7.5 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 15 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | ANCOVA | |
| Comments | Stratified by corticosteroid use at Week 0 (yes/no); clinical remission status at Week 0 (yes/no); Bio-IR status at Baseline (Bio-IR or Non-Bio-IR) | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 5.1 | |
| Confidence Interval |
(2-Sided) 95% 2.67 to 7.52 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 15 mg - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SS1: Placebo, SS1: Upadacitinib 15 mg |
|---|---|---|
| Comments | Substudy 3: Upadacitinib 30 mg vs Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | The primary and ranked secondary efficacy endpoints were tested with graphical multiplicity adjustment to ensure a strong control of family-wise type I error rate at significance level α= 0.05 (2-sided). | |
| Method | ANCOVA | |
| Comments | Stratified by corticosteroid use at Week 0 (yes/no); clinical remission status at Week 0 (yes/no); Bio-IR status at Baseline (Bio-IR or Non-Bio-IR) | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 5.9 | |
| Confidence Interval |
(2-Sided) 95% 3.44 to 8.27 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference = Upadacitinib 30 mg - Placebo | |
Adverse Events
| Time Frame | All-cause mortality is reported from enrollment to end of study; median time on follow-up was up to 57, 61, and 364 days for Substudies 1, 2, and 3, respectively. TEAEs and SAEs were collected from first dose of study drug until 30 days after last dose of study drug; mean duration on study drug was up to 57, 56, and 364 days for Substudies 1, 2, and 3, respectively. | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | For safety analyses, participants were assigned to a treatment group based on the treatment actually received, regardless of the treatment randomized. The "as treated" group was determined by the most frequent dose regimen received in the analysis period. | |||||||||||||||||||||||||
| Arm/Group Title | SS1: Placebo | SS1: Upadacitinib 7.5 mg | SS1: Upadacitinib 15 mg | SS1: Upadacitinib 30 mg | SS1: Upadacitinib 45 mg | SS2: Placebo | SS2: Upadacitinib 45 mg | SS2: Placebo/Upadacitinib 45 mg | SS2: Upadacitinib 45 mg/Upadacitinib 45 mg | SS3: Placebo | SS3: Upadacitinib 7.5 mg | SS3: Upadacitinib 15 mg | SS3: Upadacitinib 30 mg | |||||||||||||
| Arm/Group Description | During the 8-week induction phase in Substudy 1, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 7.5 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 15 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the 8-week induction phase in Substudy 1, participants received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 30 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. | During the 8-week induction phase in Substudy 1, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Additional participants were enrolled during the Substudy 1 analysis period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 4 weeks. | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. | During the Substudy 2 Part 1 induction period, participants received placebo for upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Participants who did not achieve clinical response at Week 8 of Part 1 were enrolled in an open-label extended treatment period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for an additional 8 weeks. | During the Substudy 2 Part 1 induction period, participants received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for 8 weeks. Participants who did not achieve clinical response at Week 8 of Part 1 were enrolled in an open-label expended treatment period and received 45 mg upadacitinib film-coated tablets once daily by mouth (QD) for an additional 8 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at either Week 8 or Week 16, while receiving upadacitinib 15, 30, or 45 mg QD and those