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Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Upadacitinib (ABT-494) for the Induction of Symptomatic and Endoscopic Remission in Subjects with Moderately to Severely Active Crohn's Disease who have Inadequately Responded to or are Intolerant to Immunomodulators or Anti-TNF Therapy

Summary
EudraCT number	2014-003240-12
Trial protocol	BE HU DE ES DK NO SK NL CZ PL IT
Global end of trial date	03 Aug 2017

Results information
Results version number	v1(current)
This version publication date	11 Aug 2018
First version publication date	11 Aug 2018
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

M13-740

ISRCTN number

US NCT number

NCT02365649

WHO universal trial number (UTN)

Sponsor organisation name

AbbVie Deutschland GmbH & Co.KG

Sponsor organisation address

AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB

Public contact

Fabio Cataldi, AbbVie, fabio.cataldi@abbvie.com

Scientific contact

Fabio Cataldi, AbbVie, fabio.cataldi@abbvie.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

03 Aug 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 Aug 2017

Was the trial ended prematurely?

Main objective of the trial

The objectives of this study are to determine the efficacy and safety of multiple doses of ABT-494 (upadacitinib) versus placebo and to assess the pharmacokinetics (PK) of ABT-494 following oral administration in subjects with moderately to severely active Crohn's Disease with a history of inadequate response to or intolerance to immunomodulators or anti-TNF therapy.

Protection of trial subjects

Participant and/or legal guardian read and understood the information provided about the study and gave written permission.

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Mar 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 2

Country: Number of subjects enrolled

Canada: 26

Country: Number of subjects enrolled

Israel: 4

Country: Number of subjects enrolled

New Zealand: 1

Country: Number of subjects enrolled

United States: 104

Country: Number of subjects enrolled

Netherlands: 9

Country: Number of subjects enrolled

Norway: 2

Country: Number of subjects enrolled

Poland: 7

Country: Number of subjects enrolled

Romania: 5

Country: Number of subjects enrolled

Slovakia: 5

Country: Number of subjects enrolled

Spain: 4

Country: Number of subjects enrolled

United Kingdom: 6

Country: Number of subjects enrolled

Belgium: 9

Country: Number of subjects enrolled

Czech Republic: 3

Country: Number of subjects enrolled

Denmark: 4

Country: Number of subjects enrolled

France: 7

Country: Number of subjects enrolled

Germany: 17

Country: Number of subjects enrolled

Hungary: 2

Country: Number of subjects enrolled

Italy: 3

Worldwide total number of subjects

220

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

211

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

This multicenter, randomized Phase 2 study included an up to 35-day Screening Period.

Period 1 title

Double-Blind Induction (Weeks 1-16)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Subject

Blinding implementation details

The Investigator, study site personnel, the subject and all AbbVie personnel with direct oversight of the conduct and management of the trial (with the exception of AbbVie Drug Supply Management Team) remained blinded to each subject's treatment throughout the course of the study.

Are arms mutually exclusive

Yes

Placebo Twice Daily (BID)

Arm description

Placebo BID during the 16-week double-blind Induction Phase.

Arm type

Placebo

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Study drug was taken orally. Subjects were instructed to take 2 daily doses of 2 capsules (4 capsules daily) at approximately the same time each day.

Upadacitinib 3 mg BID

Arm description

Upadacitinib 3 mg BID during the 16-week double-blind Induction Phase.

Arm type

Experimental

Investigational medicinal product name

upadacitinib 3 mg

Investigational medicinal product code

ABT-494

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Study drug was taken orally. Subjects were instructed to take 2 daily doses of 2 capsules (4 capsules daily) at approximately the same time each day. Placebo was used to maintain the blind.

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Study drug was taken orally. Subjects were instructed to take 2 daily doses of 2 capsules (4 capsules daily) at approximately the same time each day. Placebo for 3 mg or 12 mg upadacitinib was used in the upadacitinib 3 mg BID, 12 mg BID and 24 mg once daily (QD) arms to maintain the blind.

Upadacitinib 6 mg BID

Arm description

Upadacitinib 6 mg BID during the 16-week double-blind Induction Phase.

Arm type

Experimental

Investigational medicinal product name

upadacitinib 3 mg

Investigational medicinal product code

ABT-494

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Study drug was taken orally. Subjects were instructed to take 2 daily doses of 2 capsules (4 capsules daily) at approximately the same time each day.

Upadacitinib 12 mg BID

Arm description

Upadacitinib 12 mg BID during the 16-week double-blind Induction Phase.

Arm type

Experimental

Investigational medicinal product name

Upadacitinib 12 mg

Investigational medicinal product code

ABT-494

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Study drug was taken orally. Subjects were instructed to take 2 daily doses of 2 capsules (4 capsules daily) at approximately the same time each day. Placebo was used to maintain the blind.

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Upadacitinib 24 mg BID

Arm description

Upadacitinib 24 mg BID during the 16-week double-blind Induction Phase.

Arm type

Experimental

Investigational medicinal product name

Upadacitinib 12 mg

Investigational medicinal product code

ABT-494

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Study drug was taken orally. Subjects were instructed to take 2 daily doses of 2 capsules (4 capsules daily) at approximately the same time each day.

Upadacitinib 24 mg QD

Arm description

Upadacitinib 24 mg once daily (consisting of two 12 mg immediate release [IR] doses) during the 16-week double-blind Induction Phase.

Arm type

Experimental

Investigational medicinal product name

Upadacitinib 12 mg

Investigational medicinal product code

ABT-494

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Study drug was taken orally. Subjects were instructed to take 2 daily doses of 2 capsules (4 capsules daily) at approximately the same time each day.

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 1	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Started	37	39	37	36	36	35
Completed	27	34	33	27	29	30
Not completed	10	5	4	9	7	5
Consent withdrawn by subject	2	-	1	-	2	-
Requires alternative therapy	-	-	-	1	-	-
Subject non-compliance	1	-	-	-	1	1
Not specified	1	-	1	-	1	1
Adverse event	3	4	-	7	1	2
Lost to follow-up	-	-	1	-	-	-
Lack of efficacy	3	1	1	1	2	1

Period 2 title

Double-Blind Extension (Weeks 16-52)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Blinding implementation details

Are arms mutually exclusive

Yes

Upadacitinib 3 mg BID

Arm description

Upadacitinib 3 mg BID during the 36-week double-blind Extension Phase.

Arm type

Experimental

Investigational medicinal product name

upadacitinib 3 mg

Investigational medicinal product code

ABT-494

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Study drug was taken orally. Subjects were instructed to take 2 daily doses of 2 capsules (4 capsules daily) at approximately the same time each day. Placebo was used to maintain the blind.

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Upadacitinib 6 mg BID

Arm description

Upadacitinib 6 mg BID during the 36-week double-blind Extension Phase.

Arm type

Experimental

Investigational medicinal product name

upadacitinib 3 mg

Investigational medicinal product code

ABT-494

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Study drug was taken orally. Subjects were instructed to take 2 daily doses of 2 capsules (4 capsules daily) at approximately the same time each day.

Upadacitinib 12 mg BID

Arm description

Upadacitinib 12 mg BID during the 36-week double-blind Extension Phase.

Arm type

Experimental

Investigational medicinal product name

Upadacitinib 12 mg

Investigational medicinal product code

ABT-494

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Study drug was taken orally. Subjects were instructed to take 2 daily doses of 2 capsules (4 capsules daily) at approximately the same time each day. Placebo was used to maintain the blind.

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Study drug was taken orally twice a day for 16 weeks beginning on Baseline. Subjects were instructed to take 2 daily doses of 2 capsules (4 capsules daily) at approximately the same time each day. Placebo for 3 mg or 12 mg upadacitinib was used in the upadacitinib 3 mg BID, 12 mg BID and 24 mg QD arms to maintain the blind.

Upadacitinib 24 mg QD

Arm description

Upadacitinib 24 mg QD (consisting of two 12 mg IR doses) during the 36-week double-blind Extension Phase.

Arm type

Experimental

Investigational medicinal product name

Upadacitinib 12 mg

Investigational medicinal product code

ABT-494

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Study drug was taken orally. Subjects were instructed to take 2 daily doses of 2 capsules (4 capsules daily) at approximately the same time each day. Placebo was used to maintain the blind.

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 2	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg QD
Started	61	23	59	37
Completed	43	21	43	22
Not completed	18	2	16	15
Consent withdrawn by subject	1	-	2	1
Requires alternative therapy	2	-	-	-
Subject non-compliance	2	-	2	-
Adverse event	6	-	4	4
Lack of efficacy	7	2	8	10

Baseline characteristics

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Reporting group title

Placebo Twice Daily (BID)

Reporting group description

Placebo BID during the 16-week double-blind Induction Phase.

Reporting group title

Upadacitinib 3 mg BID

Reporting group description

Upadacitinib 3 mg BID during the 16-week double-blind Induction Phase.

Reporting group title

Upadacitinib 6 mg BID

Reporting group description

Upadacitinib 6 mg BID during the 16-week double-blind Induction Phase.

Reporting group title

Upadacitinib 12 mg BID

Reporting group description

Upadacitinib 12 mg BID during the 16-week double-blind Induction Phase.

Reporting group title

Upadacitinib 24 mg BID

Reporting group description

Upadacitinib 24 mg BID during the 16-week double-blind Induction Phase.

Reporting group title

Upadacitinib 24 mg QD

Reporting group description

Upadacitinib 24 mg once daily (consisting of two 12 mg immediate release [IR] doses) during the 16-week double-blind Induction Phase.

Reporting group values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD	Total
Number of subjects	37	39	37	36	36	35	220
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	40.5 ( 12.14 )	39.7 ( 14.03 )	40.5 ( 13.41 )	40.8 ( 15.18 )	42.5 ( 10.02 )	40.2 ( 12.60 )	-
Gender categorical
Units: Subjects
Female	24	19	21	17	25	19	125
Male	13	20	16	19	11	16	95
High-sensitivity C-reactive protein (hsCRP)
Units: mg/L
arithmetic mean (standard deviation)	20.8 ( 34.29 )	23.6 ( 51.43 )	17.9 ( 17.92 )	26.9 ( 28.86 )	17.1 ( 26.49 )	17.1 ( 20.83 )	-
Fecal Calprotectin
n=31, 33, 36, 33, 29, 31, respectively, for placebo, upadacitinib 3 mg BID, 6 mg BID, 12 mg BID, 24 mg BID, 24 mg QD.
Units: mcg/g
arithmetic mean (standard deviation)	1734.7 ( 2444.07 )	1925.9 ( 2804.07 )	2128.5 ( 1978.73 )	2067.9 ( 2250.97 )	2074.8 ( 2324.15 )	1808.7 ( 2548.11 )	-
Inflammatory Bowel Disease Questionnaire (IBDQ)
The IBDQ is a disease-specific instrument composed of 32 Likert-scaled items. The total score ranges from 32 to 224 using the 7-point response options, with higher scores indicating better health-related quality of life. The IBDQ scale contains 4 component subscales: bowel symptoms, systemic symptoms, emotional function, and social function. Each subscale can be computed with total scores ranging from 10 to 70, 5 to 35, 12 to 84, and 5 to 35, respectively. n=37, 38, 36, 35, 36, 34, respectively, for placebo, upadacitinib 3 mg BID, 6 mg BID, 12 mg BID, 24 mg BID, 24 mg QD.
Units: units on a scale
arithmetic mean (standard deviation)	118.0 ( 28.45 )	115.2 ( 27.48 )	113.7 ( 25.86 )	115.2 ( 36.05 )	113.8 ( 35.97 )	120.7 ( 36.25 )	-

End points

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Reporting group title

Placebo Twice Daily (BID)

Reporting group description

Placebo BID during the 16-week double-blind Induction Phase.

Reporting group title

Upadacitinib 3 mg BID

Reporting group description

Upadacitinib 3 mg BID during the 16-week double-blind Induction Phase.

Reporting group title

Upadacitinib 6 mg BID

Reporting group description

Upadacitinib 6 mg BID during the 16-week double-blind Induction Phase.

Reporting group title

Upadacitinib 12 mg BID

Reporting group description

Upadacitinib 12 mg BID during the 16-week double-blind Induction Phase.

Reporting group title

Upadacitinib 24 mg BID

Reporting group description

Upadacitinib 24 mg BID during the 16-week double-blind Induction Phase.

Reporting group title

Upadacitinib 24 mg QD

Reporting group description

Upadacitinib 24 mg once daily (consisting of two 12 mg immediate release [IR] doses) during the 16-week double-blind Induction Phase.

Reporting group title

Upadacitinib 3 mg BID

Reporting group description

Upadacitinib 3 mg BID during the 36-week double-blind Extension Phase.

Reporting group title

Upadacitinib 6 mg BID

Reporting group description

Upadacitinib 6 mg BID during the 36-week double-blind Extension Phase.

Reporting group title

Upadacitinib 12 mg BID

Reporting group description

Upadacitinib 12 mg BID during the 36-week double-blind Extension Phase.

Reporting group title

Upadacitinib 24 mg QD

Reporting group description

Upadacitinib 24 mg QD (consisting of two 12 mg IR doses) during the 36-week double-blind Extension Phase.

Subject analysis set title

ITT: 3 mg BID, Upadacitinib in Induction

Subject analysis set type

Intention-to-treat

Subject analysis set description

Includes intent-to-treat responder (ITT-R) and non-responder (ITT-NR) analysis sets: all re-randomized subjects in the double-blind Extension Phase who were responders and nonresponders at Week 16 of the Induction Period, respectively. Includes only ITT subjects who were randomized to upadacitinib at Induction.

Subject analysis set title

ITT: 6 mg BID, Upadacitinib at Induction

Subject analysis set type

Intention-to-treat

Subject analysis set description

Includes ITT-R and ITT-NR analysis sets: all re-randomized subjects in the double-blind Extension Phase who were responders and nonresponders at Week 16 of the Induction Period, respectively. Includes only ITT subjects who were randomized to upadacitinib at Induction.

Subject analysis set title

ITT: 12 mg BID, Upadacitinib at Induction

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

ITT: 24 mg QD, Upadacitinib at Induction

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

ITT: 3 mg BID, Placebo in Induction

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

ITT: 6 mg BID, Placebo at Induction

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

ITT: 12 mg BID, Placebo at Induction

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

ITT: 24 mg QD, Placebo at Induction

Subject analysis set type

Intention-to-treat

Subject analysis set description

Primary: Percentage of Subjects Who Achieve Endoscopic Remission at Week 12/16

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End point title

Percentage of Subjects Who Achieve Endoscopic Remission at Week 12/16

End point description

Endoscopic remission was determined using Simplified Endoscopic Score for Crohn's Disease (SES-CD). SES-CD subscores assess the following: presence and size of ulcers in 5 visualized bowel segments; extent of ulcerated surface in 5 visualized bowel segments; extent of affected surface in 5 visualized bowel segments; presence and type of narrowings in 5 visualized bowel segments. Subscores range from 0 to 15, and are summed for a total SES-CD score ranging from 0 to 56; higher scores indicate greater severity of mucosal inflammation. Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Modified intention to Treat (mITT) Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.

End point type

Primary

End point timeframe

Up to Week 16. (At Baseline, subjects were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.)

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	37	39	37	36	36	35
Units: percentage of subjects
number (not applicable)	0	10.3	8.1	8.3	22.2	14.3

Statistical Analysis 1

Comparison groups

Upadacitinib 3 mg BID v Placebo Twice Daily (BID)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.056 ^[1]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

9.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

20.1

Notes
[1] - Statistical significance was prespecified at α = 0.1. Based on Cochran-Mantel-Haenszel (CMH) test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.108 ^[2]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

7.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

16.4

Notes
[2] - Statistical significance was prespecified at α = 0.1. Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.099 ^[3]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

7.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

16.8

Notes
[3] - Statistical significance was prespecified at α = 0.1. Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[4]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

6.8

upper limit

35.2

Notes
[4] - Statistical significance was prespecified at α = 0.1. Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.025 ^[5]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

13.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.8

upper limit

25.5

Notes
[5] - Statistical significance was prespecified at α = 0.1. Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Primary: Percentage of Subjects Who Achieve Clinical Remission at Week 16

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End point title

Percentage of Subjects Who Achieve Clinical Remission at Week 16

End point description

Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.

End point type

Primary

End point timeframe

Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	37	39	37	36	36	35
Units: percentage of subjects
number (not applicable)	10.8	12.8	27.0	11.1	22.2	14.3

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.74 ^[6]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-12.3

upper limit

17.3

Notes
[6] - Statistical significance was prespecified at α = 0.1. Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.082 ^[7]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

34.3

Notes
[7] - Statistical significance was prespecified at α = 0.1. Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.952 ^[8]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-14.1

upper limit

Notes
[8] - Statistical significance was prespecified at α = 0.1. Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.205 ^[9]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

11.2

Confidence interval

level

95%

sides

2-sided

lower limit

-6.1

upper limit

28.5

Notes
[9] - Statistical significance was prespecified at α = 0.1. Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.607 ^[10]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

4.1

Confidence interval

level

95%

sides

2-sided

lower limit

-11.5

upper limit

19.6

Notes
[10] - Statistical significance was prespecified at α = 0.1. Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Percentage of Subjects Who Achieve Crohn's Disease Activity Index (CDAI) < 150 at Week 16

Top of page

End point title

Percentage of Subjects Who Achieve Crohn's Disease Activity Index (CDAI) < 150 at Week 16

End point description

CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A score below 150 indicates remission. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	37	39	37	36	36	35
Units: percentage of subjects
number (not applicable)	16.2	20.5	29.7	38.9	30.6	20.0

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.564 ^[11]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

5.2

Confidence interval

level

95%

sides

2-sided

lower limit

-12.5

upper limit

22.9

Notes
[11] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.221 ^[12]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.2

upper limit

31.2

Notes
[12] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.036 ^[13]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

22.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.4

upper limit

Notes
[13] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.179 ^[14]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

13.4

Confidence interval

level

95%

sides

2-sided

lower limit

-6.2

upper limit

33.1

Notes
[14] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.677 ^[15]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-14.3

upper limit

Notes
[15] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Percentage of Subjects With a Decrease in CDAI ≥ 70 Points From Baseline at Week 16

Top of page

End point title

Percentage of Subjects With a Decrease in CDAI ≥ 70 Points From Baseline at Week 16

End point description

CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A 70-point decrease in the CDAI index refers to improvement in the disease activity from Baseline. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	37	39	37	36	36	35
Units: percentage of subjects
number (not applicable)	35.1	46.2	54.1	44.4	61.1	48.6

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.363 ^[16]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

10.4

Confidence interval

level

95%

sides

2-sided

lower limit

-12

upper limit

32.9

Notes
[16] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.137 ^[17]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

17.3

Confidence interval

level

95%

sides

2-sided

lower limit

-5.5

upper limit

Notes
[17] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.512 ^[18]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

7.5

Confidence interval

level

95%

sides

2-sided

lower limit

-14.9

upper limit

29.9

Notes
[18] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.035 ^[19]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

48.2

Notes
[19] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.29 ^[20]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

12.5

Confidence interval

level

95%

sides

2-sided

lower limit

-10.7

upper limit

35.6

Notes
[20] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Percentage of Subjects Who Achieve Clinical Remission at Week 12

Top of page

End point title

Percentage of Subjects Who Achieve Clinical Remission at Week 12

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	37	39	37	36	36	35
Units: percentage of subjects
number (not applicable)	10.8	10.3	29.7	13.9	25.0	8.6

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.896 ^[21]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-15

upper limit

13.1

Notes
[21] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.05 ^[22]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

18.6

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

37.3

Notes
[22] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.702 ^[23]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-12.4

upper limit

18.4

Notes
[23] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.117 ^[24]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

14.3

Confidence interval

level

95%

sides

2-sided

lower limit

-3.6

upper limit

32.2

Notes
[24] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.736 ^[25]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

-2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-16.4

upper limit

11.6

Notes
[25] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Percentage of Subjects Who Achieve Remission at Week 16

Top of page

End point title

Percentage of Subjects Who Achieve Remission at Week 16

End point description

Remission is defined as endoscopic remission at Week 12/16 AND clinical remission at Week 16. Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	37	39	37	36	36	35
Units: percentage of subjects
number (not applicable)	0	2.6	5.4	2.8	8.3	5.7

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.276 ^[26]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

8.1

Notes
[26] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.195 ^[27]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

4.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

12.4

Notes
[27] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.355 ^[28]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

Notes
[28] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.099 ^[29]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

7.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

16.8

Notes
[29] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.185 ^[30]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

5.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

12.9

Notes
[30] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Percentage of Subjects Who Achieve Response at Week 16

Top of page

End point title

Percentage of Subjects Who Achieve Response at Week 16

End point description

Response is defined as endoscopic response at Week 12/16 AND clinical response at Week 16. Endoscopic response: SES-CD at least 25% reduction from Baseline. Clinical response: average daily stool frequency at least 30% reduction from Baseline and average daily abdominal pain not worse than Baseline OR average daily abdominal pain at least 30% reduction from Baseline and average daily stool frequency not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	37	39	37	36	36	35
Units: percentage of subjects
number (not applicable)	2.7	15.4	32.4	27.8	38.9	34.3

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.05 ^[31]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

13.2

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

26.5

Notes
[31] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[32]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

29.5

Confidence interval

level

95%

sides

2-sided

lower limit

11.9

upper limit

47.1

Notes
[32] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[33]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

25.2

Confidence interval

level

95%

sides

2-sided

lower limit

8.5

upper limit

Notes
[33] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[34]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

36.5

Confidence interval

level

95%

sides

2-sided

lower limit

17.6

upper limit

55.4

Notes
[34] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[35]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

13.9

upper limit

50.2

Notes
[35] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Percentage of Subjects With Endoscopic Response at Week 12/16

Top of page

End point title

Percentage of Subjects With Endoscopic Response at Week 12/16

End point description

Endoscopic response: SES-CD at least 25% reduction from Baseline. Details of the SES-CD scale are provided in the description of the first primary endpoint. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.

