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A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Biologic Therapy

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ClinicalTrials.gov Identifier: NCT03345836
Recruitment Status : Completed
First Posted : November 17, 2017
Results First Posted : August 15, 2022
Last Update Posted : August 15, 2022
Sponsor:
Information provided by (Responsible Party):
AbbVie

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Crohn's Disease
Interventions Drug: Matching Placebo for Upadacitinib
Drug: Upadacitinib
Enrollment 624
Recruitment Details  
Pre-assignment Details

This study had 3 Parts:

Part 1:randomized,double-blind,placebo-controlled InductionPeriod(IP); Part 2:Once enrollment for Part1 completed,participants were further enrolled in open-label,single-arm active IP to receive upadacitinib 45mg.Clinical non-responders from Parts1 and 2 entered Part3; Part 3:ExtendedTreatmentPeriod for non-responders from Part1 or 2 had 3 cohorts:Cohort 1=placebo participants from Part 1,Cohort2=upadacitinib participants from Part 1.Cohort3=participants from Part2.

Arm/Group Title Part 1 (Double-blind): Placebo Part 1 (Double-blind): Upadacitinib 45 mg Part 2 (Open-label): Upadacitinib 45 mg Part 3 (Extended Treatment DB): Upadacitinib 45 mg From Part 1 DB Placebo Part 3 (Extended Treatment DB): Upadacitinib 30 mg From Part 1 DB Upadacitinib 45 mg Part 3 (Extended Treatment OL): Upadacitinib 30 mg From Part 2 OL Upadacitinib 45 mg
Hide Arm/Group Description Participants received upadacitinib matching placebo tablets, orally, once daily (QD) for 12 weeks during the Double-blind (DB) Induction Period. Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period. Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the Open-label (OL) Induction Period. Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks (until Week 24) during the Extended Treatment (ET) Period. Participants who received placebo in Part 1 and did not achieve clinical response at Week 12 were included in this group. Participants received upadacitinib 30 mg tablets, orally, QD for 12 weeks (until Week 24) during the ET Period. Participants who received DB upadacitinib 45 mg in Part 1 and did not achieve clinical response at Week 12 were included in this group. Participants received upadacitinib 30 mg tablets, orally, QD for 12 weeks (until Week 24) during the ET Period. Participants who received OL upadacitinib 45 mg during Part 2 and did not achieve clinical response at Week 12 were included in this group.
Period Title: Period 1: DB and OL Induction (12 Weeks)
Started 171 324 129 0 0 0
Completed [1] 149 291 123 0 0 0
Not Completed 22 33 6 0 0 0
Reason Not Completed
Adverse Event             5             17             2             0             0             0
Withdrew Consent             8             8             3             0             0             0
Lost to Follow-up             0             1             0             0             0             0
Lack of Efficacy             8             4             0             0             0             0
Reason not Specified             1             3             1             0             0             0
[1]
Completed=completed the study
Period Title: Period 2: 12-Week Extended Treatment
Started 0 0 0 78 69 14
Completed [1] 0 0 0 67 51 8
Not Completed 0 0 0 11 18 6
Reason Not Completed
Adverse Event             0             0             0             8             5             0
Withdrew Consent             0             0             0             0             5             1
Lost to Follow-up             0             0             0             0             0             1
Lack of Efficacy             0             0             0             2             6             3
Coronavirus Disease (COVID-19) Logistical Restrictions             0             0             0             0             1             0
Reason not Specified             0             0             0             1             1             1
[1]
Completed=completed the study
Arm/Group Title Part 1 (Double Blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg Part 2 (Open Label): Upadacitinib 45 mg Total
Hide Arm/Group Description Participants received upadacitinib matching placebo tablets, orally, QD for 12 weeks during the Double-blind Induction Period. Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the Double-blind Induction Period. Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the Open-label Induction Period. Total of all reporting groups
Overall Number of Baseline Participants 171 324 129 624
Hide Baseline Analysis Population Description
Intent-to-Treat (ITT) Population for the 12-week DB Induction Period (Part 1) i.e., ITT1 included all randomized participants who received at least one dose of DB study drug during Part 1. ITT Population for the 12-week OL Induction Period (Part 2) i.e., ITT2 included all participants who received at least one dose of study drug in Part 2.
