Flag of the European Union

EU Clinical Trials Register

Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:

interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC

clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
Clinical Trials Information System (CTIS).

The EU Clinical Trials Register currently displays 43865 clinical trials with a EudraCT protocol, of which 7286 are clinical trials conducted with subjects less than 18 years old. The register also displays information on 18700 older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).

Examples: Cancer AND drug name. Pneumonia AND sponsor name.
How to search [pdf]

Advanced Search:

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

< Back to search results

Clinical Trial Results:
Combined Phase 3, Double-blind, Randomized, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Filgotinib in the Induction and Maintenance of Remission in Subjects with Moderately to Severely Active Crohn’s Disease

Summary
EudraCT number	2016-001367-36
Trial protocol	HU BG AT CZ GB IS SE DE GR PT SK ES BE NL HR NO IT
Global end of trial date	11 Nov 2022

Results information
Results version number	v1(current)
This version publication date	08 Nov 2023
First version publication date	08 Nov 2023
Other versions

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

GS-US-419-3895

ISRCTN number

-

US NCT number

NCT02914561

WHO universal trial number (UTN)

-

Sponsor organisation name

Galapagos NV

Sponsor organisation address

Generaal De Wittelaan L11 A3, Mechelen, Belgium, 2800

Public contact

Galapagos Medical Information, Galapagos NV, medicalinfo@glpg.com

Scientific contact

Galapagos Medical Information, Galapagos NV, medicalinfo@glpg.com

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

No

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

No

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

No

Analysis stage

Final

Date of interim/final analysis

11 Nov 2022

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

11 Nov 2022

Was the trial ended prematurely?

No

Main objective of the trial

The primary objectives of this study are to evaluate the safety and efficacy of filgotinib during induction and maintenance treatment of moderately to severely active Crohn's disease (CD) in participants who are biologic-naive and biologic-experienced.

Protection of trial subjects

The study was performed in accordance with the ethical principles that have their origin in the “Declaration of Helsinki” and its amendments in force at the time of the study (2013 version). It was also carried out in conformity with the protocol, the International Council for Harmonization Guideline for Good Clinical Practice (ICH-GCP) E6 (R2), and local ethical and legal requirements. The investigator informed the subjects of the risks and benefits of the study. The subjects were informed that they could withdraw from the study at any time for any reason. Consent was obtained in writing prior to any study-related activities; the investigator retained a copy of the ICFs, which are available to the sponsor for inspection. The subjects were covered by the sponsor’s insurance according to local legal requirements.

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

31 Oct 2016

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Serbia: 3

Country: Number of subjects enrolled

Romania: 9

Country: Number of subjects enrolled

Sri Lanka: 12

Country: Number of subjects enrolled

Japan: 61

Country: Number of subjects enrolled

Ukraine: 54

Country: Number of subjects enrolled

Switzerland: 13

Country: Number of subjects enrolled

India: 91

Country: Number of subjects enrolled

Hong Kong: 4

Country: Number of subjects enrolled

United States: 303

Country: Number of subjects enrolled

Malaysia: 8

Country: Number of subjects enrolled

Russian Federation: 24

Country: Number of subjects enrolled

Korea, Republic of: 18

Country: Number of subjects enrolled

New Zealand: 11

Country: Number of subjects enrolled

Canada: 37

Country: Number of subjects enrolled

Taiwan: 10

Country: Number of subjects enrolled

South Africa: 9

Country: Number of subjects enrolled

Georgia: 4

Country: Number of subjects enrolled

Israel: 29

Country: Number of subjects enrolled

Australia: 49

Country: Number of subjects enrolled

Singapore: 4

Country: Number of subjects enrolled

Austria: 3

Country: Number of subjects enrolled

Greece: 2

Country: Number of subjects enrolled

Netherlands: 36

Country: Number of subjects enrolled

Norway: 4

Country: Number of subjects enrolled

Poland: 125

Country: Number of subjects enrolled

Portugal: 9

Country: Number of subjects enrolled

Slovakia: 15

Country: Number of subjects enrolled

Spain: 27

Country: Number of subjects enrolled

Sweden: 2

Country: Number of subjects enrolled

United Kingdom: 33

Country: Number of subjects enrolled

Croatia: 4

Country: Number of subjects enrolled

Belgium: 62

Country: Number of subjects enrolled

Czechia: 28

Country: Number of subjects enrolled

France: 130

Country: Number of subjects enrolled

Germany: 83

Country: Number of subjects enrolled

Hungary: 16

Country: Number of subjects enrolled

Iceland: 1

Country: Number of subjects enrolled

Ireland: 7

Country: Number of subjects enrolled

Italy: 32

Worldwide total number of subjects

1372

EEA total number of subjects

595

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

1313

From 65 to 84 years

59

85 years and over

0

Subject disposition

Top of page

Recruitment details

Participants with diagnosis of moderately to severely Active Crohn’s disease (CD) were enrolled in the study. Participants who were biologic-naïve or biologic-experienced were enrolled in Cohort A and participants who were biologic-experienced were enrolled in Cohort B, respectively.

Screening details

Participants who met protocol eligibility criteria were assigned to the respective Cohort and subsequently randomized in a blinded fashion in a 1:1:1 ratio to 1 of 3 treatments: filgotinib 200 milligram (mg), filgotinib 100 mg and placebo.

Period 1 title

Induction study (Day 1 to Week 10)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Cohort A: Filgotinib 200 mg (Induction Study)

Arm description

Biologic naïve and biologic experienced participants received filgotinib 200 mg with placebo-to-match (PTM) filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.

Arm type

Experimental

Investigational medicinal product name

Filgotinib

Investigational medicinal product code

GS-6034, GLPG0634

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Filgotinib film-coated tablets administered orally once daily.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo administered orally once daily.

Cohort A: Filgotinib 100 mg (Induction Study)

Arm description

Biologic naïve and biologic experienced participants received filgotinib 100 mg with PTM filgotinib 200 mg tablet orally once daily, for a period of 10 weeks.

Arm type

Experimental

Investigational medicinal product name

Filgotinib

Investigational medicinal product code

GS-6034, GLPG0634

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Filgotinib film-coated tablets administered orally once daily.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo administered orally once daily.

Cohort A: Placebo (Induction Study)

Arm description

Biologic naïve and biologic experienced participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo administered orally once daily.

Cohort B: Filgotinib 200 mg (Induction Study)

Arm description

Biologic experienced participants received filgotinib 200 mg with PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.

Arm type

Experimental

Investigational medicinal product name

Filgotinib

Investigational medicinal product code

GS-6034, GLPG0634

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Filgotinib film-coated tablets administered orally once daily.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo administered orally once daily.

Cohort B: Filgotinib 100 mg (Induction Study)

Arm description

Biologic experienced participants received filgotinib 100 mg with PTM filgotinib 200 mg tablet orally once daily, for a period of 10 weeks.

Arm type

Experimental

Investigational medicinal product name

Filgotinib

Investigational medicinal product code

GS-6034, GLPG0634

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Filgotinib film-coated tablets administered orally once daily.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo administered orally once daily.

Cohort B: Placebo (Induction Study)

Arm description

Biologic experienced participants received PTM filgotinib 200 mg with PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo administered orally once daily.

Number of subjects in period 1	Cohort A: Filgotinib 200 mg (Induction Study)	Cohort A: Filgotinib 100 mg (Induction Study)	Cohort A: Placebo (Induction Study)	Cohort B: Filgotinib 200 mg (Induction Study)	Cohort B: Filgotinib 100 mg (Induction Study)	Cohort B: Placebo (Induction Study)
Started	223	245	239	204	230	231
Completed	204	213	212	177	183	192
Not completed	19	32	27	27	47	39
Consent withdrawn by subject	1	9	6	-	7	12
Physician decision	1	5	2	-	4	4
Non-Compliance with Study Drug	-	-	1	-	-	1
Adverse event, non-fatal	15	14	14	24	31	19
Randomized but not treated	1	-	2	2	2	2
Pregnancy	1	-	-	-	-	-
Lost to follow-up	-	-	1	-	-	-
Protocol deviation	-	4	1	1	3	1

Period 2 title

Maintenance study (Weeks 11 to 58)

Is this the baseline period?

No

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study)

Arm description

Participants who received filgotinib 200 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, up to Week 58.

Arm type

Experimental

Investigational medicinal product name

Filgotinib

Investigational medicinal product code

GS-6034, GLPG0634

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Filgotinib film-coated tablets administered orally once daily.

Filgotinib 200 mg to Placebo (Maintenance Study)

Arm description

Participants who received filgotinib 200 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.

Arm type

Placebo

Investigational medicinal product name

Filgotinib

Investigational medicinal product code

GS-6034, GLPG0634

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Filgotinib film-coated tablets administered orally once daily.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo administered orally once daily.

Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study)

Arm description

Participants who received filgotinib 100 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.

Arm type

Experimental

Investigational medicinal product name

Filgotinib

Investigational medicinal product code

GS-6034, GLPG0634

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Filgotinib film-coated tablets administered orally once daily.

Filgotinib 100 mg to Placebo (Maintenance Study)

Arm description

Participants who received filgotinib 100 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, up to Week 58.

Arm type

Experimental

Investigational medicinal product name

Filgotinib

Investigational medicinal product code

GS-6034, GLPG0634

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Filgotinib film-coated tablets administered orally once daily.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo administered orally once daily.

Placebo to Placebo (Maintenance Study)

Arm description

Participants who received placebo in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo administered orally once daily.