End point type

Secondary

End point timeframe

Up to Week 16. (At Baseline, patients were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.)

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	37	39	37	36	36	35
Units: percentage of subjects
number (not applicable)	13.5	23.1	43.2	36.1	50.0	48.6

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.243 ^[36]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

10.5

Confidence interval

level

95%

sides

2-sided

lower limit

-7.2

upper limit

28.2

Notes
[36] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006 ^[37]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

29.1

Confidence interval

level

95%

sides

2-sided

lower limit

8.3

upper limit

49.9

Notes
[37] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.017 ^[38]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

24.2

Confidence interval

level

95%

sides

2-sided

lower limit

4.4

upper limit

44.1

Notes
[38] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[39]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

36.5

Confidence interval

level

95%

sides

2-sided

lower limit

14.8

upper limit

58.1

Notes
[39] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[40]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

36.8

Confidence interval

level

95%

sides

2-sided

lower limit

15.2

upper limit

58.3

Notes
[40] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Percentage of Subjects Who Achieve Clinical Response at Week 16

Top of page

End point title

Percentage of Subjects Who Achieve Clinical Response at Week 16

End point description

Clinical response: average daily stool frequency at least 30% reduction from Baseline and average daily abdominal pain not worse than Baseline OR average daily abdominal pain at least 30% reduction from Baseline and average daily stool frequency not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	37	39	37	36	36	35
Units: percentage of subjects
number (not applicable)	32.4	43.6	56.8	47.2	61.1	48.6

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.353 ^[41]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

10.5

Confidence interval

level

95%

sides

2-sided

lower limit

-11.7

upper limit

32.7

Notes
[41] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.05 ^[42]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

22.7

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

45.5

Notes
[42] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.268 ^[43]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

12.5

Confidence interval

level

95%

sides

2-sided

lower limit

-9.6

upper limit

34.6

Notes
[43] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018 ^[44]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

4.8

upper limit

51.2

Notes
[44] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.204 ^[45]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

14.9

Confidence interval

level

95%

sides

2-sided

lower limit

-8.1

upper limit

37.8

Notes
[45] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Percentage of Subjects With an Average Daily Stool Frequency ≥ 2.5 AND Average Daily Abdominal Pain ≥ 2.0 at Baseline Who Achieve Clinical Remission at Week 16

Top of page

End point title

Percentage of Subjects With an Average Daily Stool Frequency ≥ 2.5 AND Average Daily Abdominal Pain ≥ 2.0 at Baseline Who Achieve Clinical Remission at Week 16

End point description

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	14	17	16	18	12	18
Units: percentage of subjects
number (not applicable)	7.1	17.6	18.8	16.7	25.0	11.1

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.421 ^[46]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-14.4

upper limit

34.4

Notes
[46] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.371 ^[47]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

11.5

Confidence interval

level

95%

sides

2-sided

lower limit

-13.8

upper limit

36.8

Notes
[47] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.445 ^[48]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

9.2

Confidence interval

level

95%

sides

2-sided

lower limit

-14.4

upper limit

32.8

Notes
[48] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.198 ^[49]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

19.5

Confidence interval

level

95%

sides

2-sided

lower limit

-10.2

upper limit

49.3

Notes
[49] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.654 ^[50]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-17

upper limit

Notes
[50] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 at Week 16

Top of page

End point title

Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 at Week 16

End point description

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	15	21	18	17	15	10
Units: percentage of subjects
number (not applicable)	0	19.0	22.2	41.2	33.3	10.0

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.093 ^[51]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

18.7

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

40.5

Notes
[51] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.176 ^[52]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-6.1

upper limit

33.1

Notes
[52] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.017 ^[53]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

35.9

Confidence interval

level

95%

sides

2-sided

lower limit

6.3

upper limit

65.5

Notes
[53] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.044 ^[54]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

26.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

51.5

Notes
[54] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.121 ^[55]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

13.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

29.6

Notes
[55] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Perentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Remission at Week 12/16 and Clinical Remission at Week 16

Top of page

End point title

Perentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Remission at Week 12/16 and Clinical Remission at Week 16

End point description

End point type

Secondary

End point timeframe

Up to Week 16. (At Baseline, subjects were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.)

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	15	21	18	17	15	10
Units: percentage of subjects
number (not applicable)	0	0	5.6	5.9	13.3	0

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.564 ^[56]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-8.1

upper limit

14.9

Notes
[56] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.584 ^[57]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-8.8

upper limit

15.7

Notes
[57] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.326 ^[58]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

8.7

Confidence interval

level

95%

sides

2-sided

lower limit

-8.7

upper limit

26.1

Notes
[58] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission at Week 16

Top of page

End point title

Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission at Week 16

End point description

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	15	21	18	17	15	10
Units: percentage of subjects
number (not applicable)	0	14.3	22.2	11.8	33.3	10.0

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.195 ^[59]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

12.2

Confidence interval

level

95%

sides

2-sided

lower limit

-6.2

upper limit

30.7

Notes
[59] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.116 ^[60]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

17.9

Confidence interval

level

95%

sides

2-sided

lower limit

-4.4

upper limit

40.1

Notes
[60] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.178 ^[61]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

12.8

Confidence interval

level

95%

sides

2-sided

lower limit

-5.8

upper limit

31.5

Notes
[61] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.031 ^[62]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

30.4

Confidence interval

level

95%

sides

2-sided

lower limit

2.8

upper limit

Notes
[62] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.121 ^[63]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

13.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

29.6

Notes
[63] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 12/16

Top of page

End point title

Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 12/16

End point description

Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Details of the SES-CD scale are provided in the description of the first primary endpoint. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Includes only subjects taking corticosteroids at Baseline. Non-responder imputation.

End point type

Secondary

End point timeframe

Up to Week 16. (At Baseline, patients were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.)

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	15	21	18	17	15	10
Units: percentage of subjects
number (not applicable)	0	0	11.1	5.9	20.0	10.0

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.392 ^[64]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

6.8

Confidence interval

level

95%

sides

2-sided

lower limit

-8.7

upper limit

22.2

Notes
[64] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.584 ^[65]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-8.8

upper limit

15.7

Notes
[65] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.199 ^[66]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-6.8

upper limit

32.9

Notes
[66] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.439 ^[67]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

6.9

Confidence interval

level

95%

sides

2-sided

lower limit

-10.6

upper limit

24.5

Notes
[67] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Change from Baseline in Fecal Calprotectin Level Over Time During the Induction Phase

Top of page

End point title

Change from Baseline in Fecal Calprotectin Level Over Time During the Induction Phase

End point description

mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Includes only subjects with an assessment at Baseline and Week 16. n=subjects with an assessment at given time point.

End point type

Secondary

End point timeframe

Baseline, Week 4, Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	28	26	31	28	25	26
Units: µg/g
arithmetic mean (standard deviation)
Week 4; n=28, 26, 31, 28, 25, 26	83.7 ( 1024.11 )	-310.3 ( 2415.43 )	-436.9 ( 1505.75 )	-915.7 ( 1600.31 )	-876.2 ( 2240.93 )	-255.8 ( 2407.47 )
Week 16; n=18, 21, 21, 19, 12, 19	-128.9 ( 373.53 )	-534.5 ( 3279.19 )	-429.4 ( 2505.21 )	-475.1 ( 2668.93 )	-828.7 ( 986.09 )	-698.4 ( 2228.85 )

Attachments

Untitled (Filename: Table 14.2_1.23.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Change from Baseline in High-Sensitivity C-Reactive Protein (hs-CRP) at Week 16

Top of page

End point title

Change from Baseline in High-Sensitivity C-Reactive Protein (hs-CRP) at Week 16

End point description

mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Includes only subjects with an assessment at Baseline and Week 16.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	29	35	34	31	27	32
Units: mg/L
arithmetic mean (standard deviation)	-0.1 ( 11.96 )	-3.0 ( 19.60 )	-3.9 ( 19.47 )	-6.1 ( 27.02 )	-14.8 ( 26.38 )	-2.7 ( 13.74 )

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.921 ^[68]

Method

repeated measure model

Parameter type

LS Mean Difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-9.02

upper limit

9.97

Notes
[68] - P value for test of difference using the repeated measure model including treatment, Baseline disease severity (SES-CD < 15 and ≥ 15), week, Baseline, interaction of treatment and week. Statistical significance was prespecified at α = 0.1.

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.75 ^[69]

Method

repeated measure model

Parameter type

LS Mean Difference

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-11.19

upper limit

8.08

Notes
[69] - P value for test of difference using the repeated measure model including treatment, Baseline disease severity (SES-CD < 15 and ≥ 15), week, Baseline, interaction of treatment and week. Statistical significance was prespecified at α = 0.1.

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7 ^[70]

Method

repeated measure model

Parameter type

LS Mean Difference

Point estimate

-1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-11.7

upper limit

7.87

Notes
[70] - P value for test of difference using the repeated measure model including treatment, Baseline disease severity (SES-CD < 15 and ≥ 15), week, Baseline, interaction of treatment and week. Statistical significance was prespecified at α = 0.1.

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.024 ^[71]

Method

repeated measure model

Parameter type

LS Mean Difference

Point estimate

-11.4

Confidence interval

level

95%

sides

2-sided

lower limit

-21.38

upper limit

-1.51

Notes
[71] - P value for test of difference using the repeated measure model including treatment, Baseline disease severity (SES-CD < 15 and ≥ 15), week, Baseline, interaction of treatment and week. Statistical significance was prespecified at α = 0.1.

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.845 ^[72]

Method

repeated measure model

Parameter type

LS Mean Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-10.72

upper limit

8.79

Notes
[72] - P value for test of difference using the repeated measure model including treatment, Baseline disease severity (SES-CD < 15 and ≥ 15), week, Baseline, interaction of treatment and week. Statistical significance was prespecified at α = 0.1.

Secondary: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Over Time During the Induction Phase

Top of page

End point title

Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Over Time During the Induction Phase

End point description

The IBDQ is a disease-specific instrument composed of 32 Likert-scaled items. The total score ranges from 32 to 224 using the 7-point response options, with higher scores indicating better health-related quality of life. The IBDQ scale contains 4 component subscales: bowel symptoms, systemic symptoms, emotional function, and social function. Each subscale can be computed with total scores ranging from 10 to 70, 5 to 35, 12 to 84, and 5 to 35, respectively. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Includes only subjects with an assessment at Baseline and Week 16. n=number of subjects with an assessment at given time point.

End point type

Secondary

End point timeframe

Baseline, Week 8, Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	33	36	35	34	31	33
Units: units on a scale
arithmetic mean (standard deviation)
Week 8; n=33, 36, 35, 34, 31, 33	16.6 ( 25.38 )	18.9 ( 40.35 )	34.6 ( 36.22 )	24.9 ( 30.95 )	39.7 ( 40.76 )	23.3 ( 30.34 )
Week 16; n=29, 35, 33, 28, 29, 32	14.5 ( 29.15 )	24.6 ( 42.98 )	41.8 ( 47.02 )	32.1 ( 38.57 )	44.4 ( 40.05 )	22.5 ( 27.82 )

Attachments

Untitled (Filename: Table 14.2_1.25.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Isolated Ileal Crohn's Disease at Baseline Who Achieve Remission at Week 16

Top of page

End point title

Percentage of Subjects With Isolated Ileal Crohn's Disease at Baseline Who Achieve Remission at Week 16

End point description

Remission is defined as endoscopic remission AND clinical remission. Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Only mITT subjects with isolated ileal Crohn's disease at Baseline are included. Non-responder imputation.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	9	10	6	5	6	10
Units: percentage of subjects
number (not applicable)	0	20.0	16.7	20.0	0	20.0

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.167 ^[73]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-8.4

upper limit

48.4

Notes
[73] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.221 ^[74]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

16.7

Confidence interval

level

95%

sides

2-sided

lower limit

-10

upper limit

43.3

Notes
[74] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.18 ^[75]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-9.2

upper limit

49.2

Notes
[75] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.167 ^[76]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-8.4

upper limit

48.4

Notes
[76] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Percentage of Subjects With a Decrease in CDAI ≥ 100 Points From Baseline at Week 16

Top of page

End point title

Percentage of Subjects With a Decrease in CDAI ≥ 100 Points From Baseline at Week 16

End point description

CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A score below 150 indicates remission and a score above 450 indicates very severe disease. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	37	39	37	36	36	35
Units: percentage of subjects
number (not applicable)	27.0	33.3	40.5	44.4	55.6	31.4

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.607 ^[77]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

5.5

Confidence interval

level

95%

sides

2-sided

lower limit

-15.5

upper limit

26.5

Notes
[77] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.272 ^[78]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

12.2

Confidence interval

level

95%

sides

2-sided

lower limit

-9.6

upper limit

33.9

Notes
[78] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.157 ^[79]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

15.9

Confidence interval

level

95%

sides

2-sided

lower limit

-6.1

upper limit

37.9

Notes
[79] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.017 ^[80]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

27.7

Confidence interval

level

95%

sides

2-sided

lower limit

4.9

upper limit

50.6

Notes
[80] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.798 ^[81]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-18.4

upper limit

23.9

Notes
[81] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Percentage of Subjects Who Achieve > 50% Reduction From Baseline in SES-CD or Endoscopic Remission at Week 12/16

Top of page

End point title

Percentage of Subjects Who Achieve > 50% Reduction From Baseline in SES-CD or Endoscopic Remission at Week 12/16

End point description

Endoscopic remission: SES-CD ≤ 4 and at least two point reduction versus Baseline and no subscore > 1 in any individual variable. Details of the SES-CD scale are provided in the description of the first primary endpoint. mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Non-responder imputation.

End point type

Secondary

End point timeframe

Up to Week 16. (At Baseline, patients were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.)

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	37	39	37	36	36	35
Units: percentage of subjects
number (not applicable)	2.7	12.8	18.9	25.0	36.1	25.7

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.119 ^[82]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

9.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

22.1

Notes
[82] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.034 ^[83]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

15.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.1

upper limit

29.7

Notes
[83] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[84]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

23.2

Confidence interval

level

95%

sides

2-sided

lower limit

7.3

upper limit

39.2

Notes
[84] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[85]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

32.4

Confidence interval

level

95%

sides

2-sided

lower limit

14.2

upper limit

50.5

Notes
[85] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.006 ^[86]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

22.9

Confidence interval

level

95%

sides

2-sided

lower limit

6.6

upper limit

39.2

Notes
[86] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Percentage of Subjects Who Achieve Modified Clinical Remission at Week 16 Among Subjects With an Average Daily Stool Frequency ≥ 4.0 or Average Daily Abdominal Pain ≥ 2.0 at Baseline

Top of page

End point title

Percentage of Subjects Who Achieve Modified Clinical Remission at Week 16 Among Subjects With an Average Daily Stool Frequency ≥ 4.0 or Average Daily Abdominal Pain ≥ 2.0 at Baseline

End point description

Modified clinical remission was defined as average daily stool frequency <= 2.8 and not worse than Baseline and average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Includes only mITT subjects with an average daily stool frequency ≥ 4.0 or average daily abdominal pain ≥ 2.0 at Baseline. Non-responder imputation.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	33	38	33	34	30	32
Units: percentage of subjects
number (not applicable)	12.1	15.8	30.3	26.5	36.7	18.8

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.647 ^[87]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-12.7

upper limit

20.5

Notes
[87] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.093 ^[88]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

17.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

37.1

Notes
[88] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.165 ^[89]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

13.6

Confidence interval

level

95%

sides

2-sided

lower limit

-5.6

upper limit

32.8

Notes
[89] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.023 ^[90]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

24.9

Confidence interval

level

95%

sides

2-sided

lower limit

3.4

upper limit

46.3

Notes
[90] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.448 ^[91]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted risk difference from placebo

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-11

upper limit

Notes
[91] - Based on CMH test stratified by baseline SES-CD (SES-CD <15 and SES-CD >=15).

Secondary: Change From Baseline in Abdominal Pain Rating Scale at Week 12

Top of page

End point title

Change From Baseline in Abdominal Pain Rating Scale at Week 12

End point description

Abdominal pain was assessed on an abdominal pain rating scale, where subjects rated their average abdominal pain over the last 24 hours on a scale of 0 (none) to 10 (worst pain imaginable). mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Includes only mITT subjects with an assessment at baseline and given time point. Non-responder imputation.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	30	35	34	27	29	30
Units: units on a scale
arithmetic mean (standard deviation)	-1.1 ( 1.84 )	-1.0 ( 2.61 )	-2.6 ( 2.53 )	-2.4 ( 3.17 )	-2.7 ( 2.52 )	-1.0 ( 1.99 )

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.412 ^[92]

Method

repeated measure model

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.62

upper limit

1.5

Notes
[92] - P value for test of difference using the repeated measure model including treatment, Baseline disease severity (SES-CD < 15 and ≥ 15), week, Baseline, interaction of treatment and week.

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01 ^[93]

Method

repeated measure model

Parameter type

LS Mean Difference

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.47

upper limit

-0.34

Notes
[93] - P value for test of difference using the repeated measure model including treatment, Baseline disease severity (SES-CD < 15 and ≥ 15), week, Baseline, interaction of treatment and week.

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.082 ^[94]

Method

repeated measure model

Parameter type

LS Mean Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.13

upper limit

0.13

Notes
[94] - P value for test of difference using the repeated measure model including treatment, Baseline disease severity (SES-CD < 15 and ≥ 15), week, Baseline, interaction of treatment and week.

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[95]

Method

repeated measure model

Parameter type

LS Mean Difference

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.73

upper limit

-0.52

Notes
[95] - P value for test of difference using the repeated measure model including treatment, Baseline disease severity (SES-CD < 15 and ≥ 15), week, Baseline, interaction of treatment and week.

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.766 ^[96]

Method

repeated measure model

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.93

upper limit

1.26

Notes
[96] - P value for test of difference using the repeated measure model including treatment, Baseline disease severity (SES-CD < 15 and ≥ 15), week, Baseline, interaction of treatment and week.