Age, Continuous   [1] 
Mean (Full Range)
Unit of measure:  Years
Part 1 (Double Blind) Number Analyzed 171 participants 324 participants 0 participants 495 participants
37.5
(18 to 74)
38.4
(18 to 73)
38.1
(18 to 74)
Part 2 (Open Label) Number Analyzed 0 participants 0 participants 129 participants 129 participants
39.1
(18 to 68)
39.1
(18 to 68)
[1]
Measure Analysis Population Description: Results are reported separately for Part 1 (Double Blind) and Part 2 (Open Label.)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 171 participants 324 participants 129 participants 624 participants
Female
75
  43.9%
155
  47.8%
60
  46.5%
290
  46.5%
Male
96
  56.1%
169
  52.2%
69
  53.5%
334
  53.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 171 participants 324 participants 129 participants 624 participants
Hispanic or Latino
8
   4.7%
24
   7.4%
8
   6.2%
40
   6.4%
Not Hispanic or Latino
163
  95.3%
300
  92.6%
121
  93.8%
584
  93.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 171 participants 324 participants 129 participants 624 participants
American Indian or Alaska Native
1
   0.6%
1
   0.3%
0
   0.0%
2
   0.3%
Asian
38
  22.2%
69
  21.3%
11
   8.5%
118
  18.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
6
   3.5%
19
   5.9%
5
   3.9%
30
   4.8%
White
126
  73.7%
230
  71.0%
113
  87.6%
469
  75.2%
More than one race
0
   0.0%
5
   1.5%
0
   0.0%
5
   0.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Percentage of Participants With Clinical Remission Per Crohn's Disease Activity Index (CDAI) at Week 12
Hide Description The CDAI was used to evaluate the activity of Crohn's disease. Clinical remission per CDAI is defined as CDAI <150. The CDAI is calculated on the basis of a one-week evaluation of 8 items: frequency of liquid or very soft stool, abdominal pain, complications of Crohn's disease (e.g., uveitis, arthritis, fistula, and abscess), abdominal mass, hematocrit, body weight, use of antidiarrheals, and general condition. Total score ranges from 0 to about 600. Higher CDAI scores indicate more severe disease. CDAI scores below 150 represent remission and scores over 450 represent very severe Crohn's disease. Results were based on non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C).
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 Population included all randomized participants who received at least one dose of DB study drug during Part 1.
Arm/Group Title Part 1 (Double Blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg
Hide Arm/Group Description:
Participants received upadacitinib matching placebo tablets, orally, QD for 12 weeks during the DB Induction Period.
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
Overall Number of Participants Analyzed 171 324
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
21.1
(14.9 to 27.2)
38.9
(33.6 to 44.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Double Blind): Placebo, Part 1 (Double Blind): Upadacitinib 45 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was calculated using Cochran-Mantel Haenszel (CMH) test adjusted for randomization stratification factors.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Risk Difference
Estimated Value 17.9
Confidence Interval (2-Sided) 95%
10.0 to 25.8
Estimation Comments Point estimate and 95% confidence interval (CI) were calculated using CMH risk difference estimate.
2.Primary Outcome
Title Percentage of Participants With Endoscopic Response at Week 12
Hide Description Endoscopic response was defined as greater than 50% decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) from Baseline of the induction study (or for participants with an SES-CD of 4 at Baseline of the induction study, at least a 2-point reduction from Baseline), as scored by Central Reviewer. SES-CD is calculated based on the sum of individual segment values for four endoscopic variables (presence and size of ulcers, ulcerated surface, affected surface and presence of narrowing). Each variable in each segment is scored 0 to 3 resulting in SES-CD values ranging from 0 to 56 with higher scores indicating more severe disease. Results were based on NRI-C.
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 Population included all randomized participants who received at least one dose of DB study drug during Part 1.
Arm/Group Title Part 1 (Double Blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg
Hide Arm/Group Description:
Participants received upadacitinib matching placebo tablets, orally, QD for 12 weeks during the DB Induction Period.
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
Overall Number of Participants Analyzed 171 324
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.5
(0.8 to 6.3)
34.6
(29.4 to 39.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Double Blind): Placebo, Part 1 (Double Blind): Upadacitinib 45 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was calculated using CMH test adjusted for randomization stratification factors.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Risk Difference
Estimated Value 31.2
Confidence Interval (2-Sided) 95%
25.5 to 37.0
Estimation Comments Point estimate and 95% CI was calculated using CMH risk difference estimate.
3.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not the event is considered causally related to the use of the product.
Time Frame From first dose of study drug until 30 days following last dose of study drug (up to approximately 28 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population for Part 1 (SA1)=all participants who received at least one dose of the study drug in Part 1,SA2=all participants who received at least one dose of the study drug in Part 2, and SA3=all participants who received at least one dose of the study drug (upadacitinib 30 mg or upadacitinib 45 mg) in Part 3.
Arm/Group Title Part 1 (Double-blind): Placebo Part 1 (Double-blind): Upadacitinib 45 mg Part 2 (Open-label): Upadacitinib 45 mg Part 3 (Extended Treatment DB): Upadacitinib 45 mg From Part 1 DB Placebo Part 3 (Extended Treatment DB): Upadacitinib 30 mg From Part 1 DB Upadacitinib 45 mg Part 3 (Extended Treatment OL): Upadacitinib 30 mg From Part 2 OL Upadacitinib 45 mg
Hide Arm/Group Description:
Participants received upadacitinib matching placebo tablets, orally, once daily (QD) for 12 weeks during the Double-blind (DB) Induction Period.