Number of subjects in period 2 ^[1]	Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study)	Filgotinib 200 mg to Placebo (Maintenance Study)	Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study)	Filgotinib 100 mg to Placebo (Maintenance Study)	Placebo to Placebo (Maintenance Study)
Started	118	56	105	56	146
Completed	64	21	45	26	74
Not completed	54	35	60	30	72
Consent withdrawn by subject	5	1	2	1	9
Physician decision	1	-	2	1	3
Non- Compliance with Study Drug	-	-	1	-	-
Adverse event, non-fatal	9	2	11	2	12
Randomized but not treated	-	-	1	1	1
Protocol- Specified Disease Worsening	31	32	40	25	43
Pregnancy	1	-	-	-	-
Lost to follow-up	3	-	1	-	-
Protocol deviation	4	-	2	-	4

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Not all participants who completed the induction study entered the maintenance study.

Baseline characteristics

Top of page

Reporting group title

Cohort A: Filgotinib 200 mg (Induction Study)

Reporting group description

Biologic naïve and biologic experienced participants received filgotinib 200 mg with placebo-to-match (PTM) filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.

Reporting group title

Cohort A: Filgotinib 100 mg (Induction Study)

Reporting group description

Biologic naïve and biologic experienced participants received filgotinib 100 mg with PTM filgotinib 200 mg tablet orally once daily, for a period of 10 weeks.

Reporting group title

Cohort A: Placebo (Induction Study)

Reporting group description

Biologic naïve and biologic experienced participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.

Reporting group title

Cohort B: Filgotinib 200 mg (Induction Study)

Reporting group description

Biologic experienced participants received filgotinib 200 mg with PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.

Reporting group title

Cohort B: Filgotinib 100 mg (Induction Study)

Reporting group description

Biologic experienced participants received filgotinib 100 mg with PTM filgotinib 200 mg tablet orally once daily, for a period of 10 weeks.

Reporting group title

Cohort B: Placebo (Induction Study)

Reporting group description

Biologic experienced participants received PTM filgotinib 200 mg with PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.

Reporting group values	Cohort A: Filgotinib 200 mg (Induction Study)	Cohort A: Filgotinib 100 mg (Induction Study)	Cohort A: Placebo (Induction Study)	Cohort B: Filgotinib 200 mg (Induction Study)	Cohort B: Filgotinib 100 mg (Induction Study)	Cohort B: Placebo (Induction Study)	Total
Number of subjects	223	245	239	204	230	231	1372
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0
Adults (18-64 years)	213	233	229	191	220	227	1313
From 65-84 years	10	12	10	13	10	4	59
85 years and over	0	0	0	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	39 ± 13.8	39 ± 14.1	39 ± 14.0	39 ± 14.1	42 ± 13.5	39 ± 12.4	-
Gender categorical
Units: Subjects
Female	110	106	130	115	129	116	706
Male	113	139	109	89	101	115	666
Ethnicity
Not Permitted = local regulators did not allow collection of race or ethnicity information.
Units: Subjects
Hispanic or Latino	4	5	4	2	8	4	27
Not Hispanic or Latino	214	237	232	193	217	220	1313
Not Permitted	5	3	3	9	5	7	32
Race
Not Permitted = local regulators did not allow collection of race information.
Units: Subjects
American Indian or Alaska Native	0	0	0	0	1	0	1
Asian	45	52	44	24	25	31	221
Black or African American	3	6	4	6	9	6	34
Native Hawaiian or Other Pacific Islander	0	0	0	0	1	2	3
White	166	179	185	158	182	178	1048
Other	2	3	2	3	0	1	11
Not Permitted	7	5	4	13	12	13	54

End points

Top of page

Reporting group title

Cohort A: Filgotinib 200 mg (Induction Study)

Reporting group description

Biologic naïve and biologic experienced participants received filgotinib 200 mg with placebo-to-match (PTM) filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.

Reporting group title

Cohort A: Filgotinib 100 mg (Induction Study)

Reporting group description

Biologic naïve and biologic experienced participants received filgotinib 100 mg with PTM filgotinib 200 mg tablet orally once daily, for a period of 10 weeks.

Reporting group title

Cohort A: Placebo (Induction Study)

Reporting group description

Biologic naïve and biologic experienced participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.

Reporting group title

Cohort B: Filgotinib 200 mg (Induction Study)

Reporting group description

Biologic experienced participants received filgotinib 200 mg with PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.

Reporting group title

Cohort B: Filgotinib 100 mg (Induction Study)

Reporting group description

Biologic experienced participants received filgotinib 100 mg with PTM filgotinib 200 mg tablet orally once daily, for a period of 10 weeks.

Reporting group title

Cohort B: Placebo (Induction Study)

Reporting group description

Biologic experienced participants received PTM filgotinib 200 mg with PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks.

Reporting group title

Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study)

Reporting group description

Participants who received filgotinib 200 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, up to Week 58.

Reporting group title

Filgotinib 200 mg to Placebo (Maintenance Study)

Reporting group description

Participants who received filgotinib 200 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.

Reporting group title

Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study)

Reporting group description

Participants who received filgotinib 100 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.

Reporting group title

Filgotinib 100 mg to Placebo (Maintenance Study)

Reporting group description

Participants who received filgotinib 100 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, up to Week 58.

Reporting group title

Placebo to Placebo (Maintenance Study)

Reporting group description

Participants who received placebo in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.

Subject analysis set title

Filgotinib 200 mg (Maintenance Study)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who received filgotinib 200 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, up to Week 58.

Subject analysis set title

Filgotinib 100 mg (Maintenance Study)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who received filgotinib 100 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.

Primary: Induction Study: Percentage of Participants who Achieved Endoscopic Response at Week 10

Top of page

End point title

Induction Study: Percentage of Participants who Achieved Endoscopic Response at Week 10

End point description

The Simple Endoscopic Score for Crohn’s Disease (SES-CD) assessed the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater severity of disease. Endoscopic response was defined as ≥ 50% reduction from baseline in total SES-CD score. The Full Analysis Set (FAS) for each Induction Study (Cohorts A and B) included all randomized participants who took at least 1 dose of study drug in the corresponding Induction Study.

End point type

Primary

End point timeframe

Week 10

End point values	Cohort A: Filgotinib 200 mg (Induction Study)	Cohort A: Filgotinib 100 mg (Induction Study)	Cohort A: Placebo (Induction Study)	Cohort B: Filgotinib 200 mg (Induction Study)	Cohort B: Filgotinib 100 mg (Induction Study)	Cohort B: Placebo (Induction Study)
Number of subjects analysed	222	245	237	202	228	229
Units: Percentage of participiants
number (confidence interval 95%)	23.9 (18.0 to 29.7)	20.8 (15.5 to 26.1)	18.1 (13.0 to 23.3)	11.9 (7.2 to 16.6)	13.6 (8.9 to 18.3)	11.4 (7.0 to 15.7)

Statistical analysis 1

Statistical analysis description

CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, >=1).

Comparison groups

Cohort A: Filgotinib 200 mg (Induction Study) v Cohort A: Placebo (Induction Study)

Number of subjects included in analysis

459

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1365

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

5.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

12.9

Statistical Analysis 2

Statistical analysis description

CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, >=1).

Comparison groups

Cohort A: Filgotinib 100 mg (Induction Study) v Cohort A: Placebo (Induction Study)

Number of subjects included in analysis

482

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5103

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

9.5

Statistical Analysis 3

Statistical analysis description

CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (<=1, >1).

Comparison groups

Cohort B: Filgotinib 200 mg (Induction Study) v Cohort B: Placebo (Induction Study)

Number of subjects included in analysis

431

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9797

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-6.7

upper limit

6.6

Statistical Analysis 4

Statistical analysis description

CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (<=1, >1).

Comparison groups

Cohort B: Filgotinib 100 mg (Induction Study) v Cohort B: Placebo (Induction Study)

Number of subjects included in analysis

457

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4264

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3.9

upper limit

8.8

Primary: Induction Study: Percentage of Participants who Achieved Clinical Remission by PRO2 at Week 10

Top of page

End point title

Induction Study: Percentage of Participants who Achieved Clinical Remission by PRO2 at Week 10

End point description

The PRO2 was a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency and abdominal pain (rated on a scale of 0-3) assessed for 7 days. Clinical Remission was defined as the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point. FAS for induction study was analyzed.

End point type

Primary

End point timeframe

Week 10

End point values	Cohort A: Filgotinib 200 mg (Induction Study)	Cohort A: Filgotinib 100 mg (Induction Study)	Cohort A: Placebo (Induction Study)	Cohort B: Filgotinib 200 mg (Induction Study)	Cohort B: Filgotinib 100 mg (Induction Study)	Cohort B: Placebo (Induction Study)
Number of subjects analysed	222	245	237	202	228	229
Units: Percentage of participants
number (confidence interval 95%)	32.9 (26.5 to 39.3)	30.6 (24.6 to 36.6)	25.7 (20.0 to 31.5)	29.7 (23.2 to 36.3)	18.9 (13.6 to 24.2)	17.9 (12.7 to 23.1)

Statistical analysis 1

Statistical analysis description

CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, >=1).

Comparison groups

Cohort A: Filgotinib 200 mg (Induction Study) v Cohort A: Placebo (Induction Study)

Number of subjects included in analysis

459

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0963

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

6.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

15.2

Statistical Analysis 2

Statistical analysis description

CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, >=1).