who achieved clinical response while receiving upadacitinib 15 mg QD in Substudy 1 and were randomized to placebo QD in Substudy 3 for up to 52 weeks. In addition, participants who received double-blind placebo QD treatment for 8 weeks during Substudy 1, Substudy 2 Part 1, or Study M14-675 Part 1 and achieved clinical response at Week 8 continued to receive blinded placebo QD in Substudy 3 for up to 52 weeks. | Participants who received double-blinded treatment of upadacitinib 7.5 mg QD for 8 weeks during Substudy 1 and achieved clinical response at Week 8 continued to receive blinded treatment of upadacitinib 7.5 mg QD in Substudy 3 for up to 52 weeks. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at either Week 8 or Week 16, while receiving upadacitinib 15, 30, or 45 mg QD and those who achieved clinical response while receiving upadacitinib 15 mg QD in Substudy 1 and were randomized to upadacitinib 15 mg QD in Substudy 3 for up to 52 weeks. In addition, participants who received upadacitinib 45 mg QD in Induction Phase and did not achieve clinical response and received upadacitinib 45 mg QD in Extended Treatment in Substudy 2 Part 2 or in Study M14-675 Part 2 and achieved clinical response at Week 16 and were randomized to upadacitinib 15 mg QD in Substudy 3. | Participants who achieved clinical response in Substudy 1, Substudy 2, or Study M14-675 at either Week 8 or Week 16, while receiving upadacitinib 15, 30, or 45 mg QD and those who achieved clinical response while receiving upadacitinib 15 mg QD in Substudy 1 and were randomized to upadacitinib 30 mg QD in Substudy 3 for up to 52 weeks. In addition, participants who received upadacitinib 45 mg QD in Induction Phase and did not achieve clinical response and received upadacitinib 45 mg QD in Extended Treatment in Substudy 2 Part 2 or in Study M14-675 Part 2 and achieved clinical response at Week 16 and were randomized to upadacitinib 30 mg QD in Substudy 3. | |||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||
| SS1: Placebo | SS1: Upadacitinib 7.5 mg | SS1: Upadacitinib 15 mg | SS1: Upadacitinib 30 mg | SS1: Upadacitinib 45 mg | SS2: Placebo | SS2: Upadacitinib 45 mg | SS2: Placebo/Upadacitinib 45 mg | SS2: Upadacitinib 45 mg/Upadacitinib 45 mg | SS3: Placebo | SS3: Upadacitinib 7.5 mg | SS3: Upadacitinib 15 mg | SS3: Upadacitinib 30 mg | ||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/46 (0%) | 0/47 (0%) | 0/49 (0%) | 0/117 (0%) | 0/123 (0%) | 0/155 (0%) | 0/319 (0%) | 0/85 (0%) | 0/59 (0%) | 0/385 (0%) | 0/20 (0%) | 0/323 (0%) | 0/316 (0%) | |||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||
| SS1: Placebo | SS1: Upadacitinib 7.5 mg | SS1: Upadacitinib 15 mg | SS1: Upadacitinib 30 mg | SS1: Upadacitinib 45 mg | SS2: Placebo | SS2: Upadacitinib 45 mg | SS2: Placebo/Upadacitinib 45 mg | SS2: Upadacitinib 45 mg/Upadacitinib 45 mg | SS3: Placebo | SS3: Upadacitinib 7.5 mg | SS3: Upadacitinib 15 mg | SS3: Upadacitinib 30 mg | ||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/46 (10.9%) | 0/47 (0%) | 2/49 (4.1%) | 5/117 (4.3%) | 6/123 (4.9%) | 9/155 (5.8%) | 8/319 (2.5%) | 2/85 (2.4%) | 2/59 (3.4%) | 32/385 (8.3%) | 0/20 (0%) | 24/323 (7.4%) | 25/316 (7.9%) | |||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||
| ANAEMIA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 2/85 (2.4%) | 2 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| IRON DEFICIENCY ANAEMIA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||||||||||||
| ACUTE MYOCARDIAL INFARCTION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| ATRIAL FIBRILLATION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| Eye disorders | ||||||||||||||||||||||||||
| CATARACT | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||||||