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the Open-label (OL) Induction Period.
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks (until Week 24) during the Extended Treatment (ET) Period. Participants who received placebo in Part 1 and did not achieve clinical response at Week 12 were included in this group.
Participants received upadacitinib 30 mg tablets, orally, QD for 12 weeks (until Week 24) during the ET Period. Participants who received DB upadacitinib 45 mg in Part 1 and did not achieve clinical response at Week 12 were included in this group.
Participants received upadacitinib 30 mg tablets, orally, QD for 12 weeks (until Week 24) during the ET Period. Participants who received OL upadacitinib 45 mg during Part 2 and did not achieve clinical response at Week 12 were included in this group.
Overall Number of Participants Analyzed 171 324 129 78 69 14
Measure Type: Count of Participants
Unit of Measure: Participants
112
  65.5%
221
  68.2%
86
  66.7%
53
  67.9%
45
  65.2%
9
  64.3%
4.Secondary Outcome
Title Percentage of Participants With Clinical Remission Per Patient-Reported Outcomes (PROs) at Week 12
Hide Description Clinical remission per PROs was defined as average daily very soft or liquid stool frequency (SF) ≤2.8 and average daily abdominal pain (AP) score ≤1.0 and both not greater than Baseline. The number of soft or liquid stools and abdominal pain rated on a scale of 0=none to 3=severe were recorded in an electronic diary. Results were based on NRI-C.
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 Population included all randomized participants who received at least one dose of DB study drug during Part 1.
Arm/Group Title Part 1 (Double Blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg
Hide Arm/Group Description:
Participants received upadacitinib matching placebo tablets, orally, QD for 12 weeks during the DB Induction Period.
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
Overall Number of Participants Analyzed 171 324
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
14.0
(8.8 to 19.2)
39.8
(34.5 to 45.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Double Blind): Placebo, Part 1 (Double Blind): Upadacitinib 45 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was calculated using CMH test adjusted for randomization stratification factors.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 25.9
Confidence Interval (2-Sided) 95%
18.7 to 33.1
Estimation Comments Point estimate and 95% CI was calculated using CMH.
5.Secondary Outcome
Title Percentage of Participants With Endoscopic Remission at Week 12
Hide Description Endoscopic remission was defined per SES-CD. SES-CD ≤4 and at least 2-point reduction from Baseline and no subscore >1 in any individual variable, as scored by Central Reviewer. SES-CD is calculated based on the sum of individual segment values for four endoscopic variables (presence and size of ulcers, ulcerated surface, affected surface and presence of narrowing). Each variable in each segment is scored 0 to 3 resulting in SES-CD values ranging from 0 to 56 with higher scores indicating more severe disease. Results were based on NRI-C.
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 Population included all randomized participants who received at least one dose of DB study drug during Part 1.
Arm/Group Title Part 1 (Double Blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg
Hide Arm/Group Description:
Participants received upadacitinib matching placebo tablets, orally, QD for 12 weeks during the DB Induction Period.
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
Overall Number of Participants Analyzed 171 324
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
2.3
(0.1 to 4.6)
19.1
(14.9 to 23.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Double Blind): Placebo, Part 1 (Double Blind): Upadacitinib 45 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was calculated using CMH test adjusted for randomization stratification factors.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 16.8
Confidence Interval (2-Sided) 95%
12.0 to 21.6
Estimation Comments Point estimate and 95% CI was calculated using CMH.
6.Secondary Outcome
Title Percentage of Participants Who Discontinued Corticosteroid Use for Crohn's Disease (CD) and Achieved Clinical Remission Per CDAI at Week 12, in Participants Taking Corticosteroids at Baseline
Hide Description As prespecified in the protocol, this outcome measure was planned to be assessed in participants taking corticosteroids at Baseline. Clinical remission per CDAI: CDAI <150. The CDAI is used to evaluate the activity of Crohn's disease. The CDAI is calculated on the basis of a one-week evaluation of 8 items: frequency of liquid or very soft stool, abdominal pain, complications of Crohn's disease (e.g., uveitis, arthritis, fistula, and abscess), abdominal mass, hematocrit, body weight, use of antidiarrheals, and general condition. Total score ranges from 0 to about 600. Higher CDAI scores indicate more severe disease. CDAI scores below 150 represent remission and scores over 450 represent very severe Crohn's disease. Results were based on NRI-C.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 Population included all randomized participants who received at least one dose of DB study drug during Part 1. Overall Number of Participants Analyzed are the number of participants taking corticosteroids at Baseline.
Arm/Group Title Part 1 (Double Blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg
Hide Arm/Group Description:
Participants received upadacitinib matching placebo tablets, orally, QD for 12 weeks during the DB Induction Period.
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
Overall Number of Participants Analyzed 60 108
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
11.7
(3.5 to 19.8)
34.3
(25.3 to 43.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Double Blind): Placebo, Part 1 (Double Blind): Upadacitinib 45 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments P-value was calculated using CMH test adjusted for randomization stratification factors.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 22.5
Confidence Interval (2-Sided) 95%
11.1 to 34.0
Estimation Comments Point estimate and 95% CI was calculated using CMH.
7.Secondary Outcome
Title Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score at Week 12
Hide Description The FACIT-F questionnaire was developed to assess fatigue associated with anemia. It consists of 13 fatigue-related questions. The responses to the 13 items on the FACIT-F questionnaire are each measured on a 5-point Likert scale. The responses to the answers are the following: 0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4=very much. Thus, the total score ranges from 0 to 52. High scores represent less fatigue. A positive change from Baseline indicates improvement.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 Population included all randomized participants who received at least one dose of DB study drug during Part 1. Overall Number of Participants Analyzed are the number of participants with data available at the given timepoint.
Arm/Group Title Part 1 (Double Blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg
Hide Arm/Group Description:
Participants received upadacitinib matching placebo tablets, orally, QD for 12 weeks during the DB Induction Period.
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
Overall Number of Participants Analyzed 129 278
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
3.9  (0.97) 11.4  (0.69)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Double Blind): Placebo, Part 1 (Double Blind): Upadacitinib 45 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was calculated using mixed effect model repeat measurement (MMRM) with Baseline, treatment, visit, treatment by visit interaction and stratification factors in the model.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 7.5
Confidence Interval (2-Sided) 95%
5.2 to 9.8
Estimation Comments Point estimate and 95% CI was calculated using MMRM.
8.Secondary Outcome
Title Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 12
Hide Description The IBDQ is a disease-specific instrument composed of 32 Likert-scaled items. The IBDQ scale contains 4 component subscales: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function(5 items). Each item is scored on a 7-point scale where: 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 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 Population included all randomized participants who received at least one dose of DB study drug during Part 1. Overall Number of Participants Analyzed are the number of participants with data available at the given timepoint.
Arm/Group Title Part 1 (Double Blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg
Hide Arm/Group Description:
Participants received upadacitinib matching placebo tablets, orally, QD for 12 weeks during the DB Induction Period.
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
Overall Number of Participants Analyzed 130 280
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
21.6  (3.02) 46.0  (2.14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Double Blind): Placebo, Part 1 (Double Blind): Upadacitinib 45 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments P-value was calculated using MMRM with Baseline, treatment, visit, treatment by visit interaction and stratification factors in the model.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 24.3
Confidence Interval (2-Sided) 95%
17.2 to 31.5
Estimation Comments Point estimate and 95% CI was calculated using MMRM.
9.Secondary Outcome
Title Percentage of Participants Achieving Clinical Response 100 (CR-100) at Week 2
Hide Description CR-100 is defined as a decrease of at least 100 points in CDAI from Baseline at Week 2. The CDAI is used to evaluate the activity of Crohn's disease. The CDAI is calculated on the basis of a one-week evaluation of 8 items: frequency of liquid or very soft stool, abdominal pain, complications of Crohn's disease (e.g., uveitis, arthritis, fistula, and abscess), abdominal mass, hematocrit, body weight, use of antidiarrheals, and general condition. Total score ranges from 0 to about 600. Higher CDAI scores indicate more severe disease. CDAI scores below 150 represent remission and scores over 450 represent very severe Crohn's disease. Results were based on NRI-C.
Time Frame Baseline to Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 Population included all randomized participants who received at least one dose of DB study drug during Part 1.
Arm/Group Title Part 1 (Double Blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg
Hide Arm/Group Description:
Participants received upadacitinib matching placebo tablets, orally, QD for 12 weeks during the DB Induction Period.
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
Overall Number of Participants Analyzed 171 324
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
12.4
(7.4 to 17.4)
33.2
(28.0 to 38.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Double Blind): Placebo, Part 1 (Double Blind): Upadacitinib 45 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was calculated using CMH test adjusted for randomization stratification factors.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 20.7
Confidence Interval (2-Sided) 95%
13.7 to 27.8
Estimation Comments Point estimate and 95% CI was calculated using CMH.