Comparison groups

Cohort A: Filgotinib 100 mg (Induction Study) v Cohort A: Placebo (Induction Study)

Number of subjects included in analysis

482

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.305

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

4.2

Confidence interval

level

95%

sides

2-sided

lower limit

-3.9

upper limit

12.2

Statistical Analysis 3

Statistical analysis description

CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (<=1, >1).

Comparison groups

Cohort B: Filgotinib 200 mg (Induction Study) v Cohort B: Placebo (Induction Study)

Number of subjects included in analysis

431

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0039

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

11.9

Confidence interval

level

95%

sides

2-sided

lower limit

3.7

upper limit

20.2

Statistical Analysis 4

Statistical analysis description

CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (<=1, >1).

Comparison groups

Cohort B: Filgotinib 100 mg (Induction Study) v Cohort B: Placebo (Induction Study)

Number of subjects included in analysis

457

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7556

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-6.2

upper limit

8.5

Primary: Maintenance Study: Percentage of Participants who Achieved Clinical Remission by PRO2 at Week 58

Top of page

End point title

Maintenance Study: Percentage of Participants who Achieved Clinical Remission by PRO2 at Week 58

End point description

The PRO2 was a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency and abdominal pain (rated on a scale of 0-3) assessed for 7 days. Clinical Remission was defined as the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point. The FAS for the Maintenance Study included all participants randomized to either the filgotinib 200 mg or filgotinib 100 mg treatment groups in the Induction studies who were re-randomized in the Maintenance Study and took at least 1 dose of study drug in the Maintenance Study and achieved clinical remission by PRO2 or endoscopic response at Week 10.

End point type

Primary

End point timeframe

Week 58

End point values	Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study)	Filgotinib 200 mg to Placebo (Maintenance Study)	Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study)	Filgotinib 100 mg to Placebo (Maintenance Study)
Number of subjects analysed	112	53	98	53
Units: Percentage of participants
number (confidence interval 95%)	43.8 (34.1 to 53.4)	26.4 (13.6 to 39.2)	29.6 (20.0 to 39.1)	24.5 (12.0 to 37.1)

Statistical Analysis 1

Statistical analysis description

CMH test was stratified by concomitant use of immunomodulators (Yes/No), at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).

Comparison groups

Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study) v Filgotinib 200 mg to Placebo (Maintenance Study)

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0382

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

16.8

Confidence interval

level

95%

sides

2-sided

lower limit

2

upper limit

31.6

Statistical Analysis 2

Statistical analysis description

CMH test was stratified by concomitant use of immunomodulators (Yes/No), at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).

Comparison groups

Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study) v Filgotinib 100 mg to Placebo (Maintenance Study)

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4263

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-8.5

upper limit

20

Primary: Maintenance Study: Percentage of Participants who Achieved Endoscopic Response at Week 58

Top of page

End point title

Maintenance Study: Percentage of Participants who Achieved Endoscopic Response at Week 58

End point description

The SES-CD assessed the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater severity of disease. Endoscopic response was defined as ≥ 50% reduction from baseline in total SES-CD score. FAS for Maintenance study was analyzed.

End point type

Primary

End point timeframe

Week 58

End point values	Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study)	Filgotinib 200 mg to Placebo (Maintenance Study)	Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study)	Filgotinib 100 mg to Placebo (Maintenance Study)
Number of subjects analysed	112	53	98	53
Units: Percentage of participants
number (confidence interval 95%)	30.4 (21.4 to 39.3)	9.4 (0.6 to 18.2)	18.4 (10.2 to 26.5)	13.2 (3.1 to 23.3)

Statistical analysis 1

Statistical analysis description

CMH test was stratified by concomitant use of immunomodulators (Yes/No), at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).

Comparison groups

Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study) v Filgotinib 200 mg to Placebo (Maintenance Study)

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0038

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

20.6

Confidence interval

level

95%

sides

2-sided

lower limit

8.2

upper limit

33.1

Statistical Analysis 2

Statistical analysis description

CMH test was stratified by concomitant use of immunomodulators (Yes/No), at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).

Comparison groups

Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study) v Filgotinib 100 mg to Placebo (Maintenance Study)

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3466

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-6.6

upper limit

18.3

Secondary: Induction Study: Percentage of Participants Who Achieved Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10

Top of page

End point title

Induction Study: Percentage of Participants Who Achieved Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10

End point description

The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The sub scores of abdominal pains (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Clinical remission was defined as a CDAI of < 150 points. FAS for induction study was analyzed.

End point type

Secondary

End point timeframe

Week 10

End point values	Cohort A: Filgotinib 200 mg (Induction Study)	Cohort A: Filgotinib 100 mg (Induction Study)	Cohort A: Placebo (Induction Study)	Cohort B: Filgotinib 200 mg (Induction Study)	Cohort B: Filgotinib 100 mg (Induction Study)	Cohort B: Placebo (Induction Study)
Number of subjects analysed	222	245	237	202	228	229
Units: Percentage of participants
number (confidence interval 95%)	32.9 (26.5 to 39.3)	25.7 (20.0 to 31.4)	19.8 (14.5 to 25.1)	26.7 (20.4 to 33.1)	16.7 (11.6 to 21.7)	14.8 (10.0 to 19.7)

Statistical analysis 1

Statistical analysis description

Cochran-Mantel-Haenszel (CMH) test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, >=1).

Comparison groups

Cohort A: Filgotinib 200 mg (Induction Study) v Cohort A: Placebo (Induction Study)

Number of subjects included in analysis

459

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0017

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

12.7

Confidence interval

level

95%

sides

2-sided

lower limit

4.7

upper limit

20.7

Statistical Analysis 2

Statistical analysis description

Cochran-Mantel-Haenszel (CMH) test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, >=1).

Comparison groups

Cohort A: Filgotinib 100 mg (Induction Study) v Cohort A: Placebo (Induction Study)

Number of subjects included in analysis

482

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.173

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

5.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

12.7

Statistical Analysis 3

Statistical analysis description

Cochran-Mantel-Haenszel (CMH) test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (<=1, >1).

Comparison groups

Cohort B: Filgotinib 200 mg (Induction Study) v Cohort B: Placebo (Induction Study)

Number of subjects included in analysis

431

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0023

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

12

Confidence interval

level

95%

sides

2-sided

lower limit

4.1

upper limit

19.9

Statistical Analysis 4

Statistical analysis description

Cochran-Mantel-Haenszel (CMH) test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (<=1, >1).

Comparison groups

Cohort B: Filgotinib 100 mg (Induction Study) v Cohort B: Placebo (Induction Study)

Number of subjects included in analysis

457

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6038

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-5.2

upper limit

8.7

Secondary: Induction Study: Percentage of Participants who Achieved both Clinical Remission by PRO2 and Endoscopic Response at Week 10

Top of page

End point title

Induction Study: Percentage of Participants who Achieved both Clinical Remission by PRO2 and Endoscopic Response at Week 10

End point description

The PRO2 was a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency and abdominal pain (rated on a scale of 0-3) assessed for 7 days. The SES-CD assessed the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater severity of disease. Clinical remission by PRO2: liquid or very soft stool ≤3 and abdominal pain ≤1. Endoscopic response at least 50% reduction from Induction baseline in SES-CD.

End point type

Secondary

End point timeframe

Week 10

End point values	Cohort A: Filgotinib 200 mg (Induction Study)	Cohort A: Filgotinib 100 mg (Induction Study)	Cohort A: Placebo (Induction Study)	Cohort B: Filgotinib 200 mg (Induction Study)	Cohort B: Filgotinib 100 mg (Induction Study)	Cohort B: Placebo (Induction Study)
Number of subjects analysed	222 ^[1]	245 ^[2]	237 ^[3]	202 ^[4]	228 ^[5]	229 ^[6]
Units: Percentage of participants
number (confidence interval 95%)	13.5 (8.8 to 18.2)	9.8 (5.9 to 13.7)	6.8 (3.3 to 10.2)	4.5 (1.4 to 7.5)	3.9 (1.2 to 6.7)	3.9 (1.2 to 6.7)

Notes
[1] - FAS for induction study was analyzed.
[2] - FAS for induction study was analyzed.
[3] - FAS for induction study was analyzed.
[4] - FAS for induction study was analyzed.
[5] - FAS for induction study was analyzed.
[6] - FAS for induction study was analyzed.

Statistical analysis 1

Statistical analysis description

CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, >=1).

Comparison groups

Cohort A: Filgotinib 200 mg (Induction Study) v Cohort A: Placebo (Induction Study)

Number of subjects included in analysis

459

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0152

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

6.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

12.6

Statistical Analysis 2

Statistical analysis description

CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, >=1).

Comparison groups

Cohort A: Filgotinib 100 mg (Induction Study) v Cohort A: Placebo (Induction Study)

Number of subjects included in analysis

482

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2629

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

8.1

Statistical Analysis 3

Statistical analysis description

CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (≤1, >1).

Comparison groups

Cohort B: Filgotinib 200 mg (Induction Study) v Cohort B: Placebo (Induction Study)

Number of subjects included in analysis

431

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9023

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-4.4

upper limit

4.8

Statistical Analysis 4

Statistical analysis description

CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (≤1, >1).

