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Clinical Trial Results:
A Phase 3b Open-Label Study to Determine the Long-term Safety and Efficacy of Vedolizumab Subcutaneous in Subjects With Ulcerative Colitis and Crohn’s Disease

Summary
EudraCT number	2015-000482-31
Trial protocol	SK CZ NL BG GB DE BE SE DK LT ES HU RO HR IT
Global end of trial date	12 Jun 2024

Results information
Results version number	v1(current)
This version publication date	02 Apr 2025
First version publication date	02 Apr 2025
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

MLN0002SC-3030

ISRCTN number

-

US NCT number

NCT02620046

WHO universal trial number (UTN)

U1111-1168-0921

Sponsor organisation name

Takeda

Sponsor organisation address

95 Hayden Avenue, Lexington, United States, MA 02421

Public contact

Study Director, Takeda, TrialDisclosures@takeda.com

Scientific contact

Study Director, Takeda, TrialDisclosures@takeda.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

12 Jun 2024

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

12 Jun 2024

Was the trial ended prematurely?

No

Main objective of the trial

The main objective of the trial was to obtain data on long term safety and tolerability on vedolizumab SC in participants with Ulcerative Colitis (UC) or Crohn’s Disease (CD).

Protection of trial subjects

Each participant signed an informed consent form (ICF) before participating in the study.

Background therapy

NA

Evidence for comparator

-

Actual start date of recruitment

15 Apr 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

Australia: 12

Country: Number of subjects enrolled

Czechia: 48

Country: Number of subjects enrolled

Hungary: 30

Country: Number of subjects enrolled

Poland: 157

Country: Number of subjects enrolled

South Africa: 5

Country: Number of subjects enrolled

Romania: 17

Country: Number of subjects enrolled

Serbia: 13

Country: Number of subjects enrolled

Slovakia: 14

Country: Number of subjects enrolled

Japan: 58

Country: Number of subjects enrolled

Korea, Republic of: 22

Country: Number of subjects enrolled

Bosnia and Herzegovina: 3

Country: Number of subjects enrolled

Bulgaria: 5

Country: Number of subjects enrolled

Croatia: 7

Country: Number of subjects enrolled

Estonia: 2

Country: Number of subjects enrolled

Russian Federation: 50

Country: Number of subjects enrolled

Israel: 20

Country: Number of subjects enrolled

Türkiye: 7

Country: Number of subjects enrolled

Ukraine: 47

Country: Number of subjects enrolled

Canada: 34

Country: Number of subjects enrolled

United States: 131

Country: Number of subjects enrolled

Brazil: 13

Country: Number of subjects enrolled

Mexico: 3

Country: Number of subjects enrolled

Belgium: 6

Country: Number of subjects enrolled

Denmark: 4

Country: Number of subjects enrolled

Germany: 10

Country: Number of subjects enrolled

Italy: 15

Country: Number of subjects enrolled

Lithuania: 7

Country: Number of subjects enrolled

United Kingdom: 3

Country: Number of subjects enrolled

Netherlands: 2

Country: Number of subjects enrolled

Sweden: 1

Worldwide total number of subjects

746

EEA total number of subjects

325

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)

705

From 65 to 84 years

41

85 years and over

0

Subject disposition

Top of page

Recruitment details

Participants took part in the study at various investigative sites globally from 15 April 2016 to 12 June 2024.

Screening details

Participants who had previously participated in Study MLN0002SC-3027 or MLN0002SC-3031 and were eligible to participate received vedolizumab subcutaneously (SC) [either 108 milligrams (mg) once every two weeks (Q2W) or once per week (QW)] in the disease groups of Ulcerative Colitis and Crohn’s Disease in this study. Data is presented accordingly.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Ulcerative Colitis: Vedolizumab 108 mg

Arm description

Participants with UC who completed the Maintenance Phase in MLN0002SC-3027 (Week 52 assessment) or who did not achieve a clinical response at Week 6 in MLN0002SC-3027 but who did achieve a clinical response at Week 14 of the parent study after having received a third vedolizumab IV infusion at Week 6 in the parent study received vedolizumab SC 108 mg Q2W in this study whereas participants who withdrew early from the Maintenance Phase (at Week 14 onwards) in MLN0002SC-3027 due to disease worsening or need for rescue medications received vedolizumab SC 108 mg QW.

Arm type

Experimental

Investigational medicinal product name

Vedolizumab SC

Investigational medicinal product code

MLN0002 SC

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Participants were administered Vedolizumab SC once per week (QW) or once every two weeks (Q2W).

Crohn's Disease: Vedolizumab 108 mg

Arm description

Participants with CD who completed the Maintenance Phase in MLN0002SC-3031 (Week 52 assessment) or who did not achieve a clinical response at Week 6 in MLN0002SC-3031 but who did achieve a clinical response at Week 14 of the parent study after having received a third vedolizumab IV infusion at Week 6 in the parent study received vedolizumab SC 108 mg Q2W in this study whereas participants who withdrew early from the Maintenance Phase (at Week 14 onwards) in MLN0002SC-3031 due to disease worsening or need for rescue medications received vedolizumab SC 108 mg QW.