| ABDOMINAL PAIN | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 1/123 (0.8%) | 1 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| ANAL FISTULA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| COLITIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 1/155 (0.6%) | 4 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| COLITIS ULCERATIVE | 2/46 (4.3%) | 3 | 0/47 (0%) | 0 | 1/49 (2%) | 1 | 4/117 (3.4%) | 5 | 3/123 (2.4%) | 3 | 5/155 (3.2%) | 6 | 2/319 (0.6%) | 2 | 1/85 (1.2%) | 1 | 1/59 (1.7%) | 1 | 9/385 (2.3%) | 9 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 3/316 (0.9%) | 3 |
| COLON DYSPLASIA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 1/123 (0.8%) | 1 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| DIAPHRAGMATIC HERNIA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 1/155 (0.6%) | 1 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| ILEUS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 1/117 (0.9%) | 1 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| INTESTINAL OBSTRUCTION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| PANCREATITIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| General disorders | ||||||||||||||||||||||||||
| DEVICE INTOLERANCE | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| PYREXIA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 1/123 (0.8%) | 1 | 0/155 (0%) | 0 | 1/319 (0.3%) | 1 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||||||||||||
| HEPATITIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| LIVER DISORDER | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| Infections and infestations | ||||||||||||||||||||||||||
| ABDOMINAL ABSCESS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| ACUTE ENDOCARDITIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| ANAL ABSCESS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| APPENDICITIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 2/319 (0.6%) | 2 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| ARTHRITIS BACTERIAL | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| BREAST ABSCESS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| BRONCHITIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| BURSITIS INFECTIVE | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| COVID-19 | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| COVID-19 PNEUMONIA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 2/323 (0.6%) | 2 | 2/316 (0.6%) | 2 |
| CELLULITIS | 1/46 (2.2%) | 1 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 1/155 (0.6%) | 1 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| CLOSTRIDIUM DIFFICILE INFECTION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| GASTROENTERITIS NOROVIRUS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 1/319 (0.3%) | 1 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| HERPES ZOSTER | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 1/316 (0.3%) | 1 |
| HERPES ZOSTER MENINGITIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| INFECTIOUS MONONUCLEOSIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| INFLUENZA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| LARGE INTESTINE INFECTION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| MASTITIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| MUSCLE ABSCESS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 1/155 (0.6%) | 1 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| PNEUMOCYSTIS JIROVECII PNEUMONIA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| PNEUMONIA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 1/319 (0.3%) | 1 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 3/385 (0.8%) | 3 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| PNEUMONIA CRYPTOCOCCAL | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 2/316 (0.6%) | 2 |