Comparison groups

Cohort B: Filgotinib 100 mg (Induction Study) v Cohort B: Placebo (Induction Study)

Number of subjects included in analysis

457

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9094

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

4.4

Secondary: Maintenance Study: Percentage of Participants who Achieved Clinical Remission by CDAI at Week 58

Top of page

End point title

Maintenance Study: Percentage of Participants who Achieved Clinical Remission by CDAI at Week 58

End point description

The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The sub scores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Clinical remission was defined as a CDAI of < 150 points. FAS for Maintenance study was analyzed.

End point type

Secondary

End point timeframe

Week 58

End point values	Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study)	Filgotinib 200 mg to Placebo (Maintenance Study)	Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study)	Filgotinib 100 mg to Placebo (Maintenance Study)
Number of subjects analysed	112	53	98	53
Units: Percentage of participants
number (confidence interval 95%)	42.9 (33.2 to 52.5)	28.3 (15.2 to 41.4)	23.5 (14.6 to 32.4)	22.6 (10.4 to 34.9)

Statistical analysis 1

Statistical analysis description

CMH test was stratified by concomitant use of immunomodulators (Yes/No) at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).

Comparison groups

Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study) v Filgotinib 200 mg to Placebo (Maintenance Study)

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0839

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

13.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

28.4

Statistical Analysis 2

Statistical analysis description

CMH test was stratified by concomitant use of immunomodulators (Yes/No) at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).

Comparison groups

Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study) v Filgotinib 100 mg to Placebo (Maintenance Study)

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8288

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-12.1

upper limit

15

Secondary: Maintenance Study: Percentage of Participants who Achieved Sustained Clinical Remission by PRO2 at Both Weeks 10 and 58

Top of page

End point title

Maintenance Study: Percentage of Participants who Achieved Sustained Clinical Remission by PRO2 at Both Weeks 10 and 58

End point description

The PRO2 was a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency and abdominal pain (rated on a scale of 0-3) assessed for 7 days. Sustained Clinical Remission by PRO2: liquid or very soft stool ≤3 and abdominal pain ≤1 combined at both Week 10 and Week 58. The FAS for the Maintenance Study was analyzed.

End point type

Secondary

End point timeframe

Weeks 10 and 58

End point values	Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study)	Filgotinib 200 mg to Placebo (Maintenance Study)	Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study)	Filgotinib 100 mg to Placebo (Maintenance Study)
Number of subjects analysed	112	53	98	53
Units: Percentage of participants
number (confidence interval 95%)	41.1 (31.5 to 50.6)	20.8 (8.9 to 32.6)	25.5 (16.4 to 34.7)	24.5 (12.0 to 37.1)

Statistical analysis 1

Statistical analysis description

CMH test was stratified by concomitant use of immunomodulators (Yes/No), at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).

Comparison groups

Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study) v Filgotinib 200 mg to Placebo (Maintenance Study)

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0122

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

19.9

Confidence interval

level

95%

sides

2-sided

lower limit

5.7

upper limit

34

Statistical Analysis 2

Statistical analysis description

CMH test was stratified by concomitant use of immunomodulators (Yes/No), at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).

Comparison groups

Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study) v Filgotinib 100 mg to Placebo (Maintenance Study)

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7708

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

2

Confidence interval

level

95%

sides

2-sided

lower limit

-12

upper limit

16.1

Secondary: Maintenance Study: Percentage of Participants who Achieved both Clinical Remission by PRO2 and Endoscopic Response at Week 58

Top of page

End point title

Maintenance Study: Percentage of Participants who Achieved both Clinical Remission by PRO2 and Endoscopic Response at Week 58

End point description

The PRO2 was a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency and abdominal pain (rated on a scale of 0-3) assessed for 7 days. The SES-CD assessed the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater severity of disease. Clinical remission by PRO2: liquid or very soft stool ≤3 and abdominal pain ≤1. Endoscopic response at least 50% reduction from Induction baseline in SES-CD.

End point type

Secondary

End point timeframe

Week 58

End point values	Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study)	Filgotinib 200 mg to Placebo (Maintenance Study)	Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study)	Filgotinib 100 mg to Placebo (Maintenance Study)
Number of subjects analysed	112 ^[7]	53 ^[8]	98 ^[9]	53 ^[10]
Units: Percentage of participants
number (confidence interval 95%)	25.0 (16.5 to 33.5)	5.7 (0.0 to 12.8)	13.3 (6.0 to 20.5)	9.4 (0.6 to 18.2)

Notes
[7] - The FAS for Maintenance study was analyzed.
[8] - The FAS for Maintenance study was analyzed.
[9] - The FAS for Maintenance study was analyzed.
[10] - The FAS for Maintenance study was analyzed.

Statistical Analysis 1

Statistical analysis description

CMH test was stratified by concomitant use of immunomodulators (Yes/No) at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).

Comparison groups

Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study) v Filgotinib 200 mg to Placebo (Maintenance Study)

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0036

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

19

Confidence interval

level

95%

sides

2-sided

lower limit

7.7

upper limit

30.3

Statistical Analysis 2

Statistical analysis description

CMH test was stratified by concomitant use of immunomodulators (Yes/No) at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).

Comparison groups

Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study) v Filgotinib 100 mg to Placebo (Maintenance Study)

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4179

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

4.4

Confidence interval

level

95%

sides

2-sided

lower limit

-6.9

upper limit

15.6

Secondary: Maintenance Study: Percentage of Participants who Achieved 6 Month Corticosteroid-Free Remission by PRO2 at Week 58

Top of page

End point title

Maintenance Study: Percentage of Participants who Achieved 6 Month Corticosteroid-Free Remission by PRO2 at Week 58

End point description

The PRO2 was a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency and abdominal pain (rated on a scale of 0-3) assessed for 7 days. 6-month Corticosteroid-Free Clinical Remission by PRO2: liquid or very soft stool ≤3 and abdominal pain ≤1 with no corticosteroid use for at least 6 months prior to Week 58. The FAS for the Maintenance Study with available data was analyzed.

End point type

Secondary

End point timeframe

Week 58

End point values	Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study)	Filgotinib 200 mg to Placebo (Maintenance Study)	Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study)	Filgotinib 100 mg to Placebo (Maintenance Study)
Number of subjects analysed	50	25	41	25
Units: Percentage of participants
number (confidence interval 95%)	32.0 (18.1 to 45.9)	20.0 (2.3 to 37.7)	7.3 (0.0 to 16.5)	12.0 (0.0 to 26.7)

Statistical analysis 1

Statistical analysis description

CMH test was stratified by concomitant use of immunomodulators (Yes/No) at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).

Comparison groups

Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study) v Filgotinib 200 mg to Placebo (Maintenance Study)

Number of subjects included in analysis

75

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2631

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

12

Confidence interval

level

95%

sides

2-sided

lower limit

-8.3

upper limit

32.3

Statistical Analysis 2

Statistical analysis description

CMH test was stratified by concomitant use of immunomodulators (Yes/No) at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).

Comparison groups

Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study) v Filgotinib 100 mg to Placebo (Maintenance Study)

Number of subjects included in analysis

66

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6444

Method

Cochran-Mantel-Haenszel

Parameter type

Stratified Percentage Difference

Point estimate

-3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-20.9

upper limit

14

Secondary: Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 4

Top of page

End point title

Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 4 ^[11]

End point description

Plasma concentrations of filgotinib [nanogram/milliliters (ng/mL)]. Pharmacokinetic (PK) Analysis Set (included all randomized participants who took at least 1 dose of filgotinib and had at least 1 non-missing concentration value for filgotinib and/or its metabolite GS-829845reported by the PK laboratory) for Induction study was analyzed. .

End point type

Secondary

End point timeframe

Week 4: 0.5, 1, 2, and 3 hrs. post dose

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for the endpoint.

End point values	Cohort A: Filgotinib 200 mg (Induction Study)	Cohort A: Filgotinib 100 mg (Induction Study)	Cohort B: Filgotinib 200 mg (Induction Study)	Cohort B: Filgotinib 100 mg (Induction Study)
Number of subjects analysed	177	181	141	168
Units: nanogram per milliliter (ng/mL)
arithmetic mean (standard deviation)	1170 ± 1270	611 ± 634	1140 ± 1070	604 ± 634

No statistical analyses for this end point

Secondary: Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 10

Top of page

End point title

Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 10 ^[12]

End point description

Plasma concentrations of filgotinib (ng/mL). PK Analysis Set for Induction study was analyzed. .

End point type

Secondary

End point timeframe

Week 10: Predose

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for the endpoint.

End point values	Cohort A: Filgotinib 200 mg (Induction Study)	Cohort A: Filgotinib 100 mg (Induction Study)	Cohort B: Filgotinib 200 mg (Induction Study)	Cohort B: Filgotinib 100 mg (Induction Study)
Number of subjects analysed	183	180	136	135
Units: ng/mL
arithmetic mean (standard deviation)	46.8 ± 180	21.3 ± 79.5	47.9 ± 215	40.8 ± 139

No statistical analyses for this end point

Secondary: Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 4

Top of page

End point title

Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 4 ^[13]

End point description

Plasma concentrations of GS-829845 (ng/mL). PK Analysis Set for Induction study was analyzed.

End point type

Secondary

End point timeframe

Week 4: 0.5, 1, 2, and 3 hrs. post dose

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for the endpoint.

End point values	Cohort A: Filgotinib 200 mg (Induction Study)	Cohort A: Filgotinib 100 mg (Induction Study)	Cohort B: Filgotinib 200 mg (Induction Study)	Cohort B: Filgotinib 100 mg (Induction Study)
Number of subjects analysed	177	181	141	168
Units: ng/mL
arithmetic mean (standard deviation)	3100 ± 1530	1800 ± 936	3140 ± 1450	1870 ± 776

No statistical analyses for this end point

Secondary: Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 10

Top of page

End point title

Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 10 ^[14]

End point description

Plasma concentrations of GS-829845 (ng/mL). PK Analysis Set for Induction study was analyzed.