10.Secondary Outcome
Title Percentage of Participants Achieving Clinical Response 100 (CR-100) at Week 12
Hide Description CR-100 is defined as a decrease of at least 100 points in CDAI from Baseline at Week 12. The CDAI is used to evaluate the activity of Crohn's disease. The CDAI is calculated on the basis of a one-week evaluation of 8 items: frequency of liquid or very soft stool, abdominal pain, complications of Crohn's disease (e.g., uveitis, arthritis, fistula, and abscess), abdominal mass, hematocrit, body weight, use of antidiarrheals, and general condition. Total score ranges from 0 to about 600. Higher CDAI scores indicate more severe disease. CDAI scores below 150 represent remission and scores over 450 represent very severe Crohn's disease. Results were based on NRI-C.
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 Population included all randomized participants who received at least one dose of DB study drug during Part 1.
Arm/Group Title Part 1 (Double Blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg
Hide Arm/Group Description:
Participants received upadacitinib matching placebo tablets, orally, QD for 12 weeks during the DB Induction Period.
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
Overall Number of Participants Analyzed 171 324
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
27.5
(20.8 to 34.2)
50.5
(45.1 to 56.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Double Blind): Placebo, Part 1 (Double Blind): Upadacitinib 45 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was calculated using CMH test adjusted for randomization stratification factors.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 22.8
Confidence Interval (2-Sided) 95%
14.4 to 31.2
Estimation Comments Point estimate and 95% CI was calculated using CMH.
11.Secondary Outcome
Title Percentage of Participants With Clinical Remission Per Crohn's Disease Activity Index (CDAI) at Week 4
Hide Description The CDAI was used to evaluate the activity of Crohn's disease. Clinical remission per CDAI is defined as CDAI <150. The CDAI is calculated on the basis of a one-week evaluation of 8 items: frequency of liquid or very soft stool, abdominal pain, complications of Crohn's disease (e.g., uveitis, arthritis, fistula, and abscess), abdominal mass, hematocrit, body weight, use of antidiarrheals, and general condition. Total score ranges from 0 to 600. Higher CDAI scores indicate more severe disease. CDAI scores below 150 represent remission and scores over 450 represent very severe Crohn's disease. Results were based on NRI-C.
Time Frame Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 Population included all randomized participants who received at least one dose of DB study drug during Part 1.
Arm/Group Title Part 1 (Double Blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg
Hide Arm/Group Description:
Participants received upadacitinib matching placebo tablets, orally, QD for 12 weeks during the DB Induction Period.
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
Overall Number of Participants Analyzed 171 324
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
17.7
(11.9 to 23.4)
29.6
(24.7 to 34.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Double Blind): Placebo, Part 1 (Double Blind): Upadacitinib 45 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0013
Comments P-value was calculated using CMH test adjusted for randomization stratification factors.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 12.1
Confidence Interval (2-Sided) 95%
4.7 to 19.5
Estimation Comments Point estimate and 95% CI was calculated using CMH.
12.Secondary Outcome
Title Percentage of Participants With Hospitalizations Due to Crohn's Disease (CD) During Part 1 (12-week Double-blind Induction Period)
Hide Description [Not Specified]
Time Frame Up to Week 12 in Part 1: Double-blind Induction Period
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 Population included all randomized participants who received at least one dose of DB study drug during Part 1.
Arm/Group Title Part 1 (Double Blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg
Hide Arm/Group Description:
Participants received upadacitinib matching placebo tablets, orally, QD for 12 weeks during the DB Induction Period.
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
Overall Number of Participants Analyzed 171 324
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
8.8
(4.5 to 13.0)
6.2
(3.6 to 8.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Double Blind): Placebo, Part 1 (Double Blind): Upadacitinib 45 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2834
Comments P-value was calculated using Chi-squared test.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-7.6 to 2.4
Estimation Comments Point estimate and 95% CI was calculated using Chi-squared test.
13.Secondary Outcome
Title Percentage of Participants With Resolution of Extra-Intestinal Manifestations (EIMs) at Week 12, in Participants With EIMs at Baseline
Hide Description EIMs are defined as manifestations of Crohn's disease in areas of the body other than the digestive tract, including eyes, skin, joints, mouth, and liver. Results were based on NRI-C.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 Population included all randomized participants who received at least one dose of DB study drug during Part 1. Overall Number of Participants Analyzed are the number of participants with any EIMs at Baseline.
Arm/Group Title Part 1 (Double Blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg
Hide Arm/Group Description:
Participants received upadacitinib matching placebo tablets, orally, QD for 12 weeks during the DB Induction Period.
Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period.
Overall Number of Participants Analyzed 60 131
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
21.7
(11.2 to 32.1)
32.8
(24.8 to 40.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 (Double Blind): Placebo, Part 1 (Double Blind): Upadacitinib 45 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0833
Comments P-value was calculated using CMH test adjusted for randomization stratification factors.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 11.5
Confidence Interval (2-Sided) 95%
-1.5 to 24.4
Estimation Comments Point estimate and 95% CI was calculated using CMH.