| PNEUMONIA PNEUMOCOCCAL | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| POST PROCEDURAL INFECTION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| RESPIRATORY SYNCYTIAL VIRUS INFECTION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 1/123 (0.8%) | 1 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| SEPSIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 1/123 (0.8%) | 1 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| SINUSITIS | 1/46 (2.2%) | 1 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| TONSILLITIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| UROSEPSIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 1/49 (2%) | 1 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| VIRAL INFECTION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 1/319 (0.3%) | 1 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| VIRAL PHARYNGITIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 1/123 (0.8%) | 1 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||
| HIP FRACTURE | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| PULMONARY CONTUSION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| SKIN LACERATION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| THORACIC VERTEBRAL FRACTURE | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| Investigations | ||||||||||||||||||||||||||
| ASPARTATE AMINOTRANSFERASE INCREASED | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 1/123 (0.8%) | 1 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||
| HYPOALBUMINAEMIA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 1/155 (0.6%) | 1 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| HYPOPHOSPHATAEMIA | 1/46 (2.2%) | 1 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||
| ARTHRITIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| CHONDROMALACIA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||
| ADENOCARCINOMA OF COLON | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| BASAL CELL CARCINOMA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 2 |
| INVASIVE BREAST CARCINOMA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| SEBORRHOEIC KERATOSIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| SMALL CELL CARCINOMA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| Nervous system disorders | ||||||||||||||||||||||||||
| CARPAL TUNNEL SYNDROME | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| CEREBROVASCULAR ACCIDENT | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| SUBARACHNOID HAEMORRHAGE | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| Psychiatric disorders | ||||||||||||||||||||||||||
| ANXIETY | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| DEPRESSION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| MENTAL DISORDER | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| SUICIDAL IDEATION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||||||||
| CYSTITIS HAEMORRHAGIC | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 1/117 (0.9%) | 1 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| URINARY RETENTION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||||||||||||
| CERVICAL DYSPLASIA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 2/316 (0.6%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||
| ACUTE RESPIRATORY FAILURE | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| CHRONIC OBSTRUCTIVE PULMONARY DISEASE | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| INTERSTITIAL LUNG DISEASE | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| NONINFECTIVE BRONCHITIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| PULMONARY EMBOLISM | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 1/123 (0.8%) | 1 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 2/323 (0.6%) | 2 | 0/316 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||
| ERYTHEMA NODOSUM | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| PANNICULITIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| SKIN ULCER | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| Surgical and medical procedures | ||||||||||||||||||||||||||