End point type

Secondary

End point timeframe

Week 10: Predose

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for the endpoint.

End point values	Cohort A: Filgotinib 200 mg (Induction Study)	Cohort A: Filgotinib 100 mg (Induction Study)	Cohort B: Filgotinib 200 mg (Induction Study)	Cohort B: Filgotinib 100 mg (Induction Study)
Number of subjects analysed	183	180	136	135
Units: ng/mL
arithmetic mean (standard deviation)	2550 ± 1390	1290 ± 801	2640 ± 1470	1480 ± 917

No statistical analyses for this end point

Secondary: Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 26

Top of page

End point title

Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 26

End point description

Plasma concentrations of filgotinib (ng/mL). PK Analysis Set for Maintenance study was analyzed.

End point type

Secondary

End point timeframe

Week 26: At any timepoint

End point values	Filgotinib 200 mg (Maintenance Study)	Filgotinib 100 mg (Maintenance Study)
Number of subjects analysed	77	63
Units: nanogram/milliliters
arithmetic mean (standard deviation)	284 ± 623	58.5 ± 150

No statistical analyses for this end point

Secondary: Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 58

Top of page

End point title

Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 58

End point description

Plasma concentrations of filgotinib (ng/mL). PK Analysis Set for Maintenance study was analyzed.

End point type

Secondary

End point timeframe

Week 58: Pre-dose

End point values	Filgotinib 200 mg (Maintenance Study)	Filgotinib 100 mg (Maintenance Study)
Number of subjects analysed	34	27
Units: nanogram/milliliters
arithmetic mean (standard deviation)	75.8 ± 238	16.9 ± 55.5

No statistical analyses for this end point

Secondary: Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 26

Top of page

End point title

Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 26

End point description

Plasma concentrations of GS-829845 (ng/mL). PK Analysis Set for Maintenance study was analyzed.

End point type

Secondary

End point timeframe

Week 26: At any timepoint

End point values	Filgotinib 200 mg (Maintenance Study)	Filgotinib 100 mg (Maintenance Study)
Number of subjects analysed	77	63
Units: nanogram/milliliters
arithmetic mean (standard deviation)	3090 ± 1500	1460 ± 814

No statistical analyses for this end point

Secondary: Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 58

Top of page

End point title

Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 58

End point description

Plasma concentrations of GS-829845 (ng/mL). PK Analysis Set for Maintenance study was analyzed.

End point type

Secondary

End point timeframe

Week 58: Pre-dose

End point values	Filgotinib 200 mg (Maintenance Study)	Filgotinib 100 mg (Maintenance Study)
Number of subjects analysed	34	27
Units: nanogram/milliliters
arithmetic mean (standard deviation)	2430 ± 1430	1220 ± 551

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From first dose up to Week 62

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.0

Reporting group title

Cohort A: Filgotinib 100 mg (Induction Study)

Reporting group description

Participants received treatment of filgotinib 100 mg with PTM 200 mg once daily up to Week 10 after first day of randomization.

Reporting group title

Cohort A: Placebo (Induction Study)

Reporting group description

Participants received treatment of PTM filgotinib 200 mg with PTM filgotinib 100 mg once daily up to Week 10 after first day of randomization.

Reporting group title

Cohort A: Filgotinib 200 mg (Induction Study)

Reporting group description

Participants received treatment of filgotinib 200 mg with PTM 100 mg once daily up to Week 10 after first day of randomization.

Reporting group title

Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study)

Reporting group description

Participants who received filgotinib 100 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.

Reporting group title

Filgotinib 100 mg to Placebo (Maintenance Study)

Reporting group description

Participants who received filgotinib 100 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, up to Week 58.

Reporting group title

Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study)

Reporting group description

Participants who received filgotinib 200 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, up to Week 58.

Reporting group title

Filgotinib 200 mg to Placebo (Maintenance Study)

Reporting group description

Participants who received filgotinib 200 mg in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.

Reporting group title

Placebo to Placebo (Maintenance Study)

Reporting group description

Participants who received placebo in induction study and who achieved either clinical remission by PRO2 or endoscopic response at Week 10 were re-randomized to the maintenance study and received PTM filgotinib 100 mg and PTM filgotinib 200 mg tablet orally once daily, up to Week 58.

Reporting group title

Cohort B: Filgotinib 200 mg (Induction Study)

Reporting group description

Participants received treatment of filgotinib 200 mg with PTM 100 mg once daily up to Week 10 after first day of randomization.

Reporting group title

Cohort B: Filgotinib 100 mg (Induction Study)

Reporting group description

Participants received treatment of filgotinib 100 mg with PTM 200 mg once daily up to Week 10 after first day of randomization.

Reporting group title

Cohort B: Placebo (Induction Study)

Reporting group description

Participants received treatment of PTM filgotinib 200 mg with PTM filgotinib 100 mg once daily up to Week 10 after first day of randomization.