Secondary: Change From Baseline in Abdominal Pain Rating Scale at Week 16

Top of page

End point title

Change From Baseline in Abdominal Pain Rating Scale at Week 16

End point description

Abdominal pain was assessed on an abdominal pain rating scale, where subjects rated their average abdominal pain over the last 24 hours on a scale of 0 (none) to 10 (worst pain imaginable). mITT Population: all randomized subjects who took at least 1 dose of study drug in the Induction Period. Includes only mITT subjects with an assessment at Baseline and given time point. Non-responder imputation.

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	28	34	33	26	28	28
Units: units on a scale
arithmetic mean (standard deviation)	-0.9 ( 2.27 )	-1.7 ( 3.02 )	-2.8 ( 2.77 )	-1.7 ( 2.86 )	-2.3 ( 2.42 )	-1.4 ( 2.15 )

Statistical Analysis 1

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 3 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.314 ^[97]

Method

mixed effect model repeated measure

Parameter type

LS Mean Difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.75

upper limit

0.56

Notes
[97] - P value for test of difference using the repeated measure model including treatment, Baseline disease severity (SES-CD < 15 and ≥ 15), week, Baseline, interaction of treatment and week.

Statistical Analysis 2

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 6 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[98]

Method

mixed effect model repeated measure

Parameter type

LS Mean Difference

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.01

upper limit

-0.68

Notes
[98] - P value for test of difference using the repeated measure model including treatment, Baseline disease severity (SES-CD < 15 and ≥ 15), week, Baseline, interaction of treatment and week.

Statistical Analysis 3

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 12 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.255 ^[99]

Method

mixed effect model repeated measure

Parameter type

LS Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.94

upper limit

0.52

Notes
[99] - P value for test of difference using the repeated measure model including treatment, Baseline disease severity (SES-CD < 15 and ≥ 15), week, Baseline, interaction of treatment and week.

Statistical Analysis 4

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.022 ^[100]

Method

mixed effect model repeated measure

Parameter type

LS Mean Difference

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.61

upper limit

-0.2

Notes
[100] - P value for test of difference using the repeated measure model including treatment, Baseline disease severity (SES-CD < 15 and ≥ 15), week, Baseline, interaction of treatment and week.

Statistical Analysis 5

Comparison groups

Placebo Twice Daily (BID) v Upadacitinib 24 mg QD

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.239 ^[101]

Method

mixed effect model repeated measure

Parameter type

LS Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.92

upper limit

0.48

Notes
[101] - P value for test of difference using the repeated measure model including treatment, Baseline disease severity (SES-CD < 15 and ≥ 15), week, Baseline, interaction of treatment and week.

Secondary: Percentage of Subjects Who Achieve Remission at Week 52

Top of page

End point title

Percentage of Subjects Who Achieve Remission at Week 52

End point description

Remission at Week 52 was defined as both endoscopic remission at Week 52 and clinical remission at Week 52. Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). See SES-CD description details in the first primary endpoint description of this record. Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	52	18	50	33	9	5	9	4
Units: percentage of subjects
number (not applicable)
Responders; n=20, 8, 16, 10, 1, 0, 0, 0	20.0	12.5	25.0	0	0	0	0	0
Non-responders; n=32, 10, 34, 23, 8, 5, 9, 4	0	0	2.9	13.0	0	0	0	25.0
Clinical responders; n=32, 14, 29, 19, 6, 1, 4, 1	12.5	7.1	13.8	15.8	0	0	0	100
Clinical non-responders;n=20, 4, 21, 14, 3, 4, 5,3	0	0	1	0	0	0	0	0

Attachments

Untitled (Filename: Table 14.2_2.1.1.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Endoscopic Remission at Week 52

Top of page

End point title

Percentage of Subjects Who Achieve Endoscopic Remission at Week 52

End point description

Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Details of the SES-CD scale are provided in the description of the first primary endpoint. Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	52	18	50	33	9	5	9	4
Units: percentage of subjects
number (not applicable)
Responders; n=20, 8, 16, 10, 1, 0, 0, 0	25.0	25.0	37.5	10.0	0	0	0	0
Non-responders; n=32, 10, 34, 23, 8, 5, 9, 4	3.1	10.0	8.8	17.4	0	0	0	25.0
Clinical responders; n=32, 14, 29, 19, 6, 1, 4, 1	15.6	21.4	24.1	26.3	0	0	0	100
Clinical non-responders;n=20, 4, 21, 14, 3, 4, 5,3	5.0	0	9.5	0	0	0	0	0

Attachments

Untitled (Filename: Table 14.2_2.1.2.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Both Endoscopic Remission and Modified Clinical Remission at Week 52 Among Subjects With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline

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End point title

Percentage of Subjects Who Achieve Both Endoscopic Remission and Modified Clinical Remission at Week 52 Among Subjects With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline

End point description

Endoscopic remission was defined as SES-CD <= 4 and at least 2 points reduction versus induction baseline and no subscore > 1 in any individual variable. Modified clinical remission was defined as average daily stool frequency <= 2.8 and not worse than induction baseline AND average daily abdominal pain <= 1.0 and not worse than induction baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). See SES-CD description details in the first primary endpoint description of this record. Subjects from ITT population with daily stool frequency >= 4.0 or daily abdominal pain >= 2.0 at Induction Baseline. Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	45	17	48	30	8	5	8	4
Units: percentage of subjects
number (not applicable)
Responders; n=17, 8, 15, 10, 1, 0, 0, 0	29.4	12.5	33.3	10.0	0	0	0	0
Non-responders; n=28, 9, 33, 20, 7, 5, 8, 4	0	0	6.1	15.0	0	0	0	25.0
Clinical responders; n=28, 14, 27, 18, 5, 1, 3, 1	17.9	7.1	22.2	22.2	0	0	0	100
Clinical non-responders;n=17, 3, 21, 12, 3, 4, 5,3	0	0	4.8	0	0	0	0	0

Attachments

Untitled (Filename: Table 14.2_2.1.3.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Clinical Remission Over Time During Extension Phase

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End point title

Percentage of Subjects Who Achieve Clinical Remission Over Time During Extension Phase

End point description

Clinical remission was defined as average daily stool frequency <= 1.5 and not worse than Induction Baseline and average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 20, Week 28, Week 36, Week 44, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction
Number of subjects analysed	52	18	50	33
Units: percentage of subjects
number (not applicable)
Responders, Week 20; n=20, 8, 16, 10	45.0	37.5	50.0	40.0
Responders, Week 28; n=20, 8, 16, 10	45.0	37.5	56.3	50.0
Responders, Week 36; n=20, 8, 16, 10	40.0	37.5	62.5	30.0
Responders, Week 44; n=20, 8, 16, 10	40.0	12.5	68.8	40.0
Responders, Week 52; n=20, 8, 16, 10	30.0	37.5	62.5	30.0
Non-responders, Week 20; n=32, 10, 34, 23	12.5	40.0	8.8	8.7
Non-responders, Week 28; n=32, 10, 34, 23	12.5	40.0	8.8	13.0
Non-responders, Week 36; n=32, 10, 34, 23	9.4	10.0	2.9	13.0
Non-responders, Week 44; n=32, 10, 34, 23	12.5	20.0	5.9	8.7
Non-responders, Week 52; n=32, 10, 34, 23	9.4	10.0	8.8	13.0
Clinical responders, Week 20; n=32, 14, 29, 19	40.6	50.0	37.9	31.6
Clinical responders, Week 28; n=32, 14, 29, 19	37.5	50.0	41.4	42.1
Clinical responders, Week 36; n=32, 14, 29, 19	34.4	28.6	37.9	31.6
Clinical responders, Week 44; n=32, 14, 29, 19	34.4	21.4	44.8	31.6
Clinical responders, Week 52; n=32, 14, 29, 19	25.0	28.6	41.4	31.6
Clinical non-responders, Week 20; n=20,4, 21, 14	0	0	0	0
Clinical non-responders, Week 28; n=20,4, 21, 14	5.0	0	0	0
Clinical non-responders, Week 36; n=20,4, 21, 14	0	0	0	0
Clinical non-responders, Week 44; n=20,4, 21, 14	5.0	0	0	0
Clinical non-responders, Week 52; n=20,4, 21, 14	5.0	0	4.8	0

Attachments

Untitled (Filename: Table 14.2_2.2.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Maintain Clinical Remission Over Time Among Subjects in Clinical Remission at Week 16

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End point title

Percentage of Subjects Who Maintain Clinical Remission Over Time Among Subjects in Clinical Remission at Week 16

End point description

Clinical remission was defined as average daily stool frequency <= 1.5 and not worse than Induction Baseline and average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Subjects from ITT population in clinical remission at Week 16. Non responder imputation. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Week 20, Week 28, Week 36, Week 44, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction
Number of subjects analysed	13	6	9	4
Units: percentage of subjects
number (not applicable)
Responders, Week 20; n=10, 3, 7, 3	80.0	66.7	71.4	100
Responders, Week 28; n=10, 3, 7, 3	90.0	66.7	57.1	100
Responders, Week 36; n=10, 3, 7, 3	80.0	100	71.4	66.7
Responders, Week 44; n=10, 3, 7, 3	80.0	33.3	71.4	66.7
Responders, Week 52; n=10, 3, 7, 3	60.0	66.7	71.4	66.7
Non-responders, Week 20; n=3, 3, 2, 1	66.7	100	50.0	100
Non-responders, Week 28; n=3, 3, 2, 1	66.7	100	50.0	100
Non-responders, Week 36; n=3, 3, 2, 1	66.7	33.3	50.0	100
Non-responders, Week 44; n=3, 3, 2, 1	66.7	66.7	50.0	100
Non-responders, Week 52; n=3, 3, 2, 1	33.3	33.3	0	100
Clinical responders, Week 20; n=13, 6, 9, 4	76.9	83.3	66.7	100
Clinical responders, Week 28; n=13, 6, 9, 4	84.6	83.3	55.6	100
Clinical responders, Week 36; n=13, 6, 9, 4	76.9	66.7	66.7	75.0
Clinical responders, Week 44; n=13, 6, 9, 4	76.9	50.0	66.7	75.0
Clinical responders, Week 52; n=13, 6, 9, 4	53.8	50.0	55.6	75.0
Clinical non-responders, Week 20; n=0, 0, 0, 0	0	0	0	0
Clinical non-responders, Week 28; n=0, 0, 0, 0	0	0	0	0
Clinical non-responders, Week 36; n=0, 0, 0, 0	0	0	0	0
Clinical non-responders, Week 44; n=0, 0, 0, 0	0	0	0	0
Clinical non-responders, Week 52; n=0, 0, 0, 0	0	0	0	0

Attachments

Untitled (Filename: Table 14.2_2.3.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Modified Clinical Remission Over Time During Extension Phase Among Subjects With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline

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End point title

Percentage of Subjects Who Achieve Modified Clinical Remission Over Time During Extension Phase Among Subjects With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline

End point description

Modified clinical remission was defined as average daily stool frequency <= 2.8 and not worse than Induction Baseline and average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Subjects from ITT population with daily stool frequency >= 4.0 or daily abdominal pain >= 2.0 at Induction Baseline. Non responder imputation. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Week 20, Week 28, Week 36, Week 44, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	22	17	48	30	8	5	8	4
Units: percentage of subjects
number (not applicable)
Responders: Week (Wk) 20;n=17, 8, 15, 10, 1, 0,0,0	47.1	62.5	66.7	60.0	0	0	0	0
Responders: Wk 28; n=17, 8, 15, 10, 1, 0, 0, 0	70.6	50.0	66.7	60.0	0	0	0	0
Responders: Wk 36; n=17, 8, 15, 10, 1, 0, 0, 0	58.8	87.5	73.3	30.0	0	0	0	0
Responders: Wk 44; n=17, 8, 15, 10, 1, 0, 0, 0	47.1	37.5	73.3	40.0	0	0	0	0
Responders: Wk 52; n=17, 8, 15, 10, 1, 0, 0, 0	41.2	62.5	73.3	40.0	0	0	0	0
Non-responders: Wk 20; n=28, 9, 33, 20, 7, 5, 8, 4	17.9	44.4	12.1	10.0	42.9	20.0	25.0	25.0
Non-responders: Wk 28; n=5, 9, 33, 20, 7, 5, 8, 4	21.4	44.4	9.1	15.0	42.9	20.0	25.0	50.0
Non-responders: Wk 36; n=5, 9, 33, 20, 7, 5, 8, 4	14.3	11.1	6.1	15.0	57.1	20.0	25.0	25.0
Non-responders: Wk 44; n=5, 9, 33, 20, 7, 5, 8, 4	14.3	22.2	6.1	10.0	42.9	20.0	37.5	25.0
Non-responders: Wk 52; n=5, 9, 33, 20, 7, 5, 8, 4	7.1	11.1	12.1	15.0	28.6	0	37.5	50.0
Clin. responders: Wk 20; n=28, 14, 27, 18, 5,1,3,1	42.9	64.3	51.9	44.4	60.0	100	33.3	100
Clin. responders: Wk 28; n=28, 14, 27, 18, 5,1,3,1	57.1	57.1	48.1	50.0	60.0	100	33.3	100
Clin. responders: Wk 36; n=28, 14, 27, 18, 5,1,3,1	46.4	57.1	48.1	33.3	80.0	100	33.3	100
Clin. responders: Wk 44; n=28, 14, 27, 18, 5,1,3,1	39.3	35.7	48.1	33.3	60.0	100	33.3	100
Clin. responders: Wk 52; n=28, 14, 27, 18, 5,1,3,1	28.6	42.9	51.9	38.9	40.0	0	33.3	100
Clin. non-responders: Wk 20; n=17,3,21,12,3,4,5,3	5.9	0	0	0	0	0	20.0	0
Clin. non-responders: Wk 28; n=1,3,21,12,3,4,5,3	11.8	0	0	0	0	0	20.0	33.3
Clin. non-responders: Wk 36; n=1,3,21,12,3,4,5,3	5.9	0	0	0	0	0	20.0	0
Clin. non-responders: Wk 44; n=1,3,21,12,3,4,5,3	5.9	0	0	0	0	0	40.0	0
Clin. non-responders: Wk 52; n=1,3,21,12,3,4,5,3	5.9	0	4.8	0	0	0	40.0	33.3

Attachments

Untitled (Filename: Table 14.2_2.4.1.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Modified Clinical Remission Over Time During Extension Phase Among Subjects In Modified Clinical Remission At Week 16 and Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline

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End point title

Percentage of Subjects Who Achieve Modified Clinical Remission Over Time During Extension Phase Among Subjects In Modified Clinical Remission At Week 16 and Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline

End point description

Modified clinical remission was defined as average daily stool frequency <= 2.8 and not worse than Induction Baseline and average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Subjects from ITT population with modified clinical remission at Week 16 and daily stool frequency >= 4.0 or daily abdominal pain >= 2.0 at Induction Baseline. Non responder imputation. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Week 20, Week 28, Week 36, Week 44, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	15	10	12	5	2	0 ^[102]	1	1
Units: percentage of subjects
number (not applicable)
Responders: Week (Wk) 20;n=12, 5, 10, 4, 0, 0,0,0	66.7	60.0	90.0	100	0		0	0
Responders: Wk 28; n=12, 5, 10, 4, 0, 0, 0, 0	91.7	60.0	90.0	100	0		0	0
Responders: Wk 36; n=12, 5, 10, 4, 0, 0, 0, 0	66.7	100	90.0	75.0	0		0	0
Responders: Wk 44; n=12, 5, 10, 4, 0, 0, 0, 0	66.7	40.0	90.0	75.0	0		0	0
Responders: Wk 52; n=12, 5, 10, 4, 0, 0, 0, 0	58.3	80.0	90.0	75.0	0		0	0
Non-responders: Wk 20; n=3, 5, 2, 1, 2, 0, 1, 1	66.7	80.0	50.0	100	100		100	100
Non-responders: Wk 28; n=3, 5, 2, 1, 2, 0, 1, 1	100	60.0	50.0	100	100		100	100
Non-responders: Wk 36; n=3, 5, 2, 1, 2, 0, 1, 1	66.7	20.0	50.0	100	100		100	100
Non-responders: Wk 44; n=3, 5, 2, 1, 2, 0, 1, 1	66.7	40.0	50.0	100	50.0		100	100
Non-responders: Wk 52; n=3, 5, 2, 1, 2, 0, 1, 1	33.3	20.0	50.0	100	50.0		100	100
Clin. responders: Wk 20; n=15, 10, 12, 5, 2, 0,1,1	66.7	70.0	83.3	100	100		100	100
Clin. responders: Wk 28; n=15, 10, 12, 5, 2, 0,1,1	93.3	60.0	83.3	100	100		100	100
Clin. responders: Wk 36; n=15, 10, 12, 5, 2, 0,1,1	66.7	60.0	83.3	80.0	100		100	100
Clin. responders: Wk 44; n=15, 10, 12, 5, 2, 0,1,1	66.7	40.0	83.3	80.0	50.0		100	100
Clin. responders: Wk 52; n=15, 10, 12, 5, 2, 0,1,1	53.3	50.0	83.3	80.0	50.0		100	100
Clin. non-responders: Wk 20; n=0, 0, 0, 0, 0,0,0,0	0	0	0	0	0		0	0
Clin. non-responders: Wk 28; n=0, 0, 0, 0, 0,0,0,0	0	0	0	0	0		0	0
Clin. non-responders: Wk 36; n=0, 0, 0, 0, 0,0,0,0	0	0	0	0	0		0	0
Clin. non-responders: Wk 44; n=0, 0, 0, 0, 0,0,0,0	0	0	0	0	0		0	0
Clin. non-responders: Wk 52; n=0, 0, 0, 0, 0,0,0,0	0	0	0	0	0		0	0

Attachments

Untitled (Filename: Table 14.2_2.5.1.1 stat analysis.docx)

Notes
[102] - no subjects met the criteria in this arm

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Response at Week 52

Top of page

End point title

Percentage of Subjects Who Achieve Response at Week 52

End point description

Response at Week 52 was defined as both endoscopic response at Week 52 and clinical response at Week 52. Endoscopic response: SES-CD at least 25% reduction from Baseline. Clinical response: average daily stool frequency at least 30% reduction from Induction Baseline and average daily abdominal pain not worse than Induction Baseline OR average daily abdominal pain at least 30% reduction from Induction Baseline and average daily stool frequency not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint. Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	52	18	50	33	9	5	9	4
Units: percentage of subjects
number (not applicable)
Responders; n=20, 8, 16, 10, 1, 0, 0, 0	50.0	62.5	68.8	40.0	100	0	0	0
Non-responders; n=32, 10, 34, 23, 8, 5, 9, 4	6.3	10.0	14.7	13.0	0	20.0	22.2	25.0
Clinical responders; n=32, 14, 29, 19, 6, 1, 4, 1	34.4	42.9	51.7	36.8	16.7	0	0	100
Clinical non-responders;n=20, 4, 21, 14, 3, 4, 5,3	5.0	0	4.8	0	0	25.0	40.0	0

Attachments

Untitled (Filename: Table 14.2_2.6.1.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects With SES-CD ≤ 2 at Week 52

Top of page

End point title

Percentage of Subjects With SES-CD ≤ 2 at Week 52

End point description

See SES-CD description details in the first primary endpoint description of this record. Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	52	18	50	33	9	5	9	4
Units: percentage of subjects
number (not applicable)
Responders; n=20, 8, 16, 10, 1, 0, 0, 0	10.0	12.5	31.3	0	0	0	0	0
Non-responders; n=32, 10, 34, 23, 8, 5, 9, 4	6.3	0	8.8	8.7	0	0	0	25.0
Clinical responders; n=32, 14, 29, 19, 6, 1, 4, 1	6.3	7.1	20.7	10.5	0	0	0	100
Clinical non-responders;n=20, 4, 21, 14, 3, 4, 5,3	10.0	0	9.5	0	0	0	0	0

Attachments

Untitled (Filename: Table 14.2_2.1.5.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects With SES-CD = 0 at Week 52

Top of page

End point title

Percentage of Subjects With SES-CD = 0 at Week 52

End point description

See SES-CD description details in the first primary endpoint description of this record. Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	52	18	50	33	9	5	9	4
Units: percentage of subjects
number (not applicable)
Responders; n=20, 8, 16, 10, 1, 0, 0, 0	10.0	12.5	31.3	0	0	0	0	0
Non-responders; n=32, 10, 34, 23, 8, 5, 9, 4	3.1	0	8.8	4.3	0	0	0	0
Clinical responders; n=32, 14, 29, 19, 6, 1, 4, 1	6.3	7.1	20.7	5.3	0	0	0	0
Clinical non-responders;n=20, 4, 21, 14, 3, 4, 5,3	5.0	0	9.5	0	0	0	0	0

Attachments

Untitled (Filename: Table 14.2_2.1.7.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Endoscopic Response at Week 52

Top of page

End point title

Percentage of Subjects Who Achieve Endoscopic Response at Week 52

End point description

Endoscopic response was defined as SES-CD at least 25% reduction from Induction Baseline. Details of the SES-CD scale are provided in the description of the first primary endpoint. Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	52	18	50	33	9	5	9	4
Units: percentage of subjects
number (not applicable)
Responders; n=20, 8, 16, 10, 1, 0, 0, 0	60.0	75.0	75.0	40.0	100	0	0	0
Non-responders; n=32, 10, 34, 23, 8, 5, 9, 4	15.6	20.0	20.6	17.4	0	20.0	22.2	25.0
Clinical responders; n=32, 14, 29, 19, 6, 1, 4, 1	40.6	57.1	55.2	42.1	16.7	0	0	100
Clinical non-responders;n=20, 4, 21, 14, 3, 4, 5,3	20.0	0	14.3	0	0	25.0	40.0	0

Attachments

Untitled (Filename: Table 14.2_2.6.3.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Enhanced Endoscopic Response at Week 52

Top of page

End point title

Percentage of Subjects Who Achieve Enhanced Endoscopic Response at Week 52

End point description

Enhanced endoscopic response was defined as SES-CD reduction from Induction Baseline > 50% (or for an Induction Baseline SES-CD of 4, at least a 2 point reduction from Induction Baseline). Details of the SES-CD scale are provided in the description of the first primary endpoint. Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	52	18	50	33	9	5	9	4
Units: percentage of subjects
number (not applicable)
Responders; n=20, 8, 16, 10, 1, 0, 0, 0	40.0	50.0	68.8	30.0	100	0	0	0
Non-responders; n=32, 10, 34, 23, 8, 5, 9, 4	12.5	0	11.8	17.4	0	20.0	11.1	25.0
Clinical responders; n=32, 14, 29, 19, 6, 1, 4, 1	28.1	28.6	44.8	36.8	16.7	0	0	100
Clinical non-responders;n=20, 4, 21, 14, 3, 4, 5,3	15.0	0	9.5	0	0	25.0	20.0	0

Attachments

Untitled (Filename: Table 14.2_2.6.5.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Endoscopic Improvement at Week 52

Top of page

End point title

Percentage of Subjects Who Achieve Endoscopic Improvement at Week 52

End point description

Endoscopic Improvement: SES-CD reduction from Induction Baseline > 50% or endoscopic remission. Endoscopic remission was defined as SES-CD <= 4 and at least 2 points reduction versus Induction Baseline and no subscore > 1 in any individual variable. Details of the SES-CD scale are provided in the description of the first primary endpoint. Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	52	18	50	33	9	5	9	4
Units: percentage of subjects
number (not applicable)
Responders; n=20, 8, 16, 10, 1, 0, 0, 0	50.0	50.0	68.8	30.0	100	0	0	0
Non-responders; n=32, 10, 34, 23, 8, 5, 9, 4	12.5	10.0	11.8	17.4	0	20.0	11.1	25.0
Clinical responders; n=32, 14, 29, 19, 6, 1, 4, 1	34.4	35.7	44.8	36.8	16.7	0	0	100
Clinical non-responders;n=20, 4, 21, 14, 3, 4, 5,3	15.0	0	9.5	0	0	25.0	20.0	0

Attachments

Untitled (Filename: Table 14.2_2.7.1.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Endoscopic Healing at Week 52

Top of page

End point title

Percentage of Subjects Who Achieve Endoscopic Healing at Week 52

End point description

Endoscopic healing was defined as SES-CD ulcerated surface subscore of 0 in subjects with SES-CD ulcerated surface subscore >= 1 at Induction Baseline. Details of the SES-CD scale are provided in the description of the first primary endpoint. Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	52	18	50	33	9	5	9	4
Units: percentage of subjects
number (not applicable)
Responders; n=20, 8, 16, 10, 1, 0, 0, 0	15.0	25.0	50.0	0	0	0	0	0
Non-responders; n=32, 10, 34, 23, 8, 5, 9, 4	9.4	10.0	8.8	8.7	0	20.0	0	0
Clinical responders; n=32, 14, 29, 19, 6, 1, 4, 1	9.4	21.4	31.0	10.5	0	0	0	0
Clinical non-responders;n=20, 4, 21, 14, 3, 4, 5,3	15.0	0	9.5	0	0	25.0	0	0

Attachments

Untitled (Filename: Table 14.2_2.6.7.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Clinical Response Over Time During Extension Phase

Top of page

End point title

Percentage of Subjects Who Achieve Clinical Response Over Time During Extension Phase

End point description

Clinical response was defined as average daily stool frequency at least 30% reduction from Induction Baseline and average daily abdominal pain not worse than Induction Baseline OR average daily abdominal pain at least 30% reduction from Induction Baseline and average daily stool frequency not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 20, Week 28, Week 36, Week 44, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	52	18	50	33	9	5	9	4
Units: percentage of subjects
number (not applicable)
Responders: Week (Wk) 20; n=20, 8, 16, 10, 1,0,0,0	85.0	100	100	80.0	100	0	0	0
Responders: Wk 28; n=20, 8, 16, 10, 1,0,0,0	85.0	75.0	81.3	60.0	0	0	0	0
Responders: Wk 36; n=20, 8, 16, 10, 1,0,0,0	75.0	100	75.0	50.0	100	0	0	0
Responders: Wk 44; n=20, 8, 16, 10, 1,0,0,0	50.0	87.5	81.3	40.0	0	0	0	0
Responders: Wk 52; n=20, 8, 16, 10, 1,0,0,0	55.0	87.5	68.8	50.0	100	0	0	0
Non-responders: Wk 20; n=32, 10, 34, 23, 8, 5, 9,4	43.8	60.0	41.2	39.1	75.0	20.0	33.3	50.0
Non-responders: Wk 28; n=32, 10, 34, 23, 8, 5, 9,4	40.6	60.0	29.4	26.1	50.0	20.0	22.2	50.0
Non-responders: Wk 36; n=32, 10, 34, 23, 8, 5, 9,4	28.1	40.0	26.5	17.4	50.0	20.0	33.3	25.0
Non-responders: Wk 44; n=32, 10, 34, 23, 8, 5, 9,4	25.0	30.0	26.5	21.7	37.5	40.0	33.3	50.0
Non-responders: Wk 52; n=32, 10, 34, 23, 8, 5, 9,4	21.9	30.0	26.5	13.0	37.5	40.0	33.3	50.0
Clin. responders: Wk 20; n=32, 14, 29, 19, 6,1,4,1	78.1	100	93.1	78.9	100	100	25.0	100
Clin. responders: Wk 28; n=32, 14, 29, 19, 6,1,4,1	78.1	78.6	69.0	57.9	66.7	100	25.0	100
Clin. responders: Wk 36; n=32, 14, 29, 19, 6,1,4,1	65.6	78.6	65.5	47.4	83.3	100	25.0	100
Clin. responders: Wk 44; n=32, 14, 29, 19, 6,1,4,1	50.0	71.4	72.4	42.1	50.0	100	25.0	100
Clin. responders: Wk 52; n=32, 14, 29, 19, 6,1,4,1	50.0	71.4	62.1	42.1	66.7	100	25.0	100
Clin. non-responders: Wk 20; n=20, 4,21,14,3,4,5,3	30.0	0	14.3	14.3	33.3	0	40.0	33.3
Clin. non-responders: Wk 28; n=20, 4,21,14,3,4,5,3	25.0	25.0	14.3	7.1	0	0	20.0	33.3
Clin. non-responders: Wk 36; n=20, 4,21,14,3,4,5,3	15.0	25.0	9.5	0	0	0	40.0	0
Clin. non-responders: Wk 44; n=20, 4,21,14,3,4,5,3	10.0	0	4.8	7.1	0	25.0	40.0	33.3
Clin. non-responders: Wk 52; n=20, 4,21,14,3,4,5,3	10.0	0	9.5	0	0	25.0	40.0	33.3

Attachments

Untitled (Filename: Table 14.2_2.8.1.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Enhanced Clinical Response Over Time During Extension Phase

Top of page

End point title

Percentage of Subjects Who Achieve Enhanced Clinical Response Over Time During Extension Phase

End point description

Enhanced clinical response was defined as average daily stool frequency at least 60% reduction from Induction Baseline and average daily abdominal pain not worse than Induction Baseline OR average daily abdominal pain at least 35% reduction from Induction Baseline and average daily stool frequency not worse than Induction Baseline or modified clinical remission (average daily stool frequency ≤ 2.8 and not worse than Induction baseline AND average daily abdominal pain ≤ 1.0 and not worse than Induction baseline). The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 20, Week 28, Week 36, Week 44, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	52	18	50	33	9	5	9	4
Units: percentage of subjects
number (not applicable)
Responders: Week (Wk) 20; n=20, 8, 16, 10, 1,0,0,0	70.0	87.5	100	70.0	100	0	0	0
Responders: Wk 28; n=20, 8, 16, 10, 1,0,0,0	80.0	75.0	81.3	60.0	0	0	0	0
Responders: Wk 36; n=20, 8, 16, 10, 1,0,0,0	75.0	100	75.0	40.0	100	0	0	0
Responders: Wk 44; n=20, 8, 16, 10, 1,0,0,0	50.0	62.5	75.0	40.0	0	0	0	0
Responders: Wk 52; n=20, 8, 16, 10, 1,0,0,0	50.0	87.5	68.8	50.0	100	0	0	0
Non-responders: Wk 20; n=32, 10, 34, 23, 8, 5, 9,4	34.4	50.0	38.2	26.1	50.0	20.0	33.3	25.0
Non-responders: Wk 28; n=32, 10, 34, 23, 8, 5, 9,4	37.5	60.0	29.4	21.7	50.0	20.0	22.2	50.0
Non-responders: Wk 36; n=32, 10, 34, 23, 8, 5, 9,4	28.1	40.0	26.5	17.4	50.0	20.0	33.3	25.0
Non-responders: Wk 44; n=32, 10, 34, 23, 8, 5, 9,4	21.9	30.0	23.5	21.7	37.5	20.0	33.3	50.0
Non-responders: Wk 52; n=32, 10, 34, 23, 8, 5, 9,4	21.9	30.0	26.5	13.0	37.5	40.0	33.3	50.0
Clin. responders: Wk 20; n=32, 14, 29, 19, 6,1,4,1	62.5	85.7	93.1	63.2	83.3	100	25.0	100
Clin. responders: Wk 28; n=32, 14, 29, 19, 6,1,4,1	71.9	78.6	69.0	57.9	66.7	100	25.0	100
Clin. responders: Wk 36; n=32, 14, 29, 19, 6,1,4,1	65.6	78.6	65.5	42.1	83.3	100	25.0	100
Clin. responders: Wk 44; n=32, 14, 29, 19, 6,1,4,1	50.0	57.1	65.5	42.1	50.0	100	25.0	100
Clin. responders: Wk 52; n=32, 14, 29, 19, 6,1,4,1	46.9	71.4	62.1	42.1	66.7	100	25.0	100
Clin. non-responders: Wk 20; n=20, 4,21,14,3,4,5,3	25.0	0	9.5	7.1	0	0	40.0	0
Clin. non-responders: Wk 28; n=20, 4,21,14,3,4,5,3	25.0	25.0	14.3	0	0	0	20.0	33.3
Clin. non-responders: Wk 36; n=20, 4,21,14,3,4,5,3	15.0	25.0	9.5	0	0	0	40.0	0
Clin. non-responders: Wk 44; n=20, 4,21,14,3,4,5,3	5.0	0	4.8	7.1	0	0	40.0	33.3
Clin. non-responders: Wk 52; n=20, 4,21,14,3,4,5,3	10.0	0	9.5	0	0	25.0	40.0	33.3

Attachments

Untitled (Filename: Table 14.2_2.8.3.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Enhanced Clinical Response Over Time During Extension Phase Among Subjects In Enhanced Clinical Response At Week 16

Top of page

End point title

Percentage of Subjects Who Achieve Enhanced Clinical Response Over Time During Extension Phase Among Subjects In Enhanced Clinical Response At Week 16

End point description

Enhanced clinical response was defined as average daily stool frequency at least 60% reduction from Induction Baseline and average daily abdominal pain not worse than Induction Baseline or average daily abdominal pain at least 35% reduction from Induction Baseline and average daily stool frequency not worse than Induction Baseline or modified clinical remission (average daily stool frequency ≤ 2.8 and not worse than Induction baseline AND average daily abdominal pain ≤ 1.0 and not worse than Induction baseline). The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Subjects from ITT population with enhanced clinical response at Week 16. Non responder imputation. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Week 20, Week 28, Week 36, Week 44, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	30	13	28	16	4	1	2	1
Units: percentage of subjects
number (not applicable)
Responders: Week (Wk) 20; n=20, 7, 16, 9, 0,0,0,0	70.0	100	100	66.7	0	0	0	0
Responders: Wk 28; n=20, 7, 16, 9, 0,0,0,0	80.0	71.4	81.3	55.6	0	0	0	0
Responders: Wk 36; n=20, 7, 16, 9, 0,0,0,0	75.0	100	75.0	33.3	0	0	0	0
Responders: Wk 44; n=20, 7, 16, 9, 0,0,0,0	50.0	71.4	75.0	33.3	0	0	0	0
Responders: Wk 52; n=20, 7, 16, 9, 0,0,0,0	50.0	85.7	68.8	44.4	0	0	0	0
Non-responders: Wk 20; n=10, 6, 12, 7 4, 1, 2, 1	50.0	83.3	83.3	57.1	100	100	50.0	100
Non-responders: Wk 28; n=10, 6, 12, 7 4, 1, 2, 1	70.0	83.3	58.3	57.1	100	100	50.0	100
Non-responders: Wk 36; n=10, 6, 12, 7 4, 1, 2, 1	50.0	50.0	58.3	57.1	100	100	50.0	100
Non-responders: Wk 44; n=10, 6, 12, 7 4, 1, 2, 1	50.0	50.0	58.3	57.1	75.0	100	50.0	100
Non-responders: Wk 52; n=10, 6, 12, 7 4, 1, 2, 1	40.0	50.0	58.3	42.9	75.0	100	50.0	100
Clin. responders: Wk 20; n=30, 13, 28, 15, 4,1,2,1	63.3	92.3	92.9	66.7	100	100	50.0	100
Clin. responders: Wk 28; n=30, 13, 28, 15, 4,1,2,1	76.7	76.9	71.4	60.0	100	100	50.0	100
Clin. responders: Wk 36; n=30, 13, 28, 15, 4,1,2,1	66.7	76.9	67.9	46.7	100	100	50.0	100
Clin. responders: Wk 44; n=30, 13, 28, 15, 4,1,2,1	50.0	61.5	67.9	46.7	75.0	100	50.0	100
Clin. responders: Wk 52; n=30, 13, 28, 15, 4,1,2,1	46.7	69.2	64.3	46.7	75.0	100	50.0	100
Clin. non-responders: Wk 20; n=0, 0, 0, 1, 0,0,0,0	0	0	0	0	0	0	0	0
Clin. non-responders: Wk 28; n=0, 0, 0, 1, 0,0,0,0	0	0	0	0	0	0	0	0
Clin. non-responders: Wk 36; n=0, 0, 0, 1, 0,0,0,0	0	0	0	0	0	0	0	0
Clin. non-responders: Wk 44; n=0, 0, 0, 1, 0,0,0,0	0	0	0	0	0	0	0	0
Clin. non-responders: Wk 52; n=0, 0, 0, 1, 0,0,0,0	0	0	0	0	0	0	0	0

Attachments

Untitled (Filename: Table 14.2_2.9.1.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Clinical Remission Over Time During Extension Phase Among Subjects With an Average Daily Stool Frequency ≥ 2.5 and Average Daily Abdominal Pain ≥ 2.0 at Induction Baseline

Top of page

End point title

Percentage of Subjects Who Achieve Clinical Remission Over Time During Extension Phase Among Subjects With an Average Daily Stool Frequency ≥ 2.5 and Average Daily Abdominal Pain ≥ 2.0 at Induction Baseline

End point description

Clinical remission was defined as average daily stool frequency <= 1.5 and not worse than Induction Baseline AND average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Subjects from ITT population with man average daily stool frequency >= 2.5 and average daily abdominal pain >= 2.0 at Induction Baseline. Non responder imputation. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Week 20, Week 28, Week 36, Week 44, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction
Number of subjects analysed	23	11	23	14
Units: percentage of subjects
number (not applicable)
Responders: Week 20; n=9, 6, 8, 5	44.4	16.7	37.5	20.0
Responders: Week 28; n=9, 6, 8, 5	55.6	16.7	50.0	40.0
Responders: Week 36; n=9, 6, 8, 5	44.4	16.7	50.0	20.0
Responders: Week 44; n=9, 6, 8, 5	44.4	0	50.0	40.0
Responders: Week 52; n=9, 6, 8, 5	33.3	33.3	50.0	20.0
Non-responders: Week 20; n=14, 5, 15, 9	21.4	40.0	6.7	11.1
Non-responders: Week 28; n=14, 5, 15, 9	21.4	40.0	6.7	22.2
Non-responders: Week 36; n=14, 5, 15, 9	21.4	20.0	0	22.2
Non-responders: Week 44; n=14, 5, 15, 9	14.3	20.0	6.7	11.1
Non-responders: Week 52; n=14, 5, 15, 9	7.1	20.0	13.3	22.2
Clinical responders: Week 20; n=17, 10, 15, 9	41.2	30.0	26.7	22.2
Clinical responders: Week 28; n=17, 10, 15, 9	47.1	30.0	33.3	44.4
Clinical responders: Week 36; n=17, 10, 15, 9	41.2	20.0	26.7	33.3
Clinical responders: Week 44; n=17, 10, 15, 9	35.3	10.0	33.3	33.3
Clinical responders: Week 52; n=17, 10, 15, 9	23.5	30.0	40.0	33.3
Clinical non-responders: Week 20; n=6, 1, 8, 5	0	0	0	0
Clinical non-responders: Week 28; n=6, 1, 8, 5	0	0	0	0
Clinical non-responders: Week 36; n=6, 1, 8, 5	0	0	0	0
Clinical non-responders: Week 44; n=6, 1, 8, 5	0	0	0	0
Clinical non-responders: Week 52; n=6, 1, 8, 5	0	0	0	0

Attachments

Untitled (Filename: Table 14.2_2.9.3.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 Over Time

Top of page

End point title

Percentage of Subjects Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 Over Time

End point description

CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A score below 150 indicates remission. Subjects from ITT population taking corticosteroids at Induction Baseline. Non responder imputation. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Week 20, Week 28, Week 36, Week 44, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	23	7	20	14	5	0 ^[103]	3	3
Units: percentage of subjects
number (not applicable)
Responders: Week (Wk) 20; n=8, 2, 8, 5, 0, 0, 0, 0	50.0	50.0	75.0	0	0		0	0
Responders: Wk 28; n=8, 2, 8, 5, 0, 0, 0, 0	50.0	50.0	50.0	20.0	0		0	0
Responders: Wk 36; n=8, 2, 8, 5, 0, 0, 0, 0	50.0	100	50.0	0	0		0	0
Responders: Wk 44; n=8, 2, 8, 5, 0, 0, 0, 0	37.5	50.0	50.0	20.0	0		0	0
Responders: Wk 52; n=8, 2, 8, 5, 0, 0, 0, 0	50.0	100	62.5	0	0		0	0
Non-responders: Wk 20; n=15, 5, 12, 9, 5, 0, 3, 3	13.3	40.0	8.3	0	0		0	0
Non-responders: Wk 28; n=15, 5, 12, 9, 5, 0, 3, 3	6.7	40.0	16.7	11.1	0		0	0
Non-responders: Wk 36; n=15, 5, 12, 9, 5, 0, 3, 3	13.3	40.0	8.3	11.1	0		0	0
Non-responders: Wk 44; n=15, 5, 12, 9, 5, 0, 3, 3	26.7	40.0	25.0	11.1	0		0	0
Non-responders: Wk 52; n=15, 5, 12, 9, 5, 0, 3, 3	20.0	40.0	25.0	11.1	0		0	0
Clinical responders: Wk 20; n=15, 6, 14, 8,2,0,1,0	40.0	50.0	50.0	0	0		0	0
Clinical responders: Wk 28; n=15, 6, 14, 8,2,0,1,0	33.3	50.0	42.9	25.0	0		0	0
Clinical responders: Wk 36; n=15, 6, 14, 8,2,0,1,0	40.0	66.7	35.7	12.5	0		0	0
Clinical responders: Wk 44; n=15, 6, 14, 8,2,0,1,0	40.0	50.0	50.0	25.0	0		0	0
Clinical responders: Wk 52; n=15, 6, 14, 8,2,0,1,0	46.7	66.7	57.1	12.5	0		0	0
Clinical non-responders: Wk 20; n=8, 1,6,6,3,0,2,3	0	0	0	0	0		0	0
Clinical non-responders: Wk 28; n=8, 1,6,6,3,0,2,3	0	0	0	0	0		0	0
Clinical non-responders: Wk 36; n=8, 1,6,6,3,0,2,3	0	0	0	0	0		0	0
Clinical non-responders: Wk 44; n=8, 1,6,6,3,0,2,3	12.5	0	0	0	0		0	0
Clinical non-responders: Wk 52; n=8, 1,6,6,3,0,2,3	0	0	0	0	0		0	0

Attachments

Untitled (Filename: Table 14.2_2.11.5.1 stat analysis.docx)

Notes
[103] - No subjects in this arm were applicable.

No statistical analyses for this end point

Secondary: Percentage of Subjects Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Remission At Week 52

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End point title

Percentage of Subjects Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Remission At Week 52

End point description

Steroid-free remission at Week 52 was defined as both endoscopic remission at Week 52 and clinical remission at Week 52. Endoscopic remission: SES-CD ≤ 4 and at least 2 point reduction versus Induction Baseline and no subscore > 1 in any individual variable. Clinical remission: Average daily stool frequency ≤ 1.5 and not worse than baseline AND average daily abdominal pain ≤ 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). See SES-CD description details in the first primary endpoint description of this record. Subjects from ITT population taking corticosteroids at Induction Baseline. Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	23	7	20	14	5	0 ^[104]	3	3
Units: percentage of subjects
number (not applicable)
Responders; n=8, 2, 8, 5, 0, 0, 0, 0	25.0	0	37.5	0	0		0	0
Non-responders; n=15, 5, 12, 9, 5, 0, 3, 3	0	0	0	11.1	0		0	0
Clinical responders; n=15, 6, 14, 8, 2, 0, 1, 0	13.3	0	21.4	12.5	0		0	0
Clinical non-responders; n=8, 1, 6, 6, 3, 0, 2, 3	0	0	0	0	0		0	0

Attachments

Untitled (Filename: Table 14.2_2.11.1.1 stat analysis.docx)

Notes
[104] - No subjects in this arm had were applicable.

No statistical analyses for this end point

Secondary: Percentage of Subjects Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission Over Time

Top of page

End point title

Percentage of Subjects Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission Over Time

End point description

Steroid-free clinical remission was defined as average daily stool frequency <= 1.5 and not worse than Induction Baseline AND average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Subjects from ITT population taking corticosteroids at Induction Baseline. Non responder imputation. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Week 20, Week 28, Week 36, Week 44, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	23	7	20	14	5	0 ^[105]	3	3
Units: percentage of subjects
number (not applicable)
Responders: Week (Wk) 20; n=8, 2, 8, 5, 0, 0, 0, 0	50.0	50.0	50.0	0	0		0	0
Responders: Wk 28; n=8, 2, 8, 5, 0, 0, 0, 0	37.5	50.0	50.0	20.0	0		0	0
Responders: Wk 36; n=8, 2, 8, 5, 0, 0, 0, 0	37.5	100	62.5	0	0		0	0
Responders: Wk 44; n=8, 2, 8, 5, 0, 0, 0, 0	37.5	0	62.5	20.0	0		0	0
Responders: Wk 52; n=8, 2, 8, 5, 0, 0, 0, 0	25.0	100	62.5	0	0		0	0
Non-responders: Wk 20; n=15, 5, 12, 9, 5, 0, 3, 3	13.3	40.0	0	0	0		0	0
Non-responders: Wk 28; n=15, 5, 12, 9, 5, 0, 3, 3	6.7	40.0	16.7	11.1	0		0	0
Non-responders: Wk 36; n=15, 5, 12, 9, 5, 0, 3, 3	6.7	20.0	0	11.1	0		0	0
Non-responders: Wk 44; n=15, 5, 12, 9, 5, 0, 3, 3	20.0	40.0	0	11.1	0		0	0
Non-responders: Wk 52; n=15, 5, 12, 9, 5, 0, 3, 3	13.3	20.0	8.3	11.1	0		0	0
Clin. responders: Wk 20; n=15, 6, 14, 8, 2, 0,1,0	40.0	50.0	28.6	0	0		0	0
Clin. responders: Wk 28; n=15, 6, 14, 8, 2, 0,1,0	26.7	50.0	42.9	25.0	0		0	0
Clin. responders: Wk 36; n=15, 6, 14, 8, 2, 0,1,0	26.7	50.0	35.7	12.5	0		0	0
Clin. responders: Wk 44; n=15, 6, 14, 8, 2, 0,1,0	40.0	33.3	35.7	25.0	0		0	0
Clin. responders: Wk 52; n=15, 6, 14, 8, 2, 0,1,0	26.7	50.0	42.9	12.5	0		0	0
Clin. non-responders: Wk 20; n=8, 1, 6, 6, 3,0,2,3	0	0	0	0	0		0	0
Clin. non-responders: Wk 28; n=8, 1, 6, 6, 3,0,2,3	0	0	0	0	0		0	0
Clin. non-responders: Wk 36; n=8, 1, 6, 6, 3,0,2,3	0	0	0	0	0		0	0
Clin. non-responders: Wk 44; n=8, 1, 6, 6, 3,0,2,3	0	0	0	0	0		0	0
Clin. non-responders: Wk 52; n=8, 1, 6, 6, 3,0,2,3	0	0	0	0	0		0	0

Attachments

Untitled (Filename: Table 14.2_2.11.2.1 stat analysis.docx)

Notes
[105] - No subjects in this arm were applicable.

No statistical analyses for this end point

Secondary: Percentage of Subjects Taking Corticosteroids at Induction Baseline and With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Modified Clinical Remission Over Time

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End point title

Percentage of Subjects Taking Corticosteroids at Induction Baseline and With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Modified Clinical Remission Over Time

End point description

Steroid-free modified clinical remission was defined as average daily stool frequency <= 2.8 and not worse than Induction Baseline AND average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Subjects from ITT population taking corticosteroids at Induction Baseline and Daily Stool Frequency >= 4.0 OR Daily Abdominal Pain >= 2.0 at Induction Baseline. Non responder imputation. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Week 20, Week 28, Week 36, Week 44, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	18	7	20	13	4	0 ^[106]	3	3
Units: percentage of subjects
number (not applicable)
Responders: Week (Wk) 20; n=6, 2, 8, 5, 0, 0, 0, 0	33.3	50.0	62.5	20.0	0		0	0
Responders: Wk 28; n=6, 2, 8, 5, 0, 0, 0, 0	50.0	50.0	62.5	20.0	0		0	0
Responders: Wk 36; n=6, 2, 8, 5, 0, 0, 0, 0	50.0	100	62.5	0	0		0	0
Responders: Wk 44; n=6, 2, 8, 5, 0, 0, 0, 0	33.3	50.0	62.5	20.0	0		0	0
Responders: Wk 52; n=6, 2, 8, 5, 0, 0, 0, 0	33.3	100	62.5	0	0		0	0
Non-responders: Wk 20; n=12, 5, 12, 8, 4, 0, 3, 3	8.3	40.0	8.3	0	0		0	0
Non-responders: Wk 28; n=12, 5, 12, 8, 4, 0, 3, 3	16.7	40.0	16.7	12.5	0		0	0
Non-responders: Wk 36; n=12, 5, 12, 8, 4, 0, 3, 3	8.3	20.0	8.3	12.5	0		0	0
Non-responders: Wk 44; n=12, 5, 12, 8, 4, 0, 3, 3	16.7	40.0	0	12.5	0		0	0
Non-responders: Wk 52; n=12, 5, 12, 8, 4, 0, 3, 3	8.3	20.0	16.7	12.5	0		0	0
Clin. responders: Wk 20; n=12, 6, 14, 7, 1, 0,1,0	25.0	50.0	42.9	14.3	0		0	0
Clin. responders: Wk 28; n=12, 6, 14, 7, 1, 0,1,0	41.7	50.0	50.0	28.6	0		0	0
Clin. responders: Wk 36; n=12, 6, 14, 7, 1, 0,1,0	33.3	50.0	42.9	14.3	0		0	0
Clin. responders: Wk 44; n=12, 6, 14, 7, 1, 0,1,0	33.3	50.0	35.7	28.6	0		0	0
Clin. responders: Wk 52; n=12, 6, 14, 7, 1, 0,1,0	25.0	50.0	50.0	14.3	0		0	0
Clin. non-responders: Wk 20; n=6, 1, 6, 6, 3,0,2,3	0	0	0	0	0		0	0
Clin. non-responders: Wk 28; n=6, 1, 6, 6, 3,0,2,3	0	0	0	0	0		0	0
Clin. non-responders: Wk 36; n=6, 1, 6, 6, 3,0,2,3	0	0	0	0	0		0	0
Clin. non-responders: Wk 44; n=6, 1, 6, 6, 3,0,2,3	0	0	0	0	0		0	0
Clin. non-responders: Wk 52; n=6, 1, 6, 6, 3,0,2,3	0	0	0	0	0		0	0

Attachments

Untitled (Filename: Table 14.2_2.11.3.1 stat analysis.docx)

Notes
[106] - No subjects in the arm applied.

No statistical analyses for this end point

Secondary: Percentage of Subjects Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 52

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End point title

Percentage of Subjects Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 52

End point description

Steroid-free endoscopic remission was defined as SES-CD <= 4 and at least 2 points reduction versus Induction Baseline and no subscore > 1 in any individual variable. Details of the SES-CD scale are provided in the description of the first primary endpoint. Subjects from ITT population taking corticosteroids at Induction Baseline. Non responder imputation. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	23	7	20	14	5	0 ^[107]	3	3
Units: percentage of subjects
number (not applicable)
Responders; n=8, 2, 8, 5, 0, 0, 0, 0	25.0	0	50.0	0	0		0	0
Non-responders; n=15, 5, 12, 9, 5, 0, 3, 3	0	20.0	8.3	11.1	0		0	0
Clinical responders; n=15, 6, 14, 8,2, 0, 1, 0	13.3	16.7	35.7	12.5	0		0	0
Clinical non-responders; n=8, 1, 6, 6, 3, 0, 2, 3	0	0	0	0	0		0	0

Attachments

Untitled (Filename: Table 14.2_2.11.4.1 stat analysis.docx)

Notes
[107] - No subjects in this arm applied.

No statistical analyses for this end point

Secondary: Percentage Of Subjects Who Achieve CDAI < 150 Over Time During Extension Phase

Top of page

End point title

Percentage Of Subjects Who Achieve CDAI < 150 Over Time During Extension Phase

End point description

CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A score below 150 indicates remission. Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 20, Week 28, Week 36, Week 44, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	52	18	50	33	9	5	9	4
Units: percentage of subjects
number (not applicable)
Responders: Week (Wk) 20; n=20, 8, 16, 10, 1,0,0,0	65.0	50.0	75.0	50.0	0	0	0	0
Responders: Wk 28; n=20, 8, 16, 10, 1,0,0,0	75.0	25.0	62.5	60.0	0	0	0	0
Responders: Wk 36; n=20, 8, 16, 10, 1,0,0,0	70.0	75.0	62.5	30.0	0	0	0	0
Responders: Wk 44; n=20, 8, 16, 10, 1,0,0,0	45.0	37.5	62.5	40.0	0	0	0	0
Responders: Wk 52; n=20, 8, 16, 10, 1,0,0,0	55.0	50.0	68.8	40.0	0	0	0	0
Non-responders: Wk 20; n=32, 10, 34, 23, 8, 5,9,4	28.1	50.0	17.6	8.7	75.0	20.0	11.1	50.0
Non-responders: Wk 28; n=32, 10, 34, 23, 8, 5,9,4	15.6	40.0	17.6	13.0	37.5	20.0	22.2	50.0
Non-responders: Wk 36; n=32, 10, 34, 23, 8, 5,9,4	15.6	30.0	14.7	13.0	37.5	20.0	33.3	50.0
Non-responders: Wk 44; n=32, 10, 34, 23, 8, 5,9,4	18.8	30.0	17.6	8.7	25.0	20.0	33.3	25.0
Non-responders: Wk 52; n=32, 10, 34, 23, 8, 5,9,4	9.4	30.0	20.6	13.0	25.0	40.0	33.3	50.0
Clin. responders: Wk 20; n=32, 14, 29, 19, 6,1,4,1	59.4	64.3	51.7	36.8	83.3	100	0	100
Clin. responders: Wk 28; n=32, 14, 29, 19, 6,1,4,1	56.3	42.9	48.3	47.4	50.0	100	25.0	100
Clin. responders: Wk 36; n=32, 14, 29, 19, 6,1,4,1	59.4	64.3	44.8	31.6	50.0	100	25.0	100
Clin. responders: Wk 44; n=32, 14, 29, 19, 6,1,4,1	40.6	42.9	55.2	31.6	33.3	100	25.0	100
Clin. responders: Wk 52; n=32, 14, 29, 19, 6,1,4,1	43.8	50.0	55.2	36.8	33.3	100	25.0	100
Clin. non-responders: Wk 20; n=20, 4,21,14,3,4,5,3	15.0	0	14.3	0	33.3	0	20.0	33.3
Clin. non-responders: Wk 28; n=20, 4,21,14,3,4,5,3	10.0	0	9.5	0	0	0	20.0	33.3
Clin. non-responders: Wk 36; n=20, 4,21,14,3,4,5,3	0	0	9.5	0	0	0	40.0	33.3
Clin. non-responders: Wk 44; n=20, 4,21,14,3,4,5,3	10.0	0	0	0	0	0	40.0	0
Clin. non-responders: Wk 52; n=20, 4,21,14,3,4,5,3	0	0	9.5	0	0	25.0	40.0	33.3

Attachments

Untitled (Filename: Table 14.2_2.10.1.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Decrease in CDAI ≥ 70 Points From Induction Baseline Over Time During Extension Phase

Top of page

End point title

Percentage of Subjects With Decrease in CDAI ≥ 70 Points From Induction Baseline Over Time During Extension Phase

End point description

CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A 70-point decrease in the CDAI index refers to improvement in the disease activity from Baseline. Non responder imputation. n=total subjects, by Week 16 status (responder/non-responder).

End point type

Secondary

End point timeframe

Week 20, Week 28, Week 36, Week 44, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	52	18	50	33	9	5	9	4
Units: percentage of subjects
number (not applicable)
Responders: Week (Wk) 20; n=20, 8, 16, 10, 1,0,0,0	80.0	100	93.8	60.0	100	0	0	0
Responders: Wk 28; n=20, 8, 16, 10, 1,0,0,0	85.0	62.5	68.8	60.0	0	0	0	0
Responders: Wk 36; n=20, 8, 16, 10, 1,0,0,0	75.0	100	75.0	50.0	100	0	0	0
Responders: Wk 44; n=20, 8, 16, 10, 1,0,0,0	60.0	87.5	81.3	40.0	100	0	0	0
Responders: Wk 52; n=20, 8, 16, 10, 1,0,0,0	55.0	75.0	75.0	40.0	100	0	0	0
Non-responders: Wk 20; n=32, 10, 34, 23, 8, 5,9,4	46.9	70.0	47.1	34.8	75.0	20.0	22.2	50.0
Non-responders: Wk 28; n=32, 10, 34, 23, 8, 5,9,4	34.4	60.0	29.4	30.4	50.0	20.0	33.3	50.0
Non-responders: Wk 36; n=32, 10, 34, 23, 8, 5,9,4	28.1	50.0	26.5	17.4	50.0	20.0	33.3	50.0
Non-responders: Wk 44; n=32, 10, 34, 23, 8, 5,9,4	25.0	30.0	29.4	26.1	37.5	40.0	33.3	25.0
Non-responders: Wk 52; n=32, 10, 34, 23, 8, 5,9,4	12.5	40.0	26.5	17.4	37.5	40.0	33.3	50.0
Clin. responders: Wk 20; n=32, 14, 29, 19, 6,1,4,1	75.0	100	89.7	63.2	100	100	0	100
Clin. responders: Wk 28; n=32, 14, 29, 19, 6,1,4,1	75.0	71.4	58.6	57.9	66.7	100	25.0	100
Clin. responders: Wk 36; n=32, 14, 29, 19, 6,1,4,1	65.6	85.7	62.1	42.1	83.3	100	25.0	100
Clin. responders: Wk 44; n=32, 14, 29, 19, 6,1,4,1	56.3	71.4	72.4	42.1	66.7	100	25.0	100
Clin. responders: Wk 52; n=32, 14, 29, 19, 6,1,4,1	46.9	71.4	62.1	36.8	66.7	100	25.0	100
Clin. non-responders: Wk 20; n=20, 4,21,14,3,4,5,3	35.0	25.0	23.8	14.3	33.3	0	40.0	33.3
Clin. non-responders: Wk 28; n=20, 4,21,14,3,4,5,3	20.0	25.0	19.0	14.3	0	0	40.0	33.3
Clin. non-responders: Wk 36; n=20, 4,21,14,3,4,5,3	15.0	25.0	14.3	7.1	0	0	40.0	33.3
Clin. non-responders: Wk 44; n=20, 4,21,14,3,4,5,3	10.0	0	9.5	14.3	0	25.0	40.0	0
Clin. non-responders: Wk 52; n=20, 4,21,14,3,4,5,3	0	0	14.3	7.1	0	25.0	40.0	33.3

Attachments

Untitled (Filename: Table 14.2_2.10.3.1 stat analysis.docx)

No statistical analyses for this end point

Secondary: Change From Induction Baseline in Fecal Calprotectin Level Over Time During Extension Phase

Top of page

End point title

Change From Induction Baseline in Fecal Calprotectin Level Over Time During Extension Phase

End point description

Subjects from ITT population with an assessment at given time point. Last observation carried forward. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Baseline, Week 28, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	39	15	30	13	5 ^[108]	4 ^[109]	4	2
Units: mcg/g
arithmetic mean (standard deviation)
Responders: Week (Wk) 28; n=16, 7, 9, 3, 1, 0, 0,0	-153.4 ( 2722.96 )	-532.0 ( 519.42 )	-2878.6 ( 2584.43 )	-3563.7 ( 4747.26 )	-194.0 ( 99999 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Responders: Wk 52; n=16, 7, 10, 4, 1, 0, 0,0	-51.9 ( 2650.98 )	-524.1 ( 521.31 )	-3047.5 ( 2509.27 )	-2371.8 ( 2786.97 )	-44.0 ( 99999 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Non-responders: Wk 28; n=21, 7, 16, 9, 4, 4, 4, 2	-150.3 ( 958.76 )	-148.3 ( 1315.46 )	-834.5 ( 3011.51 )	-850.2 ( 1821.34 )	-16.5 ( 304.33 )	-121.0 ( 395.16 )	-326.8 ( 817.71 )	760.5 ( 1075.51 )
Non-responders: Wk 52; n=23, 8, 20, 9, 4, 4, 4, 2	-87.2 ( 1494.35 )	88.3 ( 1689.67 )	-704.0 ( 2801.08 )	-562.8 ( 1738.58 )	-8.3 ( 344.29 )	-121.0 ( 395.16 )	-434.0 ( 1030.64 )	760.5 ( 1075.51 )
Clin. responders: Wk 28; n=25, 11, 16, 9,4, 1,2,0	-226.2 ( 2261.16 )	-424.5 ( 1102.22 )	-2794.6 ( 3018.26 )	-2099.3 ( 3083.34 )	-65.0 ( 316.06 )	-694.0 ( 99999 )	117.5 ( 166.17 )	0 ( 0 )
Clin. responders: Wk 52; n=26, 12, 18, 10, 4,1,2,0	1.0 ( 2457.22 )	-239.3 ( 1443.14 )	-2617.4 ( 3232.04 )	-1510.3 ( 2773.90 )	-44.3 ( 350.61 )	-694.0 ( 99999 )	117.5 ( 166.17 )	0 ( 0 )
Clin. non-responders: Wk 28; n=12, 3, 9, 3,1,3,2,2	3.7 ( 766.69 )	-30.7 ( 32.65 )	606.0 ( 1133.70 )	183.7 ( 443.97 )	0.0 ( 99999 )	70.0 ( 123.85 )	-771.0 ( 1090.36 )	760.5 ( 1075.51 )
Clin. non-responders: Wk 52; n=13, 3, 12,3,1,3,2,2	-220.2 ( 514.97 )	-30.7 ( 32.65 )	213.3 ( 802.34 )	183.7 ( 443.97 )	0.0 ( 99999 )	70.0 ( 123.85 )	-985.5 ( 1393.71 )	760.5 ( 1075.51 )

Attachments

Untitled (Filename: Table 14.2_2.15.1 stat analysis.docx)

Notes
[108] - 99999=not applicable (1 subject in arm)
[109] - 99999=not applicable (1 subject in arm)

No statistical analyses for this end point

Secondary: Change from Induction Baseline in hs-CRP Over Time During Extension Phase

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End point title

Change from Induction Baseline in hs-CRP Over Time During Extension Phase

End point description

Subjects from ITT population with an assessment at given time point. Last observation carried forward. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Baseline, Week 20, Week 28, Week 36, Week 44, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	49	18	47	31	9 ^[110]	4 ^[111]	7	4 ^[112]
Units: mg/L
arithmetic mean (standard deviation)
Responders: Week (Wk) 20; n=19, 8, 16, 9, 1, 0,0,0	-9.5 ( 21.77 )	-9.4 ( 11.14 )	-20.8 ( 19.78 )	4.1 ( 36.50 )	-3.1 ( 99999 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Responders: Wk 28; n=19, 8, 16, 9, 1, 0,0,0	-6.0 ( 22.53 )	-3.6 ( 16.12 )	-21.8 ( 17.93 )	7.0 ( 35.65 )	-4.2 ( 99999 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Responders: Wk 36; n=19, 8, 16, 9, 1, 0,0,0	-1.8 ( 25.57 )	-7.2 ( 10.86 )	-22.5 ( 18.01 )	5.6 ( 35.87 )	-4.0 ( 99999 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Responders: Wk 44; n=19, 8, 16, 9, 1, 0,0,0	-5.4 ( 22.95 )	-8.5 ( 12.18 )	-21.5 ( 19.78 )	5.8 ( 35.77 )	10.6 ( 99999 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Responders: Wk 52; n=19, 8, 16, 9, 1, 0,0,0	-4.3 ( 22.68 )	-7.0 ( 12.66 )	-20.4 ( 18.76 )	6.2 ( 35.82 )	0.4 ( 99999 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Non-responders: Wk 20; n=30, 10, 31, 21, 7, 4,7,4	-2.2 ( 9.72 )	-1.6 ( 8.24 )	-8.5 ( 25.00 )	-8.0 ( 18.77 )	0.3 ( 10.89 )	-1.0 ( 0.97 )	-6.8 ( 8.82 )	-1.5 ( 2.39 )
Non-responders: Wk 28; n=30, 10, 31, 22, 8, 4,7,4	-3.0 ( 9.61 )	-0.2 ( 5.92 )	-6.4 ( 27.03 )	-6.5 ( 20.14 )	0.3 ( 9.78 )	-1.1 ( 1.06 )	-5.9 ( 6.58 )	3.8 ( 9.55 )
Non-responders: Wk 36; n=30, 10, 31, 22, 8, 4,7,4	-0.7 ( 8.86 )	5.2 ( 15.34 )	-7.3 ( 24.87 )	0.8 ( 45.98 )	3.3 ( 8.88 )	0.5 ( 0.41 )	-3.7 ( 7.80 )	8.3 ( 12.71 )
Non-responders: Wk 44; n=30, 10, 31, 22, 8, 4,7,4	-1.3 ( 7.82 )	11.1 ( 33.68 )	-4.1 ( 27.93 )	0.9 ( 45.88 )	3.0 ( 9.51 )	-0.9 ( 0.87 )	-4.1 ( 7.12 )	5.5 ( 9.39 )
Non-responders: Wk 52; n=30, 10, 31, 22, 8, 4,7,4	-1.2 ( 8.67 )	2.8 ( 17.81 )	-3.4 ( 32.58 )	1.3 ( 45.26 )	4.7 ( 11.50 )	-0.2 ( 0.42 )	-5.1 ( 8.52 )	2.5 ( 9.89 )
Clin. responders: Wk 20; n=30, 14, 28, 17, 6,1,3,1	-7.1 ( 18.16 )	-6.9 ( 10.80 )	-18.0 ( 29.20 )	-3.0 ( 31.35 )	-3.8 ( 5.59 )	-2.2 ( 99999 )	-9.5 ( 12.15 )	-4.4 ( 99999 )
Clin. responders: Wk 28; n=30, 14, 28, 17, 6,1,3,1	-5.4 ( 19.26 )	-2.0 ( 12.93 )	-19.2 ( 30.13 )	0.0 ( 32.17 )	-4.0 ( 4.77 )	-2.3 ( 99999 )	-6.1 ( 6.32 )	-5.3 ( 99999 )
Clin. responders: Wk 36; n=30, 14, 28, 17, 6,1,3,1	-0.8 ( 20.85 )	-0.5 ( 16.69 )	-18.6 ( 28.62 )	9.1 ( 56.33 )	0.1 ( 5.93 )	0.4 ( 99999 )	-3.2 ( 9.54 )	-4.9 ( 99999 )
Clin. responders: Wk 44; n=30, 14, 28, 17, 6,1,3,1	-3.5 ( 18.87 )	3.0 ( 31.54 )	-15.3 ( 32.75 )	9.3 ( 56.18 )	2.2 ( 7.92 )	-1.5 ( 99999 )	-1.8 ( 7.26 )	-3.9 ( 99999 )
Clin. responders: Wk 52; n=30, 14, 28, 17, 6,1,3,1	-2.8 ( 18.91 )	-2.1 ( 18.36 )	-13.9 ( 37.06 )	10.2 ( 55.66 )	2.7 ( 10.77 )	-0.7 ( 99999 )	-4.2 ( 11.29 )	-4.6 ( 99999 )
Clin. non-responders: Wk 20; n=19, 4,19,13,2,3,4,3	-1.7 ( 10.51 )	1.4 ( 2.83 )	-4.9 ( 8.36 )	-6.2 ( 15.35 )	10.9 ( 15.47 )	-0.6 ( 0.71 )	-4.8 ( 6.69 )	-0.5 ( 1.68 )
Clin. non-responders: Wk 28; n=20, 4,19,14,3,3,4,3	-2.2 ( 7.71 )	-0.6 ( 1.43 )	-0.6 ( 6.82 )	-5.7 ( 15.26 )	7.3 ( 12.63 )	-0.7 ( 0.81 )	-5.8 ( 7.73 )	6.8 ( 9.10 )
Clin. non-responders: Wk 36; n=20, 4,19,14,3,3,4,3	-1.7 ( 8.94 )	0.4 ( 0.51 )	-3.4 ( 8.04 )	-6.1 ( 13.28 )	7.3 ( 12.63 )	0.6 ( 0.50 )	-4.1 ( 7.77 )	12.7 ( 11.20 )
Clin. non-responders: Wk 44; n=20, 4,19,14,3,3,4,3	-1.9 ( 7.83 )	0.4 ( 0.51 )	-2.3 ( 9.37 )	-6.2 ( 13.15 )	7.3 ( 12.63 )	-0.7 ( 0.95 )	-5.8 ( 7.55 )	8.6 ( 8.55 )
Clin. non-responders: Wk 52; n=20, 4,19,14,3,3,4,3	-1.9 ( 8.11 )	0.4 ( 0.51 )	-2.2 ( 9.28 )	-6.3 ( 11.71 )	7.3 ( 12.63 )	0.0 ( 0.33 )	-5.8 ( 7.66 )	4.9 ( 10.60 )

Attachments

Untitled (Filename: Table 14.2_2.16.1 stat analysis.docx)

Notes
[110] - 99999=not applicable (1 subject analyzed)
[111] - 99999=not applicable (1 subject analyzed)
[112] - 99999=not applicable (1 subject analyzed)

No statistical analyses for this end point

Secondary: Change From Induction Baseline in IBDQ at Week 52

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End point title

Change From Induction Baseline in IBDQ at Week 52

End point description

The IBDQ is a disease-specific instrument composed of 32 Likert-scaled items. The total score ranges from 32 to 224 using the 7-point response options, with higher scores indicating better health-related quality of life. The IBDQ scale contains 4 component subscales: bowel symptoms, systemic symptoms, emotional function, and social function. Each subscale can be computed with total scores ranging from 10 to 70, 5 to 35, 12 to 84, and 5 to 35, respectively. Subjects from ITT population with an assessment at given time point. Observed cases. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	36	15	38	22	7 ^[113]	4 ^[114]	5	2 ^[115]
Units: units on a scale
arithmetic mean (standard deviation)
Responders; n=14, 8, 14, 7, 1, 0, 0, 0	43.9 ( 38.06 )	56.4 ( 14.52 )	82.3 ( 35.59 )	45.3 ( 49.89 )	-5.0 ( 99999 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Non-responders; n=22, 7, 24, 15, 6, 4, 5, 2	20.8 ( 43.58 )	26.0 ( 33.14 )	25.9 ( 47.05 )	2.9 ( 35.25 )	4.8 ( 16.42 )	35.5 ( 28.78 )	45.4 ( 36.16 )	41.5 ( 24.75 )
Clinical responders; n=22, 13, 23, 14, 5, 1, 2, 1	42.8 ( 44.13 )	46.6 ( 27.76 )	70.7 ( 46.99 )	26.6 ( 53.11 )	4.8 ( 18.70 )	68.0 ( 99999 )	34.5 ( 4.95 )	24.0 ( 99999 )
Clinical non-responders; n=14, 2, 15, 8, 2, 3, 3,1	9.4 ( 31.46 )	13.5 ( 19.09 )	9.8 ( 30.81 )	-1.5 ( 5.81 )	0.0 ( 0.00 )	24.6 ( 23.17 )	52.7 ( 49.03 )	59.0 ( 99999 )

Notes
[113] - 99999=not applicable (1 subject analyzed)
[114] - 99999=not applicable (1 subject analyzed)
[115] - 99999=not applicable (1 subject analyzed)

No statistical analyses for this end point

Secondary: Change From Induction Baseline in European Quality of Life (EuroQol) 5 Dimensions Questionnaire (EQ-5D) Index Score at Week 52

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End point title

Change From Induction Baseline in European Quality of Life (EuroQol) 5 Dimensions Questionnaire (EQ-5D) Index Score at Week 52

End point description

The EQ-5D is a standardized instrument for use as a measure of health-related quality of life. The EQ-5D Index Score has five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Health states are converted into a weighted health state index. These weights lie on a scale on which full health has a value of 1 and dead has a value of 0. A positive change represents an improvement in health-related quality of life. Subjects from ITT population with an assessment at given time point. Observed cases. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	36	15	38	22	7 ^[116]	4 ^[117]	6	3 ^[118]
Units: units on a scale
arithmetic mean (standard deviation)
Responders; n=14, 8, 14, 7, 1, 0, 0, 0	0.1350 ( 0.1473 )	0.1673 ( 0.1090 )	0.2274 ( 0.1524 )	0.0122 ( 0.1276 )	0.3260 ( 99999 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Non-responders; n=22, 7, 24, 15, 6, 4, 6, 3	0.0208 ( 0.2231 )	0.0697 ( 0.2091 )	0.1090 ( 0.1791 )	0.0449 ( 0.1008 )	0.1288 ( 0.1674 )	0.1125 ( 0.2210 )	0.1542 ( 0.2377 )	0.1187 ( 0.1128 )
Clinical responders; n=11, 13, 23, 14, 5, 1, 3, 1	0.1435 ( 0.1461 )	0.1334 ( 0.1740 )	0.2306 ( 0.1840 )	0.0587 ( 0.1298 )	0.2198 ( 0.1615 )	0.4325 ( 99999 )	0.1758 ( 0.3559 )	0.1316 ( 99999 )
Clinical non-responders; n=14, 2, 15, 8, 2, 3, 3,2	-0.0577 ( 0.2225 )	0.0455 ( 0.0643 )	0.0330 ( 0.0677 )	-0.0079 ( 0.0228 )	0.0000 ( 0.0000 )	0.0058 ( 0.0708 )	0.1325 ( 0.1148 )	0.1122 ( 0.1587 )

Attachments

Untitled (Filename: Table 14.2_2.19.1 stat analysis EQ-5D.docx)

Notes
[116] - 99999=not applicable (1 subject was analyzed)
[117] - 99999=not applicable (1 subject was analyzed)
[118] - 99999=not applicable (1 subject was analyzed)

No statistical analyses for this end point

Secondary: Change From Induction Baseline in EQ-5D VAS at Week 52

Top of page

End point title

Change From Induction Baseline in EQ-5D VAS at Week 52

End point description

The EQ-5D is a standardized instrument for use as a measure of health-related quality of life. The EQ-5D VAS is a 20-cm scale with endpoints labeled "best imaginable health" and "worst imaginable health" anchored at 100 and 0, respectively. A positive change represents an improvement in health-related quality of life. Subjects from ITT population with an assessment at given time point. Observed cases. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	36	15	37	22	7 ^[119]	4 ^[120]	6	3 ^[121]
Units: units on a scale
arithmetic mean (standard deviation)
Responders; n=14, 8, 14, 7, 1, 0, 0, 0	12.9 ( 14.65 )	26.9 ( 12.80 )	34.8 ( 22.55 )	5.0 ( 17.80 )	5.0 ( 99999 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Non-responders; n=22, 7, 23, 15, 6, 4, 6, 3	12.3 ( 24.79 )	11.9 ( 18.73 )	13.9 ( 27.81 )	4.7 ( 14.22 )	12.2 ( 16.01 )	17.5 ( 16.58 )	20.3 ( 21.23 )	0.0 ( 15.00 )
Clinical responders; n=22, 13, 22, 14, 5, 1, 3, 1	18.2 ( 19.19 )	22.2 ( 17.16 )	36.1 ( 26.19 )	8.1 ( 17.95 )	15.6 ( 15.63 )	40.0 ( 99999 )	11.7 ( 16.07 )	-15.0 ( 99999 )
Clinical non-responders; n=14, 2, 15, 8, 2, 3,3,2	3.7 ( 21.79 )	5.0 ( 7.07 )	0.8 ( 11.72 )	-1.0 ( 4.24 )	0.0 ( 0.00 )	10.0 ( 8.66 )	29.0 ( 25.36 )	7.5 ( 10.61 )

Attachments

Untitled (Filename: Table 14.2_2.19.1 stat analysis VAS.docx)

Notes
[119] - 99999=not applicable (1 subject analyzed)
[120] - 99999=not applicable (1 subject analyzed)
[121] - 99999=not applicable (1 subject analyzed)

No statistical analyses for this end point

Secondary: Cross Tabulation of Induction Baseline and Week 52 in Total Number of Extra-Intestinal Manifestations (EIMs) of Crohn's Disease

Top of page

End point title

Cross Tabulation of Induction Baseline and Week 52 in Total Number of Extra-Intestinal Manifestations (EIMs) of Crohn's Disease

End point description

Presented as percentage of subjects with given number of EIMs at Baseline and Week (Wk) 52. EIMs of Crohn's disease included anemia, autoimmune hepatitis, axial arthropathy, bronchiectasis, chronic obstructive pulmonary disease, episcleritis, erythema nodosum, iritis, nephrolithiasis, oral aphthous ulcers, peripheral arthropathy, primary sclerosing cholangitis, pyoderma gangrenosum, Sweet's syndrome, uveitis, and venous thromboembolism. Subjects from modified ITT population (all randomized subjects who took at least 1 dose of study drug in the Induction Period). n=total subjects, by number of EIMs at Induction Baseline (BL).

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	Placebo Twice Daily (BID)	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 24 mg BID	Upadacitinib 24 mg QD
Number of subjects analysed	37	39	37	36	36	35
Units: percentage of subjects
number (not applicable)
0 at BL/0 at Wk 52; n=14, 13, 22, 25, 15, 20	85.7	100	86.4	76.0	73.3	85.0
0 at BL/1 at Wk 52; n=14, 13, 22, 25, 15, 20	7.1	0	9.1	16.0	13.3	10.0
0 at BL/2 at Wk 52; n=14, 13, 22, 25, 15, 20	0	0	0	0	0	0
0 at BL/3 at Wk 52; n=14, 13, 22, 25, 15, 20	0	0	0	0	0	0
0 at BL/4 at Wk 52; n=14, 13, 22, 25, 15, 20	0	0	0	0	0	0
0 at BL/5 at Wk 52; n=14, 13, 22, 25, 15, 20	0	0	0	0	0	0
0 at BL/missing at Wk 52; n=14, 13, 22, 25, 15, 20	7.1	0	4.5	8.0	13.3	5.0
1 at BL/0 at Wk 52; n=14, 19, 10, 8, 18, 11	42.9	31.6	40.0	62.5	50.0	54.5
1 at BL/1 at Wk 52; n=14, 19, 10, 8, 18, 11	50.0	57.9	60.0	12.5	33.3	36.4
1 at BL/2 at Wk 52; n=14, 19, 10, 8, 18, 11	7.1	5.3	0	25.0	11.1	9.1
1 at BL/3 at Wk 52; n=14, 19, 10, 8, 18, 11	0	0	0	0	0	0
1 at BL/4 at Wk 52; n=14, 19, 10, 8, 18, 11	0	0	0	0	0	0
1 at BL/5 at Wk 52; n=14, 19, 10, 8, 18, 11	0	0	0	0	0	0
1 at BL/missing at Wk 52; n=14, 19, 10, 8, 18, 11	0	5.3	0	0	5.6	0
2 at BL/0 at Wk 52; n=5, 4, 3, 3, 0, 4	20.0	50.0	0	33.3	0	25.0
2 at BL/1 at Wk 52; n=5, 4, 3, 3, 0, 4	0	25.0	66.7	33.3	0	25.0
2 at BL/2 at Wk 52; n=5, 4, 3, 3, 0, 4	60.0	25.0	33.3	33.3	0	50.0
2 at BL/3 at Wk 52; n=5, 4, 3, 3, 0, 4	0	0	0	0	0	0
2 at BL/4 at Wk 52; n=5, 4, 3, 3, 0, 4	0	0	0	0	0	0
2 at BL/5 at Wk 52; n=5, 4, 3, 3, 0, 4	0	0	0	0	0	0
2 at BL/missing at Wk 52; n=5, 4, 3, 3, 0, 4	20.0	0	0	0	0	0
3 at BL/0 at Wk 52; n=2, 2, 1, 0, 3, 0	0	50.0	0	0	66.7	0
3 at BL/1 at Wk 52; n=2, 2, 1, 0, 3, 0	50.0	50.0	0	0	0	0
3 at BL/2 at Wk 52; n=2, 2, 1, 0, 3, 0	0	0	100	0	33.3	0
3 at BL/3 at Wk 52; n=2, 2, 1, 0, 3, 0	0	0	0	0	0	0
3 at BL/4 at Wk 52; n=2, 2, 1, 0, 3, 0	50.0	0	0	0	0	0
3 at BL/5 at Wk 52; n=2, 2, 1, 0, 3, 0	0	0	0	0	0	0
3 at BL/missing at Wk 52; n=2, 2, 1, 0, 3, 0	0	0	0	0	0	0
4 at BL/0 at Wk 52; n=1, 1, 1, 0, 0, 0	0	100	0	0	0	0
4 at BL/1 at Wk 52; n=1, 1, 1, 0, 0, 0	0	0	0	0	0	0
4 at BL/2 at Wk 52; n=1, 1, 1, 0, 0, 0	0	0	0	0	0	0
4 at BL/3 at Wk 52; n=1, 1, 1, 0, 0, 0	0	0	0	0	0	0
4 at BL/4 at Wk 52; n=1, 1, 1, 0, 0, 0	100	0	0	0	0	0
4 at BL/5 at Wk 52; n=1, 1, 1, 0, 0, 0	0	0	0	0	0	0
4 at BL/missing at Wk 52; n=1, 1, 1, 0, 0, 0	0	0	100	0	0	0
5 at BL/0 at Wk 52; n=1, 0, 0, 0, 0, 0	0	0	0	0	0	0
5 at BL/1 at Wk 52; n=1, 0, 0, 0, 0, 0	0	0	0	0	0	0
5 at BL/2 at Wk 52; n=1, 0, 0, 0, 0, 0	0	0	0	0	0	0
5 at BL/3 at Wk 52; n=1, 0, 0, 0, 0, 0	0	0	0	0	0	0
5 at BL/4 at Wk 52; n=1, 0, 0, 0, 0, 0	0	0	0	0	0	0
5 at BL/5 at Wk 52; n=1, 0, 0, 0, 0, 0	100	0	0	0	0	0
5 at BL/missing at Wk 52; n=1, 0, 0, 0, 0, 0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Remission at Week 52 Among Subjects With Isolated Ileal Crohn's Disease at Baseline

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End point title

Percentage of Subjects Who Achieve Remission at Week 52 Among Subjects With Isolated Ileal Crohn's Disease at Baseline

End point description

Remission at Week 52 is defined as endoscopic remission at Week 52 AND clinical remission at Week 52. Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint. Subjects from ITT population with isolated ileal Crohn's disease at Induction Baseline. Non responder imputation. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	15	4	7	3 ^[122]	2	2	2	0 ^[123]
Units: percentage of subjects
number (not applicable)
Responders; n=4, 0, 1, 0, 0, 0, 0, 0	50.0	0	0	0	0	0	0
Non-responders; n=11, 4, 6, 3, 2, 2, 2, 0	0	0	0	0	0	0	0
Clinical responders; n=8, 2, 3, 2, 2, 1, 1, 0	25.0	0	0	0	0	0	0
Clinical non-responders; n=7, 2, 4, 1, 0, 1, 1, 0	0	0	0	0	0	0	0

Attachments

Untitled (Filename: Table 14.2_2.5.3.1 stat analysis.docx)

Notes
[122] - not applicable in this arm
[123] - not applicable in this arm

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Achieve Modified Clinical Remission at Week 52 Among Subjects With Isolated Ileal Crohn's Disease at Baseline And Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline

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End point title

Percentage of Subjects Who Achieve Modified Clinical Remission at Week 52 Among Subjects With Isolated Ileal Crohn's Disease at Baseline And Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline

End point description

Modified clinical remission was defined as average daily stool frequency <= 2.8 and not worse than induction baseline AND average daily abdominal pain <= 1.0 and not worse than induction baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Subjects from ITT population with isolated ileal Crohn's disease at Induction Baseline and daily stool frequency >= 4.0 or daily abdominal pain >=2.0 at Induction Baseline. Non responder imputation. n=total subjects, by Week 16 status (responder/nonresponder).

End point type

Secondary

End point timeframe

Week 52

End point values	ITT: 3 mg BID, Upadacitinib in Induction	ITT: 6 mg BID, Upadacitinib at Induction	ITT: 12 mg BID, Upadacitinib at Induction	ITT: 24 mg QD, Upadacitinib at Induction	ITT: 3 mg BID, Placebo in Induction	ITT: 6 mg BID, Placebo at Induction	ITT: 12 mg BID, Placebo at Induction	ITT: 24 mg QD, Placebo at Induction
Number of subjects analysed	12	3	7	2	2	2	2	0 ^[124]
Units: percentage of subjects
number (not applicable)
Responders; n=3, 0, 1, 0, 0, 0, 0, 0	66.7	0	0	0	0	0	0
Non-responders; n=9, 3, 6, 2, 2, 2, 2, 0	0	33.3	0	0	50.0	0	0
Clinical responders; n=6, 2, 3, 1, 2, 1, 1, 0	33.3	50.0	0	0	50.0	0	0
Clinical non-responders; n=6, 1, 4, 1, 0, 1, 1, 0	0	0	0	0	0	0	0

Attachments

Untitled (Filename: Table 14.2_2.5.4.1 stat analysis.docx)

Notes
[124] - no subjects applicable in this arm

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Treatment-emergent adverse events AEs (TEAEs): collected from the first dose of study drug through Week 52 plus 30 days.

Adverse event reporting additional description

For the Extension Phase, a TEAE was defined as any AE with an onset date on or after the first dose of double-blind Extension dose and prior to the open-label dose or up to 30 days after the last dose of double-blind Extension dose if subject discontinued prematurely in the double-blind Extension Phase.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

Double-Blind Induction Phase: Placebo BID

Reporting group description

Placebo BID during the 16-week double-blind Induction Phase.

Reporting group title

Double-Blind Induction Phase: Upadacitinib 3 mg BID

Reporting group description

Upadacitinib 3 mg BID during the 16-week double-blind Induction Phase.

Reporting group title

Double-Blind Induction Phase: Upadacitinib 6 mg BID

Reporting group description

Upadacitinib 6 mg BID during the 16-week double-blind Induction Phase.

Reporting group title

Double-Blind Induction Phase: Upadacitinib 12 mg BID

Reporting group description

Upadacitinib 12 mg BID during the 16-week double-blind Induction Phase.

Reporting group title

Double-Blind Induction Phase: Upadacitinib 24 mg BID

Reporting group description

Upadacitinib 24 mg BID during the 16-week double-blind Induction Phase.

Reporting group title

Double-Blind Induction Phase: Upadacitinib 24 mg QD

Reporting group description

Upadacitinib 24 mg QD (consisting of two 12 mg IR doses) during the 16-week double-blind Induction Phase.

Reporting group title

Double-Blind Extension Phase: Upadacitinib 3 mg BID

Reporting group description

Upadacitinib 3 mg BID during the 36-week double-blind Extension Phase.

Reporting group title

Double-Blind Extension Phase: Upadacitinib 6 mg BID

Reporting group description

Upadacitinib 6 mg BID during the 36-week double-blind Extension Phase.

Reporting group title

Double-Blind Extension Phase: Upadacitinib 12 mg BID

Reporting group description

Upadacitinib 12 mg BID during the 36-week double-blind Extension Phase.

Reporting group title

Double-Blind Extension Phase: Upadacitinib 24 mg QD

Reporting group description

Upadacitinib 24 mg QD (consisting of two 12 mg IR doses) during the 36-week double-blind Extension Phase.

Reporting group title

Open Label (OL) Extension: Upadacitinib 12 mg BID Only

Reporting group description

Subjects who met inadequate response criteria at or after Week 20 in the Extension Phase and switched to OL upadacitinib 12 mg BID for the remainder of the Extension Phase.

Reporting group title

OL Extension: Received OL 24 mg BID

Reporting group description

Subjects who met inadequate response criteria at or after Week 20 in the Extension Phase and switched to OL upadacitinib 12 mg BID for the remainder of the Extension Phase, and were further dose escalated to OL upadacitinib 24 mg BID after continuing to meet the criteria for inadequate response following a 4-week course of OL upadacitinib 12 mg BID.

Double-Blind Induction Phase: Placebo BID

Double-Blind Induction Phase: Upadacitinib 3 mg BID

Double-Blind Induction Phase: Upadacitinib 6 mg BID

Double-Blind Induction Phase: Upadacitinib 12 mg BID

Double-Blind Induction Phase: Upadacitinib 24 mg BID

Double-Blind Induction Phase: Upadacitinib 24 mg QD

Double-Blind Extension Phase: Upadacitinib 3 mg BID

Double-Blind Extension Phase: Upadacitinib 6 mg BID

Double-Blind Extension Phase: Upadacitinib 12 mg BID

Double-Blind Extension Phase: Upadacitinib 24 mg QD

Open Label (OL) Extension: Upadacitinib 12 mg BID Only

OL Extension: Received OL 24 mg BID

Total subjects affected by serious adverse events

subjects affected / exposed

2 / 37 (5.41%)

5 / 39 (12.82%)

2 / 37 (5.41%)

10 / 36 (27.78%)

3 / 36 (8.33%)

7 / 35 (20.00%)

15 / 60 (25.00%)

2 / 23 (8.70%)

5 / 59 (8.47%)

4 / 36 (11.11%)

11 / 33 (33.33%)

4 / 27 (14.81%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Hodgkin's disease

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

1 / 59 (1.69%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malignant neoplasm of thymus

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

1 / 59 (1.69%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Chest pain

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

1 / 23 (4.35%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure

subjects affected / exposed

0 / 37 (0.00%)

1 / 39 (2.56%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia aspiration

subjects affected / exposed

0 / 37 (0.00%)

1 / 39 (2.56%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

1 / 60 (1.67%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Bipolar disorder

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Depression

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 36 (0.00%)

0 / 35 (0.00%)

1 / 60 (1.67%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Suicide attempt

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 36 (2.78%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Blood creatine phosphokinase increased

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Post procedural haemorrhage

subjects affected / exposed

0 / 37 (0.00%)

1 / 39 (2.56%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Acute myocardial infarction

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulseless electrical activity

subjects affected / exposed

0 / 37 (0.00%)

1 / 39 (2.56%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sinus bradycardia

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

1 / 33 (3.03%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sinus tachycardia

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ventricular tachycardia

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Syncope

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

1 / 59 (1.69%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal pain

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

1 / 59 (1.69%)

2 / 36 (5.56%)

1 / 33 (3.03%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Anal fistula

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Anal haemorrhage

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Constipation

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

1 / 60 (1.67%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Crohn's disease

subjects affected / exposed

1 / 37 (2.70%)

2 / 39 (5.13%)

2 / 37 (5.41%)

1 / 36 (2.78%)

2 / 36 (5.56%)

0 / 35 (0.00%)

7 / 60 (11.67%)

0 / 23 (0.00%)

2 / 59 (3.39%)

4 / 36 (11.11%)

7 / 33 (21.21%)

3 / 27 (11.11%)

occurrences causally related to treatment / all

1 / 1

0 / 2

0 / 3

1 / 1

2 / 3

0 / 0

0 / 8

0 / 0

0 / 2

1 / 4

1 / 9

1 / 3

deaths causally related to treatment / all

0 / 0

Fistula of small intestine

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

1 / 33 (3.03%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal obstruction

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

1 / 60 (1.67%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ileal perforation

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 35 (2.86%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ileus

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 35 (2.86%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intestinal fistula

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 35 (2.86%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intestinal obstruction

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

1 / 60 (1.67%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intestinal stenosis

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

1 / 60 (1.67%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

1 / 33 (3.03%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Irritable bowel syndrome

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 36 (2.78%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Mesenteric vein thrombosis

subjects affected / exposed

0 / 37 (0.00%)

1 / 39 (2.56%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Peritoneal adhesions

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 35 (2.86%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small intestinal obstruction

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 36 (0.00%)

2 / 35 (5.71%)

2 / 60 (3.33%)

0 / 23 (0.00%)

1 / 59 (1.69%)

0 / 36 (0.00%)

1 / 33 (3.03%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 4

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small intestinal perforation

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 36 (2.78%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nephrolithiasis

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

1 / 27 (3.70%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Intervertebral disc protrusion

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

1 / 60 (1.67%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Osteoarthritis

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

1 / 60 (1.67%)

1 / 23 (4.35%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Abdominal abscess

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

1 / 60 (1.67%)

0 / 23 (0.00%)

1 / 59 (1.69%)

0 / 36 (0.00%)

0 / 33 (0.00%)

1 / 27 (3.70%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Abscess

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

1 / 33 (3.03%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abscess intestinal

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

1 / 33 (3.03%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Anal abscess

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

1 / 60 (1.67%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cellulitis

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

1 / 60 (1.67%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Escherichia bacteraemia

subjects affected / exposed

0 / 37 (0.00%)

1 / 39 (2.56%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Influenza

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

1 / 60 (1.67%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Peritonitis

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 35 (2.86%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rectal abscess

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sepsis

subjects affected / exposed

0 / 37 (0.00%)

1 / 39 (2.56%)

0 / 37 (0.00%)

1 / 36 (2.78%)

1 / 35 (2.86%)

1 / 60 (1.67%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Subcutaneous abscess

subjects affected / exposed

0 / 37 (0.00%)

1 / 39 (2.56%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

1 / 36 (2.78%)

0 / 36 (0.00%)

1 / 35 (2.86%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Dehydration

subjects affected / exposed

1 / 37 (2.70%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

0 / 35 (0.00%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypokalaemia

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 35 (2.86%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypomagnesaemia

subjects affected / exposed

0 / 37 (0.00%)

0 / 39 (0.00%)

0 / 37 (0.00%)

0 / 36 (0.00%)

1 / 35 (2.86%)

0 / 60 (0.00%)

0 / 23 (0.00%)

0 / 59 (0.00%)

0 / 36 (0.00%)

0 / 33 (0.00%)

0 / 27 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Double-Blind Induction Phase: Placebo BID	Double-Blind Induction Phase: Upadacitinib 3 mg BID	Double-Blind Induction Phase: Upadacitinib 6 mg BID	Double-Blind Induction Phase: Upadacitinib 12 mg BID	Double-Blind Induction Phase: Upadacitinib 24 mg BID	Double-Blind Induction Phase: Upadacitinib 24 mg QD	Double-Blind Extension Phase: Upadacitinib 3 mg BID	Double-Blind Extension Phase: Upadacitinib 6 mg BID	Double-Blind Extension Phase: Upadacitinib 12 mg BID	Double-Blind Extension Phase: Upadacitinib 24 mg QD	Open Label (OL) Extension: Upadacitinib 12 mg BID Only	OL Extension: Received OL 24 mg BID
Total subjects affected by non serious adverse events
subjects affected / exposed	25 / 37 (67.57%)	32 / 39 (82.05%)	27 / 37 (72.97%)	23 / 36 (63.89%)	28 / 36 (77.78%)	25 / 35 (71.43%)	31 / 60 (51.67%)	6 / 23 (26.09%)	33 / 59 (55.93%)	9 / 36 (25.00%)	8 / 33 (24.24%)	17 / 27 (62.96%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma
subjects affected / exposed	0 / 37 (0.00%)	2 / 39 (5.13%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0	0
Vascular disorders
Hot flush
subjects affected / exposed	0 / 37 (0.00%)	2 / 39 (5.13%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	2	0	0	1	0	0	0	0	0	0	0
Hypertension
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	2 / 37 (5.41%)	1 / 36 (2.78%)	0 / 36 (0.00%)	2 / 35 (5.71%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	0	2	1	0	2	0	0	0	0	0	0
General disorders and administration site conditions
Chills
subjects affected / exposed	1 / 37 (2.70%)	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	2 / 36 (5.56%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	1	0	0	0	2	0	0	0	0	0	0	0
Fatigue
subjects affected / exposed	3 / 37 (8.11%)	8 / 39 (20.51%)	2 / 37 (5.41%)	2 / 36 (5.56%)	4 / 36 (11.11%)	2 / 35 (5.71%)	2 / 60 (3.33%)	1 / 23 (4.35%)	2 / 59 (3.39%)	2 / 36 (5.56%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	3	9	2	2	4	2	2	1	2	2	0	0
Influenza like illness
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 37 (0.00%)	1 / 36 (2.78%)	2 / 36 (5.56%)	0 / 35 (0.00%)	3 / 60 (5.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	1 / 36 (2.78%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	0	0	1	2	0	3	0	0	1	0	0
Oedema peripheral
subjects affected / exposed	0 / 37 (0.00%)	1 / 39 (2.56%)	2 / 37 (5.41%)	1 / 36 (2.78%)	1 / 36 (2.78%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	1	2	1	1	0	0	0	0	0	0	0
Pyrexia
subjects affected / exposed	3 / 37 (8.11%)	5 / 39 (12.82%)	0 / 37 (0.00%)	2 / 36 (5.56%)	1 / 36 (2.78%)	1 / 35 (2.86%)	1 / 60 (1.67%)	0 / 23 (0.00%)	3 / 59 (5.08%)	1 / 36 (2.78%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	3	6	0	2	2	2	2	0	3	1	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)	3 / 60 (5.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	1 / 36 (2.78%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0	0	1	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 37 (0.00%)	3 / 39 (7.69%)	2 / 37 (5.41%)	0 / 36 (0.00%)	2 / 36 (5.56%)	0 / 35 (0.00%)	3 / 60 (5.00%)	0 / 23 (0.00%)	3 / 59 (5.08%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	3	2	0	2	0	3	0	4	0	0	0
Pleural effusion
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)	2 / 35 (5.71%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	2 / 37 (5.41%)	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 36 (2.78%)	2 / 35 (5.71%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	2	0	0	0	1	2	0	0	0	0	0	0
Insomnia
subjects affected / exposed	0 / 37 (0.00%)	1 / 39 (2.56%)	1 / 37 (2.70%)	2 / 36 (5.56%)	2 / 36 (5.56%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	1	1	2	2	0	0	0	0	0	0	0
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	1 / 37 (2.70%)	1 / 39 (2.56%)	1 / 37 (2.70%)	1 / 36 (2.78%)	3 / 36 (8.33%)	0 / 35 (0.00%)	4 / 60 (6.67%)	1 / 23 (4.35%)	2 / 59 (3.39%)	1 / 36 (2.78%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	1	1	1	1	3	0	5	1	2	1	0	0
C-reactive protein increased
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)	3 / 60 (5.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0	0	0	0	0
Haemoglobin decreased
subjects affected / exposed	0 / 37 (0.00%)	1 / 39 (2.56%)	1 / 37 (2.70%)	0 / 36 (0.00%)	2 / 36 (5.56%)	1 / 35 (2.86%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	1	1	0	2	1	0	0	0	0	0	0
Injury, poisoning and procedural complications
Post procedural haemorrhage
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	2 / 27 (7.41%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2
Nervous system disorders
Headache
subjects affected / exposed	3 / 37 (8.11%)	7 / 39 (17.95%)	7 / 37 (18.92%)	3 / 36 (8.33%)	8 / 36 (22.22%)	5 / 35 (14.29%)	0 / 60 (0.00%)	1 / 23 (4.35%)	5 / 59 (8.47%)	1 / 36 (2.78%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	3	8	11	3	9	5	0	1	6	1	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 37 (0.00%)	2 / 39 (5.13%)	1 / 37 (2.70%)	3 / 36 (8.33%)	1 / 36 (2.78%)	2 / 35 (5.71%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	2	1	3	1	3	0	0	0	0	0	0
Lymphadenopathy
subjects affected / exposed	1 / 37 (2.70%)	2 / 39 (5.13%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	0	0	0	0
Eye disorders
Eye pain
subjects affected / exposed	0 / 37 (0.00%)	2 / 39 (5.13%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 37 (0.00%)	5 / 39 (12.82%)	2 / 37 (5.41%)	6 / 36 (16.67%)	2 / 36 (5.56%)	5 / 35 (14.29%)	4 / 60 (6.67%)	0 / 23 (0.00%)	1 / 59 (1.69%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	6	2	8	2	5	4	0	1	0	0	0
Abdominal pain upper
subjects affected / exposed	2 / 37 (5.41%)	0 / 39 (0.00%)	0 / 37 (0.00%)	1 / 36 (2.78%)	0 / 36 (0.00%)	1 / 35 (2.86%)	3 / 60 (5.00%)	0 / 23 (0.00%)	1 / 59 (1.69%)	0 / 36 (0.00%)	0 / 33 (0.00%)	2 / 27 (7.41%)
occurrences all number	2	0	0	1	0	1	3	0	1	0	0	2
Anorectal discomfort
subjects affected / exposed	2 / 37 (5.41%)	0 / 39 (0.00%)	1 / 37 (2.70%)	0 / 36 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	2	0	1	0	0	0	0	0	0	0	0	0
Constipation
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 36 (2.78%)	2 / 35 (5.71%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	0	0	0	1	3	0	0	0	0	0	0
Crohn's disease
subjects affected / exposed	6 / 37 (16.22%)	6 / 39 (15.38%)	4 / 37 (10.81%)	7 / 36 (19.44%)	3 / 36 (8.33%)	2 / 35 (5.71%)	6 / 60 (10.00%)	2 / 23 (8.70%)	6 / 59 (10.17%)	2 / 36 (5.56%)	2 / 33 (6.06%)	3 / 27 (11.11%)
occurrences all number	6	6	4	8	3	2	6	2	7	2	3	4
Diarrhoea
subjects affected / exposed	3 / 37 (8.11%)	1 / 39 (2.56%)	0 / 37 (0.00%)	3 / 36 (8.33%)	0 / 36 (0.00%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	2 / 27 (7.41%)
occurrences all number	3	1	0	3	0	0	0	0	0	0	0	2
Dyspepsia
subjects affected / exposed	0 / 37 (0.00%)	2 / 39 (5.13%)	0 / 37 (0.00%)	1 / 36 (2.78%)	0 / 36 (0.00%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	2	0	1	0	0	0	0	0	0	0	0
Flatulence
subjects affected / exposed	1 / 37 (2.70%)	1 / 39 (2.56%)	0 / 37 (0.00%)	0 / 36 (0.00%)	3 / 36 (8.33%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	1	1	0	0	3	0	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)	0 / 60 (0.00%)	1 / 23 (4.35%)	2 / 59 (3.39%)	2 / 36 (5.56%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	2	2	0	0
Haematochezia
subjects affected / exposed	1 / 37 (2.70%)	1 / 39 (2.56%)	0 / 37 (0.00%)	2 / 36 (5.56%)	0 / 36 (0.00%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	1	1	0	2	0	0	0	0	0	0	0	0
Intestinal obstruction
subjects affected / exposed	2 / 37 (5.41%)	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0	0
Nausea
subjects affected / exposed	3 / 37 (8.11%)	2 / 39 (5.13%)	3 / 37 (8.11%)	3 / 36 (8.33%)	3 / 36 (8.33%)	1 / 35 (2.86%)	1 / 60 (1.67%)	1 / 23 (4.35%)	3 / 59 (5.08%)	1 / 36 (2.78%)	2 / 33 (6.06%)	1 / 27 (3.70%)
occurrences all number	3	2	4	3	4	1	1	1	3	1	2	1
Proctalgia
subjects affected / exposed	0 / 37 (0.00%)	3 / 39 (7.69%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	3	0	0	1	0	0	0	0	0	0	0
Vomiting
subjects affected / exposed	1 / 37 (2.70%)	4 / 39 (10.26%)	1 / 37 (2.70%)	3 / 36 (8.33%)	3 / 36 (8.33%)	1 / 35 (2.86%)	1 / 60 (1.67%)	0 / 23 (0.00%)	3 / 59 (5.08%)	1 / 36 (2.78%)	1 / 33 (3.03%)	3 / 27 (11.11%)
occurrences all number	1	4	1	3	3	1	1	0	3	1	1	3
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	1 / 37 (2.70%)	1 / 39 (2.56%)	2 / 37 (5.41%)	2 / 36 (5.56%)	3 / 36 (8.33%)	3 / 35 (8.57%)	1 / 60 (1.67%)	0 / 23 (0.00%)	4 / 59 (6.78%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	1	1	2	2	3	3	1	0	4	0	0	0
Alopecia
subjects affected / exposed	1 / 37 (2.70%)	0 / 39 (0.00%)	2 / 37 (5.41%)	0 / 36 (0.00%)	2 / 36 (5.56%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	1	0	2	0	2	0	0	0	0	0	0	0
Dermatitis acneiform
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	1 / 37 (2.70%)	2 / 36 (5.56%)	1 / 36 (2.78%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	0	1	2	1	0	0	0	0	0	0	0
Rash
subjects affected / exposed	0 / 37 (0.00%)	1 / 39 (2.56%)	0 / 37 (0.00%)	1 / 36 (2.78%)	0 / 36 (0.00%)	3 / 35 (8.57%)	0 / 60 (0.00%)	1 / 23 (4.35%)	3 / 59 (5.08%)	2 / 36 (5.56%)	2 / 33 (6.06%)	3 / 27 (11.11%)
occurrences all number	0	1	0	1	0	4	0	1	3	2	2	3
Rash erythematous
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)	2 / 35 (5.71%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0
Rosacea
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 37 (0.00%)	2 / 36 (5.56%)	1 / 36 (2.78%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	2 / 36 (5.56%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	0	0	2	1	0	0	0	0	2	0	0
Urticaria
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	1 / 37 (2.70%)	0 / 36 (0.00%)	0 / 36 (0.00%)	2 / 35 (5.71%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	0	1	0	0	2	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	4 / 37 (10.81%)	2 / 39 (5.13%)	2 / 37 (5.41%)	1 / 36 (2.78%)	1 / 36 (2.78%)	3 / 35 (8.57%)	5 / 60 (8.33%)	1 / 23 (4.35%)	2 / 59 (3.39%)	2 / 36 (5.56%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	4	2	2	1	1	3	5	1	2	2	0	0
Back pain
subjects affected / exposed	2 / 37 (5.41%)	1 / 39 (2.56%)	1 / 37 (2.70%)	0 / 36 (0.00%)	0 / 36 (0.00%)	1 / 35 (2.86%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	2 / 27 (7.41%)
occurrences all number	2	1	1	0	0	1	0	0	0	0	0	2
Muscle spasms
subjects affected / exposed	0 / 37 (0.00%)	1 / 39 (2.56%)	2 / 37 (5.41%)	2 / 36 (5.56%)	1 / 36 (2.78%)	1 / 35 (2.86%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	1	4	2	1	2	0	0	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	1 / 37 (2.70%)	0 / 39 (0.00%)	2 / 37 (5.41%)	0 / 36 (0.00%)	1 / 36 (2.78%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	1	0	2	0	1	0	0	0	0	0	0	0
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	3 / 27 (11.11%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	3
Gastroenteritis
subjects affected / exposed	1 / 37 (2.70%)	1 / 39 (2.56%)	0 / 37 (0.00%)	0 / 36 (0.00%)	1 / 36 (2.78%)	2 / 35 (5.71%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	1	2	0	0	1	2	0	0	0	0	0	0
Influenza
subjects affected / exposed	0 / 37 (0.00%)	3 / 39 (7.69%)	0 / 37 (0.00%)	1 / 36 (2.78%)	1 / 36 (2.78%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	3	0	1	1	0	0	0	0	0	0	0
Lower respiratory tract infection
subjects affected / exposed	2 / 37 (5.41%)	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0	0
Oral herpes
subjects affected / exposed	0 / 37 (0.00%)	1 / 39 (2.56%)	0 / 37 (0.00%)	1 / 36 (2.78%)	2 / 36 (5.56%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	4 / 59 (6.78%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	1	0	1	2	0	0	0	4	0	0	0
Pneumonia
subjects affected / exposed	0 / 37 (0.00%)	0 / 39 (0.00%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	3 / 59 (5.08%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	3	0	0	0
Sinusitis
subjects affected / exposed	1 / 37 (2.70%)	0 / 39 (0.00%)	2 / 37 (5.41%)	0 / 36 (0.00%)	2 / 36 (5.56%)	0 / 35 (0.00%)	1 / 60 (1.67%)	2 / 23 (8.70%)	1 / 59 (1.69%)	1 / 36 (2.78%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	2	0	2	0	2	0	1	2	1	1	0	0
Upper respiratory tract infection
subjects affected / exposed	2 / 37 (5.41%)	2 / 39 (5.13%)	2 / 37 (5.41%)	4 / 36 (11.11%)	4 / 36 (11.11%)	1 / 35 (2.86%)	3 / 60 (5.00%)	1 / 23 (4.35%)	4 / 59 (6.78%)	2 / 36 (5.56%)	0 / 33 (0.00%)	2 / 27 (7.41%)
occurrences all number	2	3	2	4	4	2	5	1	4	2	0	2
Urinary tract infection
subjects affected / exposed	2 / 37 (5.41%)	1 / 39 (2.56%)	4 / 37 (10.81%)	0 / 36 (0.00%)	5 / 36 (13.89%)	2 / 35 (5.71%)	4 / 60 (6.67%)	1 / 23 (4.35%)	5 / 59 (8.47%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	2	1	4	0	5	2	5	1	6	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 37 (2.70%)	4 / 39 (10.26%)	4 / 37 (10.81%)	4 / 36 (11.11%)	3 / 36 (8.33%)	2 / 35 (5.71%)	5 / 60 (8.33%)	1 / 23 (4.35%)	7 / 59 (11.86%)	2 / 36 (5.56%)	2 / 33 (6.06%)	3 / 27 (11.11%)
occurrences all number	2	5	5	4	5	2	5	1	8	3	2	3
Metabolism and nutrition disorders
Hypokalaemia
subjects affected / exposed	2 / 37 (5.41%)	1 / 39 (2.56%)	1 / 37 (2.70%)	0 / 36 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	2	1	1	0	0	0	0	0	0	0	0	0
Malnutrition
subjects affected / exposed	0 / 37 (0.00%)	2 / 39 (5.13%)	0 / 37 (0.00%)	0 / 36 (0.00%)	0 / 36 (0.00%)	0 / 35 (0.00%)	0 / 60 (0.00%)	0 / 23 (0.00%)	0 / 59 (0.00%)	0 / 36 (0.00%)	0 / 33 (0.00%)	0 / 27 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

19 Feb 2015

(19 February 2015, 120 subjects enrolled): Substantive changes were made to allow for extension of the Screening Period as necessary, clarification on approved birth control methods, addition of nitrite and leukocyte tests, and updates to the blinding and toxicity management sections.

20 Oct 2015

Updated number of study sites to 165. A 6 mg BID group was added to replace the 24 mg QD group in the DB Extension Phase and to replace the 24 mg QD dose with 12 mg BID in the OL Extension Phase for subjects who inadequately responded during the DB Extension Phase, based on recent Phase 2 clinical trial data with upadacitinib in subjects with RA.

05 Feb 2016

Updated protocol to expand the patient population to include subjects with moderately to severely active CD who are inadequate responders or intolerant to immunomodulators or prior anti-TNF use. Decreased the enrollment threshold for subjects with primary non-response to prior anti-TNF treatment from 35% to 30%.

15 Apr 2016

Updated definition of inadequate response to: 1) prior immunomodulator therapy; and 2) prior induction therapy with infliximab. Updated stem cell transplant restriction, liver transaminases upper limit of normal (ULN), and the number of subjects participating in the Gene Expression testing to 70 to maintain the sample size accounting for subject drop out and even stratification. Also included clarifications regarding sample collection.

07 Nov 2016

Updated window for subject rollover to the OL Extension Phase; updated timing of the second interim analysis for the DB Extension Phase; clarifications made regarding required contraception; updated the number of subjects participating in the gene expression testing to 80. Other substantive changes made throughout protocol for clarity.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects Who Achieve Endoscopic Remission at Week 12/16

Primary: Percentage of Subjects Who Achieve Endoscopic Remission at Week 12/16

Primary: Percentage of Subjects Who Achieve Clinical Remission at Week 16

Primary: Percentage of Subjects Who Achieve Clinical Remission at Week 16

Secondary: Percentage of Subjects Who Achieve Crohn's Disease Activity Index (CDAI) < 150 at Week 16

Secondary: Percentage of Subjects Who Achieve Crohn's Disease Activity Index (CDAI) < 150 at Week 16

Secondary: Percentage of Subjects With a Decrease in CDAI ≥ 70 Points From Baseline at Week 16

Secondary: Percentage of Subjects With a Decrease in CDAI ≥ 70 Points From Baseline at Week 16

Secondary: Percentage of Subjects Who Achieve Clinical Remission at Week 12

Secondary: Percentage of Subjects Who Achieve Clinical Remission at Week 12

Secondary: Percentage of Subjects Who Achieve Remission at Week 16

Secondary: Percentage of Subjects Who Achieve Remission at Week 16

Secondary: Percentage of Subjects Who Achieve Response at Week 16

Secondary: Percentage of Subjects Who Achieve Response at Week 16

Secondary: Percentage of Subjects With Endoscopic Response at Week 12/16

Secondary: Percentage of Subjects With Endoscopic Response at Week 12/16

Secondary: Percentage of Subjects Who Achieve Clinical Response at Week 16

Secondary: Percentage of Subjects Who Achieve Clinical Response at Week 16

Secondary: Percentage of Subjects With an Average Daily Stool Frequency ≥ 2.5 AND Average Daily Abdominal Pain ≥ 2.0 at Baseline Who Achieve Clinical Remission at Week 16

Secondary: Percentage of Subjects With an Average Daily Stool Frequency ≥ 2.5 AND Average Daily Abdominal Pain ≥ 2.0 at Baseline Who Achieve Clinical Remission at Week 16

Secondary: Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 at Week 16

Secondary: Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 at Week 16

Secondary: Perentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Remission at Week 12/16 and Clinical Remission at Week 16

Secondary: Perentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Remission at Week 12/16 and Clinical Remission at Week 16

Secondary: Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission at Week 16

Secondary: Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission at Week 16

Secondary: Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 12/16

Secondary: Percentage of Subjects Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 12/16

Secondary: Change from Baseline in Fecal Calprotectin Level Over Time During the Induction Phase

Secondary: Change from Baseline in Fecal Calprotectin Level Over Time During the Induction Phase

Secondary: Change from Baseline in High-Sensitivity C-Reactive Protein (hs-CRP) at Week 16

Secondary: Change from Baseline in High-Sensitivity C-Reactive Protein (hs-CRP) at Week 16

Secondary: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Over Time During the Induction Phase

Secondary: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Over Time During the Induction Phase

Secondary: Percentage of Subjects With Isolated Ileal Crohn's Disease at Baseline Who Achieve Remission at Week 16

Secondary: Percentage of Subjects With Isolated Ileal Crohn's Disease at Baseline Who Achieve Remission at Week 16

Secondary: Percentage of Subjects With a Decrease in CDAI ≥ 100 Points From Baseline at Week 16

Secondary: Percentage of Subjects With a Decrease in CDAI ≥ 100 Points From Baseline at Week 16

Secondary: Percentage of Subjects Who Achieve > 50% Reduction From Baseline in SES-CD or Endoscopic Remission at Week 12/16

Secondary: Percentage of Subjects Who Achieve > 50% Reduction From Baseline in SES-CD or Endoscopic Remission at Week 12/16

Secondary: Percentage of Subjects Who Achieve Modified Clinical Remission at Week 16 Among Subjects With an Average Daily Stool Frequency ≥ 4.0 or Average Daily Abdominal Pain ≥ 2.0 at Baseline

Secondary: Percentage of Subjects Who Achieve Modified Clinical Remission at Week 16 Among Subjects With an Average Daily Stool Frequency ≥ 4.0 or Average Daily Abdominal Pain ≥ 2.0 at Baseline

Secondary: Change From Baseline in Abdominal Pain Rating Scale at Week 12

Secondary: Change From Baseline in Abdominal Pain Rating Scale at Week 12

Secondary: Change From Baseline in Abdominal Pain Rating Scale at Week 16

Secondary: Change From Baseline in Abdominal Pain Rating Scale at Week 16

Secondary: Percentage of Subjects Who Achieve Remission at Week 52

Secondary: Percentage of Subjects Who Achieve Remission at Week 52

Secondary: Percentage of Subjects Who Achieve Endoscopic Remission at Week 52

Secondary: Percentage of Subjects Who Achieve Endoscopic Remission at Week 52

Secondary: Percentage of Subjects Who Achieve Both Endoscopic Remission and Modified Clinical Remission at Week 52 Among Subjects With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline

Secondary: Percentage of Subjects Who Achieve Both Endoscopic Remission and Modified Clinical Remission at Week 52 Among Subjects With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline

Secondary: Percentage of Subjects Who Achieve Clinical Remission Over Time During Extension Phase

Secondary: Percentage of Subjects Who Achieve Clinical Remission Over Time During Extension Phase

Secondary: Percentage of Subjects Who Maintain Clinical Remission Over Time Among Subjects in Clinical Remission at Week 16

Secondary: Percentage of Subjects Who Maintain Clinical Remission Over Time Among Subjects in Clinical Remission at Week 16

Secondary: Percentage of Subjects Who Achieve Modified Clinical Remission Over Time During Extension Phase Among Subjects With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline

Secondary: Percentage of Subjects Who Achieve Modified Clinical Remission Over Time During Extension Phase Among Subjects With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline

Secondary: Percentage of Subjects Who Achieve Modified Clinical Remission Over Time During Extension Phase Among Subjects In Modified Clinical Remission At Week 16 and Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline

Secondary: Percentage of Subjects Who Achieve Modified Clinical Remission Over Time During Extension Phase Among Subjects In Modified Clinical Remission At Week 16 and Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline

Secondary: Percentage of Subjects Who Achieve Response at Week 52

Secondary: Percentage of Subjects Who Achieve Response at Week 52

Secondary: Percentage of Subjects With SES-CD ≤ 2 at Week 52

Secondary: Percentage of Subjects With SES-CD ≤ 2 at Week 52

Secondary: Percentage of Subjects With SES-CD = 0 at Week 52

Secondary: Percentage of Subjects With SES-CD = 0 at Week 52

Secondary: Percentage of Subjects Who Achieve Endoscopic Response at Week 52

Secondary: Percentage of Subjects Who Achieve Endoscopic Response at Week 52

Secondary: Percentage of Subjects Who Achieve Enhanced Endoscopic Response at Week 52

Secondary: Percentage of Subjects Who Achieve Enhanced Endoscopic Response at Week 52

Secondary: Percentage of Subjects Who Achieve Endoscopic Improvement at Week 52