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Clinical Trial Results:
A Phase I/II, randomised, controlled study to assess the safety, effectiveness and immune response of meningococcal combined ABCWY vaccine when administered to healthy adults (Phase I) and to healthy adolescents and adults (Phase II).

Summary
EudraCT number	2020-004741-37
Trial protocol	BE FI Outside EU/EEA PL SE
Global end of trial date	15 Nov 2024

Results information
Results version number	v1(current)
This version publication date	30 May 2025
First version publication date	30 May 2025
Other versions

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

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Trial information

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Sponsor protocol code

212458

ISRCTN number

US NCT number

NCT04886154

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

Rue de l’Institut, 89,, Rixensart, Belgium, 1330

Public contact

GSK Response Center, GlaxoSmithKline, 044 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, 044 8664357343, GSKClinicalSupportHD@gsk.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-003359-PIP01-22

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

03 Dec 2024

Is this the analysis of the primary completion data?

Yes

Primary completion date

02 Feb 2024

Global end of trial reached?

Yes

Global end of trial date

15 Nov 2024

Was the trial ended prematurely?

Main objective of the trial

Phase I: •To evaluate the safety and reactogenicity of the 2 formulations of MenABCWY-2Gen vaccine Phase II: •To demonstrate the superiority of the effectiveness of MenABCWY-2Gen vaccine when administered at 0,2- or 0,6-months schedule, compared to the MenB vaccine administered at 0,6-months schedule •To demonstrate the immunological non-inferiority (NI) of MenABCWY-2Gen vaccine administered at 0,2- or 0,6-months schedule compared to the MenACWY vaccine (single dose) •To evaluate the safety and reactogenicity of the MenABCWY-2Gen, the MenB and the MenACWY vaccines Phase II-Sourcing: •To evaluate the safety and reactogenicity of the 2 formulations of MenABCWY-2Gen vaccine.

Protection of trial subjects

All participants were followed for safety up to 6 months in Phase I and Phase II (Sourcing) and 12 months in Phase II (Formulation and Schedule-finding) after the last vaccination. The participants were observed closely for at least 30 minutes following the administration of the vaccine(s)/product(s), with appropriate medical treatment readily available in case of anaphylaxis and/or syncope.

Background therapy

Evidence for comparator

Actual start date of recruitment

14 Jun 2021

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 227

Country: Number of subjects enrolled

Belgium: 169

Country: Number of subjects enrolled

Brazil: 147

Country: Number of subjects enrolled

Finland: 157

Country: Number of subjects enrolled

Poland: 596

Country: Number of subjects enrolled

Sweden: 35

Country: Number of subjects enrolled

Türkiye: 26

Country: Number of subjects enrolled

United States: 83

Worldwide total number of subjects

1440

EEA total number of subjects

957

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

122

Adolescents (12-17 years)

272

Adults (18-64 years)

1046

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Out of 1440 participants enrolled, 3 participants from Phase II (Formulation and Schedule-finding) did not receive vaccination as they did not meet the eligibility criteria, therefore only 1437 participants were included in the Exposed Set and started the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

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

Are arms mutually exclusive

Yes

ABCWY low dose Group

Arm description

Participants received two doses of the MenABCWY-2Gen low-dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In).

Arm type

Experimental

Investigational medicinal product name

MenABCWY-2Gen low dose vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

MenABCWY-2Gen low dose vaccine is administered intramuscularly as 2 doses to participants.

Placebo low dose Group

Arm description

Participants received two doses of a placebo on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In), as the control group for the ABCWY low-dose group.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Placebo is administered intramuscularly as 2 doses to participants.

ABCWY high dose Group

Arm description

Participants received two doses of the MenABCWY-2Gen high-dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In).

Arm type

Experimental

Investigational medicinal product name

MenABCWY-2Gen high dose vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

MenABCWY-2Gen high dose vaccine is administered intramuscularly as 2 doses to participants.

Placebo high dose Group

Arm description

Participants received two doses of a placebo on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In), as the control group for the ABCWY high-dose group.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Placebo is administered intramuscularly as 2 doses to participants.

ABCWY low dose_06 Group

Arm description

Participants received two doses of the MenABCWY-2Gen low-dose vaccine on Day 1 and Day 181, following a 0, 6-month schedule, along with one dose of a placebo on Day 121 during Phase II (Formulation and Schedule-Finding).

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Placebo is administered intramuscularly as 1 dose to participants.

Investigational medicinal product name

MenABCWY-2Gen low dose vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

MenABCWY-2Gen low dose vaccine is administered intramuscularly as 2 doses to participants.

ABCWY low dose_02 Group

Arm description

Participants received two doses of the MenABCWY-2Gen low-dose vaccine on Day 121 and Day 181, following a 0, 2-month schedule, along with one dose of a placebo on Day 1 during Phase II (Formulation and Schedule-Finding).

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Placebo is administered intramuscularly as 1 dose to participants.

Investigational medicinal product name

MenABCWY-2Gen low dose vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

MenABCWY-2Gen low dose vaccine is administered intramuscularly as 2 doses to participants.

ABCWY high dose_06 Group

Arm description

Participants received two doses of the MenABCWY-2Gen high-dose vaccine on Day 1 and Day 181, following a 0, 6-month schedule, along with one dose of a placebo on Day 121 during Phase II (Formulation and Schedule-Finding).

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Placebo is administered intramuscularly as 1 dose to participants.

Investigational medicinal product name

MenABCWY-2Gen high dose vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

MenABCWY-2Gen high dose vaccine is administered intramuscularly as 2 doses to participants.

ABCWY high dose_02 Group

Arm description

Participants received two doses of the MenABCWY-2Gen high-dose vaccine on Day 121 and Day 181, following a 0, 2-month schedule, along with one dose of a placebo on Day 1 during Phase II (Formulation and Schedule-Finding).

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Placebo is administered intramuscularly as 1 dose to participants.

Investigational medicinal product name

MenABCWY-2Gen high dose vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

MenABCWY-2Gen high dose vaccine is administered intramuscularly as 2 doses to participants.

Control Group

Arm description

Participants randomized to the control group received two doses of the Bexsero (MenB) vaccine on Day 1 and Day 181, following a 0, 6-month schedule, and one dose of Menveo (MenACWY) on Day 1 during Study Phase II (Formulation and Schedule-Finding).

Arm type

Active comparator

Investigational medicinal product name

MenACWY

Investigational medicinal product code

Other name

GSK's combined meningococcal groups A, C, Y and W-135 conjugate vaccine, Menveo

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

MenACWY vaccine is administered intramuscularly as 1 dose to participants.

Investigational medicinal product name

Meningococcal Group B Vaccine (rMenB+OMV NZ)

Investigational medicinal product code

Other name

GSK’s meningococcal group B vaccine, Bexsero

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

MenB vaccine is administered intramuscularly as 2 doses in a 0,6-months schedule to participants.

ABCWY low dose_01 Group

Arm description

Participants received two doses of MenABCWY-2Gen low dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during study Phase II (Sourcing).

Arm type

Experimental

Investigational medicinal product name

MenABCWY-2Gen low dose vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

MenABCWY-2Gen low dose vaccine is administered intramuscularly as 2 doses to participants.

ABCWY high dose_01 Group

Arm description

Participants received two doses of MenABCWY-2Gen high dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during study Phase II (Sourcing).

Arm type

Experimental

Investigational medicinal product name

MenABCWY-2Gen high dose vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

MenABCWY-2Gen high dose vaccine is administered intramuscularly as 2 doses to participants.

ABCWY low doseS_02 Group

Arm description

Participants received two doses of MenABCWY-2Gen low dose vaccine on Day 1 and day 61 following a 0, 2-month schedule during study Phase II (Sourcing).

Arm type

Experimental

Investigational medicinal product name

MenABCWY-2Gen low dose vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

MenABCWY-2Gen low dose vaccine is administered intramuscularly as 2 doses to participants.

ABCWY high doseS_02 Group

Arm description

Participants received two doses of MenABCWY-2Gen high dose vaccine on Day 1 and day 61 following a 0, 2-month schedule during study Phase II (Sourcing).

Arm type

Experimental

Investigational medicinal product name

MenABCWY-2Gen high dose vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

MenABCWY-2Gen high dose vaccine is administered intramuscularly as 2 doses to participants.

ABCWY low doseS_06 Group

Arm description

Participants received two doses of MenABCWY-2Gen low dose vaccine on Day 1 and day 181 following a 0, 6-month schedule during study Phase II (Sourcing).

Arm type

Experimental

Investigational medicinal product name

MenABCWY-2Gen low dose vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

MenABCWY-2Gen low dose vaccine is administered intramuscularly as 2 doses to participants.

ABCWY high doseS_06 Group

Arm description

Participants received two doses of MenABCWY-2Gen high dose vaccine on Day 1 and day 181 following a 0, 6-month schedule during study Phase II (Sourcing).

Arm type

Experimental

Investigational medicinal product name

MenABCWY-2Gen high dose vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

MenABCWY-2Gen high dose vaccine is administered intramuscularly as 2 doses to participants.

Number of subjects in period 1 ^[1]	ABCWY low dose Group	Placebo low dose Group	ABCWY high dose Group	Placebo high dose Group	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group	ABCWY low dose_01 Group	ABCWY high dose_01 Group	ABCWY low doseS_02 Group	ABCWY high doseS_02 Group	ABCWY low doseS_06 Group	ABCWY high doseS_06 Group
Started	12	4	13	3	239	181	238	194	197	54	53	62	62	62	63
Completed	11	4	11	3	209	166	218	175	182	53	50	59	61	60	56
Not completed	1	0	2	0	30	15	20	19	15	1	3	3	1	2	7
ADVERSE EVENT REQUIRING EXPEDITED REPORT	-	-	-	-	-	-	1	-	-	-	-	-	-	-	-
Adverse event, non-fatal	-	-	-	-	1	-	-	1	1	-	-	1	-	-	3
MIGRATED / MOVED FROM THE STUDY AREA	-	-	-	-	1	-	2	1	-	-	-	-	-	-	1
Lost to follow-up	1	-	2	-	17	7	8	7	8	-	2	-	-	-	-
Other, Not Specified	-	-	-	-	11	8	9	10	6	1	1	2	1	2	3

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Out of 1440 participants enrolled, 3 participants from Phase II (Formulation and Schedule-finding) did not receive vaccination as they did not meet the eligibility criteria, therefore only 1437 participants were included in the Exposed Set and started the study.

Baseline characteristics

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Reporting group title

ABCWY low dose Group

Reporting group description

Participants received two doses of the MenABCWY-2Gen low-dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In).

Reporting group title

Placebo low dose Group

Reporting group description

Participants received two doses of a placebo on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In), as the control group for the ABCWY low-dose group.

Reporting group title

ABCWY high dose Group

Reporting group description

Participants received two doses of the MenABCWY-2Gen high-dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In).

Reporting group title

Placebo high dose Group

Reporting group description

Participants received two doses of a placebo on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In), as the control group for the ABCWY high-dose group.

Reporting group title

ABCWY low dose_06 Group

Reporting group description

Reporting group title

ABCWY low dose_02 Group

Reporting group description

Reporting group title

ABCWY high dose_06 Group

Reporting group description

Reporting group title

ABCWY high dose_02 Group

Reporting group description

Reporting group title

Control Group

Reporting group description

Reporting group title

ABCWY low dose_01 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen low dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during study Phase II (Sourcing).

Reporting group title

ABCWY high dose_01 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen high dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during study Phase II (Sourcing).

Reporting group title

ABCWY low doseS_02 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen low dose vaccine on Day 1 and day 61 following a 0, 2-month schedule during study Phase II (Sourcing).

Reporting group title

ABCWY high doseS_02 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen high dose vaccine on Day 1 and day 61 following a 0, 2-month schedule during study Phase II (Sourcing).

Reporting group title

ABCWY low doseS_06 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen low dose vaccine on Day 1 and day 181 following a 0, 6-month schedule during study Phase II (Sourcing).

Reporting group title

ABCWY high doseS_06 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen high dose vaccine on Day 1 and day 181 following a 0, 6-month schedule during study Phase II (Sourcing).

Reporting group values	ABCWY low dose Group	Placebo low dose Group	ABCWY high dose Group	Placebo high dose Group	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group	ABCWY low dose_01 Group	ABCWY high dose_01 Group	ABCWY low doseS_02 Group	ABCWY high doseS_02 Group	ABCWY low doseS_06 Group	ABCWY high doseS_06 Group	Total
Number of subjects	12	4	13	3	239	181	238	194	197	54	53	62	62	62	63	1437
Age categorical
Units: Subjects
Children (2-11 years)	0	0	0	0	26	19	30	23	24	0	0	0	0	0	0	122
Adolescents (12-17 years)	1	0	0	0	59	49	59	48	55	0	0	0	0	0	0	271
Adults (18-64 years)	11	4	13	3	154	113	149	123	118	54	53	62	62	62	63	1044
Age Continuous
Units: years
arithmetic mean (standard deviation)	28.6 ( 7.5 )	30.8 ( 6.2 )	31.7 ( 6.0 )	28.7 ( 3.8 )	18.9 ( 4.7 )	18.6 ( 4.6 )	18.7 ( 5.0 )	18.6 ( 4.7 )	18.4 ( 4.6 )	34.6 ( 8.9 )	31.7 ( 7.3 )	35.2 ( 9.1 )	34.6 ( 8.4 )	37.0 ( 8.7 )	37.3 ( 8.8 )	-
Sex: Female, Male
Units: Participants
Male	6	2	6	2	86	85	82	73	84	26	19	24	23	25	26	569
Female	6	2	7	1	153	96	156	121	113	28	34	38	39	37	37	868
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	0	0	0	0	41	29	30	29	35	3	6	0	0	3	0	176
Not Hispanic or Latino	11	4	13	3	198	152	208	165	162	50	46	62	62	59	63	1258
Unknown or Not Reported	1	0	0	0	0	0	0	0	0	1	1	0	0	0	0	3

End points

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Reporting group title

ABCWY low dose Group

Reporting group description

Participants received two doses of the MenABCWY-2Gen low-dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In).

Reporting group title

Placebo low dose Group

Reporting group description

Participants received two doses of a placebo on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In), as the control group for the ABCWY low-dose group.

Reporting group title

ABCWY high dose Group

Reporting group description

Participants received two doses of the MenABCWY-2Gen high-dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In).

Reporting group title

Placebo high dose Group

Reporting group description

Participants received two doses of a placebo on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In), as the control group for the ABCWY high-dose group.

Reporting group title

ABCWY low dose_06 Group

Reporting group description

Reporting group title

ABCWY low dose_02 Group

Reporting group description

Reporting group title

ABCWY high dose_06 Group

Reporting group description

Reporting group title

ABCWY high dose_02 Group

Reporting group description

Reporting group title

Control Group

Reporting group description

Reporting group title

ABCWY low dose_01 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen low dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during study Phase II (Sourcing).

Reporting group title

ABCWY high dose_01 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen high dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during study Phase II (Sourcing).

Reporting group title

ABCWY low doseS_02 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen low dose vaccine on Day 1 and day 61 following a 0, 2-month schedule during study Phase II (Sourcing).

Reporting group title

ABCWY high doseS_02 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen high dose vaccine on Day 1 and day 61 following a 0, 2-month schedule during study Phase II (Sourcing).

Reporting group title

ABCWY low doseS_06 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen low dose vaccine on Day 1 and day 181 following a 0, 6-month schedule during study Phase II (Sourcing).

Reporting group title

ABCWY high doseS_06 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen high dose vaccine on Day 1 and day 181 following a 0, 6-month schedule during study Phase II (Sourcing).

Subject analysis set title

Control (MenACWY) Group

Subject analysis set type

Intention-to-treat

Subject analysis set description

Participants randomized to Control Group received a single dose of Menveo (MenACWY) on Day 1 during study Phase II (Formulation and Schedule-finding).

Subject analysis set title

Control (MenB_06) Group

Subject analysis set type

Intention-to-treat

Subject analysis set description

Participants randomized to Control Group received 2 doses of Bexsero (MenB) vaccine on Day 1 and Day 181 following in a 0, 6- month schedule during study Phase II (Formulation and Schedule-finding).

Subject analysis set title

Control (MenB_06) Group

Subject analysis set type

Intention-to-treat

Subject analysis set description

Participants randomized to Control Group received 2 doses of Bexsero (MenB) vaccine on Day 1 and Day 181 following in a 0, 6- month schedule during study Phase II (Formulation and Schedule-finding).

Primary: Number of participants with solicited administration site events in study Phase I (Safety Lead-in) Day 1

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End point title

Number of participants with solicited administration site events in study Phase I (Safety Lead-in) Day 1 ^[1] ^[2]

End point description

The solicited administration site events include injection site pain, erythema (redness), swelling and induration. Any solicited administration site AEs = occurrence of the symptom regardless of intensity grade. Analysis was performed on the Phase I Exposed set (ES), which included all participants who received at least one dose of the study treatment and have post-vaccination data for the specified analysis at specified timepoints. Allocation per group using the enrolled set is based on the treatment administered.

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 1

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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[2] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase I (Safety Lead-in) groups.

End point values	ABCWY low dose Group	Placebo low dose Group	ABCWY high dose Group	Placebo high dose Group
Number of subjects analysed	12	4	13	3
Units: Participants
Erythema (N= 12, 4,13, 3)	0	0	0	0
Induration (N= 12, 4,13, 3)	1	0	0	0
Pain (N= 12, 4,13, 3)	11	1	13	0
Swelling (N= 12, 4,13, 3)	1	0	0	0

No statistical analyses for this end point

Primary: Number of participants with solicited administration site events in study Phase I (Safety Lead-in) at Day 31

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End point title

Number of participants with solicited administration site events in study Phase I (Safety Lead-in) at Day 31 ^[3] ^[4]

End point description

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 31

Notes
[3] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[4] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase I (Safety Lead-in) groups.