Serious adverse events	Cohort A: Filgotinib 100 mg (Induction Study)	Cohort A: Placebo (Induction Study)	Cohort A: Filgotinib 200 mg (Induction Study)	Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study)	Filgotinib 100 mg to Placebo (Maintenance Study)	Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study)	Filgotinib 200 mg to Placebo (Maintenance Study)	Placebo to Placebo (Maintenance Study)	Cohort B: Filgotinib 200 mg (Induction Study)	Cohort B: Filgotinib 100 mg (Induction Study)	Cohort B: Placebo (Induction Study)
Total subjects affected by serious adverse events
subjects affected / exposed	16 / 245 (6.53%)	15 / 237 (6.33%)	18 / 222 (8.11%)	14 / 104 (13.46%)	3 / 55 (5.45%)	13 / 118 (11.02%)	5 / 56 (8.93%)	14 / 145 (9.66%)	19 / 202 (9.41%)	36 / 228 (15.79%)	26 / 229 (11.35%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lung
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	1 / 104 (0.96%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	1 / 118 (0.85%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombophlebitis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	1 / 118 (0.85%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Systemic inflammatory response syndrome
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian cyst
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	1 / 202 (0.50%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute respiratory failure
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 245 (0.00%)	1 / 237 (0.42%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	1 / 118 (0.85%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epistaxis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	1 / 118 (0.85%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 245 (0.00%)	1 / 237 (0.42%)	0 / 222 (0.00%)	1 / 104 (0.96%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	1 / 202 (0.50%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Influenza A virus test positive
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Hip fracture
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	1 / 145 (0.69%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	0 / 245 (0.00%)	1 / 237 (0.42%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Procedural intestinal perforation
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrioventricular block
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune myocarditis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Palpitations
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ventricular tachycardia
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cauda equina syndrome
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	1 / 145 (0.69%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intensive care unit acquired weakness
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	1 / 145 (0.69%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Paraesthesia
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	1 / 118 (0.85%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sciatica
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	1 / 55 (1.82%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 245 (0.00%)	1 / 237 (0.42%)	0 / 222 (0.00%)	1 / 104 (0.96%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	1 / 145 (0.69%)	0 / 202 (0.00%)	1 / 228 (0.44%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anaemia of chronic disease
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood loss anaemia
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Iron deficiency anaemia
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lymphopenia
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	1 / 202 (0.50%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myelosuppression
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo positional
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Central serous chorioretinopathy
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Corneal scar
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	1 / 118 (0.85%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 245 (0.41%)	1 / 237 (0.42%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	1 / 56 (1.79%)	1 / 145 (0.69%)	1 / 202 (0.50%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal fistula
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	1 / 118 (0.85%)	0 / 56 (0.00%)	1 / 145 (0.69%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Crohn's disease
subjects affected / exposed	9 / 245 (3.67%)	7 / 237 (2.95%)	7 / 222 (3.15%)	7 / 104 (6.73%)	1 / 55 (1.82%)	3 / 118 (2.54%)	2 / 56 (3.57%)	4 / 145 (2.76%)	9 / 202 (4.46%)	10 / 228 (4.39%)	10 / 229 (4.37%)
occurrences causally related to treatment / all	1 / 9	0 / 8	0 / 7	0 / 7	0 / 1	1 / 3	0 / 2	0 / 4	0 / 9	1 / 10	2 / 10
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 245 (0.00%)	1 / 237 (0.42%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal fistula
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal wall thickening
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ileal perforation
subjects affected / exposed	1 / 245 (0.41%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematochezia
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	1 / 118 (0.85%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal fistula
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	2 / 245 (0.82%)	0 / 237 (0.00%)	0 / 222 (0.00%)	1 / 104 (0.96%)	0 / 55 (0.00%)	0 / 118 (0.00%)	1 / 56 (1.79%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal perforation
subjects affected / exposed	1 / 245 (0.41%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	1 / 202 (0.50%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intra-abdominal fluid collection
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large intestinal stenosis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large intestine perforation
subjects affected / exposed	2 / 245 (0.82%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	1 / 118 (0.85%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Megacolon
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower gastrointestinal haemorrhage
subjects affected / exposed	1 / 245 (0.41%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Obstructive pancreatitis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rectal ulcer haemorrhage
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	2 / 145 (1.38%)	1 / 202 (0.50%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subileus
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	1 / 56 (1.79%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 245 (0.41%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 245 (0.00%)	1 / 237 (0.42%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 245 (0.00%)	2 / 237 (0.84%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	1 / 202 (0.50%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Drug-induced liver injury
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Calculus urinary
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	1 / 202 (0.50%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal colic
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	1 / 104 (0.96%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	1 / 145 (0.69%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal infarct
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	1 / 145 (0.69%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	0 / 245 (0.00%)	1 / 237 (0.42%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Primary adrenal insufficiency
subjects affected / exposed	0 / 245 (0.00%)	1 / 237 (0.42%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthritis enteropathic
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral spondyloarthritis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc degeneration
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	1 / 145 (0.69%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abdominal abscess
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	1 / 202 (0.50%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abscess intestinal
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	1 / 202 (0.50%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis perforated
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	2 / 118 (1.69%)	0 / 56 (0.00%)	1 / 145 (0.69%)	0 / 202 (0.00%)	3 / 228 (1.32%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0	0 / 1	0 / 0	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bartholinitis
subjects affected / exposed	1 / 245 (0.41%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	2 / 222 (0.90%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	1 / 145 (0.69%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	1 / 104 (0.96%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile infection
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colonic abscess
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia bacteraemia
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epstein-Barr virus infection
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	1 / 202 (0.50%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	1 / 104 (0.96%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large intestine infection
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oral candidiasis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oral herpes
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	1 / 145 (0.69%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pelvic abscess
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peritoneal abscess
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	1 / 202 (0.50%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peritonsillar abscess
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	1 / 202 (0.50%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumocystis jirovecii pneumonia
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	1 / 118 (0.85%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 245 (0.41%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	1 / 145 (0.69%)	0 / 202 (0.00%)	1 / 228 (0.44%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	1 / 55 (1.82%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Systemic candida
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	1 / 104 (0.96%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diabetes mellitus inadequate control
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	0 / 245 (0.00%)	1 / 237 (0.42%)	1 / 222 (0.45%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	0 / 145 (0.00%)	1 / 202 (0.50%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Cohort A: Filgotinib 100 mg (Induction Study)	Cohort A: Placebo (Induction Study)	Cohort A: Filgotinib 200 mg (Induction Study)	Filgotinib 100 mg to Filgotinib 100 mg (Maintenance Study)	Filgotinib 100 mg to Placebo (Maintenance Study)	Filgotinib 200 mg to Filgotinib 200 mg (Maintenance Study)	Filgotinib 200 mg to Placebo (Maintenance Study)	Placebo to Placebo (Maintenance Study)	Cohort B: Filgotinib 200 mg (Induction Study)	Cohort B: Filgotinib 100 mg (Induction Study)	Cohort B: Placebo (Induction Study)
Total subjects affected by non serious adverse events