Arm type

Experimental

Investigational medicinal product name

Vedolizumab SC

Investigational medicinal product code

MLN0002 SC

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Participants were administered Vedolizumab SC once per week (QW) or once every two weeks (Q2W).

Number of subjects in period 1	Ulcerative Colitis: Vedolizumab 108 mg	Crohn's Disease: Vedolizumab 108 mg
Started	288	458
Completed	125	162
Not completed	163	296
Consent withdrawn by subject	36	66
Adverse event, non-fatal	22	42
Reason Not Specified	13	21
Significant Protocol Deviation	-	1
Pregnancy	3	7
Leukopenia or Lymphopenia	1	-
Lost to follow-up	4	10
Site Termination	3	3
Lack of efficacy	81	146

Baseline characteristics

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Reporting group title

Ulcerative Colitis: Vedolizumab 108 mg

Reporting group description

Participants with UC who completed the Maintenance Phase in MLN0002SC-3027 (Week 52 assessment) or who did not achieve a clinical response at Week 6 in MLN0002SC-3027 but who did achieve a clinical response at Week 14 of the parent study after having received a third vedolizumab IV infusion at Week 6 in the parent study received vedolizumab SC 108 mg Q2W in this study whereas participants who withdrew early from the Maintenance Phase (at Week 14 onwards) in MLN0002SC-3027 due to disease worsening or need for rescue medications received vedolizumab SC 108 mg QW.

Reporting group title

Crohn's Disease: Vedolizumab 108 mg

Reporting group description

Participants with CD who completed the Maintenance Phase in MLN0002SC-3031 (Week 52 assessment) or who did not achieve a clinical response at Week 6 in MLN0002SC-3031 but who did achieve a clinical response at Week 14 of the parent study after having received a third vedolizumab IV infusion at Week 6 in the parent study received vedolizumab SC 108 mg Q2W in this study whereas participants who withdrew early from the Maintenance Phase (at Week 14 onwards) in MLN0002SC-3031 due to disease worsening or need for rescue medications received vedolizumab SC 108 mg QW.

Reporting group values	Ulcerative Colitis: Vedolizumab 108 mg	Crohn's Disease: Vedolizumab 108 mg	Total
Number of subjects	288	458
Age Categorical
Units: Subjects
Gender categorical
Units: Subjects
Female	120	214	334
Male	168	244	412
Age categorical
Units: Subjects
<= 18 years	0	0	0
Between 18 and 65	265	440	705
>= 65 years	23	18	41
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	2	2	4
Asian	58	28	86
Native Hawaiian or Other Pacific Islander	0	1	1
Black or African American	2	9	11
White	226	417	643
More than one race	0	1	1
Unknown or Not Reported	0	0	0
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	1	3	4
Not Hispanic or Latino	34	94	128
Unknown or Not Reported	253	361	614

End points

Top of page

Reporting group title

Ulcerative Colitis: Vedolizumab 108 mg

Reporting group description

Participants with UC who completed the Maintenance Phase in MLN0002SC-3027 (Week 52 assessment) or who did not achieve a clinical response at Week 6 in MLN0002SC-3027 but who did achieve a clinical response at Week 14 of the parent study after having received a third vedolizumab IV infusion at Week 6 in the parent study received vedolizumab SC 108 mg Q2W in this study whereas participants who withdrew early from the Maintenance Phase (at Week 14 onwards) in MLN0002SC-3027 due to disease worsening or need for rescue medications received vedolizumab SC 108 mg QW.

Reporting group title

Crohn's Disease: Vedolizumab 108 mg

Reporting group description

Participants with CD who completed the Maintenance Phase in MLN0002SC-3031 (Week 52 assessment) or who did not achieve a clinical response at Week 6 in MLN0002SC-3031 but who did achieve a clinical response at Week 14 of the parent study after having received a third vedolizumab IV infusion at Week 6 in the parent study received vedolizumab SC 108 mg Q2W in this study whereas participants who withdrew early from the Maintenance Phase (at Week 14 onwards) in MLN0002SC-3031 due to disease worsening or need for rescue medications received vedolizumab SC 108 mg QW.

Subject analysis set title

Ulcerative Colitis: Vedolizumab 108 mg

Subject analysis set type

Per protocol

Subject analysis set description

Participants with UC who completed the Maintenance Phase in MLN0002SC-3027 (Week 52 assessment) or who did not achieve a clinical response at Week 6 in MLN0002SC-3027 but who did achieve a clinical response at Week 14 of the parent study after having received a third vedolizumab IV infusion at Week 6 in the parent study received vedolizumab SC 108 mg Q2W in this study whereas participants who withdrew early from the Maintenance Phase (at Week 14 onwards) in MLN0002SC-3027 due to disease worsening or need for rescue medications received vedolizumab SC 108 mg QW.