End point values	ABCWY low dose Group	Placebo low dose Group	ABCWY high dose Group	Placebo high dose Group
Number of subjects analysed	12	4	11	3
Units: Participants
Erythema (N=12,4,11,3)	2	0	0	0
Induration (N=12,4,11,3)	0	0	0	0
Pain (N=12,4,11,3)	8	1	8	1
Swelling (N=12,4,11,3)	0	0	0	0

No statistical analyses for this end point

Primary: Number of participants with solicited systemic events in study Phase I (Safety Lead-in) Day 1

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End point title

Number of participants with solicited systemic events in study Phase I (Safety Lead-in) Day 1 ^[5] ^[6]

End point description

The solicited systemic events include fever (temperature ≥ 38.0°C), nausea, fatigue, myalgia, arthralgia, and headache. Analysis was performed on the Phase I Exposed set (ES), which included all participants who received at least one dose of the study treatment and have post-vaccination data for the specified analysis at specified timepoints. Allocation per group using the enrolled set is based on the treatment administered.

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 1

Notes
[5] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[6] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase I (Safety Lead-in) groups.

End point values	ABCWY low dose Group	Placebo low dose Group	ABCWY high dose Group	Placebo high dose Group
Number of subjects analysed	12	4	13	3
Units: Participants
Arthralgia (N=12,4,13,3)	1	1	2	1
Fatigue (N=12,4,13,3)	4	1	11	2
Headache (N=12,4,13,3)	4	0	4	1
Myalgia (N=12,4,13,3)	4	0	3	1
Nausea (N=12,4,13,3)	0	0	3	0
Fever (N=12,4,13,3)	1	0	0	0

No statistical analyses for this end point

Primary: Number of participants with solicited systemic events in study Phase I (Safety Lead-in) Day 31

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End point title

Number of participants with solicited systemic events in study Phase I (Safety Lead-in) Day 31 ^[7] ^[8]

End point description

The solicited systemic events include fever (temperature ≥ 38.0°C), nausea, fatigue, myalgia, arthralgia and headache. Analysis was performed on the Phase I Exposed set (ES), which included all participants who received at least one dose of the study treatment and have post-vaccination data for the specified analysis at specified timepoints. Allocation per group using the enrolled set is based on the treatment administered.

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 31

Notes
[7] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[8] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase I (Safety Lead-in) groups.

End point values	ABCWY low dose Group	Placebo low dose Group	ABCWY high dose Group	Placebo high dose Group
Number of subjects analysed	12	4	11	3
Units: Participants
Arthralgia (N= 12, 4, 11, 3)	1	2	2	0
Fatigue (N= 12, 4, 11, 3)	1	2	7	2
Headache (N= 12, 4, 11, 3)	4	2	3	1
Myalgia (N= 12, 4, 11, 3)	1	1	2	0
Nausea (N= 12, 4, 11, 3)	1	1	2	0
Fever (N= 12, 4, 11, 3)	1	0	0	0

No statistical analyses for this end point

Primary: Number of participants with any unsolicited adverse events (AEs), including all serious adverse events (SAEs), AEs leading to withdrawal and AEs of special interest (AESIs) in study Phase I (Safety Lead-in)

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End point title

Number of participants with any unsolicited adverse events (AEs), including all serious adverse events (SAEs), AEs leading to withdrawal and AEs of special interest (AESIs) in study Phase I (Safety Lead-in) ^[9] ^[10]

End point description

Unsolicited AEs includes any AE reported in addition to those solicited during the clinical study. Any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires or prolongs hospitalization, results in disability/incapacity and is a congenital anomaly/birth defect in a subject’s offspring. AESIs are predefined (serious or non-serious) AEs of scientific and medical concern specific to the product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate, because such an event might warrant further investigation to characterize and understand it. A participant was considered withdrawn if no study procedures occurred, and no follow-up or further information has been collected from the date of withdrawal or last contact. Analysis was performed on the Phase I ES.

End point type

Primary

End point timeframe

During the 30 days (including the day of vaccination) following vaccination at Day 1

Notes
[9] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[10] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase I (Safety Lead-in) groups.

End point values	ABCWY low dose Group	Placebo low dose Group	ABCWY high dose Group	Placebo high dose Group
Number of subjects analysed	12	4	13	3
Units: Participants	4	1	8	1

No statistical analyses for this end point

Primary: Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase I (Safety Lead-in)

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End point title

Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase I (Safety Lead-in) ^[11] ^[12]

End point description

A SAEs is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity and is a congenital anomaly/birth defect in the offspring of a study subject. AESIs are predefined (serious or non-serious) AEs of scientific and medical concern specific to the product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate, because such an event might warrant further investigation to characterize and understand it. A participant was considered withdrawn if no study procedures occurred, and no follow-up or further information has been collected from the date of withdrawal or last contact. Analysis was performed on the Phase I ES.

End point type

Primary

End point timeframe

Throughout the Phase 1 study period (Day 1 through Day 211)

Notes
[11] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase I (Safety Lead-in) groups.

End point values	ABCWY low dose Group	Placebo low dose Group	ABCWY high dose Group	Placebo high dose Group
Number of subjects analysed	12	4	13	3
Units: Participants
SAEs (N=12, 4, 13, 3)	0	0	0	0
AEs leading to withdrawal (N=12, 4, 13, 3)	0	0	0	0
AESIs (N=12, 4, 13, 3)	0	0	0	0

No statistical analyses for this end point

Primary: Number of participants with any unsolicited AEs, including all SAEs, AEs leading to withdrawal and AESIs in study Phase I (Safety Lead-in)

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End point title

Number of participants with any unsolicited AEs, including all SAEs, AEs leading to withdrawal and AESIs in study Phase I (Safety Lead-in) ^[13] ^[14]

End point description

Unsolicited AEs includes any AE reported in addition to those solicited during the clinical study. Any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as unsolicited AE. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires or prolongs hospitalization, results in disability/incapacity and is a congenital anomaly/birth defect in a subject’s offspring. AESIs are predefined (serious or non-serious) AEs of scientific and medical concern specific to the product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate, because such an event might warrant further investigation to characterize and understand it. A participant was considered withdrawn if no study procedures occurred, and no follow-up or further information has been collected from the date of withdrawal or last contact. Analysis was performed on the Phase I ES.

End point type

Primary

End point timeframe

During the 30 days (including the day of vaccination) following vaccination at Day 31

Notes
[13] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase I (Safety Lead-in) groups.

End point values	ABCWY low dose Group	Placebo low dose Group	ABCWY high dose Group	Placebo high dose Group
Number of subjects analysed	12	4	11	3
Units: Participants	6	1	7	0

No statistical analyses for this end point

Primary: Number of participants with change from baseline in haematological and biochemical laboratory values, in study Phase I (Safety Lead-in)

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End point title

Number of participants with change from baseline in haematological and biochemical laboratory values, in study Phase I (Safety Lead-in) ^[15] ^[16]

End point description

The safety laboratory data included haematological parameters [basophils, eosinophils, Erythrocytes, hemoglobin (Hb), leukocytes, lymphocytes, monocytes, platelets, and neutrophils], and chemical parameters (Alanine Aminotransferase [ALT], Aspartate Aminotransferase [AST], Creatinine) Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Analysis was performed on the Phase I ES.

End point type

Primary

End point timeframe

At Day (D) 8 (7 days after the first vaccination)

Notes
[15] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[16] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase I (Safety Lead-in) groups.

End point values	ABCWY low dose Group	Placebo low dose Group	ABCWY high dose Group	Placebo high dose Group
Number of subjects analysed	12	4	13	3
Units: Participants
Basophils\|Below(baseline)-below(D 8)N=12,4,13,3	0	0	0	0
Eosinophils\|Below(baseline)-below(D8)N=12,4,13,3	0	0	0	0
Erythrocytes\|Below(baseline)-below(D8)N=12,4,13,3	0	0	0	0
Hb\|Below(baseline)-below(D8)N=12,4,13,3	0	0	0	0
Leukocytes\|Below(baseline)-below(D8)N=12,4,13,3	0	0	0	0
Lymphocytes\|Below(baseline)-below(D8)N=12,4,13,3	0	0	0	0
Monocytes\|Below(baseline)-below (D8)N=12,4,13,3	0	0	0	0
Neutrophils\|Below(baseline)-below(D8)N=12,4,13,3	0	0	0	0
Platelets\|Below(baseline)-below(D 8)N=12,4,13,3	0	0	0	0
ALT\|Below(baseline)-below(D8)N=12,4,13,3	0	0	0	0
AST\|Below(baseline)-below (D8)N=12,4,13,3	0	0	0	0
Creatinine\|Below(baseline)-below (D8)N=12,4,13,3	0	0	0	0
Basophils\|Within(baseline)-below(D 8)N=12,4,13,3	0	0	0	0
Eosinophils\|Within(baseline)-below(D8)N=12,4,13,3	0	0	0	0
Erythrocyte\|Within(baseline)-below (D8)N=12,4,13,3	0	0	0	0
Hb\|Within(baseline)-below (D8)N=12,4,13,3	0	0	2	0
Leukocytes\|Within(baseline)-below (D8)N=12,4,13,3	0	0	0	0
Lymphocytes\|Within(baseline)-below (D8)N=12,4,13,3	0	0	0	0
Monocytes\|Within(baseline)-below (D8)N=12,4,13,3	0	0	0	0
Neutrophils\|Within(baseline)-below (D8)N=12,4,13,3	0	1	0	0
Platelets\|Within(baseline)-below(D8)N=12,4,13,3	0	0	0	0
ALT\|Within(baseline)-below(D8)N=12,4,13,3	0	0	0	0
AST\|Within(baseline)-below(D8)N=12,4,13,3	0	0	0	0
Creatinine\|Within(baseline)-below (D8)N=12,4,13,3	0	0	0	0
Basophils\|Above(baseline)-below (D8)N=12,4,13,3	0	0	0	0
Eosinophils\|Above(baseline)-below(D8)N=12,4,13,3	0	0	0	0
Erythrocytes\|Above(baseline)-below(D8)N=12,4,13,3	0	0	0	0
Hb\|Above(baseline)-below(D8)N=12,4,13,3	0	0	0	0
Leukocytes\|Above(baseline)-below (D8)N=12,4,13,3	0	0	0	0
Lymphocytes\|Above(baseline)-below (D8)N=12,4,13,3	0	0	0	0
Monocytes\|Above(baseline)-below (D8)N=12,4,13,3	0	0	0	0
Neutrophils\|Above(baseline)-below (D8)N=12,4,13,3	0	0	0	0
Platelets\|Above(baseline)-below (D8)N=12,4,13,3	0	0	0	0
ALT\|Above(baseline)-below (D8)N=12,4,13,3	0	0	0	0
AST\|Above(baseline)-below (D8)N=12,4,13,3	0	0	0	0
Creatinine\|Above(baseline)-below (D8)N=12,4,13,3	0	0	0	0
Basophils\|Below(baseline)-within (D8)N=12,4,13,3	0	0	0	0
Eosinophil\|Below(baseline)-within(D8)N=12,4,13,3	0	0	0	0
Erythrocyte\|Below(baseline)-within (D8)N=12,4,13,3	0	0	1	0
Hb\|Below(baseline)-within (D8)N=12,4,13,3	0	0	0	0
Leukocytes\|Below(baseline)-within (D8)N=12,4,13,3	0	0	0	0
Lymphocytes\|Below(baseline)-within (D8)N=12,4,13,3	0	0	0	0
Monocytes\|Below(baseline)-within (D8)N=12,4,13,3	0	0	0	0
Neutrophils\|Below(baseline)-within (D8)N=12,4,13,3	0	0	1	0
Platelets\|Below(baseline)-within (D8)N=12,4,13,3	1	0	1	0
ALT\|Below(baseline)-within (D8)N=12,4,13,3	0	0	0	0
AST\|Below(baseline)-within (D8)N=12,4,13,3	0	0	0	0
Creatinine\|Below(baseline)-within (D8)N=12,4,13,3	0	0	1	0
Basophils\|Within(baseline)-within (D8)N=12,4,13,3	12	4	13	3
Eosinophil\|Within(baseline)-within(D8)N=12,4,13,3	11	4	13	3
Erythrocyte\|Within(baseline)-within(D8)N=12,4,13,3	12	4	12	3
Hb\|Within(baseline)-within (D8)N=12,4,13,3	12	4	11	3
Leukocytes\|Within(baseline)-within (D8)N=12,4,13,3	12	4	13	3
Lymphocytes\|Within(baseline)-within(D8)N=12,4,13,3	12	4	13	3
Monocytes\|Within(baseline)-within (D8)N=12,4,13,3	12	4	13	3
Neutrophils\|Within(baseline)-within(D8)N=12,4,13,3	12	3	12	3
Platelets\|Within(baseline)-within (D8)N=12,4,13,3	11	4	12	3
ALT\|Within(baseline)-within (D8)N=12,4,13,3	10	4	10	2
AST\|Within(baseline)-within (D8)N=12,4,13,3	12	4	12	2
Creatinine\|Within(baseline)-within (D8)N=12,4,13,3	12	3	12	2
Basophils\|Above(baseline)-within (D8)N=12,4,13,3	0	0	0	0
Eosinophil\|Above(baseline)-within(D8)N=12,4,13,3	0	0	0	0
Erythrocyte\|Above(baseline)-within (D8)N=12,4,13,3	0	0	0	0
Hb\|Above(baseline)-within (D8)N=12,4,13,3	0	0	0	0
Leukocytes\|Above(baseline)-within (D8)N=12,4,13,3	0	0	0	0
Lymphocytes\|Above(baseline)-within (D8)N=12,4,13,3	0	0	0	0
Monocytes\|Above(baseline)-within (D8)N=12,4,13,3	0	0	0	0
Neutrophils\|Above(baseline)-within (D8)N=12,4,13,3	0	0	0	0
Platelets\|Above(baseline)-within (D8)N=12,4,13,3	0	0	0	0
ALT\|Above(baseline)-within (D8)N=12,4,13,3	1	0	0	0
AST\|Above(baseline)-within (D8)N=12,4,13,3	0	0	0	0
Creatinine\|Above(baseline)-within (D8)N=12,4,13,3	0	1	0	1
Basophils\|Below(baseline)- above(D8)N=12,4,13,3	0	0	0	0
Eosinophil\|Below(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Erythrocytes\|Below(baseline)- above(D8)N=12,4,13,3	0	0	0	0
Hb\|Below(baseline)- above(D8)N=12,4,13,3	0	0	0	0
Leukocytes\|Below(baseline)- above(D8)N=12,4,13,3	0	0	0	0
Lymphocytes\|Below(baseline)- above(D8)N=12,4,13,3	0	0	0	0
Monocytes\|Below(baseline)- above(D8)N=12,4,13,3	0	0	0	0
Neutrophils\|Below(baseline)- above(D8)N=12,4,13,3	0	0	0	0
Platelets\|Below(baseline)- above(D8)N=12,4,13,3	0	0	0	0
ALT\|Below(baseline)- above(D8)N=12,4,13,3	0	0	0	0
AST\|Below(baseline)- above(D8)N=12,4,13,3	0	0	0	0
Creatinine\|Below(baseline)- above(D8)N=12,4,13,3	0	0	0	0
Basophils\|Within(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Eosinophils\|Within (baseline)-above(D8)N=12,4,13,3	1	0	0	0
Erythrocyte\|Within(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Hb\|Within(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Leukocytes\|Within(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Lymphocytes\|Within(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Monocytes\|Within(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Neutrophils\|Within(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Platelets\|Within(baseline)-above(D8)N=12,4,13,3	0	0	0	0
ALT\|Within(baseline)-above(D8)N=12,4,13,3	0	0	1	1
AST\|Within(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Creatinine\|Within(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Basophils\|Above(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Eosinophils\|Above(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Erythrocytes\|Above(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Hemoglobin\|Above(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Leukocytes\|Above(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Lymphocytes\|Above(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Monocytes\|Above(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Neutrophils\|Above(baseline)-above(D8)N=12,4,13,3	0	0	0	0
Platelets\|Above(baseline)-above(D8)N=12,4,13,3	0	0	0	0
ALT\|Above(baseline)-above(D8)N=12,4,13,3	1	0	2	0
AST\|Above(baseline)-above(D8)N=12,4,13,3	0	0	1	1
Creatinine\|Above(baseline)-above(D8)N=12,4,13,3	0	0	0	0

No statistical analyses for this end point

Primary: Number of Participants with Clinically Significant Haematological and Biochemical Laboratory Values, in study Phase I (Safety Lead-in)

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End point title

Number of Participants with Clinically Significant Haematological and Biochemical Laboratory Values, in study Phase I (Safety Lead-in) ^[17] ^[18]

End point description

Clinical laboratory testing included hematological and biochemical laboratory values. Any abnormal laboratory test result (e.g., in hematology or clinical chemistry) that was deemed clinically significant by the investigator’s medical and scientific judgment, and not related to an underlying disease, was reported as an unsolicited adverse event (AE) unless it was considered by the investigator to be more severe than expected for the participant’s condition. The safety laboratory data included hematological parameters (basophils, eosinophils, erythrocytes, hemoglobin, leukocytes, lymphocytes, monocytes, platelets, and neutrophils) and chemical parameters (Alanine Aminotransferase [ALT], Aspartate Aminotransferase [AST], and creatinine).

End point type

Primary

End point timeframe

At Day 8 (7 days after the first vaccination)

Notes
[17] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[18] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase I (Safety Lead-in) groups.

End point values	ABCWY low dose Group	Placebo low dose Group	ABCWY high dose Group	Placebo high dose Group
Number of subjects analysed	12	4	13	3
Units: Participants
Basophils (N=12,4,13,3)	0	0	0	0
Eosinophils (N=12,4,13,3)	0	0	0	0
Erythrocytes (N=12,4,13,3)	0	0	0	0
Hemoglobin (N=12,4,13,3)	0	0	0	0
Leukocytes (N=12,4,13,3)	0	0	0	0
Lymphocytes (N=12,4,13,3)	0	0	0	0
Monocytes (N=12,4,13,3)	0	0	0	0
Neutrophils (N=12,4,13,3)	0	0	0	0
Platelets (N=12,4,13,3)	0	0	0	0
ALT (N=12,4,13,3)	0	0	0	0
AST (N=12,4,13,3)	0	0	0	0
Creatinine (N=12,4,13,3)	0	0	0	0

No statistical analyses for this end point

Primary: Percentage of blood samples with bactericidal serum activity using enc-hSBA against a panel of 110 randomly selected endemic US N. meningitidis serogroup B invasive disease strains at study Phase II (Formulation and Schedule-finding)

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End point title

Percentage of blood samples with bactericidal serum activity using enc-hSBA against a panel of 110 randomly selected endemic US N. meningitidis serogroup B invasive disease strains at study Phase II (Formulation and Schedule-finding) ^[19]

End point description

The effectiveness of the MenABCWY-2Gen (low & high dose) vaccine when administered at 0,2- or 0,6-months schedule compared to MenB vaccine administered at 0,6-months schedule, against a panel of 110 randomly selected endemic N. meningitidis serogroup B strains is measured in terms of percentage of samples with bactericidal activity using endogenous complement human Serum Bactericidal Assay (enc-hSBA), which provides a qualitative assessment (yes/no) of the presence of sufficient bactericidal antibodies in human sera to kill a meningococcal strain at a specific dilution of 1:4.

End point type

Primary

End point timeframe

At Day 211 (1 month after the last vaccination)

Notes
[19] - 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: As specified in the Protocol, the analysis assesses the immune response to the MenABCWY-2Gen and Men B vaccine against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	230 ^[20]	177 ^[21]	235 ^[22]	189 ^[23]	194 ^[24]
Units: Percentage of blood Samples
number (not applicable)
Number Analyzed	91.0	86.2	91.0	88.4	86.4

Notes
[20] - Number of Samples Analyzed:6714
[21] - Number of Samples Analyzed:5383
[22] - Number of Samples Analyzed:7063
[23] - Number of Samples Analyzed:5540,
[24] - Number of Samples Analyzed:5620

Statistical Analysis 1

Statistical analysis description

To demonstrate the superiority of the effectiveness of the MenABCWY-2Gen vaccine (low dose) when administered at 0,6-months schedule, compared to the MenB vaccine administered at 0,6-months schedule.

Comparison groups

ABCWY low dose_06 Group v Control Group

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

^[25]

Method

Parameter type

Difference in percentage

Point estimate

4.67

Confidence interval

level

97.5%

sides

2-sided

lower limit

3.38

upper limit

5.97

Notes
[25] - Superiority was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of samples with bactericidal serum activity is above 5% between the ABCWY low dose_06 group compared to the Control group at 1 month after the last vaccination.

Statistical Analysis 2

Statistical analysis description

To demonstrate the superiority of the effectiveness of the MenABCWY-2Gen vaccine (low dose) when administered at 0,2- months schedule, compared to the MenB vaccine administered at 0,6-months schedule.

Comparison groups

ABCWY low dose_02 Group v Control Group

Number of subjects included in analysis

371

Analysis specification

Pre-specified

Analysis type

^[26]

Method

Parameter type

Difference in percentage

Point estimate

-0.17

Confidence interval

level

97.5%

sides

2-sided

lower limit

-1.65

upper limit

1.3

Notes
[26] - Superiority was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of samples with bactericidal serum activity is above 5% between the ABCWY low dose_02 group compared to the Control group at 1 month after the last vaccination.

Statistical Analysis 3

Statistical analysis description

To demonstrate the superiority of the effectiveness of the MenABCWY-2Gen vaccine (high dose) when administered at 0,6- months schedule, compared to the MenB vaccine administered at 0,6-months schedule.

Comparison groups

ABCWY high dose_06 Group v Control Group

Number of subjects included in analysis

429

Analysis specification

Pre-specified

Analysis type

^[27]

Method

Parameter type

Difference in percentage

Point estimate

4.6

Confidence interval

level

97.5%

sides

2-sided

lower limit

3.33

upper limit

5.89

Notes
[27] - Superiority was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of samples with bactericidal serum activity is above 5% between the ABCWY high dose_06 group compared to the Control group at 1 month after the last vaccination.

Statistical Analysis 4

Statistical analysis description

To demonstrate the superiority of the effectiveness of the MenABCWY-2Gen vaccine (high dose) when administered at 0,2- months schedule, compared to the MenB vaccine administered at 0,6-months schedule.

Comparison groups

ABCWY high dose_02 Group v Control Group

Number of subjects included in analysis

383

Analysis specification

Pre-specified

Analysis type

^[28]

Method

Parameter type

Difference in percentage

Point estimate

2.01

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.6

upper limit

3.42

Notes
[28] - Superiority was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of samples with bactericidal serum activity is above 5% between the ABCWY high dose_02 group compared to the Control group at 1 month after the last vaccination.

Primary: Number of participants with a 4-fold rise in hSBA titers against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding) At Day 211

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End point title

Number of participants with a 4-fold rise in hSBA titers against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding) At Day 211 ^[29]

End point description

The immune response to the MenABCWY-2Gen (low and high dose) vaccine when administered at 0,2- or 0,6-months schedule compared to MenACWY vaccine (single dose), relative to day 1 in the ABCWY and control groups (0, 6 month schedule) and day 31 in ABCWY (0, 2 month schedule) is measured in terms of number of participants achieving a 4-fold rise in hSBA titers against serogroups A, C, W and Y. The 4-fold rise is defined as: -a post-vaccination hSBA titer ≥ 16 for participants with a pre-vaccination hSBA titer < 4, -a post-vaccination hSBA titer ≥ 4 times the lower limit of quantitation (LLOQ) for participants with a pre-vaccination hSBA titer ≥LOD but <LLOQ, and. -a post-vaccination hSBA titer ≥ 4 times the pre-vaccination hSBA titer for participants with a pre-vaccination hSBA titer ≥LLOQ.

End point type

Primary

End point timeframe

At Day 211 for ABCWY groups (1 month after the last MenABCWY-2Gen vaccination) and at Day 31 for Control group (1 month after the last MenACWY vaccination)

Notes
[29] - 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: As specified in the Protocol, the analysis assesses the immune response to the MenABCWY-2Gen and Men B vaccine against serogroup A, C, W and Y in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	135	116	147	118	159
Units: Participants
Men A (N= 132,109,140,112,156)	125	105	136	107	143
Men C (N=135,113,146,118,152)	129	107	132	111	92
Men W (N=134,114,143,116,156)	129	108	135	105	102
Men Y (N=131,116,147,115,159)	122	102	131	100	95

Statistical Analysis 3

Statistical analysis description

To demonstrate the immunological non-inferiority of the MenABCWY-2Gen vaccine (high dose) administered at 0,6-months schedule compared to the MenACWY vaccine administered at month 0 in the control group (Men A).

Comparison groups

ABCWY high dose_06 Group v Control Group

Number of subjects included in analysis

306

Analysis specification

Pre-specified

Analysis type

^[30]

Method

Parameter type

Difference in percentage

Point estimate

5.48

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.71

upper limit

12.25

Notes
[30] - NI was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the last MenABCWY-2Gen vaccination in the ABCWY high dose_06 group compared to the MenACWY vaccination in the Control group.

Statistical Analysis 2

Statistical analysis description

To demonstrate the immunological non-inferiority of the MenABCWY-2Gen vaccine (low dose) administered at 0,2-months schedule compared to the MenACWY vaccine administered at month 0 in the control group (Men A).

Comparison groups

ABCWY low dose_02 Group v Control Group

Number of subjects included in analysis

275

Analysis specification

Pre-specified

Analysis type

^[31]

Method

Parameter type

Difference in percentage

Point estimate

4.66

Confidence interval

level

97.5%

sides

2-sided

lower limit

-2.71

upper limit

11.64

Notes
[31] - NI was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the last MenABCWY-2Gen vaccination in the ABCWY low dose_02 group compared to the MenACWY vaccination in the Control group.

Statistical Analysis 1

Statistical analysis description

To demonstrate the immunological non-inferiority of the MenABCWY-2Gen vaccine (low dose) administered at 0,6-months schedule compared to the MenACWY vaccine administered at month 0 in the control group (Men A).

Comparison groups

ABCWY low dose_06 Group v Control Group

Number of subjects included in analysis

294

Analysis specification

Pre-specified

Analysis type

^[32]

Method

Parameter type

Difference in percentage

Point estimate

3.03

Confidence interval

level

97.5%

sides

2-sided

lower limit

-4.21

upper limit

10.17

Notes
[32] - Non-inferiority (NI) was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the last MenABCWY-2Gen vaccination in the ABCWY low dose_06 group compared to the MenACWY vaccination in the Control group.

Statistical Analysis 4

Statistical analysis description

To demonstrate the immunological non-inferiority of the MenABCWY-2Gen vaccine (high dose) administered at 0,2-months schedule compared to the MenACWY vaccine administered at month 0 in the control group (Men A).

Comparison groups

ABCWY high dose_02 Group v Control Group

Number of subjects included in analysis

277

Analysis specification

Pre-specified

Analysis type

^[33]

Method

Parameter type

Difference in percentage

Point estimate

3.87

Confidence interval

level

97.5%

sides

2-sided

lower limit

-3.7

upper limit

10.97

Notes
[33] - NI was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the last MenABCWY-2Gen vaccination in the ABCWY high dose_02 group compared to the MenACWY vaccination in the Control group.

Statistical Analysis 7

Statistical analysis description

Comparison groups

ABCWY high dose_06 Group v Control Group

Number of subjects included in analysis

306

Analysis specification

Pre-specified

Analysis type

^[34]

Method

Parameter type

Difference in percentage

Point estimate

29.88

Confidence interval

level

97.5%

sides

2-sided

lower limit

19.26

upper limit

40.19

Notes
[34] - NI was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the last MenABCWY-2Gen vaccination in the ABCWY high dose_06 group compared to the MenACWY vaccination in the Control group.

Statistical Analysis 6

Statistical analysis description

Comparison groups

ABCWY low dose_02 Group v Control Group

Number of subjects included in analysis

275

Analysis specification

Pre-specified

Analysis type

^[35]

Method

Parameter type

Difference in percentage

Point estimate

34.16

Confidence interval

level

97.5%

sides

2-sided

lower limit

23.76

upper limit

44.1

Notes
[35] - NI was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the last MenABCWY-2Gen vaccination in the ABCWY low dose_02 group compared to the MenACWY vaccination in the Control group.

Statistical Analysis 5

Statistical analysis description

Comparison groups

ABCWY low dose_06 Group v Control Group

Number of subjects included in analysis

294

Analysis specification

Pre-specified

Analysis type

^[36]

Method

Parameter type

Difference in percentage

Point estimate

35.03

Confidence interval

level

97.5%

sides

2-sided

lower limit

25.22

upper limit

44.75

Notes
[36] - Non-inferiority (NI) was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the last MenABCWY-2Gen vaccination in the ABCWY low dose_06 group compared to the MenACWY vaccination in the Control group.

Statistical Analysis 8

Statistical analysis description

Comparison groups

ABCWY high dose_02 Group v Control Group

Number of subjects included in analysis

277

Analysis specification

Pre-specified

Analysis type

^[37]

Method

Parameter type

Difference in percentage

Point estimate

33.54

Confidence interval

level

97.5%

sides

2-sided

lower limit

23.09

upper limit

43.54

Notes
[37] - NI was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the last MenABCWY-2Gen vaccination in the ABCWY high dose_02 group compared to the MenACWY vaccination in the Control group.

Statistical Analysis 11

Statistical analysis description

Comparison groups

ABCWY high dose_06 Group v Control Group

Number of subjects included in analysis

306

Analysis specification

Pre-specified

Analysis type

^[38]

Method

Parameter type

Difference in percentage

Point estimate

29.02

Confidence interval

level

97.5%

sides

2-sided

lower limit

19.42

upper limit

38.67

Notes
[38] - NI was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the last MenABCWY-2Gen vaccination in the ABCWY high dose_06 group compared to the MenACWY vaccination in the Control group.

Statistical Analysis 10

Statistical analysis description

Comparison groups

ABCWY low dose_02 Group v Control Group

Number of subjects included in analysis

275

Analysis specification

Pre-specified

Analysis type

^[39]

Method

Parameter type

Difference in percentage

Point estimate

29.35

Confidence interval

level

97.5%

sides

2-sided

lower limit

19.31

upper limit

39.08

Notes
[39] - NI was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the MenABCWY-2Gen MenACWY vaccination in the ABCWY low dose_02 group compared to the MenACWY vaccination in the Control group.

Statistical Analysis 9

Statistical analysis description

Comparison groups

ABCWY low dose_06 Group v Control Group

Number of subjects included in analysis

294

Analysis specification

Pre-specified

Analysis type

^[40]

Method

Parameter type

Difference in percentage

Point estimate

30.88

Confidence interval

level

97.5%

sides

2-sided

lower limit

21.61

upper limit

40.32

Notes
[40] - Non-inferiority (NI) was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the last MenABCWY-2Gen vaccination in the ABCWY low dose_06 group compared to the MenACWY vaccination in the Control group.

Statistical Analysis 12

Statistical analysis description

Comparison groups

ABCWY high dose_02 Group v Control Group

Number of subjects included in analysis

277

Analysis specification

Pre-specified

Analysis type

^[41]

Method

Parameter type

Difference in percentage

Point estimate

25.13

Confidence interval

level

97.5%

sides

2-sided

lower limit

14.2

upper limit

35.45

Notes
[41] - NI was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the last MenABCWY-2Gen vaccination in the ABCWY high dose_02 group compared to the MenACWY vaccination in the Control group.

Statistical Analysis 15

Statistical analysis description

Comparison groups

ABCWY high dose_06 Group v Control Group

Number of subjects included in analysis

306

Analysis specification

Pre-specified

Analysis type

^[42]

Method

Parameter type

Difference in percentage

Point estimate

29.37

Confidence interval

level

97.5%

sides

2-sided

lower limit

18.67

upper limit

39.63

Notes
[42] - NI was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the last MenABCWY-2Gen vaccination in the ABCWY high dose_06 group compared to the MenACWY vaccination in the Control group.

Statistical Analysis 14

Statistical analysis description

Comparison groups

ABCWY low dose_02 Group v Control Group

Number of subjects included in analysis

275

Analysis specification

Pre-specified

Analysis type

^[43]

Method

Parameter type

Difference in percentage

Point estimate

28.18

Confidence interval

level

97.5%

sides

2-sided

lower limit

16.61

upper limit

38.86

Notes
[43] - NI was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the last MenABCWY-2Gen vaccination in the ABCWY low dose_02 group compared to the MenACWY vaccination in the Control group.

Statistical Analysis 13

Statistical analysis description

Comparison groups

ABCWY low dose_06 Group v Control Group

Number of subjects included in analysis

294

Analysis specification

Pre-specified

Analysis type

^[44]

Method

Parameter type

Difference in percentage

Point estimate

33.38

Confidence interval

level

97.5%

sides

2-sided

lower limit

23.08

upper limit

43.26

Notes
[44] - Non-inferiority (NI) was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the last MenABCWY-2Gen vaccination in the ABCWY low dose_06 group compared to the MenACWY vaccination in the Control group.

Statistical Analysis 16

Statistical analysis description

Comparison groups

ABCWY high dose_02 Group v Control Group

Number of subjects included in analysis

277

Analysis specification

Pre-specified

Analysis type

^[45]

Method

Parameter type

Difference in percentage

Point estimate

27.21

Confidence interval

level

97.5%

sides

2-sided

lower limit

15.46

upper limit

38.02

Notes
[45] - NI was to be demonstrated if the lower limit of the 2-sided 97.5% CI for the difference in percentages of participants achieving a 4-fold rise in hSBA titres is above -10% at 1 month after the last MenABCWY-2Gen vaccination in the ABCWY high dose_02 group compared to the MenACWY vaccination in the Control group.

Primary: Number of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding) at Day 1

Top of page

End point title

Number of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding) at Day 1 ^[46] ^[47]

End point description

Assessed solicited administration site events included injection site pain, erythema (redness), swelling and induration. Any = occurrence of the event regardless of intensity grade.

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 1

Notes
[46] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[47] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen and Men B vaccine in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control (MenACWY) Group	Control (MenB_06) Group
Number of subjects analysed	239	181	238	194	178	178
Units: Participants
Erythema (N=239, 181, 238, 194 178, 178)	32	0	29	0	6	13
Induration (N=239, 181, 238, 194 178, 178)	22	1	30	1	6	11
Pain (N=239, 181, 238, 194, 178 ,178)	217	39	220	42	76	145
Swelling (N=239, 181, 238, 194 178,178)	34	0	32	0	4	8

No statistical analyses for this end point

Primary: Number of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding) at Day 121

Top of page

End point title

Number of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding) at Day 121 ^[48] ^[49]

End point description

Assessed solicited administration site events included injection site pain, erythema (redness), swelling and induration. Any = occurrence of the event regardless of intensity grade.

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 121

Notes
[48] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[49] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen and Men B vaccine in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group
Number of subjects analysed	220	170	224	182
Units: Participants
Erythema (N=220,170,224, 182,0,0)	0	17	0	14
Induration (N=220,170,224, 182,0,0)	1	15	0	18
Pain (N=220,170,224,182,0,0)	28	143	26	153
Swelling (N=220,170,224,182,0,0)	1	21	0	21

No statistical analyses for this end point

Primary: Number of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding) at Day 181

Top of page

End point title

Number of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding) at Day 181 ^[50] ^[51]

End point description

Assessed solicited administration site events included injection site pain, erythema (redness), swelling and induration. Any = occurrence of the event regardless of intensity grade.

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 181

Notes
[50] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[51] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen and Men B vaccine in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control (MenB_06) Group
Number of subjects analysed	216	163	220	176	187
Units: Participants
Erythema(N=216,163,220,176,0,187)	23	15	21	17	18
Induration(N=216,163,220,176,0,187)	18	17	20	15	16
Pain(N=216,163,220,176,0,187)	191	134	187	146	154
Swelling(N=216,163,220,176,0,187)	27	25	27	23	23

No statistical analyses for this end point

Primary: Number of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding) at Day 1

Top of page

End point title

Number of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding) at Day 1 ^[52] ^[53]

End point description

Assessed solicited systemic events included fever (temperature ≥ 38.0°C), nausea, fatigue, myalgia, arthralgia and headache. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 1

Notes
[52] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[53] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen and Men B vaccine in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	239	181	238	194	197
Units: Participants
Arthralgia (N=239, 181, 238, 194,197)	17	6	16	6	11
Fatigue (N=239, 181, 238, 194,197)	123	60	109	73	91
Headache (N=239, 181, 238, 194,197)	92	60	102	63	78
Myalgia (N=239, 181, 238, 194,197)	28	6	23	9	18
Nausea (N=239, 181, 238, 194,197)	30	16	23	13	19
Fever (N=239, 181, 238, 194,197)	4	2	8	1	8

No statistical analyses for this end point

Primary: Number of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding) at Day 121

Top of page

End point title

Number of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding) at Day 121 ^[54] ^[55]

End point description

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 121

Notes
[54] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[55] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen and Men B vaccine in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	220	170	224	182	0 ^[56]
Units: Participants
Arthralgia(N=220, 170, 224, 182,0)	2	13	4	8
Fatigue(N=220, 170, 224, 182,0)	46	72	42	68
Headache(N=220, 170, 224, 182,0)	46	56	47	58
Myalgia(N=220, 170, 224, 182,0)	4	21	8	23
Nausea(N=220, 170, 224, 182,0)	13	8	14	19
Fever (N=220, 170, 224, 182,0)	1	5	2	5

Notes
[56] - At Day 121 no participants received vaccination.

No statistical analyses for this end point

Primary: Number of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding) at Day 181

Top of page

End point title

Number of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding) at Day 181 ^[57] ^[58]

End point description

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 181

Notes
[57] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[58] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen and Men B vaccine in in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	216	163	220	176	187
Units: Participants
Arthralgia(N=216,163,220,176,187)	14	8	22	13	6
Fatigue(N=216,163,220,176,187)	86	59	98	62	75
Headache(N=216,163,220,176,187)	75	59	90	59	64
Myalgia(N=216,163,220,176,187)	26	18	36	20	33
Nausea(N=216,163,220,176,187)	22	11	31	12	15
Fever(N=216,163,220,176,187)	4	6	8	3	5

No statistical analyses for this end point

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding) at Day 1

Top of page

End point title

Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding) at Day 1 ^[59] ^[60]

End point description

Unsolicited AEs includes any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires or prolongs hospitalization, results in disability/incapacity and is a congenital anomaly/birth defect in a subject’s offspring. AESIs are predefined (serious or non-serious) AEs of scientific and medical concern specific to the product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate, because such an event might warrant further investigation to characterize and understand it. A participant was considered withdrawn if no study procedures occurred, and no follow-up or further information has been collected from the date of withdrawal or last contact.

End point type

Primary

End point timeframe

During the 30 days (including the day of vaccination) following vaccination at Day 1

Notes
[59] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[60] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen and Men B vaccine in in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	239	181	238	194	197
Units: Participants	51	34	52	35	27

No statistical analyses for this end point

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding) at Day 121

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End point title

Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding) at Day 121 ^[61] ^[62]

End point description

End point type

Primary

End point timeframe

During the 30 days (including the day of vaccination) following vaccination at Day 121

Notes
[61] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[62] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen and Men B vaccine in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	220	170	224	182	0 ^[63]
Units: Participants	16	19	22	18

Notes
[63] - At Day 121 no participant received vaccination in Control group.

No statistical analyses for this end point

Primary: Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Formulation and Schedule-Finding)

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End point title

Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Formulation and Schedule-Finding) ^[64] ^[65]

End point description

End point type

Primary

End point timeframe

Throughout the Phase II FSF study period (Day 1 through Day 541)

Notes
[64] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[65] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen and Men B vaccine in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	239	181	238	194	197
Units: Participants
SAEs(N= 239,181,238,194,197)	9	7	4	4	2
AEs leading to withdrawal(N= 239,181,238,194,197)	1	0	1	1	0
AESIs(N=239,181,238,194,197)	4	1	2	0	1

No statistical analyses for this end point

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding) at Day 181

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End point title

Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding) at Day 181 ^[66] ^[67]

End point description

End point type

Primary

End point timeframe

During the 30 days (including the day of vaccination) following vaccination at Day 181

Notes
[66] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[67] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen and Men B vaccine in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	216	163	220	176	187
Units: Participants	28	24	42	27	28

No statistical analyses for this end point

Primary: Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 1

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End point title

Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 1 ^[68] ^[69]

End point description

Assessed solicited administration site events included injection site pain, erythema (redness), swelling and induration. Any = occurrence of the event regardless of intensity grade.

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 1

Notes
[68] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[69] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen in study Phase II (Sourcing) groups.

End point values	ABCWY low dose_01 Group	ABCWY high dose_01 Group	ABCWY low doseS_02 Group	ABCWY high doseS_02 Group	ABCWY low doseS_06 Group	ABCWY high doseS_06 Group
Number of subjects analysed	54	53	62	62	62	63
Units: Participants
Erythema (N=54,53,62,62,62,63)	0	0	0	0	0	0
Induration(N=54,53,62,62,62,63)	0	0	0	0	0	0
Pain(N=54,53,62,62,62,63)	2	4	3	1	1	2
Swelling(N=54,53,62,62,62,63)	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 31

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End point title

Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 31 ^[70] ^[71]

End point description

Assessed solicited administration site events included injection site pain, erythema (redness), swelling and induration. Any = occurrence of the event regardless of intensity grade.

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 31

Notes
[70] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[71] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase II (Sourcing) groups.

End point values	ABCWY low dose_01 Group	ABCWY high dose_01 Group
Number of subjects analysed	50	47
Units: Participants
Erythema (N=50,47)	0	1
Induration(N=50,47)	0	0
Pain(N=50,47)	0	1
Swelling(N=50,47)	0	1

No statistical analyses for this end point

Primary: Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 61

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End point title

Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 61 ^[72] ^[73]

End point description

Assessed solicited administration site events included injection site pain, erythema (redness), swelling and induration. Any = occurrence of the event regardless of intensity grade.

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 61

Notes
[72] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[73] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase II (Sourcing) groups.

End point values	ABCWY low doseS_02 Group	ABCWY high doseS_02 Group
Number of subjects analysed	58	60
Units: Participants
Erythema (N=58,60)	0	0
Induration(N=58,60)	0	0
Pain(N=58,60)	2	3
Swelling(N=58,60)	0	0

No statistical analyses for this end point

Primary: Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 181

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End point title

Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 181 ^[74] ^[75]

End point description

Assessed solicited administration site events included injection site pain, erythema (redness), swelling and induration. Any = occurrence of the event regardless of intensity grade.

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 181

Notes
[74] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[75] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase II (Sourcing) groups.

End point values	ABCWY low doseS_06 Group	ABCWY high doseS_06 Group
Number of subjects analysed	60	55
Units: Participants
Erythema(N=60,55)	0	0
Induration(N=60,55)	0	0
Pain(N=60,55)	4	3
Swelling(N=60,55)	0	0

No statistical analyses for this end point

Primary: Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 1

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End point title

Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 1 ^[76] ^[77]

End point description

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 1

Notes
[76] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[77] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase II (Sourcing) groups.

End point values	ABCWY low dose_01 Group	ABCWY high dose_01 Group	ABCWY low doseS_02 Group	ABCWY high doseS_02 Group	ABCWY low doseS_06 Group	ABCWY high doseS_06 Group
Number of subjects analysed	54	53	62	62	62	63
Units: Participants
Arthralgia (N=54,53,62,62,62,63)	1	0	1	0	0	0
Fatigue (N=54,53,62,62,62,63)	2	1	2	0	0	1
Headache (N=54,53,62,62,62,63)	3	0	0	0	0	3
Myalgia (N=54,53,62,62,62,63)	1	0	1	0	0	1
Nausea (N=54,53,62,62,62,63)	2	1	0	0	1	0
Fever (N=54,53,62,62,62,63)	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 31

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End point title

Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 31 ^[78] ^[79]

End point description

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 31

Notes
[78] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[79] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase II (Sourcing) groups.

End point values	ABCWY low dose_01 Group	ABCWY high dose_01 Group
Number of subjects analysed	50	47
Units: Participants
Arthralgia (N=50,47)	0	0
Fatigue(N=50,47)	1	0
Headache(N=50,47)	0	3
Myalgia(N=50,47)	0	0
Nausea(N=50,47)	0	2
Fever (N=50,47)	0	0

No statistical analyses for this end point

Primary: Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 61

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End point title

Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 61 ^[80] ^[81]

End point description

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 61

Notes
[80] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[81] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase II (Sourcing) groups.

End point values	ABCWY low doseS_02 Group	ABCWY high doseS_02 Group
Number of subjects analysed	58	60
Units: Participants
Arthralgia(N=58,60)	0	0
Fatigue(N=58,60)	0	0
Headache(N=58,60)	0	0
Myalgia(N=58,60)	1	0
Nausea(N=58,60)	0	0
Fever (N=58,60)	0	0

No statistical analyses for this end point

Primary: Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 181

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End point title

Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 181 ^[82] ^[83]

End point description

End point type

Primary

End point timeframe

During the 7 days (including the day of vaccination) following vaccination at Day 181

Notes
[82] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[83] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase II (Sourcing) groups.

End point values	ABCWY low doseS_06 Group	ABCWY high doseS_06 Group
Number of subjects analysed	60	55
Units: Participants
Arthralgia(N=60,55)	0	0
Fatigue(N=60,55)	0	0
Headache(N=60,55)	0	0
Myalgia(N=60,55)	0	0
Nausea(N=60,55)	0	0
Fever (N=60,55)	0	0

No statistical analyses for this end point

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 1

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End point title

Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 1 ^[84] ^[85]

End point description

End point type

Primary

End point timeframe

During the 30 days (including the day of vaccination) following vaccination at Day 1

Notes
[84] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen in study Phase II (Sourcing) groups.
[85] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase II (Sourcing) groups.

End point values	ABCWY low dose_01 Group	ABCWY high dose_01 Group	ABCWY low doseS_02 Group	ABCWY high doseS_02 Group	ABCWY low doseS_06 Group	ABCWY high doseS_06 Group
Number of subjects analysed	54	53	62	62	62	63
Units: Participants	10	12	14	8	10	18

No statistical analyses for this end point

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 31

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End point title

Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 31 ^[86] ^[87]

End point description

End point type

Primary

End point timeframe

During the 30 days (including the day of vaccination) following vaccination at Day 31

Notes
[86] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[87] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase II (Sourcing) groups.

End point values	ABCWY low dose_01 Group	ABCWY high dose_01 Group
Number of subjects analysed	50	47
Units: Participants	11	16

No statistical analyses for this end point

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 61

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End point title

Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 61 ^[88] ^[89]

End point description

End point type

Primary

End point timeframe

During the 30 days (including the day of vaccination) following vaccination at Day 61

Notes
[88] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[89] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	ABCWY low doseS_02 Group	ABCWY high doseS_02 Group
Number of subjects analysed	58	60
Units: Participants	8	7

No statistical analyses for this end point

Primary: Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Sourcing) Day 1 through Day 211

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End point title

Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Sourcing) Day 1 through Day 211 ^[90] ^[91]

End point description

End point type

Primary

End point timeframe

Throughout the study period (Day 1 through Day 211)

Notes
[90] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[91] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase II (Sourcing) groups.

End point values	ABCWY low dose_01 Group	ABCWY high dose_01 Group
Number of subjects analysed	54	53
Units: Participants
SAEs(N=54,53)	0	0
AEs leading to withdrawal(N=54,53)	0	0
AESIs(N=54,53)	0	0

No statistical analyses for this end point

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 181

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End point title

Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 181 ^[92] ^[93]

End point description

End point type

Primary

End point timeframe

During the 30 days (including the day of vaccination) following vaccination at Day 181

Notes
[92] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[93] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase II (Sourcing) groups.

End point values	ABCWY low doseS_06 Group	ABCWY high doseS_06 Group
Number of subjects analysed	60	55
Units: Participants	10	9

No statistical analyses for this end point

Primary: Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Sourcing) Day 1 through Day 241

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End point title

Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Sourcing) Day 1 through Day 241 ^[94] ^[95]

End point description

End point type

Primary

End point timeframe

Throughout the study period (Day 1 through Day 241)

Notes
[94] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[95] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase II (Sourcing) groups.

End point values	ABCWY low doseS_02 Group	ABCWY high doseS_02 Group
Number of subjects analysed	62	62
Units: Participants
SAEs (N=62,62)	2	1
AEs leading to withdrawal(N=62,62)	1	0
AESIs(N=62,62)	0	1

No statistical analyses for this end point

Primary: Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Sourcing) Day 1 through Day 361

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End point title

Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Sourcing) Day 1 through Day 361 ^[96] ^[97]

End point description

End point type

Primary

End point timeframe

Throughout the study period (Day 1 through Day 361)

Notes
[96] - 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: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[97] - 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: As specified in the Protocol, the analysis assesses the Safety of the MenABCWY-2Gen vaccine in study Phase II (Sourcing) groups.

End point values	ABCWY low doseS_06 Group	ABCWY high doseS_06 Group
Number of subjects analysed	62	63
Units: Participants
SAEs(N=62,63)	0	4
AEs leading to withdrawal(N=62,63)	0	2
AESIs(N=62,63)	0	0

No statistical analyses for this end point

Secondary: Percentage of participants classified by percentages of serogroup B invasive disease strains killed using enc-hSBA in each participant in study Phase II (Formulation and Schedule-finding)

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End point title

Percentage of participants classified by percentages of serogroup B invasive disease strains killed using enc-hSBA in each participant in study Phase II (Formulation and Schedule-finding) ^[98]

End point description

The percentages of strains killed measured by enc-hSBA against a randomly selected panel of strains and the corresponding exact 2-sided 95% CIs based on Clopper-Pearson method is calculated in all groups at 1 month after the last vaccination of MenABCWY-2Gen (low and high dose) vaccine administered at 0,2 and 0,6-months schedule and of the MenB vaccine administered at 0,6-months schedule.

End point type

Secondary

End point timeframe

At Day 211 (1 month after the last vaccination)

Notes
[98] - 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: As specified in the Protocol, the analysis describes the distribution of participants by percentages of serogroup B invasive disease strains killed using enc-hSBA of the MenABCWY-2Gen and Men B vaccine in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	205	161	215	169	176
Units: Percentage of participants
number (confidence interval 95%)
>= 50% killed strains(N=205, 161, 215,169,176)	98.5 (95.8 to 99.7)	97.5 (93.8 to 99.3)	97.7 (94.7 to 99.2)	98.8 (95.8 to 99.9)	98.3 (95.1 to 99.6)
>=55% killed strains(N=205, 161, 215,169,176)	98.0 (95.1 to 99.5)	95.7 (91.2 to 98.2)	97.7 (94.7 to 99.2)	98.2 (94.9 to 99.6)	96.6 (92.7 to 98.7)
>=60% killed strains(N=205, 161, 215,169,176)	96.6 (93.1 to 98.6)	95.0 (90.4 to 97.8)	97.2 (94.0 to 99.0)	97.0 (93.2 to 99.0)	95.5 (91.2 to 98.0)
>=65% killed strains(N=205, 161, 215,169,176)	95.6 (91.8 to 98.0)	92.5 (87.3 to 96.1)	96.3 (92.8 to 98.4)	95.9 (91.7 to 98.3)	93.8 (89.1 to 96.8)
>=70% killed strains(N=205, 161, 215,169,176)	94.1 (90.0 to 96.9)	89.4 (83.6 to 93.7)	94.4 (90.5 to 97.1)	94.7 (90.1 to 97.5)	88.6 (83.0 to 92.9)
>=75% killed strains(N=205, 161, 215,169,176)	91.2 (86.5 to 94.7)	82.0 (75.2 to 87.6)	90.2 (85.5 to 93.9)	88.8 (83.0 to 93.1)	80.7 (74.1 to 86.2)
>=80% killed strains(N=205, 161, 215,169,176)	88.8 (83.6 to 92.8)	77.6 (70.4 to 83.8)	87.4 (82.3 to 91.6)	82.8 (76.3 to 88.2)	75.6 (68.5 to 81.7)
>=85% killed strains(N=205, 161, 215,169,176)	82.9 (77.1 to 87.8)	64.6 (56.7 to 72.0)	82.8 (77.1 to 87.6)	75.1 (67.9 to 81.5)	63.6 (56.1 to 70.7)
>=90% killed strains(N=205, 161, 215,169,176)	71.2 (64.5 to 77.3)	53.4 (45.4 to 61.3)	70.7 (64.1 to 76.7)	55.0 (47.2 to 62.7)	52.3 (44.6 to 59.8)
>=95% killed strains(N=205, 161, 215,169,176)	43.4 (36.5 to 50.5)	29.2 (22.3 to 36.9)	44.2 (37.4 to 51.1)	34.3 (27.2 to 42.0)	26.1 (19.8 to 33.3)
100% killed strains(N=205, 161, 215,169,176)	23.4 (17.8 to 29.8)	14.3 (9.3 to 20.7)	24.2 (18.6 to 30.5)	17.2 (11.8 to 23.7)	15.3 (10.4 to 21.5)

No statistical analyses for this end point

Secondary: Number of participants with hSBA titers ≥ LLOQ for each and all serogroup B indicator strains in study Phase II (Formulation and Schedule-finding)

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End point title

Number of participants with hSBA titers ≥ LLOQ for each and all serogroup B indicator strains in study Phase II (Formulation and Schedule-finding) ^[99]

End point description

The immune response to MenABCWY-2Gen (low and high dose) administered at 0,2 and 0,6-months schedule and MenB vaccine administered at 0,6-months schedule is evaluated by measuring bactericidal activity using a qualified AO hSBA against a standard panel of serogroup B indicator strains.

End point type

Secondary

End point timeframe

At Day 1 in ABCWY (0,6-months) and Control groups, Day 31 in ABCWY groups (0,2-months) and Day 211 in all study groups

Notes
[99] - 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: As specified in the Protocol, the analysis assesses the immune response to the MenABCWY-2Gen and Men B vaccine against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	209	173	214	189	194
Units: Participants
fHbp, Day 1 (N=209,214,0,0,194)	9	99999	10	99999	12
fHbp, Day 31 (N=0,0,173,189,0)	99999	14	99999	14	99999
fHbp, Day 211 (N=201,213,159,168,179)	175	112	184	137	137
NadA, Day 1 (201,211,0,0,189)	16	99999	23	99999	14
NadA, Day 31 (N=0,0,168,185,0)	99999	18	99999	14	99999
NadA, Day 211 (N=197,201,150,162,171)	175	120	169	131	147
NHBA, Day 1 (N=207,213,0,0,189)	43	99999	49	99999	40
NHBA, Day 31 (N=0,0,172,186,0)	99999	46	99999	44	99999
NHBA, Day 211 (199, 212, 155,167,177)	197	148	208	163	172
PorA, Day 1 (N=208,213,0,0,190)	7	99999	9	99999	8
PorA, Day 31 (N=0,0,161,173,0)	99999	8	99999	8	99999
PorA, Day 211 (N=200,214,153,169,178)	171	106	179	136	136
fHbp V1.13, Day 1 (N=203,209,0,0,184)	32	99999	31	99999	34
fHbp V1.13, Day 31 (N=0,0,171,184 ,0)	99999	31	99999	31	99999
fHbp V1.13, Day 211 (N=188,194,142,148,168)	162	97	169	111	130
fHbp V2, Day 1 (N=203,209,0,0,185)	8	99999	12	99999	13
fHbp V2, Day 31 (N=0 ,0,171,184,0)	99999	12	99999	21	99999
fHbp V2, Day 211 (N=195,204,150, 161,172)	186	128	192	144	72
fHbp V3, Day 1 (N=203,209,0,0,185)	15	99999	16	99999	11
fHbp V3, Day 31 (N=0,0,172,184,0)	99999	13	99999	21	99999
fHbp V3, Day 211(N=1 94,204,151,162,172)	155	95	168	107	41
Composite Response, Day 1 (N=194,206,0,0,179)	1	99999	1	99999	1
Composite Response,Day 31 (N=0,0,51,164,0)	99999	3	99999	3	99999
Composite Response,Day 211(N=180, 181,131,134,158)	121	60	126	73	30

No statistical analyses for this end point

Secondary: Number of participants with 4-fold rise in hSBA titers against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding)

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End point title

Number of participants with 4-fold rise in hSBA titers against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding) ^[100]

End point description

The immune response to MenABCWY-2Gen (low and high dose) vaccine when administered at 0,2- or 0,6-months schedule and to MenB vaccine administered at 0,6-months schedule, relative to day 1 in ABCWY (0,6 month schedule) and control groups and day 31 in ABCWY (0,2 month schedule) is measured in terms of number of participants achieving a 4-fold rise in hSBA titers against serogroup B indicator strains. The 4-fold rise is defined as: -a post-vaccination hSBA titer ≥ 16 for participants with a pre-vaccination hSBA titre < 4, -a post-vaccination hSBA titer ≥ 4 times the LLOQ for participants with a pre-vaccination hSBA titer ≥LOD but <LLOQ, and. -a post-vaccination hSBA titer ≥ 4 times the pre-vaccination hSBA titer for participants with a pre-vaccination hSBA titer ≥ LLOQ.

End point type

Secondary

End point timeframe

At Day 211 (1 month after the last vaccination)

Notes
[100] - 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: As specified in the Protocol, the analysis assesses the immune response to the MenABCWY-2Gen and Men B vaccine against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	178	155	193	168	177
Units: Participants
fHbp (N=78,155,193,168,177)	144	89	155	122	119
NadA (N=166,141,179,159,167)	135	104	133	113	135
NHBA (N=174,150,191,164,171)	162	122	175	136	139
PorA (N=175,140,193,157,172)	124	69	133	92	109
fHbp V1.13 (N=161,137,173,144,158)	126	82	140	92	97
fHbp V2 (N=168,144,182,157,163)	119	69	138	91	21
fHbp V3 (N=167,146,182,158,163)	92	62	120	77	7

No statistical analyses for this end point

Secondary: hSBA Geometric mean titers (GMTs) against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding)

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End point title

hSBA Geometric mean titers (GMTs) against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding) ^[101]

End point description

For each B strains, the GMTs are calculated with their associated 2-sided 95% CIs, by exponentiating the corresponding log-transformed means and their 95% CIs.

End point type

Secondary

End point timeframe

At Day 1 in ABCWY groups (0,6-months) and Control groups, Day 31 in ABCWY groups (0,2-months) and Day 211 in all study groups

Notes
[101] - 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: As specified in the Protocol, the analysis assesses the immune response to the MenABCWY-2Gen and Men B vaccine against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	209	173	214	189	194
Units: Titers
geometric mean (confidence interval 95%)
fHbp, Day 1(N=209,214,0,0,194)	8.7 (8.1 to 9.3)	99999 (99999 to 99999)	8.8 (8.2 to 9.4)	99999 (99999 to 99999)	8.9 (8.3 to 9.6)
fHbp, Day 31(N=0,0,173,189,0)	99999 (99999 to 99999)	9.4 (8.7 to 10.1)	99999 (99999 to 99999)	9.5 (8.8 to 10.2)	99999 (99999 to 99999)
fHbp, Day 211(N=201,213,159,168,179)	109.1 (86.0 to 138.3)	47.7 (37.0 to 61.5)	140.2 (110.9 to 177.4)	82.4 (63.8 to 106.4)	62.0 (48.3 to 79.5)
NadA, Day 1 (N=201,213,159,168,179)	7.8 (7.2 to 8.4)	99999 (99999 to 99999)	8.1 (7.5 to 8.7)	99999 (99999 to 99999)	7.7 (7.1 to 8.3)
NadA, Day 31(N=0,0,168,185,0)	99999 (99999 to 99999)	8.2 (7.6 to 8.9)	99999 (99999 to 99999)	8.1 (7.5 to 8.8)	99999 (99999 to 99999)
NadA, Day 211(N=197,201,150,162,171)	82.5 (64.8 to 105.1)	58.9 (45.2 to 76.7)	88.5 (69.5 to 112.7)	56.8 (43.7 to 73.8)	109.1 (84.5 to 140.9)
NHBA, Day 1(N=207,213,0,0,189)	5.0 (4.2 to 6.0)	99999 (99999 to 99999)	5.2 (4.4 to 6.2)	99999 (99999 to 99999)	5.3 (4.4 to 6.4)
NHBA, Day 31 (N=0,0,172,186,0)	99999 (99999 to 99999)	6.3 (5.3 to 7.7)	99999 (99999 to 99999)	6.0 (5.0 to 7.2)	99999 (99999 to 99999)
NHBA, Day 211 (199, 212, 155,167,177)	128.4 (106.4 to 155.0)	75.1 (61.4 to 91.9)	169.5 (141.0 to 203.9)	101.0 (82.6 to 123.4)	58.2 (47.9 to 70.7)
PorA, Day 1 (N=208,213,0,0,190)	4.5 (4.2 to 4.8)	99999 (99999 to 99999)	4.4 (4.1 to 4.8)	99999 (99999 to 99999)	4.3 (4.0 to 4.6)
PorA, Day 31 (N=0,0,161,173,0)	99999 (99999 to 99999)	4.6 (4.3 to 5.0)	99999 (99999 to 99999)	4.6 (4.3 to 5.0)	99999 (99999 to 99999)
PorA, Day 211 (N=200,214,153,169,178)	35.7 (28.3 to 45.2)	18.4 (14.3 to 23.7)	41.1 (32.7 to 51.6)	28.2 (21.9 to 36.1)	30.4 (23.9 to 38.8)
fHbp V1.13, Day 1 (N=203,209,0,0,184)	5.1 (4.3 to 6.1)	99999 (99999 to 99999)	5.2 (4.3 to 6.2)	99999 (99999 to 99999)	5.2 (4.3 to 6.3)
fHbp V1.13, Day 31 (N=0,0,171,184 ,0)	99999 (99999 to 99999)	5.6 (4.6 to 6.7)	99999 (99999 to 99999)	5.8 (4.8 to 7.0)	99999 (99999 to 99999)
fHbp V1.13, Day 211 (N=188,194,142,148,168)	88.3 (63.4 to 122.9)	39.7 (27.8 to 56.7)	122.1 (88.3 to 169.0)	54.9 (38.2 to 78.9)	36.9 (26.3 to 51.9)
fHbp V2, Day 1 (N=203,209,0,0,185)	2.7 (2.5 to 2.9)	99999 (99999 to 99999)	2.7 (2.6 to 2.9)	99999 (99999 to 99999)	2.7 (2.6 to 2.9)
fHbp V2, Day 31 (N=0 ,0,171,184,0)	99999 (99999 to 99999)	2.8 (2.7 to 3.0)	99999 (99999 to 99999)	3.0 (2.8 to 3.2)	99999 (99999 to 99999)
fHbp V2, Day 211 (N=195,204,150, 161,172)	31.7 (25.2 to 39.8)	17.3 (13.5 to 22.1)	44.0 (35.1 to 55.2)	23.2 (18.1 to 29.7)	5.2 (4.1 to 6.6)
fHbp V3, Day 1 (N=203,209,0,0,185)	8.7 (7.9 to 9.5)	99999 (99999 to 99999)	8.7 (7.9 to 9.5)	99999 (99999 to 99999)	8.3 (7.5 to 9.1)
fHbp V3, Day 31 (N=0,0,172,184,0)	99999 (99999 to 99999)	8.7 (7.9 to 9.6)	99999 (99999 to 99999)	8.9 (8.2 to 9.8)	99999 (99999 to 99999)
fHbp V3, Day 211(N=1 94,204,151,162,172)	50.7 (40.4 to 63.7)	27.0 (21.1 to 34.4)	65.7 (52.5 to 82.3)	33.2 (25.9 to 42.4)	10.8 (8.6 to 13.7)

No statistical analyses for this end point

Secondary: hSBA Geometric mean ratios (GMRs) against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding)

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End point title

hSBA Geometric mean ratios (GMRs) against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding) ^[102]

End point description

For each B strains, the GMRs (post-vaccination/ Baseline) are calculated with their associated 2-sided 95% CIs, by exponentiating the corresponding log-transformed means and their 95% CIs.

End point type

Secondary

End point timeframe

At Day 211 in all study groups versus Day 1 in ABCWY (0,6-months) and Control groups and Day 31 in ABCWY groups (0,2-months)

Notes
[102] - 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: As specified in the Protocol, the analysis assesses the immune response to the MenABCWY-2Gen and Men B vaccine against serogroup B indicator strains in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	178	155	193	168	177
Units: Ratio
geometric mean (confidence interval 95%)
fHbp (N=78,155,193,168,177)	13.4 (10.5 to 17.2)	5.6 (4.3 to 7.2)	16.5 (12.9 to 21.0)	9.0 (6.9 to 11.6)	7.0 (5.5 to 9.1)
NadA (N=166,141,179,159,167)	11.1 (8.5 to 14.3)	7.1 (5.4 to 9.3)	10.8 (8.4 to 14.0)	7.1 (5.4 to 9.3)	14.7 (11.3 to 19.1)
NHBA (N=174,150,191,164,171)	29.3 (23.5 to 36.7)	14.0 (11.1 to 17.6)	34.2 (27.5 to 42.5)	18.4 (14.6 to 23.1)	11.5 (9.1 to 14.4)
PorA (N=175,140,193,157,172)	8.6 (6.7 to 10.9)	4.5 (3.5 to 5.8)	10.1 (8.1 to 12.8)	6.3 (4.9 to 8.1)	7.4 (5.8 to 9.4)
fHbp V1.13 (N=161,137,173,144,158)	17.8 (12.8 to 24.9)	8.2 (5.8 to 11.7)	24.9 (18.0 to 34.6)	9.8 (6.9 to 14.0)	7.0 (5.0 to 9.8)
fHbp V2(N=168,144,182,157,163)	12.7 (10.1 to 16.1)	6.9 (5.4 to 8.8)	17.1 (13.6 to 21.5)	8.0 (6.2 to 10.2)	2.0 (1.5 to 2.5)
fHbp V3(N=167,146,182,158,163)	5.9 (4.7 to 7.4)	3.5 (2.7 to 4.4)	7.7 (6.1 to 9.7)	3.7 (2.9 to 4.8)	1.3 (1.0 to 1.7)

No statistical analyses for this end point

Secondary: Number of participants with hSBA titers ≥ LLOQ for serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding)

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End point title

Number of participants with hSBA titers ≥ LLOQ for serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding) ^[103]

End point description

The number of participants with hSBA titers ≥ LLOQ and the corresponding exact 2-sided 95% CIs based on Clopper-Pearson method are calculated. Baseline (pre-vaccination) was evaluated at Day 1 for 0,6 schedules and Control, at Month 1 for 0,2 schedules. Post vaccination was evaluated at Month 7 for all MenABCWY groups, at Month 1 for Control group.

End point type

Secondary

End point timeframe

Day 1 in ABCWY (0,6 Months) & Control; Day 31 pre-vaccination in ABCWY (0,2 Months); Day 31 post-first MenABCWY-2Gen in ABCWY (0,6 Months); Day 211 post-last MenABCWY-2Gen in all ABCWY; Day 31 post-MenACWY in Control

Notes
[103] - 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: As specified in the Protocol, the analysis assesses the immune response to the MenABCWY-2Gen and Men B vaccine against serogroup A, C, W and Y in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	222	175	226	189	193
Units: Participants
Men A, Day 1 (N=208,201,0,0,190)	23	99999	12	99999	20
Men A, Day 31 (Pre vaccination) (N=0,0,170,184,0)	99999	19	99999	16	99999
Men A, Day 31(Post vaccination)N=204,221,0,0,187	170	99999	180	99999	174
Men A,Day 211(Post vaccination)N=202,212,159,167,0	198	155	208	166	99999
Men C, Day 1 (N=209,211,0,0,193)	83	99999	85	99999	88
Men C,Day 31(Pre vaccination)(N=0,0,173,189,0)	99999	69	99999	76	99999
Men C, Day 31(Post vaccination)N=219,217,0,0,181	160	99999	162	99999	141
Men C,Day 211(Post vaccination)N=204,213,160,171,0	199	158	207	167	99999
Men W, Day 1 (N=207,210,0,0,192)	40	99999	37	99999	36
Men W, Day 31(Pre vaccination)N=0,0,173,187,0	99999	36	99999	36	99999
Men W, Day 31 Post vaccination)N=222,221,0,0,188	165	99999	173	99999	140
Men W,Day 211(Post vaccination)N=204,211,157,168,0	203	157	211	168	99999
Men Y, Day 1 (N=207,211,0,0,193)	22	99999	26	99999	33
Men Y, Day 31(Pre vaccination)N=0,0,175,187,0	99999	31	99999	24	99999
Men Y, Day 31(Post vaccination)N=222,226,0,0,190	135	99999	139	99999	141
Men Y,Day 211(Post vaccination)N=203,214,161,169,0	198	152	201	158	99999

No statistical analyses for this end point

Secondary: Number of participants with a 4-fold rise in hSBA titers against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding) At Day 31

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End point title

Number of participants with a 4-fold rise in hSBA titers against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding) At Day 31 ^[104]

End point description

The immune response to the MenABCWY-2Gen (low and high dose) vaccine when administered at 0,6-months schedule, relative to day 1 was measured in terms of percentage of participants achieving a 4-fold rise in hSBA titers against serogroups A, C, W and Y. Serum bactericidal activity against MenACWY were determined by using a validated AO hSBA. The 4-fold rise is defined as: -a post-vaccination hSBA titre ≥ 16 for participants with a pre-vaccination hSBA titre < 4, -a post-vaccination hSBA titre ≥ 4 times the LLOQ for participants with a pre-vaccination hSBA titre ≥ LOD but < LLOQ, and. -a post-vaccination hSBA titre ≥4 times the pre-vaccination hSBA titre for participants with a pre-vaccination hSBA titre ≥ LLOQ.

End point type

Secondary

End point timeframe

At Day 31 (1 month after the first MenABCWY-2Gen vaccination) in ABCWY (0,6-months) groups

Notes
[104] - 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: As specified in the Protocol, the analysis assesses the immune response to the MenABCWY-2Gen and Men B vaccine against serogroup A, C, W and Y in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY high dose_06 Group	Control Group
Number of subjects analysed	194	201	186
Units: Participants
Men A (N=176,186,180)	145	145	166
Men C (N=193,192,178)	125	119	113
Men W (N=194,195,183)	132	139	124
Men Y (N=193,201,186)	105	104	116

No statistical analyses for this end point

Secondary: hSBA GMTs against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding)

Top of page

End point title

hSBA GMTs against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding) ^[105]

End point description

The immune response to the MenABCWY-2Gen (low and high dose) vaccine (0,2- and 0,6-months schedule) and MenACWY vaccine (single dose) was evaluated by hSBA titers which are logarithmically transformed (base10) to fulfil the normal distribution assumption. For each serogroup A, C, W and Y, the GMTs are calculated with their associated 2-sided 95% CIs, by exponentiating the corresponding log-transformed means and their 95% CIs.

End point type

Secondary

End point timeframe

Notes
[105] - 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: As specified in the Protocol, the analysis assesses the immune response to the MenABCWY-2Gen and Men B vaccine against serogroup A, C, W and Y in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	222	181	226	194	193
Units: Titers
geometric mean (confidence interval 95%)
Men A, Day 1 (N=208,201,0,0,190)	9.7 (8.5 to 11.2)	99999 (99999 to 99999)	8.7 (7.5 to 10.0)	99999 (99999 to 99999)	9.3 (8.0 to 10.7)
Men A,Day 31 (Pre vaccination) (N=0,0,181,194,0)	99999 (99999 to 99999)	9.9 (8.5 to 11.4)	99999 (99999 to 99999)	8.7 (7.5 to 10.1)	99999 (99999 to 99999)
Men A,Day 31(Post vaccination)N=204,221,0,0,187	174.3 (127.6 to 238.1)	99999 (99999 to 99999)	169.5 (124.6 to 230.5)	99999 (99999 to 99999)	410.6 (299.0 to 564.1)
Men A,Day 211(Post vaccination)N=202,212,159,167,0	356.3 (296.7 to 427.9)	339.5 (278.9 to 413.1)	422.8 (352.8 to 506.7)	356.9 (293.8 to 433.4)	99999 (99999 to 99999)
Men C, Day 1 (N=209,211,0,0,193)	10.7 (8.6 to 13.3)	99999 (99999 to 99999)	10.3 (8.2 to 12.8)	99999 (99999 to 99999)	11.5 (9.2 to 14.3)
Men C,Day 31(Pre vaccination)(N=0,0,173,189,0)	99999 (99999 to 99999)	10.4 (8.3 to 13.1)	99999 (99999 to 99999)	10.9 (8.7 to 13.6)	99999 (99999 to 99999)
Men C, Day 31(Post vaccination)N=219,217,0,0,181	170.4 (106.8 to 272.0)	99999 (99999 to 99999)	162.0 (100.9 to 259.9)	99999 (99999 to 99999)	209.5 (128.4 to 341.9)
Men C,Day 211(Post vaccination)N=204,213,160,171,0	768.4 (601.2 to 982.0)	677.6 (521.0 to 881.2)	738.9 (579.1 to 942.8)	652.5 (502.5 to 847.3)	99999 (99999 to 99999)
Men W, Day 1 (N=207,210,0,0,192)	8.0 (6.5 to 9.9)	99999 (99999 to 99999)	7.2 (5.8 to 8.9)	99999 (99999 to 99999)	7.6 (6.1 to 9.5)
Men W, Day 31(Pre vaccination)N=0,0,173,187,0	99999 (99999 to 99999)	8.5 (6.8 to 10.7)	99999 (99999 to 99999)	8.1 (6.5 to 10.0)	99999 (99999 to 99999)
Men W, Day 31 Post vaccination)N=222,221,0,0,188	89.9 (61.9 to 130.7)	99999 (99999 to 99999)	122.6 (84.1 to 178.6)	99999 (99999 to 99999)	87.0 (59.0 to 128.3)
Men W,Day 211(Post vaccination)N=204,213,161,169,0	683.2 (572.6 to 815.1)	366.4 (303.4 to 442.5)	800.6 (671.8 to 954.1)	481.0 (398.2 to 580.9)	99999 (99999 to 99999)
Men Y, Day 1 (N=207,211,0,0,193)	7.4 (6.3 to 8.7)	99999 (99999 to 99999)	7.7 (6.5 to 9.0)	99999 (99999 to 99999)	8.7 (7.4 to 10.3)
Men Y, Day 31(Pre vaccination)N=0,0,175,187,0	99999 (99999 to 99999)	8.8 (7.4 to 10.4)	99999 (99999 to 99999)	7.7 (6.5 to 9.1)	99999 (99999 to 99999)
Men Y, Day 31(Post vaccination)N=222,226,0,0,190	62.8 (43.8 to 90.2)	99999 (99999 to 99999)	64.2 (44.7 to 92.2)	99999 (99999 to 99999)	100.0 (68.7 to 145.5)
Men Y,Day 211(Post vaccination)N=203,214,161,169,0	406.9 (315.8 to 524.4)	239.5 (182.7 to 314.0)	353.1 (274.6 to 454.0)	215.1 (164.1 to 281.9)	99999 (99999 to 99999)

No statistical analyses for this end point

Secondary: hSBA GMRs against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding)

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End point title

hSBA GMRs against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding) ^[106]

End point description

For each serogroup A, C, W and Y, the GMRs (post-vaccination/ Day 1 (Month 0)) are calculated with their associated 2-sided 95% CIs, by exponentiating the corresponding log-transformed means and their 95% CIs.

End point type

Secondary

End point timeframe

At Day 31 [for ABCWY (0,6-months) and Control group compared to Day 1 (Baseline)], at Day 211 [for ABCWY (0,6-months) groups compared to Day 1 (baseline) and for ABCWY (0,2-months) groups compared to Day 31]

Notes
[106] - 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: As specified in the Protocol, the analysis assesses the immune response to the MenABCWY-2Gen and Men B vaccine against serogroup A, C, W and Y in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	194	159	201	171	186
Units: Ratio
geometric mean (confidence interval 95%)
Men A, Day 31(N=176,186,0,0,180)	19.1 (14.2 to 25.8)	99999 (99999 to 99999)	17.0 (12.5 to 22.9)	99999 (99999 to 99999)	42.9 (31.9 to 57.8)
Men A, Day 211 (N=177,181,152,163,0)	43.0 (35.3 to 52.5)	38.4 (31.2 to 47.4)	53.3 (43.6 to 65.3)	45.8 (37.3 to 56.3)	99999 (99999 to 99999)
Men C, Day 31 (N=193,192,0,0,178)	14.8 (9.6 to 22.7)	99999 (99999 to 99999)	13.9 (8.9 to 21.6)	99999 (99999 to 99999)	15.6 (10.0 to 24.2)
Men C, Day 211 (N=180,190,156,171,0)	91.5 (68.4 to 122.5)	77.3 (57.0 to 104.8)	78.4 (58.5 to 105.1)	66.2 (49.1 to 89.4)	99999 (99999 to 99999)
Men W, Day 31 (N=194,195,10,0,83)	13.2 (9.3 to 18.8)	99999 (99999 to 99999)	17.5 (12.2 to 24.9)	99999 (99999 to 99999)	12.5 (8.7 to 17.9)
Men W, Day 211 (N=178,189,157,167,0)	101.6 (78.7 to 131.2)	54.0 (41.4 to 70.4)	127.9 (99.4 to 164.7)	69.8 (53.6 to 90.9)	99999 (99999 to 99999)
Men Y, Day 31 (N=193,201,0,0,186)	9.5 (6.6 to 13.7)	99999 (99999 to 99999)	9.3 (6.4 to 13.4)	99999 (99999 to 99999)	13.1 (9.0 to 19.0)
Men Y, Day 211 (N=177,192,159,167,0)	61.6 (46.3 to 81.8)	32.2 (24.0 to 43.2)	51.7 (39.0 to 68.4)	31.6 (23.5 to 42.3)	99999 (99999 to 99999)

No statistical analyses for this end point

Secondary: Immunoglobulin G (IgG) antibodies against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding)

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End point title

Immunoglobulin G (IgG) antibodies against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding) ^[107]

End point description

The immune responses to MenABCWY-2Gen (low and high dose) and MenACWY vaccines are evaluated by measuring the total IgG in terms of electrochemiluminescence-based (ECL) multiplex assay Geometric Mean Concentrations (GMCs).

End point type

Secondary

End point timeframe

Notes
[107] - 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: As specified in the Protocol, the analysis assesses the immune response to the MenABCWY-2Gen and Men B vaccine against serogroup A, C, W and Y in study Phase II (Formulation and Schedule-finding) groups.

End point values	ABCWY low dose_06 Group	ABCWY low dose_02 Group	ABCWY high dose_06 Group	ABCWY high dose_02 Group	Control Group
Number of subjects analysed	211	170	223	184	187
Units: Microgram per milliliter(µg/mL)
geometric mean (confidence interval 95%)
Men A Ab, Day 1 (N=197,201,0,0,176)	2.3 (2.0 to 2.6)	99999 (99999 to 99999)	2.1 (1.8 to 2.4)	99999 (99999 to 99999)	2.3 (2.0 to 2.6)
Men A Ab,Day 31 (Pre vaccination)N=0,0,168,184,0	99999 (99999 to 99999)	2.4 (2.1 to 2.8)	99999 (99999 to 99999)	2.3 (2.0 to 2.7)	99999 (99999 to 99999)
Men A Ab,Day 31(Post vaccination)N=207,221,0,0,183	10.5 (8.0 to 13.8)	99999 (99999 to 99999)	9.3 (7.1 to 12.2)	99999 (99999 to 99999)	20.3 (15.4 to 26.7)
MenA Ab,Day211(Postvaccination)N=178,189,135,139,0	14.6 (11.5 to 18.6)	14.0 (10.9 to 18.1)	13.1 (10.4 to 16.5)	14.0 (10.9 to 18.1)	99999 (99999 to 99999)
Men C Ab, Day 1(N=197,202,0,0,178)	1.1 (1.0 to 1.2)	99999 (99999 to 99999)	1.1 (1.0 to 1.2)	99999 (99999 to 99999)	1.1 (1.0 to 1.3)
Men C Ab, Day 31 (Pre vaccination)N=0,0,169,183,0	99999 (99999 to 99999)	1.0 (0.9 to 1.1)	99999 (99999 to 99999)	1.1 (1.0 to 1.2)	99999 (99999 to 99999)
Men C Ab,Day 31(Post vaccination)N=208,217,0,0,181	8.0 (6.1 to 10.6)	99999 (99999 to 99999)	8.1 (6.2 to 10.7)	99999 (99999 to 99999)	8.6 (6.5 to 11.4)
MenC Ab,Day211(Postvaccination)N=164,172,116,128,0	8.6 (6.9 to 10.7)	11.7 (9.3 to 14.8)	8.0 (6.5 to 9.8)	11.2 (8.9 to 14.1)	99999 (99999 to 99999)
Men W Ab, Day 1(N=197,201,0,0,178)	1.3 (1.1 to 1.4)	99999 (99999 to 99999)	1.2 (1.1 to 1.3)	99999 (99999 to 99999)	1.2 (1.1 to 1.4)
Men W Ab, Day 31 (Pre vaccination)N=0,0,170,182,0	99999 (99999 to 99999)	1.2 (1.1 to 1.4)	99999 (99999 to 99999)	1.2 (1.1 to 1.4)	99999 (99999 to 99999)
Men W Ab,Day 31(Post vaccination)N=211,223,0,0,187	4.6 (3.5 to 6.1)	99999 (99999 to 99999)	4.3 (3.3 to 5.7)	99999 (99999 to 99999)	3.6 (2.7 to 4.8)
MenWAb,Day 211(Postvaccination)N=180,187,125,136,0	8.2 (6.4 to 10.5)	6.2 (4.7 to 8.1)	8.7 (6.8 to 11.1)	7.2 (5.5 to 9.5)	99999 (99999 to 99999)
Men Y Ab, Day 1(N=196,202,0,0,177)	1.3 (1.2 to 1.5)	99999 (99999 to 99999)	1.3 (1.2 to 1.4)	99999 (99999 to 99999)	1.3 (1.2 to 1.5)
Men Y Ab, Day 31(Pre vaccination)N=0,0,169,183,0	99999 (99999 to 99999)	1.4 (1.2 to 1.5)	99999 (99999 to 99999)	1.3 (1.2 to 1.4)	99999 (99999 to 99999)
Men Y Ab,Day 31(Post vaccination)N=208,221,0,0,185	4.2 (3.2 to 5.5)	99999 (99999 to 99999)	4.4 (3.4 to 5.8)	99999 (99999 to 99999)	5.3 (4.0 to 7.0)
MenYAb,Day211(Post vaccination)N=180,189,136,139,0	10.1 (7.8 to 13.1)	11.3 (8.6 to 15.0)	10.0 (7.8 to 12.9)	9.8 (7.4 to 12.9)	99999 (99999 to 99999)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited AEs: up to day 7 post vaccination; Unsolicited AEs: up to day 30 post vaccination, SAEs: from Day 1 to Day 211 (Phase I Safety Lead-in); from Day 1 to Day 541(Phase II Formulation and Schedule-Finding); from Day 1 to Day 361 (Phase II Sourcing)

Assessment type

Systematic

Dictionary name

v27.0

Dictionary version

27.0

Reporting group title

ABCWY low dose Group

Reporting group description

Participants received two doses of the MenABCWY-2Gen low-dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In).

Reporting group title

ABCWY high dose Group

Reporting group description

Participants received two doses of the MenABCWY-2Gen high-dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In).

Reporting group title

Placebo low dose Group

Reporting group description

Participants received two doses of a placebo on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In), as the control group for the ABCWY low-dose group.

Reporting group title

ABCWY high dose_06 Group

Reporting group description

Reporting group title

ABCWY low dose_02 Group

Reporting group description

Reporting group title

ABCWY low dose_06 Group

Reporting group description

Reporting group title

Placebo high dose Group

Reporting group description

Participants received two doses of a placebo on Day 1 and Day 31, following a 0, 1-month schedule during Study Phase I (Safety Lead-In), as the control group for the ABCWY high-dose group.

Reporting group title

ABCWY high dose_02 Group

Reporting group description

Reporting group title

ABCWY high doseS_02 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen high dose vaccine on Day 1 and day 61 following a 0, 2-month schedule during study Phase II (Sourcing).

Reporting group title

Control Group

Reporting group description

Reporting group title

ABCWY low dose_01 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen low dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during study Phase II (Sourcing).

Reporting group title

ABCWY high dose_01 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen high dose vaccine on Day 1 and Day 31, following a 0, 1-month schedule during study Phase II (Sourcing).

Reporting group title

ABCWY low doseS_02 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen low dose vaccine on Day 1 and day 61 following a 0, 2-month schedule during study Phase II (Sourcing).

Reporting group title

ABCWY low doseS_06 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen low dose vaccine on Day 1 and day 181 following a 0, 6-month schedule during study Phase II (Sourcing).

Reporting group title

ABCWY high doseS_06 Group

Reporting group description

Participants received two doses of MenABCWY-2Gen high dose vaccine on Day 1 and day 181 following a 0, 6-month schedule during study Phase II (Sourcing).

ABCWY low dose Group

ABCWY high dose Group

Placebo low dose Group

ABCWY high dose_06 Group

ABCWY low dose_02 Group

ABCWY low dose_06 Group

Placebo high dose Group

ABCWY high dose_02 Group

ABCWY high doseS_02 Group

Control Group

ABCWY low dose_01 Group

ABCWY high dose_01 Group

ABCWY low doseS_02 Group

ABCWY low doseS_06 Group

ABCWY high doseS_06 Group

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

4 / 238 (1.68%)

7 / 181 (3.87%)

9 / 239 (3.77%)

0 / 3 (0.00%)

4 / 194 (2.06%)

1 / 62 (1.61%)

2 / 197 (1.02%)

0 / 54 (0.00%)

0 / 53 (0.00%)

2 / 62 (3.23%)

0 / 62 (0.00%)

4 / 63 (6.35%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Prostate cancer

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

1 / 63 (1.59%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pregnancy, puerperium and perinatal conditions

Abortion spontaneous

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

1 / 63 (1.59%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Ectopic pregnancy

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

1 / 63 (1.59%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Premature labour

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

1 / 238 (0.42%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Cyst

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

1 / 63 (1.59%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Asthma

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

1 / 194 (0.52%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchospasm

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

1 / 239 (0.42%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Depression

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

1 / 181 (0.55%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Paranoid personality disorder

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

1 / 239 (0.42%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychotic disorder

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

1 / 181 (0.55%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Congenital, familial and genetic disorders

Benign familial haematuria

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

1 / 181 (0.55%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Arrhythmia

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

1 / 239 (0.42%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial fibrillation

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

1 / 62 (1.61%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Myocarditis

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

1 / 239 (0.42%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Bell's palsy

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

1 / 239 (0.42%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Epilepsy

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

1 / 194 (0.52%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Migraine

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

2 / 181 (1.10%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Blood loss anaemia

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

1 / 239 (0.42%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Mesenteric lymphadenitis

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

1 / 197 (0.51%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Colitis ulcerative

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

1 / 62 (1.61%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Autoimmune hepatitis

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

1 / 197 (0.51%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cholelithiasis

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

1 / 194 (0.52%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Nephrolithiasis

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

1 / 238 (0.42%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ureteric stenosis

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

1 / 238 (0.42%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Appendicitis

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

1 / 239 (0.42%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cellulitis

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

1 / 197 (0.51%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Enterobiasis

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

1 / 238 (0.42%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pharyngeal abscess

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

1 / 181 (0.55%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pilonidal disease

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

1 / 63 (1.59%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

1 / 62 (1.61%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia bacterial

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

1 / 181 (0.55%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyelonephritis

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

1 / 181 (0.55%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tonsillitis bacterial

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

1 / 239 (0.42%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vestibular neuronitis

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

1 / 239 (0.42%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Viral infection

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

1 / 238 (0.42%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

0 / 194 (0.00%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Hyperlipidaemia

subjects affected / exposed

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 238 (0.00%)

0 / 181 (0.00%)

0 / 239 (0.00%)

0 / 3 (0.00%)

1 / 194 (0.52%)