Time Frame From first dose of study drug until 30 days following last dose of study drug (up to approximately 28 weeks)
Adverse Event Reporting Description Safety Population for Part 1 (SA1)=all participants who received at least one dose of the study drug in Part 1,SA2=all participants who received at least one dose of the study drug in Part 2, and SA3=all participants who received at least one dose of the study drug (upadacitinib 30 mg or upadacitinib 45 mg) in Part 3.
 
Arm/Group Title Part 1 (Double-blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg Part 2 (Open Label): Upadacitinib 45 mg Part 3 (Extended Treatment DB): Upadacitinib 45 mg From Part 1 DB Placebo Part 3 (Extended Treatment DB): Upadacitinib 30 mg From Part 1 DB Upadacitinib 45 mg Part 3 (Extended Treatment OL): Upadacitinib 30 mg From Part 2 OL Upadacitinib 45 mg
Hide Arm/Group Description Participants received upadacitinib matching placebo tablets, orally, QD for 12 weeks during the DB Induction Period. Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the DB Induction Period. Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks during the OL Induction Period. Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks (until Week 24) during the Extended Treatment Period. Participants who received placebo in Part 1 and did not achieve clinical response at Week 12 were included in this group. Participants received upadacitinib 45 mg tablets, orally, QD for 12 weeks (until Week 24) during the Extended Treatment Period. Participants who received placebo in Part 1 and did not achieve clinical response at Week 12 were included in this group. Participants received upadacitinib 30 mg tablets, orally, QD for 12 weeks (until Week 24) during the Extended Treatment Period. Participants who received OL upadacitinib 45 mg during Part 2 and did not achieve clinical response at Week 12 were included in this group.
All-Cause Mortality
Part 1 (Double-blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg Part 2 (Open Label): Upadacitinib 45 mg Part 3 (Extended Treatment DB): Upadacitinib 45 mg From Part 1 DB Placebo Part 3 (Extended Treatment DB): Upadacitinib 30 mg From Part 1 DB Upadacitinib 45 mg Part 3 (Extended Treatment OL): Upadacitinib 30 mg From Part 2 OL Upadacitinib 45 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/171 (0.00%)      1/324 (0.31%)      0/129 (0.00%)      0/78 (0.00%)      0/69 (0.00%)      0/14 (0.00%)    
Hide Serious Adverse Events
Part 1 (Double-blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg Part 2 (Open Label): Upadacitinib 45 mg Part 3 (Extended Treatment DB): Upadacitinib 45 mg From Part 1 DB Placebo Part 3 (Extended Treatment DB): Upadacitinib 30 mg From Part 1 DB Upadacitinib 45 mg Part 3 (Extended Treatment OL): Upadacitinib 30 mg From Part 2 OL Upadacitinib 45 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
Total   17/171 (9.94%)      30/324 (9.26%)      9/129 (6.98%)      11/78 (14.10%)      7/69 (10.14%)      5/14 (35.71%)    
Blood and lymphatic system disorders             
ANAEMIA  1  1/171 (0.58%)  1 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
FEBRILE NEUTROPENIA  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 1/69 (1.45%)  1 0/14 (0.00%)  0
LEUKOPENIA  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 1/69 (1.45%)  1 0/14 (0.00%)  0
Ear and labyrinth disorders             
VERTIGO  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
Gastrointestinal disorders             
ABDOMINAL PAIN  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 1/78 (1.28%)  1 0/69 (0.00%)  0 0/14 (0.00%)  0
ABDOMINAL PAIN UPPER  1  1/171 (0.58%)  1 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
COLITIS  1  1/171 (0.58%)  1 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
CONSTIPATION  1  1/171 (0.58%)  1 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
CROHN'S DISEASE  1  10/171 (5.85%)  13 7/324 (2.16%)  7 4/129 (3.10%)  4 3/78 (3.85%)  3 4/69 (5.80%)  5 3/14 (21.43%)  3
ENTEROCUTANEOUS FISTULA  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 1/78 (1.28%)  1 0/69 (0.00%)  0 0/14 (0.00%)  0
GASTROINTESTINAL HAEMORRHAGE  1  0/171 (0.00%)  0 3/324 (0.93%)  3 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