Subject analysis set title

Crohn's Disease: Vedolizumab 108 mg

Subject analysis set type

Per protocol

Subject analysis set description

Participants with CD who completed the Maintenance Phase in MLN0002SC-3031 (Week 52 assessment) or who did not achieve a clinical response at Week 6 in MLN0002SC-3031 but who did achieve a clinical response at Week 14 of the parent study after having received a third vedolizumab IV infusion at Week 6 in the parent study received vedolizumab SC 108 mg Q2W in this study whereas participants who withdrew early from the Maintenance Phase (at Week 14 onwards) in MLN0002SC-3031 due to disease worsening or need for rescue medications received vedolizumab SC 108 mg QW.

Primary: Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Adjusted by Duration of Participant’s Exposure to Long-term Vedolizumab Treatment

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End point title

Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Adjusted by Duration of Participant’s Exposure to Long-term Vedolizumab Treatment ^[1]

End point description

Adverse event (AE):any untoward medical occurrence in clinical investigation participant administered drug; it does not necessarily have to have causal relationship with this treatment. AE can therefore be any unfavorable & unintended sign (e.g., clinically significant abnormal laboratory finding), symptom/disease temporally associated with use of drug whether or not it is considered related to drug. TEAE:AE that starts/worsens on or after Study Day 1 (day first dosed in 3030), & no more than 18 weeks/126 days after last dose of study drug. SAEs:serious TEAEs with onset on or after Study Day 1 (defined as day first dosed in 3030), & no more than 18 weeks/126 days after last dose of study drug. Participant years:total exposure-time of participants in respective treatment group. Incidence per 100 participant years:(Number of participants with events*100/participant years). As per planned analysis, data for this endpoint is grouped & presented per disease condition. SAF set.

End point type

Primary

End point timeframe

Up to 97.9 months

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	Ulcerative Colitis: Vedolizumab 108 mg	Crohn's Disease: Vedolizumab 108 mg
Number of subjects analysed	288	458
Units: participants
TEAEs	231	390
SAEs	65	121

No statistical analyses for this end point

Secondary: Number of Adverse Events of Special Interest (AESIs) Adjusted by Duration of Participant’s Exposure to Long-term Vedolizumab Treatment

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End point title

Number of Adverse Events of Special Interest (AESIs) Adjusted by Duration of Participant’s Exposure to Long-term Vedolizumab Treatment

End point description

AESIs included hypersensitivity reactions (including injections site reactions), serious infections, malignancies, hepatotoxicity (abnormal liver function test) and progressive multifocal leukoencephalopathy (PML). Participant years is defined as the total exposure-time of the participants in the respective treatment group. Incidence per 100 participant years is defined as (Number of participants with events*100/participant years). As per planned analysis, data for this outcome measure is grouped and presented per disease condition. SAF included all participants who had received at least 1 dose of study medication during this study (MLN0002SC-3030).

End point type

Secondary

End point timeframe

Up to 97.9 months

End point values	Ulcerative Colitis: Vedolizumab 108 mg	Crohn's Disease: Vedolizumab 108 mg
Number of subjects analysed	288	458
Units: events per 100 participant years
number (not applicable)	16.3	17.4

No statistical analyses for this end point

Secondary: Number of Participants with Ulcerative Colitis Achieving Partial Mayo Scoring Clinical Response at Week 48

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End point title

Number of Participants with Ulcerative Colitis Achieving Partial Mayo Scoring Clinical Response at Week 48

End point description

Clinical response is defined as a decrease in the partial Mayo score of at least 2 points and ≥25% from baseline, with an accompanying decrease in rectal bleeding subscore of ≥1 point from baseline or absolute rectal bleeding subscore of ≤1 point. As per planned analysis, data for this outcome measure is grouped and presented for participants with ulcerative colitis. Full Analysis Set (FAS) included all enrolled participants of this study MLN0002SC-3030. Subjects analysed is the number of participants with data available for analyses.

End point type

Secondary

End point timeframe

Week 48

End point values	Ulcerative Colitis: Vedolizumab 108 mg
Number of subjects analysed	288
Units: participants
Week 48	168

No statistical analyses for this end point

Secondary: Number of Participants with Crohn's Disease Achieving Clinical Response Based on Harvey-Bradshaw Index (HBI) Scores at Week 48

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End point title

Number of Participants with Crohn's Disease Achieving Clinical Response Based on Harvey-Bradshaw Index (HBI) Scores at Week 48

End point description

Clinical response is defined as a decrease in HBI score of ≥3 points from baseline in CD participants (randomized early terminator CD participants only [defined as randomized CD participants withdrawn from the parent study between Week 6 and Week 52]). As per planned analysis, data for this outcome measure is grouped and presented for participants with Crohn’s disease. FAS included all enrolled participants of this study MLN0002SC-3030. Subjects analysed is the number of randomised CD participants withdrawn from the parent study between Week 6 and Week 52.

End point type

Secondary

End point timeframe

Week 48

End point values	Crohn's Disease: Vedolizumab 108 mg
Number of subjects analysed	114
Units: participants
Week 48	32

No statistical analyses for this end point

Secondary: Number of Participants with Ulcerative Colitis Achieving Clinical Remission Based on Partial Mayo Score

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End point title

Number of Participants with Ulcerative Colitis Achieving Clinical Remission Based on Partial Mayo Score

End point description

Clinical remission is defined as a partial Mayo score of ≤2 with no individual subscore >1. As per planned analysis, data for this outcome measure is grouped and presented for participants with ulcerative colitis. FAS included all enrolled participants of this study MLN0002SC-3030.

End point type

Secondary

End point timeframe

Week 48

End point values	Ulcerative Colitis: Vedolizumab 108 mg
Number of subjects analysed	288
Units: participants
Week 48	150

No statistical analyses for this end point

Secondary: Number of Participants with Crohn's Disease Achieving Clinical Remission Based on Harvey-Bradshaw Index (HBI) Scores

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End point title

Number of Participants with Crohn's Disease Achieving Clinical Remission Based on Harvey-Bradshaw Index (HBI) Scores

End point description

Clinical remission is defined as total HBI score of ≤4 points. As per planned analysis, data for this outcome measure is grouped and presented for participants with Crohn’s disease. FAS included all enrolled participants of this study MLN0002SC-3030.

End point type

Secondary

End point timeframe

Week 48

End point values	Crohn's Disease: Vedolizumab 108 mg
Number of subjects analysed	458
Units: participants
Week 48	217

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to 97.9 months

Adverse event reporting additional description

The SAF included all participants who had received at least 1 dose of study medication in this study (MLN0002SC-3030). Adverse events and All-cause mortality are presented as per the dosing regimen.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.1

Reporting group title

Ulcerative Colitis: Only Vedolizumab Q2W

Reporting group description

Participants with UC who received vedolizumab SC 108 mg Q2W in this study were included in this arm group.

Reporting group title

Ulcerative Colitis: Only Vedolizumab QW

Reporting group description

Participants with UC who received vedolizumab SC 108 mg QW in this study were included in this arm group.

Reporting group title

Crohn's Disease: Vedolizumab Dose Escalation From Q2W to QW

Reporting group description

Participants with CD who experienced treatment failure (i.e., disease worsening or need for rescue medications) while receiving vedolizumab 108 mg Q2W during this study and underwent dose escalation to receive vedolizumab SC 108 mg QW were included in this arm group.

Reporting group title

Crohn's Disease: Only Vedolizumab Q2W

Reporting group description

Participants with CD who received vedolizumab SC 108 mg Q2W in this study were included in this arm group.

Reporting group title

Crohn's Disease: Only Vedolizumab QW

Reporting group description

Participants with CD who received vedolizumab SC 108 mg QW in this study were included in this arm group.

Reporting group title

Ulcerative Colitis: Vedolizumab Dose Escalation From Q2W to QW

Reporting group description

Participants with UC who experienced treatment failure (i.e., disease worsening or need for rescue medications) while receiving vedolizumab 108 mg Q2W during this study and underwent dose escalation to receive vedolizumab SC 108 mg QW were included in this arm group.

Serious adverse events	Ulcerative Colitis: Only Vedolizumab Q2W	Ulcerative Colitis: Only Vedolizumab QW	Crohn's Disease: Vedolizumab Dose Escalation From Q2W to QW	Crohn's Disease: Only Vedolizumab Q2W	Crohn's Disease: Only Vedolizumab QW	Ulcerative Colitis: Vedolizumab Dose Escalation From Q2W to QW
Total subjects affected by serious adverse events
subjects affected / exposed	29 / 163 (17.79%)	12 / 60 (20.00%)	31 / 102 (30.39%)	55 / 239 (23.01%)	35 / 117 (29.91%)	24 / 65 (36.92%)
number of deaths (all causes)	3	0	0	2	0	0
number of deaths resulting from adverse events	3	0	0	2	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Bladder cancer
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Colorectal adenoma
subjects affected / exposed	0 / 163 (0.00%)	1 / 60 (1.67%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	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
Colon cancer
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Breast cancer
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colorectal cancer
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Lip squamous cell carcinoma
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Malignant melanoma stage II
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Prostate cancer
Additional description: Number of participants at risk in each arm is based on the male population in this study.
subjects affected / exposed ^[1]	0 / 102 (0.00%)	0 / 33 (0.00%)	0 / 57 (0.00%)	1 / 133 (0.75%)	0 / 54 (0.00%)	0 / 33 (0.00%)
occurrences causally related to treatment / all	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
Rectal cancer
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seminoma
Additional description: Number of participants at risk in each arm is based on the male population in this study.
subjects affected / exposed ^[2]	0 / 102 (0.00%)	0 / 33 (0.00%)	0 / 57 (0.00%)	1 / 133 (0.75%)	0 / 54 (0.00%)	0 / 33 (0.00%)
occurrences causally related to treatment / all	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
Uterine leiomyoma
Additional description: Number of participants at risk in each arm is based on the female population in this study.
subjects affected / exposed ^[3]	1 / 61 (1.64%)	0 / 27 (0.00%)	1 / 45 (2.22%)	0 / 106 (0.00%)	0 / 63 (0.00%)	0 / 32 (0.00%)
occurrences causally related to treatment / all	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
Intraductal papilloma of breast
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Superficial vein thrombosis
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Peripheral artery stenosis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Reproductive system and breast disorders
Dysmenorrhoea
Additional description: Number of participants at risk in each arm is based on the female population in this study.
subjects affected / exposed ^[4]	0 / 61 (0.00%)	0 / 27 (0.00%)	0 / 45 (0.00%)	1 / 106 (0.94%)	0 / 63 (0.00%)	0 / 32 (0.00%)
occurrences causally related to treatment / all	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
Intermenstrual bleeding
Additional description: Number of participants at risk in each arm is based on the female population in this study.
subjects affected / exposed ^[5]	0 / 61 (0.00%)	0 / 27 (0.00%)	0 / 45 (0.00%)	1 / 106 (0.94%)	0 / 63 (0.00%)	0 / 32 (0.00%)
occurrences causally related to treatment / all	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
Prostatitis
Additional description: Number of participants at risk in each arm is based on the male population in this study.
subjects affected / exposed ^[6]	0 / 102 (0.00%)	0 / 33 (0.00%)	0 / 57 (0.00%)	1 / 133 (0.75%)	0 / 54 (0.00%)	0 / 33 (0.00%)
occurrences causally related to treatment / all	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
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Cough
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Hypoxia
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Pleural effusion
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Pulmonary embolism
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Pulmonary pneumatocele
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Psychiatric disorders
Suicidal ideation
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Major depression
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Investigations
Hepatic enzyme increased
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Fibrin D dimer increased
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Injury, poisoning and procedural complications
Intestinal anastomosis complication
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Hip fracture
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Gastrointestinal organ contusion
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
Procedural pain
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Multiple fractures
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Meniscus injury
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	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
Lumbar vertebral fracture
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Liver contusion
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Ligament injury
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Skin laceration
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Wound
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Spinal compression fracture
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Angina pectoris
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Aortic valve stenosis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Myocardial infarction
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Hypertensive heart disease
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Coronary artery disease
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Cardiac arrest
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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 / 1	0 / 0	0 / 0
Nervous system disorders
Presyncope
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Ischaemic stroke
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Headache
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	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
Cerebrovascular accident
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Cerebral ischaemia
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Syncope
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Transient ischaemic attack
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Vascular headache
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	3 / 163 (1.84%)	1 / 60 (1.67%)	0 / 102 (0.00%)	3 / 239 (1.26%)	3 / 117 (2.56%)	6 / 65 (9.23%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 0	0 / 5	0 / 3	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune haemolytic anaemia
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	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
Iron deficiency anaemia
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	2 / 239 (0.84%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 8	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Leukocytosis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Ear and labyrinth disorders
Sudden hearing loss
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Gastrointestinal disorders
Abdominal adhesions
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Abdominal pain
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	3 / 239 (1.26%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspepsia
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Diarrhoea
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	2 / 117 (1.71%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Crohn's disease
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	14 / 102 (13.73%)	4 / 239 (1.67%)	10 / 117 (8.55%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 16	1 / 5	1 / 10	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis ulcerative
subjects affected / exposed	4 / 163 (2.45%)	7 / 60 (11.67%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	11 / 65 (16.92%)
occurrences causally related to treatment / all	0 / 4	1 / 7	0 / 0	0 / 0	0 / 0	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal fistula
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	2 / 239 (0.84%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	1 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal fissure
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	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
Enterovesical fistula
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Gastrointestinal inflammation
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 163 (0.00%)	1 / 60 (1.67%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Femoral hernia
subjects affected / exposed	0 / 163 (0.00%)	1 / 60 (1.67%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Gastrointestinal toxicity
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Ileal stenosis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	1 / 239 (0.42%)	2 / 117 (1.71%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ileal ulcer perforation
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Inguinal hernia
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Intestinal perforation
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Intestinal obstruction
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Intestinal fibrosis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Large intestinal stenosis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Lower gastrointestinal haemorrhage
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Large intestine polyp
subjects affected / exposed	0 / 163 (0.00%)	1 / 60 (1.67%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Pancreatitis
subjects affected / exposed	0 / 163 (0.00%)	1 / 60 (1.67%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	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
Pancreatitis acute
subjects affected / exposed	0 / 163 (0.00%)	1 / 60 (1.67%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Pancreatitis chronic
subjects affected / exposed	0 / 163 (0.00%)	1 / 60 (1.67%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	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
Pancreatitis necrotising
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	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
Proctitis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Small intestinal obstruction
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	5 / 239 (2.09%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 3	0 / 10	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rectal polyp
subjects affected / exposed	0 / 163 (0.00%)	1 / 60 (1.67%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Small intestinal stenosis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Subileus
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	2 / 117 (1.71%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tooth impacted
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Cholelithiasis
subjects affected / exposed	0 / 163 (0.00%)	1 / 60 (1.67%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Gallbladder enlargement
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Skin and subcutaneous tissue disorders
Onychoclasis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Renal and urinary disorders
Hydronephrosis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Glomerulonephritis rapidly progressive
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Acute kidney injury
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	2 / 65 (3.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
IgA nephropathy
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Nephrolithiasis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Renal colic
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tubulointerstitial nephritis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Ureterolithiasis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	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
Endocrine disorders
Parathyroid disorder
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	2 / 117 (1.71%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arthritis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	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
Back pain
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Fistula
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	2 / 65 (3.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myalgia
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	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
Patellofemoral pain syndrome
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	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
Rotator cuff syndrome
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Infections and infestations
Abdominal abscess
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal wall abscess
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Bronchitis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Appendicitis
subjects affected / exposed	1 / 163 (0.61%)	1 / 60 (1.67%)	1 / 102 (0.98%)	1 / 239 (0.42%)	1 / 117 (0.85%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendiceal abscess
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Abscess
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Abscess intestinal
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Anal abscess
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	3 / 239 (1.26%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	2 / 163 (1.23%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
Endocarditis staphylococcal
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Diverticulitis
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Cytomegalovirus enteritis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	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
Clostridium difficile infection
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Campylobacter gastroenteritis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
COVID-19 pneumonia
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	4 / 239 (1.67%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enteritis infectious
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Gastroenteritis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Herpes zoster
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Influenza
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Orchitis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Peritoneal abscess
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Peritonitis
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	3 / 102 (2.94%)	1 / 239 (0.42%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Pyelonephritis acute
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Rectal abscess
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	2 / 117 (1.71%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Respiratory tract infection bacterial
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Sepsis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Subcutaneous abscess
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Suspected COVID-19
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Urinary tract infection
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	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
Tooth abscess
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Tonsillitis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	1 / 102 (0.98%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Urosepsis
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 239 (0.42%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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
Hypokalaemia
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 239 (0.00%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	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