| ABORTION INDUCED | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 2/323 (0.6%) | 2 | 0/316 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||||||
| DEEP VEIN THROMBOSIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 1/123 (0.8%) | 1 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| HYPOTENSION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 1/59 (1.7%) | 1 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||||
| SS1: Placebo | SS1: Upadacitinib 7.5 mg | SS1: Upadacitinib 15 mg | SS1: Upadacitinib 30 mg | SS1: Upadacitinib 45 mg | SS2: Placebo | SS2: Upadacitinib 45 mg | SS2: Placebo/Upadacitinib 45 mg | SS2: Upadacitinib 45 mg/Upadacitinib 45 mg | SS3: Placebo | SS3: Upadacitinib 7.5 mg | SS3: Upadacitinib 15 mg | SS3: Upadacitinib 30 mg | ||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 27/46 (58.7%) | 18/47 (38.3%) | 22/49 (44.9%) | 58/117 (49.6%) | 50/123 (40.7%) | 62/155 (40%) | 121/319 (37.9%) | 36/85 (42.4%) | 17/59 (28.8%) | 216/385 (56.1%) | 18/20 (90%) | 181/323 (56%) | 166/316 (52.5%) | |||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||
| ANAEMIA | 3/46 (6.5%) | 3 | 0/47 (0%) | 0 | 3/49 (6.1%) | 3 | 4/117 (3.4%) | 4 | 1/123 (0.8%) | 1 | 9/155 (5.8%) | 9 | 8/319 (2.5%) | 8 | 5/85 (5.9%) | 5 | 1/59 (1.7%) | 1 | 20/385 (5.2%) | 24 | 1/20 (5%) | 2 | 11/323 (3.4%) | 12 | 7/316 (2.2%) | 7 |
| LYMPHOPENIA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 1/117 (0.9%) | 1 | 1/123 (0.8%) | 1 | 1/155 (0.6%) | 1 | 6/319 (1.9%) | 7 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 3/385 (0.8%) | 4 | 1/20 (5%) | 1 | 3/323 (0.9%) | 4 | 1/316 (0.3%) | 1 |
| Ear and labyrinth disorders | ||||||||||||||||||||||||||
| CERUMEN IMPACTION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| Eye disorders | ||||||||||||||||||||||||||
| CATARACT | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 1/319 (0.3%) | 1 | 1/85 (1.2%) | 1 | 0/59 (0%) | 0 | 2/385 (0.5%) | 2 | 1/20 (5%) | 2 | 1/323 (0.3%) | 1 | 2/316 (0.6%) | 2 |
| VISUAL IMPAIRMENT | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||||||
| ABDOMINAL DISTENSION | 0/46 (0%) | 0 | 3/47 (6.4%) | 3 | 1/49 (2%) | 1 | 0/117 (0%) | 0 | 1/123 (0.8%) | 1 | 0/155 (0%) | 0 | 3/319 (0.9%) | 4 | 1/85 (1.2%) | 1 | 0/59 (0%) | 0 | 2/385 (0.5%) | 2 | 1/20 (5%) | 1 | 2/323 (0.6%) | 2 | 5/316 (1.6%) | 5 |
| ABDOMINAL PAIN | 1/46 (2.2%) | 1 | 0/47 (0%) | 0 | 1/49 (2%) | 1 | 1/117 (0.9%) | 1 | 3/123 (2.4%) | 3 | 1/155 (0.6%) | 1 | 4/319 (1.3%) | 5 | 1/85 (1.2%) | 1 | 2/59 (3.4%) | 2 | 8/385 (2.1%) | 8 | 1/20 (5%) | 2 | 8/323 (2.5%) | 9 | 5/316 (1.6%) | 5 |
| ABDOMINAL TENDERNESS | 1/46 (2.2%) | 1 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 1/117 (0.9%) | 1 | 3/123 (2.4%) | 3 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 0/323 (0%) | 0 | 2/316 (0.6%) | 2 |
| APHTHOUS ULCER | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 2/319 (0.6%) | 2 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 3/385 (0.8%) | 4 | 1/20 (5%) | 1 | 1/323 (0.3%) | 1 | 4/316 (1.3%) | 4 |
| COLITIS ULCERATIVE | 4/46 (8.7%) | 4 | 1/47 (2.1%) | 1 | 2/49 (4.1%) | 2 | 4/117 (3.4%) | 4 | 3/123 (2.4%) | 3 | 16/155 (10.3%) | 16 | 1/319 (0.3%) | 1 | 2/85 (2.4%) | 2 | 1/59 (1.7%) | 1 | 101/385 (26.2%) | 110 | 3/20 (15%) | 3 | 40/323 (12.4%) | 47 | 24/316 (7.6%) | 25 |
| CONSTIPATION | 1/46 (2.2%) | 1 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 1/117 (0.9%) | 1 | 1/123 (0.8%) | 1 | 0/155 (0%) | 0 | 6/319 (1.9%) | 6 | 2/85 (2.4%) | 2 | 0/59 (0%) | 0 | 2/385 (0.5%) | 2 | 2/20 (10%) | 2 | 4/323 (1.2%) | 5 | 7/316 (2.2%) | 7 |
| DIARRHOEA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 2/123 (1.6%) | 2 | 0/155 (0%) | 0 | 1/319 (0.3%) | 1 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 4/385 (1%) | 4 | 2/20 (10%) | 2 | 2/323 (0.6%) | 2 | 2/316 (0.6%) | 2 |
| NAUSEA | 2/46 (4.3%) | 2 | 1/47 (2.1%) | 1 | 1/49 (2%) | 1 | 8/117 (6.8%) | 8 | 0/123 (0%) | 0 | 3/155 (1.9%) | 3 | 4/319 (1.3%) | 5 | 1/85 (1.2%) | 1 | 0/59 (0%) | 0 | 6/385 (1.6%) | 7 | 1/20 (5%) | 1 | 6/323 (1.9%) | 6 | 7/316 (2.2%) | 7 |