HAEMATOCHEZIA  1  1/171 (0.58%)  1 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
HAEMORRHOIDS  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 1/78 (1.28%)  1 0/69 (0.00%)  0 0/14 (0.00%)  0
ILEAL PERFORATION  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 1/78 (1.28%)  1 0/69 (0.00%)  0 0/14 (0.00%)  0
ILEUS  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
INTESTINAL OBSTRUCTION  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 1/78 (1.28%)  1 0/69 (0.00%)  0 0/14 (0.00%)  0
INTESTINAL PERFORATION  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
INTESTINAL STENOSIS  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
PANCREATITIS ACUTE  1  1/171 (0.58%)  1 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
SMALL INTESTINAL OBSTRUCTION  1  0/171 (0.00%)  0 1/324 (0.31%)  1 1/129 (0.78%)  1 0/78 (0.00%)  0 1/69 (1.45%)  1 0/14 (0.00%)  0
General disorders             
PYREXIA  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 1/78 (1.28%)  1 0/69 (0.00%)  0 0/14 (0.00%)  0
Hepatobiliary disorders             
CHOLELITHIASIS  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
Infections and infestations             
ABDOMINAL ABSCESS  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 1/14 (7.14%)  1
ABDOMINAL WALL ABSCESS  1  0/171 (0.00%)  0 0/324 (0.00%)  0 1/129 (0.78%)  2 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
ANAL ABSCESS  1  2/171 (1.17%)  2 3/324 (0.93%)  4 1/129 (0.78%)  1 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
COVID-19  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
COVID-19 PNEUMONIA  1  0/171 (0.00%)  0 0/324 (0.00%)  0 2/129 (1.55%)  2 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
COLONIC ABSCESS  1  0/171 (0.00%)  0 0/324 (0.00%)  0 1/129 (0.78%)  1 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
CYTOMEGALOVIRUS INFECTION  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
GASTROENTERITIS  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 1/14 (7.14%)  1
GASTROENTERITIS VIRAL  1  1/171 (0.58%)  1 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
PNEUMOCYSTIS JIROVECII PNEUMONIA  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
PYELONEPHRITIS ACUTE  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
RETROPERITONEAL ABSCESS  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 1/78 (1.28%)  1 0/69 (0.00%)  0 0/14 (0.00%)  0
SEPTIC SHOCK  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
UPPER RESPIRATORY TRACT INFECTION  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 1/78 (1.28%)  1 0/69 (0.00%)  0 0/14 (0.00%)  0
URINARY TRACT INFECTION  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
Injury, poisoning and procedural complications             
FALL  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 1/78 (1.28%)  1 0/69 (0.00%)  0 0/14 (0.00%)  0
POSTOPERATIVE ILEUS  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 1/78 (1.28%)  1 0/69 (0.00%)  0 0/14 (0.00%)  0
SPINAL COMPRESSION FRACTURE  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 1/78 (1.28%)  1 0/69 (0.00%)  0 0/14 (0.00%)  0
Metabolism and nutrition disorders             
GOUT  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
HYPOKALAEMIA  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 1/14 (7.14%)  1
TYPE 1 DIABETES MELLITUS  1  1/171 (0.58%)  1 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
Musculoskeletal and connective tissue disorders             
ANKYLOSING SPONDYLITIS  1  1/171 (0.58%)  1 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
Psychiatric disorders             
DEPRESSION  1  1/171 (0.58%)  1 0/324 (0.00%)  0 0/129 (0.00%)  0 1/78 (1.28%)  1 0/69 (0.00%)  0 0/14 (0.00%)  0
DRUG ABUSE  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
DRUG USE DISORDER  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
PSYCHOTIC DISORDER  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
Renal and urinary disorders             
NEPHROLITHIASIS  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 1/69 (1.45%)  1 0/14 (0.00%)  0
URETEROLITHIASIS  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
Reproductive system and breast disorders             
FEMALE GENITAL TRACT FISTULA  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