0 / 62 (0.00%)

0 / 197 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 62 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	ABCWY low dose Group	ABCWY high dose Group	Placebo low dose Group	ABCWY high dose_06 Group	ABCWY low dose_02 Group	ABCWY low dose_06 Group	Placebo high dose Group	ABCWY high dose_02 Group	ABCWY high doseS_02 Group	Control Group	ABCWY low dose_01 Group	ABCWY high dose_01 Group	ABCWY low doseS_02 Group	ABCWY low doseS_06 Group	ABCWY high doseS_06 Group
Total subjects affected by non serious adverse events
subjects affected / exposed	12 / 12 (100.00%)	13 / 13 (100.00%)	3 / 4 (75.00%)	234 / 238 (98.32%)	170 / 181 (93.92%)	229 / 239 (95.82%)	2 / 3 (66.67%)	182 / 194 (93.81%)	58 / 62 (93.55%)	192 / 197 (97.46%)	50 / 54 (92.59%)	53 / 53 (100.00%)	61 / 62 (98.39%)	60 / 62 (96.77%)	62 / 63 (98.41%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Uterine leiomyoma
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Vascular disorders
Haematoma
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Hot flush
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
General disorders and administration site conditions
Administration site erythema
subjects affected / exposed	2 / 12 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	45 / 238 (18.91%)	25 / 181 (13.81%)	46 / 239 (19.25%)	0 / 3 (0.00%)	29 / 194 (14.95%)	20 / 62 (32.26%)	32 / 197 (16.24%)	14 / 54 (25.93%)	8 / 53 (15.09%)	22 / 62 (35.48%)	26 / 62 (41.94%)	24 / 63 (38.10%)
occurrences all number	2	0	0	51	33	56	0	32	28	37	16	11	33	31	28
Administration site hypoaesthesia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Administration site pain
subjects affected / exposed	11 / 12 (91.67%)	13 / 13 (100.00%)	2 / 4 (50.00%)	232 / 238 (97.48%)	160 / 181 (88.40%)	226 / 239 (94.56%)	1 / 3 (33.33%)	173 / 194 (89.18%)	55 / 62 (88.71%)	186 / 197 (94.42%)	50 / 54 (92.59%)	51 / 53 (96.23%)	61 / 62 (98.39%)	59 / 62 (95.16%)	60 / 63 (95.24%)
occurrences all number	19	21	2	440	321	443	1	346	98	340	91	86	110	107	102
Administration site induration
subjects affected / exposed	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 4 (0.00%)	44 / 238 (18.49%)	27 / 181 (14.92%)	32 / 239 (13.39%)	0 / 3 (0.00%)	27 / 194 (13.92%)	18 / 62 (29.03%)	29 / 197 (14.72%)	8 / 54 (14.81%)	9 / 53 (16.98%)	18 / 62 (29.03%)	16 / 62 (25.81%)	20 / 63 (31.75%)
occurrences all number	1	0	0	50	34	41	0	35	20	32	9	12	26	21	25
Administration site swelling
subjects affected / exposed	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 4 (0.00%)	52 / 238 (21.85%)	34 / 181 (18.78%)	48 / 239 (20.08%)	0 / 3 (0.00%)	33 / 194 (17.01%)	22 / 62 (35.48%)	31 / 197 (15.74%)	10 / 54 (18.52%)	14 / 53 (26.42%)	25 / 62 (40.32%)	24 / 62 (38.71%)	26 / 63 (41.27%)
occurrences all number	1	0	0	59	47	62	0	45	28	35	11	22	36	31	34
Axillary pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	2 / 238 (0.84%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	2	0	1	0	0	0	0	0	0	0	0	0
Administration site warmth
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Asthenia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	2 / 181 (1.10%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	2	0	0	1	0	0	0	0	0	0	0
Chills
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	2 / 239 (0.84%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	2	0	1	0	1	0	1	0	0	1
Chest pain
subjects affected / exposed	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	1	0	0	0	2	0	0	0	0	0	0	0	0	0
Hangover
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	1 / 3 (33.33%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Fatigue
subjects affected / exposed	6 / 12 (50.00%)	12 / 13 (92.31%)	3 / 4 (75.00%)	147 / 238 (61.76%)	104 / 181 (57.46%)	152 / 239 (63.60%)	2 / 3 (66.67%)	115 / 194 (59.28%)	37 / 62 (59.68%)	118 / 197 (59.90%)	31 / 54 (57.41%)	36 / 53 (67.92%)	50 / 62 (80.65%)	49 / 62 (79.03%)	41 / 63 (65.08%)
occurrences all number	7	18	3	252	193	256	4	206	51	167	45	51	78	71	56
Influenza like illness
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	12 / 238 (5.04%)	8 / 181 (4.42%)	4 / 239 (1.67%)	0 / 3 (0.00%)	8 / 194 (4.12%)	0 / 62 (0.00%)	5 / 197 (2.54%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	1 / 63 (1.59%)
occurrences all number	0	0	0	17	14	6	0	14	0	8	0	0	0	1	1
Inflammation
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Injection site bruising
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	2 / 194 (1.03%)	0 / 62 (0.00%)	2 / 197 (1.02%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	2	0	2	1	0	0	0	0
Injection site discomfort
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Injection site erythema
subjects affected / exposed	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Injection site haemorrhage
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	0	1	0	0	0	0	0
Injection site hypoaesthesia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Injection site induration
subjects affected / exposed	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Injection site lymphadenopathy
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0
Injection site mass
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Injection site oedema
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0
Injection site nodule
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Injection site pain
subjects affected / exposed	2 / 12 (16.67%)	5 / 13 (38.46%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	5	5	0	0	0	4	0	0	0	0	0	1	0	0	1
Injection site pruritus
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	2 / 239 (0.84%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	3 / 197 (1.52%)	1 / 54 (1.85%)	1 / 53 (1.89%)	1 / 62 (1.61%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	1	0	2	0	1	0	3	1	1	1	0	1
Injection site paraesthesia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Injection site rash
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	1 / 62 (1.61%)	2 / 197 (1.02%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	2 / 63 (3.17%)
occurrences all number	0	0	0	0	0	0	0	0	1	3	0	0	0	0	2
Injection site swelling
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Injection site reaction
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	2 / 238 (0.84%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	2	1	0	0	1	0	1	0	0	0	0	0
Injection site warmth
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0
Malaise
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	1 / 181 (0.55%)	1 / 239 (0.42%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	1	1	0	1	0	1	0	1	0	0	0
Medical device site pruritus
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Pain
subjects affected / exposed	0 / 12 (0.00%)	2 / 13 (15.38%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	2	0	1	0	0	0	0	0	0	0	0	0	0	0
Peripheral swelling
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Pyrexia
subjects affected / exposed	2 / 12 (16.67%)	2 / 13 (15.38%)	0 / 4 (0.00%)	18 / 238 (7.56%)	12 / 181 (6.63%)	14 / 239 (5.86%)	0 / 3 (0.00%)	10 / 194 (5.15%)	3 / 62 (4.84%)	15 / 197 (7.61%)	3 / 54 (5.56%)	7 / 53 (13.21%)	3 / 62 (4.84%)	5 / 62 (8.06%)	5 / 63 (7.94%)
occurrences all number	2	2	0	21	13	15	0	10	3	16	3	7	3	5	5
Swelling
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Swelling face
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	1 / 62 (1.61%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Vaccination site erythema
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Vaccination site pruritus
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Vaccination site pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Vaccination site swelling
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Vessel puncture site pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Vaccination site warmth
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Immune system disorders
Food allergy
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Mite allergy
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0
Hypersensitivity
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Mycotic allergy
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Seasonal allergy
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	2 / 238 (0.84%)	1 / 181 (0.55%)	1 / 239 (0.42%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	2	2	1	0	1	0	1	0	0	0	0	1
Reproductive system and breast disorders
Adenomyosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Cervical polyp
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Heavy menstrual bleeding
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0
Endometriosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0
Dysmenorrhoea
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	3 / 238 (1.26%)	3 / 181 (1.66%)	1 / 239 (0.42%)	0 / 3 (0.00%)	3 / 194 (1.55%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	1 / 62 (1.61%)	0 / 63 (0.00%)
occurrences all number	0	0	0	3	3	1	0	3	0	0	0	0	1	1	0
Menstrual disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	2	0	0	0	0	0
Menstruation irregular
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Ovarian cyst
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0
Vaginal haemorrhage
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Allergic sinusitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Dyspnoea exertional
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Dyspnoea
subjects affected / exposed	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	2	0	0	0	0	0	1	0	0	0	0	0	0	0
Cough
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	4 / 238 (1.68%)	0 / 181 (0.00%)	4 / 239 (1.67%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	3 / 197 (1.52%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	4	0	4	0	1	0	3	0	0	1	0	0
Epistaxis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	1	0	0	1	2
Asthma
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0	0	1	0	1
Nasal pruritus
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Nasal obstruction
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0
Nasal congestion
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	1	0	0	1	0	0	0	0	0	0	0
Nasal septum deviation
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	1 / 62 (1.61%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Nasal septum perforation
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Paranasal sinus discomfort
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	6 / 238 (2.52%)	7 / 181 (3.87%)	1 / 239 (0.42%)	0 / 3 (0.00%)	7 / 194 (3.61%)	0 / 62 (0.00%)	4 / 197 (2.03%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	2 / 63 (3.17%)
occurrences all number	0	0	0	7	8	1	0	7	0	4	0	1	0	0	2
Rhinorrhoea
subjects affected / exposed	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 4 (0.00%)	6 / 238 (2.52%)	1 / 181 (0.55%)	1 / 239 (0.42%)	0 / 3 (0.00%)	1 / 194 (0.52%)	1 / 62 (1.61%)	3 / 197 (1.52%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	1	0	0	6	1	1	0	1	1	5	0	0	1	0	0
Rhinitis allergic
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	2 / 239 (0.84%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	2 / 197 (1.02%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	2	0	0	0	3	0	0	1	0	0
Pharyngeal swelling
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Throat irritation
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Tonsillolith
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Psychiatric disorders
Anxiety disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Anxiety
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	3 / 194 (1.55%)	1 / 62 (1.61%)	1 / 197 (0.51%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	3	1	1	1	0	0	1	0
Anger
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Attention deficit hyperactivity disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	2 / 238 (0.84%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	2 / 53 (3.77%)	0 / 62 (0.00%)	0 / 62 (0.00%)	2 / 63 (3.17%)
occurrences all number	0	0	0	2	0	1	0	0	0	0	0	2	0	0	2
Depression
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	3 / 238 (1.26%)	0 / 181 (0.00%)	2 / 239 (0.84%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	2 / 62 (3.23%)	0 / 63 (0.00%)
occurrences all number	0	0	0	3	0	2	0	1	0	1	0	0	0	2	0
Eating disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Initial insomnia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0
Insomnia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	2 / 62 (3.23%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Mixed anxiety and depressive disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Neurosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Obsessive-compulsive disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Social anxiety disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Sleep disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0
Stress
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	1 / 62 (1.61%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Suicidal ideation
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Investigations
Blood iron decreased
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Human metapneumovirus test positive
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Body temperature increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Streptococcus test positive
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Accident
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Accidental exposure to product
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Animal bite
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Ankle fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Arthropod bite
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0
Concussion
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Cartilage injury
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Bone contusion
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Eyelid injury
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Epicondylitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Craniofacial fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Contusion
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	1 / 197 (0.51%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	1	0	0	0	0
Fall
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	2	0	0	1	0	0
Foot fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	1 / 181 (0.55%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	1	1	0	0	0	1	0	0	0	0	0
Forearm fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0
Heat exhaustion
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Ligament rupture
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Joint injury
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	1	0	0	0
Joint dislocation
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Immunisation reaction
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	1 / 54 (1.85%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	1	1	0	0	0
Ligament sprain
subjects affected / exposed	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	2 / 238 (0.84%)	2 / 181 (1.10%)	0 / 239 (0.00%)	0 / 3 (0.00%)	3 / 194 (1.55%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	1	0	2	2	0	0	3	0	1	0	0	1	0	0
Limb injury
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	2 / 197 (1.02%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	2	0	0	1	0	0
Muscle strain
subjects affected / exposed	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	1 / 62 (1.61%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	1	0	0	0	0	0	0
Post procedural complication
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	2 / 197 (1.02%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Post-traumatic neck syndrome
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 4 (25.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Procedural complication
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Procedural pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	3 / 181 (1.66%)	1 / 239 (0.42%)	0 / 3 (0.00%)	2 / 194 (1.03%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	1	3	1	0	2	0	0	0	1	0	0	1
Radius fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Road traffic accident
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Repetitive strain injury
subjects affected / exposed	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Skin laceration
subjects affected / exposed	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Skin abrasion
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0
Skin injury
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0
Spinal fracture
subjects affected / exposed	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Stress fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0
Sunburn
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Tendon rupture
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Thermal burn
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Traumatic pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0
Cardiac disorders
Sinus tachycardia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Tachycardia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Nervous system disorders
Disturbance in attention
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Headache
subjects affected / exposed	7 / 12 (58.33%)	5 / 13 (38.46%)	2 / 4 (50.00%)	157 / 238 (65.97%)	110 / 181 (60.77%)	140 / 239 (58.58%)	2 / 3 (66.67%)	112 / 194 (57.73%)	31 / 62 (50.00%)	104 / 197 (52.79%)	33 / 54 (61.11%)	29 / 53 (54.72%)	38 / 62 (61.29%)	36 / 62 (58.06%)	37 / 63 (58.73%)
occurrences all number	11	9	2	250	180	234	2	190	44	146	43	41	52	49	47
Dizziness
subjects affected / exposed	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	2 / 181 (1.10%)	0 / 239 (0.00%)	0 / 3 (0.00%)	4 / 194 (2.06%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	1	0	0	1	2	0	0	4	0	1	0	0	0	0	0
Hyperaesthesia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Hypoaesthesia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Lethargy
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Migraine
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	4 / 238 (1.68%)	1 / 181 (0.55%)	2 / 239 (0.84%)	0 / 3 (0.00%)	2 / 194 (1.03%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	4	1	2	0	2	0	0	0	0	0	0	0
Migraine with aura
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Paraesthesia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Presyncope
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0
Sciatica
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0	0	2	1
Tension headache
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Syncope
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Somnolence
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Trigeminal neuralgia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Blood and lymphatic system disorders
Iron deficiency anaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	2 / 194 (1.03%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Anaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Lymphadenitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Lymphadenopathy
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	3 / 238 (1.26%)	1 / 181 (0.55%)	1 / 239 (0.42%)	0 / 3 (0.00%)	3 / 194 (1.55%)	1 / 62 (1.61%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	1 / 62 (1.61%)	0 / 63 (0.00%)
occurrences all number	0	0	0	4	1	1	0	3	1	0	0	0	1	2	0
Lymph node pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	1 / 62 (1.61%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	1 / 62 (1.61%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1	2	0
Ear and labyrinth disorders
Cerumen impaction
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Ear discomfort
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Ear pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	1 / 181 (0.55%)	2 / 239 (0.84%)	0 / 3 (0.00%)	2 / 194 (1.03%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	1	2	0	2	0	0	0	1	1	0	0
Inner ear inflammation
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Motion sickness
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0
Tinnitus
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Tympanic membrane perforation
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Vertigo
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)
occurrences all number	0	0	0	2	0	1	0	0	0	0	0	0	0	1	0
Eye disorders
Blepharitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Conjunctivitis allergic
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	2 / 239 (0.84%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	2	0	1	0	0	0	0	0	0	0
Eye irritation
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Conjunctival hyperaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Panophthalmitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	2 / 238 (0.84%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0
Eye pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Photophobia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	4 / 238 (1.68%)	1 / 181 (0.55%)	2 / 239 (0.84%)	0 / 3 (0.00%)	0 / 194 (0.00%)	1 / 62 (1.61%)	3 / 197 (1.52%)	2 / 54 (3.70%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	2	0	5	1	2	0	0	1	3	2	0	0	0	0
Anal fissure
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Abdominal pain upper
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	2 / 181 (1.10%)	2 / 239 (0.84%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	2	2	0	1	0	0	0	0	0	0	0
Colitis ulcerative
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Coeliac disease
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Diarrhoea
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	6 / 238 (2.52%)	2 / 181 (1.10%)	5 / 239 (2.09%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	3 / 197 (1.52%)	0 / 54 (0.00%)	1 / 53 (1.89%)	1 / 62 (1.61%)	2 / 62 (3.23%)	2 / 63 (3.17%)
occurrences all number	0	0	0	6	2	7	0	0	0	3	0	1	1	2	2
Dyspepsia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	2 / 181 (1.10%)	2 / 239 (0.84%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	2	2	0	0	0	1	0	1	0	0	0
Enteritis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Dental caries
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Constipation
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	1 / 62 (1.61%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0
Food poisoning
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0
Gastritis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0	0	1	0
Gastrointestinal inflammation
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0
Gingival swelling
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	1 / 62 (1.61%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Haematemesis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Hypoaesthesia oral
subjects affected / exposed	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Irritable bowel syndrome
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Lip swelling
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Nausea
subjects affected / exposed	1 / 12 (8.33%)	4 / 13 (30.77%)	1 / 4 (25.00%)	57 / 238 (23.95%)	34 / 181 (18.78%)	57 / 239 (23.85%)	0 / 3 (0.00%)	35 / 194 (18.04%)	10 / 62 (16.13%)	30 / 197 (15.23%)	9 / 54 (16.67%)	13 / 53 (24.53%)	10 / 62 (16.13%)	11 / 62 (17.74%)	11 / 63 (17.46%)
occurrences all number	2	5	2	69	37	68	0	47	11	35	11	15	12	12	14
Odynophagia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	2 / 238 (0.84%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	2	1	0	0	0	0	0	0	0	0	0	0
Lower gastrointestinal haemorrhage
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0
Stomatitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Vomiting
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	3 / 197 (1.52%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	3	0	0	0	0	0
Toothache
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	2 / 238 (0.84%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	2 / 194 (1.03%)	1 / 62 (1.61%)	0 / 197 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	2	3	0	0	2	1	0	1	0	0	0	1
Tooth impacted
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	4 / 238 (1.68%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	4	0	0	0	1	0	0	0	0	0	0	0
Alopecia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Alopecia areata
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Blister
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Dermatitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	2 / 238 (0.84%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	1	0	0
Dermatitis allergic
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Dermatitis atopic
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	1	0	1	0	0	0	0	0	0	0
Drug eruption
subjects affected / exposed	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Dyshidrotic eczema
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Eczema
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Erythema
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	2 / 181 (1.10%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	2	0	0	0	0	0	0	0	0	0	0
Lichen planus
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Onychalgia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Parapsoriasis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Pruritus
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1
Psoriasis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Rash
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	3 / 239 (1.26%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	2 / 53 (3.77%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	3	0	0	0	0	0	2	0	0	0
Sea bather's eruption
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Rash macular
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Rash erythematous
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	2 / 53 (3.77%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	2	0	0	0
Skin mass
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Solar dermatitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Transient acantholytic dermatosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Urticaria
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	2 / 238 (0.84%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)
occurrences all number	0	0	0	2	1	0	0	0	0	1	0	0	0	1	0
Urticaria papular
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Urticaria chronic
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Renal and urinary disorders
Cystitis noninfective
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Haematuria
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Urethral haemorrhage
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Urethral pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Urge incontinence
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Hypothyroidism
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	2 / 239 (0.84%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	1	0	0	1	0	0
Hyperprolactinaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Polycystic ovarian syndrome
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	2 / 238 (0.84%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Axillary mass
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Arthralgia
subjects affected / exposed	2 / 12 (16.67%)	4 / 13 (30.77%)	2 / 4 (50.00%)	44 / 238 (18.49%)	26 / 181 (14.36%)	27 / 239 (11.30%)	1 / 3 (33.33%)	21 / 194 (10.82%)	13 / 62 (20.97%)	20 / 197 (10.15%)	10 / 54 (18.52%)	11 / 53 (20.75%)	11 / 62 (17.74%)	15 / 62 (24.19%)	20 / 63 (31.75%)
occurrences all number	2	4	3	51	29	33	1	27	14	21	11	15	15	20	29
Back pain
subjects affected / exposed	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	2 / 238 (0.84%)	3 / 181 (1.66%)	0 / 239 (0.00%)	0 / 3 (0.00%)	2 / 194 (1.03%)	0 / 62 (0.00%)	0 / 197 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	2 / 62 (3.23%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	1	0	2	3	0	0	2	0	0	1	0	2	0	0
Flank pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Inguinal mass
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Intervertebral disc protrusion
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Limb discomfort
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Joint range of motion decreased
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Jaw disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Muscle disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Muscle tightness
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Neck pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	3 / 194 (1.55%)	1 / 62 (1.61%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	1	1	0	0	3	1	0	0	0	0	0	1
Myalgia
subjects affected / exposed	4 / 12 (33.33%)	6 / 13 (46.15%)	1 / 4 (25.00%)	57 / 238 (23.95%)	34 / 181 (18.78%)	53 / 239 (22.18%)	1 / 3 (33.33%)	41 / 194 (21.13%)	17 / 62 (27.42%)	47 / 197 (23.86%)	18 / 54 (33.33%)	18 / 53 (33.96%)	19 / 62 (30.65%)	25 / 62 (40.32%)	23 / 63 (36.51%)
occurrences all number	5	7	1	71	45	63	1	55	20	51	21	25	23	27	30
Musculoskeletal stiffness
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	1 / 62 (1.61%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0
Pain in jaw
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Pain in extremity
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	2 / 181 (1.10%)	3 / 239 (1.26%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	1	2	3	0	0	0	1	0	0	1	0	1
Rotator cuff syndrome
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	1	0	0	0	0
Synovial cyst
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Tendonitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	2 / 239 (0.84%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	2	0	1	0	0	0	0	0	0	0
Infections and infestations
Abscess neck
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Acarodermatitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Acute sinusitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0
Adenovirus infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Alveolar osteitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Body tinea
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Bronchitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	2 / 238 (0.84%)	4 / 181 (2.21%)	3 / 239 (1.26%)	0 / 3 (0.00%)	1 / 194 (0.52%)	1 / 62 (1.61%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	2 / 62 (3.23%)	0 / 63 (0.00%)
occurrences all number	0	0	0	2	5	3	0	1	1	0	0	0	0	2	0
Cellulitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0
COVID-19
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	12 / 238 (5.04%)	14 / 181 (7.73%)	14 / 239 (5.86%)	0 / 3 (0.00%)	16 / 194 (8.25%)	4 / 62 (6.45%)	6 / 197 (3.05%)	4 / 54 (7.41%)	5 / 53 (9.43%)	3 / 62 (4.84%)	2 / 62 (3.23%)	3 / 63 (4.76%)
occurrences all number	0	0	0	12	16	14	0	17	4	6	4	5	3	2	3
Chlamydial infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Coronavirus infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	2 / 239 (0.84%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0
Cystitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	3 / 238 (1.26%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	3	0	0	0	1	0	1	0	0	0	0	0
Dengue fever
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	2 / 239 (0.84%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	2	0	1	0	0	0	0	0	0	0
Ear infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Folliculitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Enterovirus infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	2 / 194 (1.03%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0
Gastroenteritis viral
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	1 / 62 (1.61%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0
Gastroenteritis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	3 / 181 (1.66%)	4 / 239 (1.67%)	0 / 3 (0.00%)	1 / 194 (0.52%)	1 / 62 (1.61%)	2 / 197 (1.02%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	2 / 63 (3.17%)
occurrences all number	0	0	0	1	3	4	0	1	1	2	0	1	0	0	2
Gastrointestinal infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Helicobacter infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Hordeolum
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Herpes simplex
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Impetigo
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0
Infectious mononucleosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Influenza
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	7 / 238 (2.94%)	4 / 181 (2.21%)	9 / 239 (3.77%)	0 / 3 (0.00%)	7 / 194 (3.61%)	0 / 62 (0.00%)	3 / 197 (1.52%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	7	4	10	0	7	0	3	1	0	0	0	1
Laryngitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	3 / 239 (1.26%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	1	0	3	0	0	0	1	0	0	0	0	1
Metapneumovirus infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Lyme disease
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Nasopharyngitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	17 / 238 (7.14%)	14 / 181 (7.73%)	21 / 239 (8.79%)	0 / 3 (0.00%)	12 / 194 (6.19%)	2 / 62 (3.23%)	5 / 197 (2.54%)	0 / 54 (0.00%)	0 / 53 (0.00%)	3 / 62 (4.84%)	4 / 62 (6.45%)	4 / 63 (6.35%)
occurrences all number	0	0	0	22	18	26	0	15	3	5	0	0	3	4	5
Onychomycosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0
Oral fungal infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Oral herpes
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	2 / 239 (0.84%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	4	0	0	0	0	0	0	0	0	0
Norovirus infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Otitis externa
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0
Ovarian bacterial infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Otitis media acute
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	2 / 238 (0.84%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	2	0	0	0	1	0	0	0	0	0	0	0
Otitis media
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	2 / 239 (0.84%)	0 / 3 (0.00%)	2 / 194 (1.03%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	2	0	2	0	0	0	0	0	0	0
Paronychia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	1	0	1	0	0	0	0	0	0	0
Pharyngitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	3 / 238 (1.26%)	1 / 181 (0.55%)	5 / 239 (2.09%)	0 / 3 (0.00%)	2 / 194 (1.03%)	2 / 62 (3.23%)	2 / 197 (1.02%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	4	1	5	0	2	2	2	0	0	0	0	0
Pharyngitis bacterial
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Pharyngitis streptococcal
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	2 / 238 (0.84%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	2	0	0	0	1	0	1	0	0	0	0	0
Post-acute COVID-19 syndrome
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	1 / 62 (1.61%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Pneumonia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	2 / 238 (0.84%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	1
Pustule
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Respiratory tract infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	4 / 181 (2.21%)	2 / 239 (0.84%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	4	2	0	1	0	1	0	0	0	0	0
Rhinitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	3 / 238 (1.26%)	2 / 181 (1.10%)	2 / 239 (0.84%)	0 / 3 (0.00%)	3 / 194 (1.55%)	0 / 62 (0.00%)	2 / 197 (1.02%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	3	2	2	0	3	0	2	0	0	0	0	0
Sinusitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	5 / 238 (2.10%)	6 / 181 (3.31%)	1 / 239 (0.42%)	0 / 3 (0.00%)	4 / 194 (2.06%)	0 / 62 (0.00%)	3 / 197 (1.52%)	0 / 54 (0.00%)	0 / 53 (0.00%)	2 / 62 (3.23%)	1 / 62 (1.61%)	0 / 63 (0.00%)
occurrences all number	0	0	0	7	6	1	0	4	0	3	0	0	2	1	0
Skin infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0
Sinusitis bacterial
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Suspected COVID-19
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	3 / 238 (1.26%)	3 / 181 (1.66%)	2 / 239 (0.84%)	0 / 3 (0.00%)	3 / 194 (1.55%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	3	3	2	0	3	0	1	0	0	0	0	0
Tonsillitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	3 / 181 (1.66%)	6 / 239 (2.51%)	0 / 3 (0.00%)	2 / 194 (1.03%)	0 / 62 (0.00%)	4 / 197 (2.03%)	0 / 54 (0.00%)	1 / 53 (1.89%)	1 / 62 (1.61%)	1 / 62 (1.61%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	3	6	0	2	0	4	0	1	1	2	1
Tinea versicolour
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Tonsillitis bacterial
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	2 / 238 (0.84%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	2	0	1	0	0	0	1	0	0	0	0	0
Tooth abscess
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Tonsillitis streptococcal
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	1 / 62 (1.61%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Tracheitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	2 / 12 (16.67%)	2 / 13 (15.38%)	0 / 4 (0.00%)	12 / 238 (5.04%)	8 / 181 (4.42%)	16 / 239 (6.69%)	0 / 3 (0.00%)	8 / 194 (4.12%)	4 / 62 (6.45%)	12 / 197 (6.09%)	2 / 54 (3.70%)	2 / 53 (3.77%)	1 / 62 (1.61%)	2 / 62 (3.23%)	7 / 63 (11.11%)
occurrences all number	2	2	0	15	11	19	0	8	5	12	2	2	2	2	7
Viral infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	4 / 238 (1.68%)	3 / 181 (1.66%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	5	3	0	0	1	0	1	0	0	2	0	0
Viral pharyngitis
subjects affected / exposed	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	1	0	0	1	1	0	0	0	0	0	0	0	0	0
Viral rash
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Vulval abscess
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	1 / 62 (1.61%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0
Vulvovaginal candidiasis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	1	0	2	0	0	0	0	0	0	0
Vulvovaginal mycotic infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	2	0	0	1	0	0	0	0	0	0	0
Vulvovaginitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Metabolism and nutrition disorders
Hypercholesterolaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0
Decreased appetite
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	2 / 181 (1.10%)	0 / 239 (0.00%)	0 / 3 (0.00%)	1 / 194 (0.52%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	2	0	0	1	0	1	0	2	0	0	0
Hypovitaminosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Insulin resistance
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 238 (0.42%)	0 / 181 (0.00%)	1 / 239 (0.42%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0
Vitamin D deficiency
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	1 / 181 (0.55%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	1 / 197 (0.51%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	1	0	0
Iron deficiency
subjects affected / exposed	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 238 (0.00%)	0 / 181 (0.00%)	0 / 239 (0.00%)	0 / 3 (0.00%)	0 / 194 (0.00%)	0 / 62 (0.00%)	0 / 197 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1

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Were there any global substantial amendments to the protocol? Yes

21 Jun 2021

This protocol was amended primarily for 3 reasons: 1. To eliminate the Tdap vaccine in the Phase II Formulation and Schedule-finding and replace by placebo to avoid potential confounding factors that might impact selection of dosage and schedule for further development which is one of the primary aims of the study. 2. Due to the decision to parallelly test low and high dose in Phase II Formulation and Schedule-finding, the alpha has been split leading to an increase in the sample size to maintain the power of the analysis. 3. Increasing the number of participants in Phase II sourcing to support the meningitis assay development, clinical testing and maintenance strategies. Additionally, considering that some of the study interventions are combination products constituted of a device and biologic product (pre-filled syringes), the amended protocol provides instructions for collection of safety information related to the use of medical devices. Additional changes have been made to align with the current guidelines or to improve the clarity of the text.

29 Sep 2021

The study design for Phase II Formulation and Schedule Findings has been updated.

22 Mar 2022

This protocol has been amended to add dosing schedules in the Phase II Sourcing part to support the further assay development.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase I/II, randomised, controlled study to assess the safety, effectiveness and immune response of meningococcal combined ABCWY vaccine when administered to healthy adults (Phase I) and to healthy adolescents and adults (Phase II).

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of participants with solicited administration site events in study Phase I (Safety Lead-in) Day 1

Primary: Number of participants with solicited administration site events in study Phase I (Safety Lead-in) Day 1

Primary: Number of participants with solicited administration site events in study Phase I (Safety Lead-in) at Day 31

Primary: Number of participants with solicited administration site events in study Phase I (Safety Lead-in) at Day 31

Primary: Number of participants with solicited systemic events in study Phase I (Safety Lead-in) Day 1

Primary: Number of participants with solicited systemic events in study Phase I (Safety Lead-in) Day 1

Primary: Number of participants with solicited systemic events in study Phase I (Safety Lead-in) Day 31

Primary: Number of participants with solicited systemic events in study Phase I (Safety Lead-in) Day 31

Primary: Number of participants with any unsolicited adverse events (AEs), including all serious adverse events (SAEs), AEs leading to withdrawal and AEs of special interest (AESIs) in study Phase I (Safety Lead-in)

Primary: Number of participants with any unsolicited adverse events (AEs), including all serious adverse events (SAEs), AEs leading to withdrawal and AEs of special interest (AESIs) in study Phase I (Safety Lead-in)

Primary: Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase I (Safety Lead-in)

Primary: Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase I (Safety Lead-in)

Primary: Number of participants with any unsolicited AEs, including all SAEs, AEs leading to withdrawal and AESIs in study Phase I (Safety Lead-in)

Primary: Number of participants with any unsolicited AEs, including all SAEs, AEs leading to withdrawal and AESIs in study Phase I (Safety Lead-in)

Primary: Number of participants with change from baseline in haematological and biochemical laboratory values, in study Phase I (Safety Lead-in)

Primary: Number of participants with change from baseline in haematological and biochemical laboratory values, in study Phase I (Safety Lead-in)

Primary: Number of Participants with Clinically Significant Haematological and Biochemical Laboratory Values, in study Phase I (Safety Lead-in)

Primary: Number of Participants with Clinically Significant Haematological and Biochemical Laboratory Values, in study Phase I (Safety Lead-in)

Primary: Percentage of blood samples with bactericidal serum activity using enc-hSBA against a panel of 110 randomly selected endemic US N. meningitidis serogroup B invasive disease strains at study Phase II (Formulation and Schedule-finding)

Primary: Percentage of blood samples with bactericidal serum activity using enc-hSBA against a panel of 110 randomly selected endemic US N. meningitidis serogroup B invasive disease strains at study Phase II (Formulation and Schedule-finding)

Primary: Number of participants with a 4-fold rise in hSBA titers against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding) At Day 211

Primary: Number of participants with a 4-fold rise in hSBA titers against serogroups A, C, W and Y in study Phase II (Formulation and Schedule-finding) At Day 211

Primary: Number of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding) at Day 1

Primary: Number of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding) at Day 1

Primary: Number of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding) at Day 121

Primary: Number of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding) at Day 121

Primary: Number of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding) at Day 181

Primary: Number of participants with solicited administration site events in study Phase II (Formulation and Schedule-finding) at Day 181

Primary: Number of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding) at Day 1

Primary: Number of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding) at Day 1

Primary: Number of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding) at Day 121

Primary: Number of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding) at Day 121

Primary: Number of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding) at Day 181

Primary: Number of participants with solicited systemic events in study Phase II (Formulation and Schedule-finding) at Day 181

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding) at Day 1

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding) at Day 1

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding) at Day 121

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding) at Day 121

Primary: Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Formulation and Schedule-Finding)

Primary: Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Formulation and Schedule-Finding)

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding) at Day 181

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Formulation and Schedule-finding) at Day 181

Primary: Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 1

Primary: Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 1

Primary: Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 31

Primary: Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 31

Primary: Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 61

Primary: Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 61

Primary: Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 181

Primary: Number of participants with solicited administration site events in study Phase II (Sourcing) at Day 181

Primary: Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 1

Primary: Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 1

Primary: Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 31

Primary: Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 31

Primary: Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 61

Primary: Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 61

Primary: Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 181

Primary: Number of participants with solicited systemic events in study Phase II (Sourcing) at Day 181

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 1

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 1

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 31

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 31

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 61

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 61

Primary: Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Sourcing) Day 1 through Day 211

Primary: Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Sourcing) Day 1 through Day 211

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 181

Primary: Number of participants with any unsolicited AEs (including all SAEs, AEs leading to withdrawal, and AESIs) in study Phase II (Sourcing) at Day 181

Primary: Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Sourcing) Day 1 through Day 241

Primary: Number of participants with SAEs, AEs leading to withdrawal and AESIs in study Phase II (Sourcing) Day 1 through Day 241

Clinical Trial Results:
A Phase I/II, randomised, controlled study to assess the safety, effectiveness and immune response of meningococcal combined ABCWY vaccine when administered to healthy adults (Phase I) and to healthy adolescents and adults (Phase II).