| PERIANAL ERYTHEMA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| VOMITING | 1/46 (2.2%) | 1 | 1/47 (2.1%) | 1 | 1/49 (2%) | 1 | 1/117 (0.9%) | 1 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 2/319 (0.6%) | 2 | 1/85 (1.2%) | 1 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 1/20 (5%) | 1 | 1/323 (0.3%) | 1 | 3/316 (0.9%) | 3 |
| General disorders | ||||||||||||||||||||||||||
| INFLUENZA LIKE ILLNESS | 1/46 (2.2%) | 1 | 1/47 (2.1%) | 1 | 0/49 (0%) | 0 | 1/117 (0.9%) | 1 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 2/385 (0.5%) | 2 | 1/20 (5%) | 1 | 0/323 (0%) | 0 | 2/316 (0.6%) | 2 |
| PSEUDOPOLYP | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 1/117 (0.9%) | 1 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| PYREXIA | 1/46 (2.2%) | 1 | 1/47 (2.1%) | 1 | 0/49 (0%) | 0 | 5/117 (4.3%) | 5 | 1/123 (0.8%) | 1 | 2/155 (1.3%) | 3 | 8/319 (2.5%) | 8 | 6/85 (7.1%) | 7 | 0/59 (0%) | 0 | 11/385 (2.9%) | 13 | 1/20 (5%) | 1 | 10/323 (3.1%) | 10 | 18/316 (5.7%) | 19 |
| Infections and infestations | ||||||||||||||||||||||||||
| BRONCHITIS | 2/46 (4.3%) | 2 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 2/117 (1.7%) | 2 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 2/85 (2.4%) | 2 | 0/59 (0%) | 0 | 4/385 (1%) | 4 | 1/20 (5%) | 1 | 4/323 (1.2%) | 4 | 2/316 (0.6%) | 2 |
| CYSTITIS | 0/46 (0%) | 0 | 1/47 (2.1%) | 1 | 0/49 (0%) | 0 | 1/117 (0.9%) | 1 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 1/319 (0.3%) | 1 | 1/85 (1.2%) | 1 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 1/20 (5%) | 1 | 3/323 (0.9%) | 3 | 2/316 (0.6%) | 3 |
| EAR INFECTION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 1/117 (0.9%) | 1 | 0/123 (0%) | 0 | 2/155 (1.3%) | 2 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 1/59 (1.7%) | 1 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 3/323 (0.9%) | 3 | 3/316 (0.9%) | 3 |
| HERPES ZOSTER | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 1/319 (0.3%) | 1 | 5/85 (5.9%) | 5 | 3/59 (5.1%) | 3 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 10/323 (3.1%) | 10 | 15/316 (4.7%) | 16 |
| INFLUENZA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 2/117 (1.7%) | 2 | 3/123 (2.4%) | 3 | 1/155 (0.6%) | 1 | 3/319 (0.9%) | 3 | 1/85 (1.2%) | 1 | 0/59 (0%) | 0 | 4/385 (1%) | 4 | 1/20 (5%) | 2 | 10/323 (3.1%) | 10 | 8/316 (2.5%) | 10 |
| NASOPHARYNGITIS | 3/46 (6.5%) | 3 | 1/47 (2.1%) | 1 | 3/49 (6.1%) | 3 | 3/117 (2.6%) | 3 | 4/123 (3.3%) | 4 | 6/155 (3.9%) | 6 | 15/319 (4.7%) | 16 | 4/85 (4.7%) | 4 | 1/59 (1.7%) | 1 | 27/385 (7%) | 28 | 0/20 (0%) | 0 | 31/323 (9.6%) | 40 | 30/316 (9.5%) | 43 |
| ORAL HERPES | 1/46 (2.2%) | 1 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 2/117 (1.7%) | 2 | 1/123 (0.8%) | 1 | 0/155 (0%) | 0 | 4/319 (1.3%) | 4 | 2/85 (2.4%) | 2 | 0/59 (0%) | 0 | 7/385 (1.8%) | 8 | 1/20 (5%) | 1 | 6/323 (1.9%) | 8 | 9/316 (2.8%) | 11 |
| PULPITIS DENTAL | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 1/323 (0.3%) | 1 | 1/316 (0.3%) | 1 |
| RESPIRATORY TRACT INFECTION VIRAL | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 1/155 (0.6%) | 1 | 1/319 (0.3%) | 1 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 1/20 (5%) | 1 | 4/323 (1.2%) | 4 | 0/316 (0%) | 0 |
| SKIN CANDIDA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| UPPER RESPIRATORY TRACT INFECTION | 0/46 (0%) | 0 | 1/47 (2.1%) | 1 | 4/49 (8.2%) | 4 | 3/117 (2.6%) | 3 | 6/123 (4.9%) | 7 | 6/155 (3.9%) | 6 | 8/319 (2.5%) | 9 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 11/385 (2.9%) | 12 | 2/20 (10%) | 2 | 19/323 (5.9%) | 20 | 15/316 (4.7%) | 18 |
| URINARY TRACT INFECTION | 0/46 (0%) | 0 | 1/47 (2.1%) | 1 | 0/49 (0%) | 0 | 3/117 (2.6%) | 3 | 1/123 (0.8%) | 1 | 3/155 (1.9%) | 3 | 3/319 (0.9%) | 3 | 2/85 (2.4%) | 3 | 0/59 (0%) | 0 | 9/385 (2.3%) | 10 | 2/20 (10%) | 2 | 10/323 (3.1%) | 13 | 4/316 (1.3%) | 6 |
| VAGINAL INFECTION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||
| ACCIDENTAL OVERDOSE | 3/46 (6.5%) | 3 | 0/47 (0%) | 0 | 2/49 (4.1%) | 2 | 5/117 (4.3%) | 5 | 3/123 (2.4%) | 3 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 0/20 (0%) | 0 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| FALL | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| Investigations | ||||||||||||||||||||||||||
| BLOOD CREATINE PHOSPHOKINASE INCREASED | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 3/49 (6.1%) | 3 | 4/117 (3.4%) | 4 | 8/123 (6.5%) | 8 | 3/155 (1.9%) | 3 | 16/319 (5%) | 18 | 5/85 (5.9%) | 5 | 4/59 (6.8%) | 4 | 7/385 (1.8%) | 7 | 0/20 (0%) | 0 | 20/323 (6.2%) | 21 | 21/316 (6.6%) | 25 |
| HAEMOGLOBIN DECREASED | 0/46 (0%) | 0 | 1/47 (2.1%) | 1 | 1/49 (2%) | 1 | 0/117 (0%) | 0 | 2/123 (1.6%) | 2 | 3/155 (1.9%) | 4 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 1/59 (1.7%) | 1 | 1/385 (0.3%) | 1 | 1/20 (5%) | 1 | 2/323 (0.6%) | 2 | 2/316 (0.6%) | 3 |
| LYMPHOCYTE COUNT DECREASED | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 1/49 (2%) | 1 | 1/117 (0.9%) | 1 | 2/123 (1.6%) | 2 | 0/155 (0%) | 0 | 3/319 (0.9%) | 3 | 0/85 (0%) | 0 | 1/59 (1.7%) | 1 | 3/385 (0.8%) | 3 | 1/20 (5%) | 1 | 6/323 (1.9%) | 7 | 5/316 (1.6%) | 6 |
| LYMPHOCYTE COUNT INCREASED | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 3/319 (0.9%) | 3 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 1/20 (5%) | 1 | 1/323 (0.3%) | 1 | 2/316 (0.6%) | 2 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||
| DECREASED APPETITE | 2/46 (4.3%) | 2 | 0/47 (0%) | 0 | 1/49 (2%) | 1 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 1/155 (0.6%) | 1 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 2/385 (0.5%) | 2 | 1/20 (5%) | 1 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| HYPOKALAEMIA | 0/46 (0%) | 0 | 1/47 (2.1%) | 1 | 0/49 (0%) | 0 | 1/117 (0.9%) | 1 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 1/319 (0.3%) | 1 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 5/385 (1.3%) | 5 | 1/20 (5%) | 1 | 3/323 (0.9%) | 3 | 0/316 (0%) | 0 |
| IRON DEFICIENCY | 1/46 (2.2%) | 1 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 1/123 (0.8%) | 1 | 2/155 (1.3%) | 2 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 2/385 (0.5%) | 2 | 1/20 (5%) | 1 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||
| ARTHRALGIA | 1/46 (2.2%) | 1 | 2/47 (4.3%) | 2 | 0/49 (0%) | 0 | 2/117 (1.7%) | 2 | 3/123 (2.4%) | 3 | 7/155 (4.5%) | 7 | 5/319 (1.6%) | 5 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 28/385 (7.3%) | 28 | 4/20 (20%) | 5 | 19/323 (5.9%) | 19 | 8/316 (2.5%) | 9 |
| BACK PAIN | 1/46 (2.2%) | 1 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 2/117 (1.7%) | 2 | 1/123 (0.8%) | 1 | 1/155 (0.6%) | 1 | 3/319 (0.9%) | 3 | 1/85 (1.2%) | 1 | 0/59 (0%) | 0 | 15/385 (3.9%) | 15 | 1/20 (5%) | 1 | 11/323 (3.4%) | 11 | 4/316 (1.3%) | 4 |
| BURSITIS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 1/49 (2%) | 1 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| MUSCLE SPASMS | 1/46 (2.2%) | 1 | 0/47 (0%) | 0 | 1/49 (2%) | 1 | 2/117 (1.7%) | 2 | 2/123 (1.6%) | 2 | 1/155 (0.6%) | 1 | 1/319 (0.3%) | 1 | 2/85 (2.4%) | 2 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| MUSCULOSKELETAL PAIN | 1/46 (2.2%) | 1 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 1/117 (0.9%) | 1 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 1/319 (0.3%) | 1 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 3/385 (0.8%) | 3 | 1/20 (5%) | 1 | 2/323 (0.6%) | 2 | 1/316 (0.3%) | 1 |
| OSTEOPENIA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 1/155 (0.6%) | 1 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 1/323 (0.3%) | 1 | 2/316 (0.6%) | 2 |
| PAIN IN EXTREMITY | 3/46 (6.5%) | 3 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 2/123 (1.6%) | 2 | 1/155 (0.6%) | 1 | 1/319 (0.3%) | 1 | 2/85 (2.4%) | 2 | 0/59 (0%) | 0 | 4/385 (1%) | 4 | 0/20 (0%) | 0 | 1/323 (0.3%) | 1 | 6/316 (1.9%) | 6 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||
| MALIGNANT MELANOMA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| MELANOCYTIC NAEVUS | 0/46 (0%) | 0 | 1/47 (2.1%) | 1 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| SKIN PAPILLOMA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 2/319 (0.6%) | 2 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 0/323 (0%) | 0 | 1/316 (0.3%) | 2 |
| Nervous system disorders | ||||||||||||||||||||||||||
| HEADACHE | 5/46 (10.9%) | 5 | 4/47 (8.5%) | 4 | 4/49 (8.2%) | 4 | 9/117 (7.7%) | 9 | 8/123 (6.5%) | 9 | 4/155 (2.6%) | 4 | 13/319 (4.1%) | 16 | 4/85 (4.7%) | 4 | 2/59 (3.4%) | 3 | 16/385 (4.2%) | 16 | 0/20 (0%) | 0 | 10/323 (3.1%) | 10 | 14/316 (4.4%) | 16 |
| Psychiatric disorders | ||||||||||||||||||||||||||
| DEPRESSED MOOD | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 0/323 (0%) | 0 | 1/316 (0.3%) | 1 |
| IRRITABILITY | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 2/385 (0.5%) | 2 | 1/20 (5%) | 1 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||
| ASTHMA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 2 | 1/323 (0.3%) | 1 | 1/316 (0.3%) | 1 |
| COUGH | 1/46 (2.2%) | 1 | 1/47 (2.1%) | 1 | 1/49 (2%) | 1 | 3/117 (2.6%) | 3 | 4/123 (3.3%) | 4 | 2/155 (1.3%) | 2 | 5/319 (1.6%) | 5 | 2/85 (2.4%) | 2 | 1/59 (1.7%) | 1 | 6/385 (1.6%) | 6 | 2/20 (10%) | 2 | 6/323 (1.9%) | 6 | 4/316 (1.3%) | 5 |
| NASAL CONGESTION | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 1/117 (0.9%) | 1 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 1/85 (1.2%) | 1 | 0/59 (0%) | 0 | 3/385 (0.8%) | 3 | 1/20 (5%) | 1 | 1/323 (0.3%) | 1 | 2/316 (0.6%) | 2 |
| OROPHARYNGEAL PAIN | 0/46 (0%) | 0 | 1/47 (2.1%) | 1 | 2/49 (4.1%) | 2 | 4/117 (3.4%) | 4 | 0/123 (0%) | 0 | 1/155 (0.6%) | 1 | 6/319 (1.9%) | 6 | 1/85 (1.2%) | 1 | 0/59 (0%) | 0 | 6/385 (1.6%) | 6 | 1/20 (5%) | 1 | 5/323 (1.5%) | 5 | 8/316 (2.5%) | 8 |
| PULMONARY MASS | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 0/117 (0%) | 0 | 0/123 (0%) | 0 | 2/155 (1.3%) | 2 | 1/319 (0.3%) | 1 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 2 | 0/323 (0%) | 0 | 0/316 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||
| ACNE | 0/46 (0%) | 0 | 1/47 (2.1%) | 1 | 1/49 (2%) | 1 | 6/117 (5.1%) | 6 | 6/123 (4.9%) | 6 | 1/155 (0.6%) | 1 | 15/319 (4.7%) | 15 | 2/85 (2.4%) | 2 | 1/59 (1.7%) | 1 | 8/385 (2.1%) | 8 | 0/20 (0%) | 0 | 7/323 (2.2%) | 8 | 11/316 (3.5%) | 14 |
| DERMATITIS ACNEIFORM | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 2/117 (1.7%) | 2 | 0/123 (0%) | 0 | 1/155 (0.6%) | 1 | 4/319 (1.3%) | 4 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 0/385 (0%) | 0 | 1/20 (5%) | 1 | 1/323 (0.3%) | 1 | 0/316 (0%) | 0 |
| PRURITUS | 1/46 (2.2%) | 1 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 1/117 (0.9%) | 1 | 0/123 (0%) | 0 | 4/155 (2.6%) | 4 | 1/319 (0.3%) | 1 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 9/385 (2.3%) | 12 | 1/20 (5%) | 1 | 2/323 (0.6%) | 2 | 2/316 (0.6%) | 2 |
| RASH | 0/46 (0%) | 0 | 1/47 (2.1%) | 1 | 0/49 (0%) | 0 | 5/117 (4.3%) | 5 | 1/123 (0.8%) | 1 | 1/155 (0.6%) | 1 | 8/319 (2.5%) | 8 | 0/85 (0%) | 0 | 1/59 (1.7%) | 1 | 14/385 (3.6%) | 14 | 2/20 (10%) | 2 | 9/323 (2.8%) | 9 | 14/316 (4.4%) | 15 |
| ROSACEA | 0/46 (0%) | 0 | 0/47 (0%) | 0 | 0/49 (0%) | 0 | 1/117 (0.9%) | 1 | 0/123 (0%) | 0 | 0/155 (0%) | 0 | 0/319 (0%) | 0 | 0/85 (0%) | 0 | 0/59 (0%) | 0 | 1/385 (0.3%) | 1 | 1/20 (5%) | 1 | 4/323 (1.2%) | 4 | 1/316 (0.3%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Results Point of Contact
| Name/Title | Global Medical Services |
|---|---|
| Organization | AbbVie |
| Phone | 800-633-9110 |
| abbvieclinicaltrials@abbvie.com |
Responsible Party:
AbbVie
ClinicalTrials.gov Identifier:
NCT02819635
Other Study ID Numbers:
- M14-234
- 2016-000641-31
First Posted:
Jun 30, 2016
Last Update Posted:
Jun 30, 2022
Last Verified:
Jun 1, 2022