subjects affected / exposed	90 / 245 (36.73%)	90 / 237 (37.97%)	87 / 222 (39.19%)	59 / 104 (56.73%)	25 / 55 (45.45%)	59 / 118 (50.00%)	28 / 56 (50.00%)	77 / 145 (53.10%)	106 / 202 (52.48%)	107 / 228 (46.93%)	109 / 229 (47.60%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	3 / 145 (2.07%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	0	0
Vascular disorders
Hypertension
subjects affected / exposed	3 / 245 (1.22%)	5 / 237 (2.11%)	2 / 222 (0.90%)	3 / 104 (2.88%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	4 / 145 (2.76%)	4 / 202 (1.98%)	1 / 228 (0.44%)	1 / 229 (0.44%)
occurrences all number	3	5	2	3	0	0	0	4	4	1	2
General disorders and administration site conditions
Asthenia
subjects affected / exposed	2 / 245 (0.82%)	2 / 237 (0.84%)	3 / 222 (1.35%)	2 / 104 (1.92%)	1 / 55 (1.82%)	2 / 118 (1.69%)	1 / 56 (1.79%)	2 / 145 (1.38%)	2 / 202 (0.99%)	3 / 228 (1.32%)	8 / 229 (3.49%)
occurrences all number	2	2	3	2	1	2	1	2	2	3	9
Fatigue
subjects affected / exposed	5 / 245 (2.04%)	4 / 237 (1.69%)	7 / 222 (3.15%)	2 / 104 (1.92%)	0 / 55 (0.00%)	2 / 118 (1.69%)	0 / 56 (0.00%)	2 / 145 (1.38%)	3 / 202 (1.49%)	6 / 228 (2.63%)	5 / 229 (2.18%)
occurrences all number	5	4	7	2	0	2	0	3	3	6	5
Pyrexia
subjects affected / exposed	10 / 245 (4.08%)	6 / 237 (2.53%)	10 / 222 (4.50%)	3 / 104 (2.88%)	2 / 55 (3.64%)	6 / 118 (5.08%)	4 / 56 (7.14%)	2 / 145 (1.38%)	11 / 202 (5.45%)	8 / 228 (3.51%)	10 / 229 (4.37%)
occurrences all number	10	7	11	4	2	6	4	2	17	8	12
Oedema peripheral
subjects affected / exposed	1 / 245 (0.41%)	1 / 237 (0.42%)	2 / 222 (0.90%)	0 / 104 (0.00%)	0 / 55 (0.00%)	2 / 118 (1.69%)	0 / 56 (0.00%)	1 / 145 (0.69%)	1 / 202 (0.50%)	5 / 228 (2.19%)	0 / 229 (0.00%)
occurrences all number	1	1	2	0	0	2	0	1	1	5	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	5 / 245 (2.04%)	4 / 237 (1.69%)	4 / 222 (1.80%)	2 / 104 (1.92%)	0 / 55 (0.00%)	1 / 118 (0.85%)	0 / 56 (0.00%)	2 / 145 (1.38%)	2 / 202 (0.99%)	4 / 228 (1.75%)	3 / 229 (1.31%)
occurrences all number	5	4	4	2	0	1	0	2	2	4	3
Cough
subjects affected / exposed	0 / 245 (0.00%)	1 / 237 (0.42%)	3 / 222 (1.35%)	5 / 104 (4.81%)	2 / 55 (3.64%)	2 / 118 (1.69%)	2 / 56 (3.57%)	2 / 145 (1.38%)	4 / 202 (1.98%)	3 / 228 (1.32%)	3 / 229 (1.31%)
occurrences all number	0	1	3	5	2	2	2	2	4	3	3
Psychiatric disorders
Insomnia
subjects affected / exposed	2 / 245 (0.82%)	0 / 237 (0.00%)	3 / 222 (1.35%)	3 / 104 (2.88%)	1 / 55 (1.82%)	1 / 118 (0.85%)	0 / 56 (0.00%)	2 / 145 (1.38%)	2 / 202 (0.99%)	3 / 228 (1.32%)	5 / 229 (2.18%)
occurrences all number	2	0	3	3	1	1	0	2	2	3	5
Investigations
Weight decreased
subjects affected / exposed	3 / 245 (1.22%)	0 / 237 (0.00%)	1 / 222 (0.45%)	3 / 104 (2.88%)	0 / 55 (0.00%)	0 / 118 (0.00%)	2 / 56 (3.57%)	1 / 145 (0.69%)	4 / 202 (1.98%)	5 / 228 (2.19%)	4 / 229 (1.75%)
occurrences all number	3	0	1	3	0	0	2	1	5	6	4
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	0 / 222 (0.00%)	4 / 104 (3.85%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	1 / 145 (0.69%)	0 / 202 (0.00%)	1 / 228 (0.44%)	0 / 229 (0.00%)
occurrences all number	0	0	0	6	0	0	0	1	0	1	0
Nervous system disorders
Dizziness
subjects affected / exposed	4 / 245 (1.63%)	4 / 237 (1.69%)	5 / 222 (2.25%)	1 / 104 (0.96%)	1 / 55 (1.82%)	1 / 118 (0.85%)	1 / 56 (1.79%)	0 / 145 (0.00%)	7 / 202 (3.47%)	1 / 228 (0.44%)	3 / 229 (1.31%)
occurrences all number	4	4	7	1	1	1	1	0	7	2	3
Headache
subjects affected / exposed	16 / 245 (6.53%)	12 / 237 (5.06%)	13 / 222 (5.86%)	4 / 104 (3.85%)	2 / 55 (3.64%)	4 / 118 (3.39%)	1 / 56 (1.79%)	10 / 145 (6.90%)	17 / 202 (8.42%)	14 / 228 (6.14%)	15 / 229 (6.55%)
occurrences all number	17	12	14	4	2	4	1	13	19	15	18
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	8 / 245 (3.27%)	7 / 237 (2.95%)	3 / 222 (1.35%)	3 / 104 (2.88%)	1 / 55 (1.82%)	3 / 118 (2.54%)	3 / 56 (5.36%)	4 / 145 (2.76%)	6 / 202 (2.97%)	8 / 228 (3.51%)	2 / 229 (0.87%)
occurrences all number	8	7	3	3	1	3	3	5	7	8	2
Lymphopenia
subjects affected / exposed	2 / 245 (0.82%)	4 / 237 (1.69%)	2 / 222 (0.90%)	1 / 104 (0.96%)	0 / 55 (0.00%)	1 / 118 (0.85%)	1 / 56 (1.79%)	3 / 145 (2.07%)	5 / 202 (2.48%)	0 / 228 (0.00%)	2 / 229 (0.87%)
occurrences all number	2	5	2	2	0	1	1	5	5	0	2
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	0 / 245 (0.00%)	3 / 237 (1.27%)	3 / 222 (1.35%)	1 / 104 (0.96%)	0 / 55 (0.00%)	1 / 118 (0.85%)	3 / 56 (5.36%)	1 / 145 (0.69%)	3 / 202 (1.49%)	3 / 228 (1.32%)	3 / 229 (1.31%)
occurrences all number	0	3	3	1	0	1	3	1	4	3	3
Abdominal pain
subjects affected / exposed	6 / 245 (2.45%)	8 / 237 (3.38%)	16 / 222 (7.21%)	9 / 104 (8.65%)	3 / 55 (5.45%)	8 / 118 (6.78%)	6 / 56 (10.71%)	9 / 145 (6.21%)	10 / 202 (4.95%)	8 / 228 (3.51%)	15 / 229 (6.55%)
occurrences all number	6	8	16	9	3	8	9	11	14	12	15
Abdominal pain upper
subjects affected / exposed	2 / 245 (0.82%)	2 / 237 (0.84%)	5 / 222 (2.25%)	4 / 104 (3.85%)	0 / 55 (0.00%)	1 / 118 (0.85%)	3 / 56 (5.36%)	4 / 145 (2.76%)	4 / 202 (1.98%)	7 / 228 (3.07%)	5 / 229 (2.18%)
occurrences all number	2	2	5	4	0	1	3	4	4	7	5
Aphthous ulcer
subjects affected / exposed	2 / 245 (0.82%)	3 / 237 (1.27%)	2 / 222 (0.90%)	2 / 104 (1.92%)	2 / 55 (3.64%)	1 / 118 (0.85%)	0 / 56 (0.00%)	0 / 145 (0.00%)	0 / 202 (0.00%)	2 / 228 (0.88%)	3 / 229 (1.31%)
occurrences all number	2	3	2	2	2	3	0	0	0	2	4
Crohn's disease
subjects affected / exposed	15 / 245 (6.12%)	16 / 237 (6.75%)	5 / 222 (2.25%)	22 / 104 (21.15%)	15 / 55 (27.27%)	15 / 118 (12.71%)	10 / 56 (17.86%)	26 / 145 (17.93%)	8 / 202 (3.96%)	14 / 228 (6.14%)	18 / 229 (7.86%)
occurrences all number	15	16	5	24	15	16	10	26	8	16	18
Diarrhoea
subjects affected / exposed	2 / 245 (0.82%)	2 / 237 (0.84%)	4 / 222 (1.80%)	1 / 104 (0.96%)	1 / 55 (1.82%)	5 / 118 (4.24%)	1 / 56 (1.79%)	2 / 145 (1.38%)	3 / 202 (1.49%)	6 / 228 (2.63%)	6 / 229 (2.62%)
occurrences all number	2	2	4	1	1	6	1	2	3	6	6
Dyspepsia
subjects affected / exposed	2 / 245 (0.82%)	1 / 237 (0.42%)	0 / 222 (0.00%)	3 / 104 (2.88%)	2 / 55 (3.64%)	1 / 118 (0.85%)	0 / 56 (0.00%)	0 / 145 (0.00%)	4 / 202 (1.98%)	2 / 228 (0.88%)	3 / 229 (1.31%)
occurrences all number	2	1	0	3	2	1	0	0	4	2	3
Flatulence
subjects affected / exposed	4 / 245 (1.63%)	2 / 237 (0.84%)	3 / 222 (1.35%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	3 / 56 (5.36%)	0 / 145 (0.00%)	7 / 202 (3.47%)	1 / 228 (0.44%)	1 / 229 (0.44%)
occurrences all number	4	2	3	0	0	0	4	0	7	1	1
Gastroesophageal reflux disease
subjects affected / exposed	1 / 245 (0.41%)	0 / 237 (0.00%)	2 / 222 (0.90%)	1 / 104 (0.96%)	0 / 55 (0.00%)	1 / 118 (0.85%)	0 / 56 (0.00%)	3 / 145 (2.07%)	4 / 202 (1.98%)	0 / 228 (0.00%)	4 / 229 (1.75%)
occurrences all number	1	0	2	1	0	1	0	3	4	0	4
Nausea
subjects affected / exposed	10 / 245 (4.08%)	11 / 237 (4.64%)	11 / 222 (4.95%)	3 / 104 (2.88%)	2 / 55 (3.64%)	6 / 118 (5.08%)	3 / 56 (5.36%)	4 / 145 (2.76%)	20 / 202 (9.90%)	10 / 228 (4.39%)	18 / 229 (7.86%)
occurrences all number	10	11	11	3	3	6	4	4	21	12	19
Vomiting
subjects affected / exposed	7 / 245 (2.86%)	7 / 237 (2.95%)	2 / 222 (0.90%)	5 / 104 (4.81%)	1 / 55 (1.82%)	5 / 118 (4.24%)	1 / 56 (1.79%)	3 / 145 (2.07%)	5 / 202 (2.48%)	6 / 228 (2.63%)	9 / 229 (3.93%)
occurrences all number	7	8	2	5	1	5	1	3	11	7	9
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	2 / 245 (0.82%)	2 / 237 (0.84%)	5 / 222 (2.25%)	0 / 104 (0.00%)	0 / 55 (0.00%)	1 / 118 (0.85%)	2 / 56 (3.57%)	1 / 145 (0.69%)	4 / 202 (1.98%)	1 / 228 (0.44%)	1 / 229 (0.44%)
occurrences all number	2	2	5	0	0	1	2	1	5	1	1
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	2 / 245 (0.82%)	0 / 237 (0.00%)	1 / 222 (0.45%)	3 / 104 (2.88%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	1 / 145 (0.69%)	1 / 202 (0.50%)	0 / 228 (0.00%)	2 / 229 (0.87%)
occurrences all number	2	0	1	3	0	0	0	1	1	0	2
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	11 / 245 (4.49%)	6 / 237 (2.53%)	5 / 222 (2.25%)	10 / 104 (9.62%)	4 / 55 (7.27%)	3 / 118 (2.54%)	2 / 56 (3.57%)	10 / 145 (6.90%)	7 / 202 (3.47%)	14 / 228 (6.14%)	9 / 229 (3.93%)
occurrences all number	12	7	6	12	5	3	4	11	10	14	15
Back pain
subjects affected / exposed	7 / 245 (2.86%)	2 / 237 (0.84%)	0 / 222 (0.00%)	1 / 104 (0.96%)	2 / 55 (3.64%)	2 / 118 (1.69%)	0 / 56 (0.00%)	3 / 145 (2.07%)	5 / 202 (2.48%)	5 / 228 (2.19%)	2 / 229 (0.87%)
occurrences all number	7	2	0	1	2	2	0	3	5	5	2
Muscle spasms
subjects affected / exposed	1 / 245 (0.41%)	2 / 237 (0.84%)	0 / 222 (0.00%)	1 / 104 (0.96%)	0 / 55 (0.00%)	3 / 118 (2.54%)	0 / 56 (0.00%)	0 / 145 (0.00%)	1 / 202 (0.50%)	3 / 228 (1.32%)	2 / 229 (0.87%)
occurrences all number	1	2	0	1	0	3	0	0	1	4	2
Pain in extremity
subjects affected / exposed	0 / 245 (0.00%)	2 / 237 (0.84%)	0 / 222 (0.00%)	2 / 104 (1.92%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	4 / 145 (2.76%)	1 / 202 (0.50%)	0 / 228 (0.00%)	2 / 229 (0.87%)
occurrences all number	0	2	0	3	0	0	0	4	1	0	2
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 245 (0.00%)	0 / 237 (0.00%)	1 / 222 (0.45%)	1 / 104 (0.96%)	0 / 55 (0.00%)	4 / 118 (3.39%)	2 / 56 (3.57%)	5 / 145 (3.45%)	2 / 202 (0.99%)	3 / 228 (1.32%)	1 / 229 (0.44%)
occurrences all number	0	0	2	1	0	4	2	6	2	3	1
Gastroenteritis
subjects affected / exposed	2 / 245 (0.82%)	4 / 237 (1.69%)	3 / 222 (1.35%)	2 / 104 (1.92%)	2 / 55 (3.64%)	1 / 118 (0.85%)	0 / 56 (0.00%)	4 / 145 (2.76%)	4 / 202 (1.98%)	5 / 228 (2.19%)	0 / 229 (0.00%)
occurrences all number	2	4	3	2	3	1	0	4	4	5	0
COVID-19
subjects affected / exposed	0 / 245 (0.00%)	2 / 237 (0.84%)	3 / 222 (1.35%)	1 / 104 (0.96%)	0 / 55 (0.00%)	3 / 118 (2.54%)	0 / 56 (0.00%)	3 / 145 (2.07%)	0 / 202 (0.00%)	0 / 228 (0.00%)	0 / 229 (0.00%)
occurrences all number	0	2	3	1	0	3	0	4	0	0	0
Nasopharyngitis
subjects affected / exposed	6 / 245 (2.45%)	8 / 237 (3.38%)	7 / 222 (3.15%)	6 / 104 (5.77%)	2 / 55 (3.64%)	6 / 118 (5.08%)	4 / 56 (7.14%)	9 / 145 (6.21%)	9 / 202 (4.46%)	9 / 228 (3.95%)	17 / 229 (7.42%)
occurrences all number	6	9	8	6	2	11	4	9	9	11	18
Influenza
subjects affected / exposed	1 / 245 (0.41%)	0 / 237 (0.00%)	2 / 222 (0.90%)	2 / 104 (1.92%)	0 / 55 (0.00%)	0 / 118 (0.00%)	2 / 56 (3.57%)	3 / 145 (2.07%)	2 / 202 (0.99%)	2 / 228 (0.88%)	2 / 229 (0.87%)
occurrences all number	1	0	2	2	0	0	2	3	2	2	2
Sinusitis
subjects affected / exposed	2 / 245 (0.82%)	2 / 237 (0.84%)	0 / 222 (0.00%)	2 / 104 (1.92%)	1 / 55 (1.82%)	0 / 118 (0.00%)	1 / 56 (1.79%)	3 / 145 (2.07%)	4 / 202 (1.98%)	0 / 228 (0.00%)	2 / 229 (0.87%)
occurrences all number	2	2	0	2	1	0	1	3	4	0	2
Tooth abscess
subjects affected / exposed	0 / 245 (0.00%)	1 / 237 (0.42%)	0 / 222 (0.00%)	0 / 104 (0.00%)	0 / 55 (0.00%)	0 / 118 (0.00%)	0 / 56 (0.00%)	3 / 145 (2.07%)	0 / 202 (0.00%)	0 / 228 (0.00%)	1 / 229 (0.44%)
occurrences all number	0	1	0	0	0	0	0	3	0	0	1
Urinary tract infection
subjects affected / exposed	5 / 245 (2.04%)	1 / 237 (0.42%)	3 / 222 (1.35%)	2 / 104 (1.92%)	0 / 55 (0.00%)	5 / 118 (4.24%)	1 / 56 (1.79%)	4 / 145 (2.76%)	5 / 202 (2.48%)	10 / 228 (4.39%)	3 / 229 (1.31%)
occurrences all number	5	1	3	2	0	5	1	5	6	11	3
Upper respiratory tract infection
subjects affected / exposed	1 / 245 (0.41%)	5 / 237 (2.11%)	4 / 222 (1.80%)	3 / 104 (2.88%)	1 / 55 (1.82%)	5 / 118 (4.24%)	0 / 56 (0.00%)	3 / 145 (2.07%)	4 / 202 (1.98%)	10 / 228 (4.39%)	9 / 229 (3.93%)
occurrences all number	1	5	4	3	1	6	0	3	4	11	9
Metabolism and nutrition disorders
Hypophosphataemia
subjects affected / exposed	1 / 245 (0.41%)	2 / 237 (0.84%)	3 / 222 (1.35%)	1 / 104 (0.96%)	0 / 55 (0.00%)	4 / 118 (3.39%)	0 / 56 (0.00%)	1 / 145 (0.69%)	2 / 202 (0.99%)	2 / 228 (0.88%)	5 / 229 (2.18%)
occurrences all number	1	2	4	1	0	5	0	2	2	2	5