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Number of subjects exposed in each arm is based on the male population in this study.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Number of subjects exposed in each arm is based on the male population in this study.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Number of subjects exposed in each arm is based on the female population in this study.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Number of subjects exposed in each arm is based on the female population in this study.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Number of subjects exposed in each arm is based on the female population in this study.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Number of subjects exposed in each arm is based on the male population in this study.

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

Non-serious adverse events	Ulcerative Colitis: Only Vedolizumab Q2W	Ulcerative Colitis: Only Vedolizumab QW	Crohn's Disease: Vedolizumab Dose Escalation From Q2W to QW	Crohn's Disease: Only Vedolizumab Q2W	Crohn's Disease: Only Vedolizumab QW	Ulcerative Colitis: Vedolizumab Dose Escalation From Q2W to QW
Total subjects affected by non serious adverse events
subjects affected / exposed	94 / 163 (57.67%)	41 / 60 (68.33%)	90 / 102 (88.24%)	151 / 239 (63.18%)	78 / 117 (66.67%)	55 / 65 (84.62%)
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	8 / 163 (4.91%)	4 / 60 (6.67%)	5 / 102 (4.90%)	13 / 239 (5.44%)	2 / 117 (1.71%)	4 / 65 (6.15%)
occurrences all number	12	4	7	17	2	4
Vascular disorders
Hypertension
subjects affected / exposed	8 / 163 (4.91%)	0 / 60 (0.00%)	5 / 102 (4.90%)	12 / 239 (5.02%)	3 / 117 (2.56%)	4 / 65 (6.15%)
occurrences all number	8	0	5	15	3	4
Nervous system disorders
Headache
subjects affected / exposed	8 / 163 (4.91%)	3 / 60 (5.00%)	14 / 102 (13.73%)	19 / 239 (7.95%)	5 / 117 (4.27%)	7 / 65 (10.77%)
occurrences all number	25	4	14	34	7	10
Blood and lymphatic system disorders
Lymphopenia
subjects affected / exposed	1 / 163 (0.61%)	5 / 60 (8.33%)	3 / 102 (2.94%)	3 / 239 (1.26%)	1 / 117 (0.85%)	1 / 65 (1.54%)
occurrences all number	1	6	3	3	1	1
Anaemia
subjects affected / exposed	3 / 163 (1.84%)	5 / 60 (8.33%)	6 / 102 (5.88%)	14 / 239 (5.86%)	3 / 117 (2.56%)	9 / 65 (13.85%)
occurrences all number	8	5	7	20	5	9
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	5 / 163 (3.07%)	4 / 60 (6.67%)	10 / 102 (9.80%)	12 / 239 (5.02%)	9 / 117 (7.69%)	3 / 65 (4.62%)
occurrences all number	5	4	18	13	12	6
Injection site reaction
subjects affected / exposed	2 / 163 (1.23%)	4 / 60 (6.67%)	0 / 102 (0.00%)	2 / 239 (0.84%)	1 / 117 (0.85%)	0 / 65 (0.00%)
occurrences all number	21	23	0	2	4	0
Injection site erythema
subjects affected / exposed	2 / 163 (1.23%)	5 / 60 (8.33%)	1 / 102 (0.98%)	3 / 239 (1.26%)	2 / 117 (1.71%)	1 / 65 (1.54%)
occurrences all number	7	21	1	5	2	1
Fatigue
subjects affected / exposed	6 / 163 (3.68%)	0 / 60 (0.00%)	5 / 102 (4.90%)	13 / 239 (5.44%)	5 / 117 (4.27%)	1 / 65 (1.54%)
occurrences all number	6	0	6	16	5	1
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	2 / 163 (1.23%)	0 / 60 (0.00%)	7 / 102 (6.86%)	10 / 239 (4.18%)	3 / 117 (2.56%)	1 / 65 (1.54%)
occurrences all number	2	0	8	12	4	1
Abdominal pain
subjects affected / exposed	8 / 163 (4.91%)	3 / 60 (5.00%)	15 / 102 (14.71%)	33 / 239 (13.81%)	20 / 117 (17.09%)	2 / 65 (3.08%)
occurrences all number	8	3	21	49	25	2
Anal fistula
subjects affected / exposed	0 / 163 (0.00%)	0 / 60 (0.00%)	4 / 102 (3.92%)	5 / 239 (2.09%)	7 / 117 (5.98%)	0 / 65 (0.00%)
occurrences all number	0	0	4	7	8	0
Vomiting
subjects affected / exposed	4 / 163 (2.45%)	1 / 60 (1.67%)	8 / 102 (7.84%)	13 / 239 (5.44%)	4 / 117 (3.42%)	2 / 65 (3.08%)
occurrences all number	5	1	10	15	9	2
Crohn's disease
subjects affected / exposed	1 / 163 (0.61%)	0 / 60 (0.00%)	53 / 102 (51.96%)	26 / 239 (10.88%)	30 / 117 (25.64%)	0 / 65 (0.00%)
occurrences all number	1	0	106	28	36	0
Diarrhoea
subjects affected / exposed	12 / 163 (7.36%)	2 / 60 (3.33%)	10 / 102 (9.80%)	18 / 239 (7.53%)	12 / 117 (10.26%)	8 / 65 (12.31%)
occurrences all number	12	2	16	29	20	9
Gastrooesophageal reflux disease
subjects affected / exposed	3 / 163 (1.84%)	0 / 60 (0.00%)	6 / 102 (5.88%)	3 / 239 (1.26%)	0 / 117 (0.00%)	1 / 65 (1.54%)
occurrences all number	5	0	6	3	0	1
Nausea
subjects affected / exposed	7 / 163 (4.29%)	1 / 60 (1.67%)	13 / 102 (12.75%)	14 / 239 (5.86%)	7 / 117 (5.98%)	3 / 65 (4.62%)
occurrences all number	10	1	17	19	13	3
Colitis ulcerative
subjects affected / exposed	8 / 163 (4.91%)	14 / 60 (23.33%)	0 / 102 (0.00%)	0 / 239 (0.00%)	0 / 117 (0.00%)	33 / 65 (50.77%)
occurrences all number	12	15	0	0	0	44
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	12 / 163 (7.36%)	1 / 60 (1.67%)	8 / 102 (7.84%)	10 / 239 (4.18%)	2 / 117 (1.71%)	4 / 65 (6.15%)
occurrences all number	13	1	8	12	2	5
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	9 / 163 (5.52%)	2 / 60 (3.33%)	9 / 102 (8.82%)	14 / 239 (5.86%)	4 / 117 (3.42%)	3 / 65 (4.62%)
occurrences all number	10	2	10	16	6	3
Arthralgia
subjects affected / exposed	8 / 163 (4.91%)	3 / 60 (5.00%)	11 / 102 (10.78%)	34 / 239 (14.23%)	14 / 117 (11.97%)	5 / 65 (7.69%)
occurrences all number	14	3	13	45	17	9
Infections and infestations
Bronchitis
subjects affected / exposed	9 / 163 (5.52%)	1 / 60 (1.67%)	8 / 102 (7.84%)	16 / 239 (6.69%)	8 / 117 (6.84%)	6 / 65 (9.23%)
occurrences all number	12	1	10	22	9	7
Pneumonia
subjects affected / exposed	3 / 163 (1.84%)	1 / 60 (1.67%)	2 / 102 (1.96%)	3 / 239 (1.26%)	1 / 117 (0.85%)	4 / 65 (6.15%)
occurrences all number	3	1	3	3	1	4
Pharyngitis
subjects affected / exposed	7 / 163 (4.29%)	1 / 60 (1.67%)	3 / 102 (2.94%)	6 / 239 (2.51%)	6 / 117 (5.13%)	4 / 65 (6.15%)
occurrences all number	7	2	3	6	7	4
Nasopharyngitis
subjects affected / exposed	23 / 163 (14.11%)	11 / 60 (18.33%)	20 / 102 (19.61%)	26 / 239 (10.88%)	16 / 117 (13.68%)	15 / 65 (23.08%)
occurrences all number	52	22	31	44	21	26
Influenza
subjects affected / exposed	4 / 163 (2.45%)	3 / 60 (5.00%)	3 / 102 (2.94%)	12 / 239 (5.02%)	5 / 117 (4.27%)	7 / 65 (10.77%)
occurrences all number	4	3	3	14	6	7
Herpes zoster
subjects affected / exposed	4 / 163 (2.45%)	1 / 60 (1.67%)	1 / 102 (0.98%)	2 / 239 (0.84%)	5 / 117 (4.27%)	4 / 65 (6.15%)
occurrences all number	4	1	1	3	5	4
Gastroenteritis
subjects affected / exposed	4 / 163 (2.45%)	4 / 60 (6.67%)	4 / 102 (3.92%)	11 / 239 (4.60%)	6 / 117 (5.13%)	2 / 65 (3.08%)
occurrences all number	7	6	4	14	7	2
COVID-19
subjects affected / exposed	24 / 163 (14.72%)	2 / 60 (3.33%)	9 / 102 (8.82%)	29 / 239 (12.13%)	4 / 117 (3.42%)	5 / 65 (7.69%)
occurrences all number	27	2	11	30	4	5
Sinusitis
subjects affected / exposed	9 / 163 (5.52%)	2 / 60 (3.33%)	8 / 102 (7.84%)	12 / 239 (5.02%)	6 / 117 (5.13%)	4 / 65 (6.15%)
occurrences all number	12	2	11	19	9	5
Urinary tract infection
subjects affected / exposed	8 / 163 (4.91%)	2 / 60 (3.33%)	9 / 102 (8.82%)	12 / 239 (5.02%)	5 / 117 (4.27%)	1 / 65 (1.54%)
occurrences all number	9	2	13	18	7	3
Upper respiratory tract infection
subjects affected / exposed	28 / 163 (17.18%)	6 / 60 (10.00%)	18 / 102 (17.65%)	38 / 239 (15.90%)	13 / 117 (11.11%)	7 / 65 (10.77%)
occurrences all number	52	14	31	57	20	13

More information

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Were there any global substantial amendments to the protocol? Yes

04 Sep 2015

The following changes were made as per Amendment 1: 1. Included product complaints section in the study. 2. Updated the clinical pharmacology background and pharmacokinetic (PK) endpoints to reflect dosing simulation modeling.

10 Feb 2016

The following changes were made as per Amendment 2: 1. Included a benefit-risk assessment in the protocol. 2. Updated the expected treatment duration to a maximum of 5 years. 3. Updated inclusion criterion to clarify colorectal cancer surveillance requirements where enrolled participants were encouraged to undergo surveillance colonoscopies in accordance with local guidelines throughout their participation in the study.

12 May 2016

The following changes were made as per Amendment 3: Added inclusion criterion where participants who had participated in either parent study and, in the opinion of the investigator, tolerated the study drug well could participate in this study.

01 Aug 2016

The following changes were made as per Amendment 4: 1. Updated schedule of study procedures. 2. Footnotes were updated in the body of the protocol.

08 Nov 2016

The following changes were made as per Amendment 5: 1. Updated Amendment 4 from non-substantial to substantial.

23 Apr 2018

The following changes were made as per Amendment 7: 1. Updated the PK analysis text. 2. Updated the antivedolizumab antibodies (AVA) analysis text. 3. Updated the visit window for the QW dosing group from ±1 week to ±3 days. 4. Updated the permitted medications to allow topical steroid treatment for new extraintestinal manifestations (only) of CD after approval by the sponsor.

20 Oct 2022

The following changes were made as per Amendment 10: Updated the treatment duration to remove the maximum treatment duration of 5 years and to allow treatment to continue until vedolizumab SC was available in the participant’s country commercially or through other access programs.

Were there any global interruptions to the trial? No

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

None reported

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