UTERINE POLYP  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
LUNG DISORDER  1  0/171 (0.00%)  0 1/324 (0.31%)  1 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 0/14 (0.00%)  0
Skin and subcutaneous tissue disorders             
ANGIOEDEMA  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 1/78 (1.28%)  1 0/69 (0.00%)  0 0/14 (0.00%)  0
1
Term from vocabulary, MedDRA 24.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1 (Double-blind): Placebo Part 1 (Double Blind): Upadacitinib 45 mg Part 2 (Open Label): Upadacitinib 45 mg Part 3 (Extended Treatment DB): Upadacitinib 45 mg From Part 1 DB Placebo Part 3 (Extended Treatment DB): Upadacitinib 30 mg From Part 1 DB Upadacitinib 45 mg Part 3 (Extended Treatment OL): Upadacitinib 30 mg From Part 2 OL Upadacitinib 45 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
Total   69/171 (40.35%)      126/324 (38.89%)      44/129 (34.11%)      29/78 (37.18%)      12/69 (17.39%)      7/14 (50.00%)    
Blood and lymphatic system disorders             
ANAEMIA  1  9/171 (5.26%)  12 16/324 (4.94%)  17 6/129 (4.65%)  6 3/78 (3.85%)  3 1/69 (1.45%)  1 0/14 (0.00%)  0
Gastrointestinal disorders             
ABDOMINAL PAIN  1  11/171 (6.43%)  13 9/324 (2.78%)  10 1/129 (0.78%)  1 3/78 (3.85%)  3 0/69 (0.00%)  0 0/14 (0.00%)  0
CONSTIPATION  1  1/171 (0.58%)  1 7/324 (2.16%)  7 7/129 (5.43%)  7 1/78 (1.28%)  1 0/69 (0.00%)  0 0/14 (0.00%)  0
CROHN'S DISEASE  1  13/171 (7.60%)  13 12/324 (3.70%)  12 5/129 (3.88%)  5 5/78 (6.41%)  5 4/69 (5.80%)  4 1/14 (7.14%)  1
NAUSEA  1  8/171 (4.68%)  9 15/324 (4.63%)  15 3/129 (2.33%)  3 3/78 (3.85%)  3 1/69 (1.45%)  1 2/14 (14.29%)  2
VOMITING  1  4/171 (2.34%)  5 8/324 (2.47%)  8 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 2/14 (14.29%)  2
General disorders             
PYREXIA  1  8/171 (4.68%)  8 13/324 (4.01%)  13 4/129 (3.10%)  5 4/78 (5.13%)  4 1/69 (1.45%)  1 0/14 (0.00%)  0
Infections and infestations             
FOLLICULITIS  1  1/171 (0.58%)  1 5/324 (1.54%)  5 2/129 (1.55%)  2 5/78 (6.41%)  5 0/69 (0.00%)  0 0/14 (0.00%)  0
INFLUENZA  1  2/171 (1.17%)  2 9/324 (2.78%)  10 1/129 (0.78%)  1 2/78 (2.56%)  2 3/69 (4.35%)  3 1/14 (7.14%)  1
NASOPHARYNGITIS  1  5/171 (2.92%)  5 23/324 (7.10%)  24 2/129 (1.55%)  2 3/78 (3.85%)  4 2/69 (2.90%)  2 0/14 (0.00%)  0
UPPER RESPIRATORY TRACT INFECTION  1  5/171 (2.92%)  5 17/324 (5.25%)  18 1/129 (0.78%)  1 2/78 (2.56%)  3 2/69 (2.90%)  2 0/14 (0.00%)  0
Investigations             
BLOOD PHOSPHORUS DECREASED  1  0/171 (0.00%)  0 1/324 (0.31%)  1 1/129 (0.78%)  1 0/78 (0.00%)  0 0/69 (0.00%)  0 1/14 (7.14%)  2
Musculoskeletal and connective tissue disorders             
ARTHRALGIA  1  11/171 (6.43%)  11 7/324 (2.16%)  7 2/129 (1.55%)  2 2/78 (2.56%)  2 1/69 (1.45%)  1 0/14 (0.00%)  0
BACK PAIN  1  11/171 (6.43%)  12 4/324 (1.23%)  4 0/129 (0.00%)  0 2/78 (2.56%)  2 1/69 (1.45%)  1 0/14 (0.00%)  0
FISTULA DISCHARGE  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 1/14 (7.14%)  1
Nervous system disorders             
HEADACHE  1  9/171 (5.26%)  10 20/324 (6.17%)  24 8/129 (6.20%)  8 2/78 (2.56%)  2 0/69 (0.00%)  0 0/14 (0.00%)  0
Psychiatric disorders             
INSOMNIA  1  2/171 (1.17%)  2 5/324 (1.54%)  5 1/129 (0.78%)  1 1/78 (1.28%)  1 0/69 (0.00%)  0 1/14 (7.14%)  1
Renal and urinary disorders             
HAEMATURIA  1  0/171 (0.00%)  0 0/324 (0.00%)  0 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 1/14 (7.14%)  1
Skin and subcutaneous tissue disorders             
ACNE  1  4/171 (2.34%)  4 15/324 (4.63%)  16 18/129 (13.95%)  18 5/78 (6.41%)  5 0/69 (0.00%)  0 0/14 (0.00%)  0
ALOPECIA  1  0/171 (0.00%)  0 3/324 (0.93%)  3 0/129 (0.00%)  0 0/78 (0.00%)  0 0/69 (0.00%)  0 1/14 (7.14%)  1
1
Term from vocabulary, MedDRA 24.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
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Name/Title: Global Medical Services
Organization: AbbVie
Phone: 800-633-9110
EMail: abbvieclinicaltrials@abbvie.com
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03345836    
Other Study ID Numbers: M14-431
2017-001226-18 ( EudraCT Number )
First Submitted: November 15, 2017
First Posted: November 17, 2017
Results First Submitted: July 18, 2022
Results First Posted: August 15, 2022
Last Update Posted: August 15, 2022