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

07 Sep 2016

− The number of possible sites had been updated based on results of recent feasibility analysis. − The text of the objectives was updated for further clarification and additional exploratory analyses were added. − Text was revised and added to reflect the new study design of the GS-US-419-3896 study and to ensure subjects who completed 58 weeks of therapy continued on their current dose in a blinded manner. − Criteria for discontinuation for febrile neutropenia, anemia, and international normalized ratio (INR) value when considering hepatic laboratory changes had been added at request of the Agency to ensure subject safety. Additional text surrounding departure from the study was added to clarify that pregnant subjects had to discontinue the study and that early termination (ET) and PTx visits were requested for subjects that withdrew. − Eligibility criteria: • Inclusion criteria: Duration of stable dosing had been updated at request of the Agency for 6-MP, MTX, and azathioprine. The same modification had been applied to 5-ASA for internal consistency. Clarity had been added to the stable dose duration to confirm that subjects had been prescribed stable doses as directed by their physicians. The duration of vaccine restriction had been lengthened at the request of the Agency. Minimum treatment requirement for newly diagnosed TB had been added at the request of the Agency. • An exclusion criterion of severe hepatic impairment defined by Child-Pugh Class C had been added at request of Agency.

11 Nov 2016

Upon Voluntary Harmonization Procedure request, additional Week 26 and Week 58 ECG procedures had been added to the protocol.

19 Jan 2017

- Upon FDA request, a VAS was replaced by an 11-point NRS to assess abdominal pain. - Eligibility criteria: • Text was added to clarify that known hypersensitivity to filgotinib metabolites or formulation excipients were exclusionary. Text was added to clarify that subjects with history of extensive colectomy were excluded, and only enteric pathogens detected in the stool sample were exclusionary. • Upon regulatory approval of ustekinumab, text was added in the eligibility criteria to exclude the entry of subjects who had been treated with ustekinumab.

15 Jun 2017

- The use of 200 mg in males in Korea was limited to subjects who had failed 2 classes of biologic therapies (any TNFα antagonist and vedolizumab), in response to the South Korean Ministry of Food and Drug Safety. - Consistency with the Investigator’s Brochure (IB). - Eligibility criteria: • Inclusion criteria: To ensure subject safety and eligibility, the protocol now required that subjects be up to date on colorectal cancer screening and surveillance prior to entering the study. Quantiferon and reference laboratory text wording was revised and was administrative in nature. • Exclusion criteria: An administrative clarification made clear that any personal history of disseminated zoster (rather than any zoster) was exclusionary for the study.

05 Mar 2018

− Secondary endpoint: “At Week 58” text was added to the secondary endpoint considering PRO2 during the maintenance study to clarify the underlying intent of the endpoint; the corticosteroid free remission was analyzed only at the maintenance Week 58 timepoint, and the 6-month period was a lookback from the Week 58 timepoint rather than any 6-month period during maintenance − Additional clarity on eligibility criteria including those for hepatitis. − Additional flexibility for enhanced safety monitoring (with increased flexibility for DMC meeting scheduling and suggested infectious workups for disease worsening). − Exclusion criteria: • Text was updated to provide flexibility as there were multiple established therapeutic methods of cytapheresis (leukocytapheresis and granulocytapheresis) as treatment for CD and they had shown to be safe considering its mechanism of action. • Text was updated to enhance subject safety so that both the investigator and the sponsor determined the suitability of any chronic medical condition that was not specifically listed out but could impact efficacy and safety assessment in the study.

07 Feb 2019

- Due to the difficulty in recruiting subjects with moderately to severely active CD who had not been treated with a biologic agent, the protocol was amended to allow also biologic experienced subjects in Cohort A to facilitate enrolment completion in Cohort A. In recognition of the potential impact of exposure to a biologic agent on the efficacy results, an additional stratification factor accounting for prior exposure to a biologic agent (yes or no) was added for the Cohort A Induction Study, in addition to the existing stratification factors (concomitant use of oral, systemically absorbed corticosteroids, and concomitant use of immunomodulators). Several sections (design, eligibility criteria, stratification factors, …) were revised to allow for the inclusion of biologic-experienced subjects into Cohort A. - Inclusion criterion 5 was revised to reduce the minimum duration of disease from diagnosis from 6 months to 3 months to permit more recently diagnosed subjects to enroll. - The statistical analysis was updated to allow for sequential testing of co-primary endpoints and secondary endpoints.

22 Aug 2019

− Changed eligibility criteria to allow for the inclusion of subjects who had discontinued biological treatment for reasons other than inadequate response, loss of response, or intolerance into Cohort A, as well as the inclusion of subjects with active perianal fistulas into Cohorts A and B. − Additional applicable fistula assessment was added. − The exploratory objectives and endpoints were updated to include evaluation of the efficacy of filgotinib in establishing perianal fistula closure.

01 May 2020

- The co-primary endpoint had been revised from PRO2 to CDAI remission based on consultation with FDA. The rationale for the change in the clinical co-primary endpoint from PRO2 to CDAI is that the FDA informed Gilead, in 2019, that it had recently accepted proposals from other sponsors to define the co-primary endpoints in CD studies as clinical remission using a CDAI score of < 150 and endoscopic remission or response using the SESCD score. The rationale provided by the FDA for this recommendation was the paucity of available prospective data validating the best cut-offs for PRO-based scoring that define either eligibility or clinical remission. Secondary and exploratory endpoints were revised accordingly. As the endpoints were updated, several sections of the protocol were revised to reflect the changes to the endpoints. - The original Cohort A and Cohort B Induction Study and Maintenance Study objectives had been moved to be EU-specific objectives. - Sample size calculation was added for the non-EU co-primary endpoint clinical remission by CDAI, and sample size calculation was provided for EU-specific co-primary endpoint clinical remission by PRO2 as new text. - The following changes were also implemented at the request of FDA in response to safety information suggesting an increased risk of thromboembolism in patients treated with a JAK inhibitor: • Inclusion of discontinuation criteria for serious thromboembolic events. • Specification of follow-up testing/referral to a specialist for subjects who experienced a thromboembolic event, to evaluate for risk factors of thromboembolic events, and to document the result of that evaluation. • Inclusion of criteria to be met for the DMC to recommend study discontinuation and inclusion of a criterion to trigger an ad-hoc DMC meeting. • Description of a Cardiovascular Safety Endpoint Adjudication Committee(CVEAC) that Gilead was establishing. - A new section on blinding was added to clarify blinding procedur

02 Dec 2021

− Change of sponsorship from Gilead to Galapagos. − Information on filgotinib approval was added. − The Galapagos study number was added to ensure a link between Gilead and Galapagos study numbers for internal documentation purposes.

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

For support, Contact us.

The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

European Medicines Agency © 1995-Sun Apr 28 06:30:17 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands