Download PDF

Clinical Trial Results:
A Phase I/II, randomized, placebo-controlled, observer-blind, multicenter study to evaluate the safety, reactogenicity and immunogenicity of GSK Biologicals’ investigational respiratory syncytial virus (RSV) vaccine (adjuvanted with AS01E or AS01B or unadjuvanted) when administered intramuscularly according to a 0, 2 month schedule in adults aged 18 40 or 60-80 years.

Summary
EudraCT number	2018-000849-38
Trial protocol	BE
Global end of trial date	23 Feb 2021

Results information
Results version number	v2(current)
This version publication date	10 Sep 2022
First version publication date	10 Mar 2022
Other versions	v1
Version creation reason

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

208851

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

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

Public contact

GSK Response Center, GSKClinicalSupportHD@gsk.com, 044 2089-904466, GSKClinicalSupportHD@gsk.com

Scientific contact

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

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

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

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

Analysis stage

Final

Date of interim/final analysis

31 Mar 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

12 Dec 2019

Global end of trial reached?

Yes

Global end of trial date

23 Feb 2021

Was the trial ended prematurely?

Main objective of the trial

To evaluate the safety and reactogenicity of 2 doses of the investigational RSV vaccine administered IM according to a 0, 2 month schedule, up to one month after the last dose (Day 91, Visit 6).

Protection of trial subjects

The subjects were observed closely for at least 60 minutes following the administration of the vaccines, with appropriate medical treatment readily available in case of anaphylaxis.

Background therapy

Evidence for comparator

Actual start date of recruitment

21 Jan 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 333

Country: Number of subjects enrolled

United States: 720

Worldwide total number of subjects

1053

EEA total number of subjects

333

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

387

From 65 to 84 years

666

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

1053 participants received the study vaccine or placebo and were included in the Exposed Set.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Single blind ^[1]

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

The study was conducted in an observer-blind manner during the vaccination phase. The persistence phase of Part B was considered as single-blind, given that the availability of safety results from the First analysis may have led to unblinding of specific subjects. The subjects remained blinded up to the study end.

Are arms mutually exclusive

Yes

Low Dose_PLAIN_A Group

Arm description

Subjects in Part A, aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted low dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Arm type

Experimental

Investigational medicinal product name

RSV Vaccine (GSK3844766A) unadjuvanted low dose

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

Medium Dose_PLAIN_A Group

Arm description

Subjects in Part A aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted medium dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Arm type

Experimental

Investigational medicinal product name

RSV Vaccine (GSK3844766A) unadjuvanted medium dose

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

High Dose_PLAIN_A Group

Arm description

Subjects in Part A aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted high dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Arm type

Experimental

Investigational medicinal product name

RSV Vaccine (GSK3844766A) unadjuvanted high dose

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

Placebo_A Group

Arm description

Subjects in Part A aged 18-40 years, receiving 2 doses of placebo (Saline solution) control, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Arm type

Placebo

Investigational medicinal product name

Placebo (Saline solution)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

Low Dose_PLAIN_B Group

Arm description

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted low dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Arm type

Experimental

Investigational medicinal product name

RSV Vaccine (GSK3844766A) unadjuvanted low dose

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

Medium Dose_PLAIN_B Group

Arm description

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted medium dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Arm type

Experimental

Investigational medicinal product name

RSV Vaccine (GSK3844766A) unadjuvanted medium dose

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

High Dose_PLAIN_B Group

Arm description

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted high dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Arm type

Experimental

Investigational medicinal product name

RSV Vaccine (GSK3844766A) unadjuvanted high dose

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

Low Dose_AS01E_B Group

Arm description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Arm type

Experimental

Investigational medicinal product name

RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01E

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

Medium Dose_AS01E_B Group

Arm description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Arm type

Experimental

Investigational medicinal product name

RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01E

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

High Dose_AS01E_B Group

Arm description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Arm type

Experimental

Investigational medicinal product name

RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

Low Dose_AS01B_B Group

Arm description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Arm type

Experimental

Investigational medicinal product name

RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01B

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

Medium Dose_AS01B_B Group

Arm description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Arm type

Experimental

Investigational medicinal product name

RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01B

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

High Dose_AS01B_B Group

Arm description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Arm type

Experimental

Investigational medicinal product name

RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01B

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

Placebo_B Group

Arm description

Subjects in Part B aged 60-80 years, receiving 2 doses of placebo (Saline solution) control, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Arm type

Placebo

Investigational medicinal product name

Placebo (Saline solution)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

Notes
[1] - The number of roles blinded appears inconsistent with a single blinded trial. It is expected that there will be one role blinded in a single blind trial.
Justification: The study was conducted in an observer-blind manner during the vaccination phase. The persistence phase of Part B was considered as single-blind, given that the availability of safety results from the First analysis may have led to unblinding of specific subjects. The subjects remained blinded up to the study end.

Number of subjects in period 1	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Started	12	12	12	12	101	97	100	101	101	100	103	100	101	101
Completed	12	10	11	12	100	92	97	95	101	95	100	100	97	98
Not completed	0	2	1	0	1	5	3	6	0	5	3	0	4	3
Adverse event, non-fatal	-	-	-	-	-	1	1	1	-	-	1	-	3	-
CONSENT WITHDRAWAL,DUE TO COVID-19 BUT NOT TO AEs	-	-	-	-	-	-	-	-	-	1	-	-	-	-
MIGRATED / MOVED FROM THE STUDY AREA	-	-	-	-	-	-	-	1	-	1	-	-	-	-
Lost to follow-up	-	2	1	-	1	1	1	1	-	-	1	-	-	1
UNKNOWN REASON	-	-	-	-	-	-	-	1	-	-	-	-	-	-
CONSENT WITHDRAWAL,NOT DUE TO COVID-19 OR TO AN AE	-	-	-	-	-	3	1	2	-	3	1	-	1	2

Baseline characteristics

Top of page

Reporting group title

Low Dose_PLAIN_A Group

Reporting group description

Subjects in Part A, aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted low dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Medium Dose_PLAIN_A Group

Reporting group description

Subjects in Part A aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted medium dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

High Dose_PLAIN_A Group

Reporting group description

Subjects in Part A aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted high dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Placebo_A Group

Reporting group description

Subjects in Part A aged 18-40 years, receiving 2 doses of placebo (Saline solution) control, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Low Dose_PLAIN_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted low dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Medium Dose_PLAIN_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted medium dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

High Dose_PLAIN_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted high dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Low Dose_AS01E_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Medium Dose_AS01E_B Group

Reporting group description

Reporting group title

High Dose_AS01E_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Low Dose_AS01B_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Medium Dose_AS01B_B Group

Reporting group description

Reporting group title

High Dose_AS01B_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Placebo_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of placebo (Saline solution) control, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group values	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group	Total
Number of subjects	12	12	12	12	101	97	100	101	101	100	103	100	101	101	1053
Age categorical
Units: Subjects
Adults (18-64 years)	12	12	12	12	38	34	26	28	43	37	33	32	36	32	387
From 65-84 years	0	0	0	0	63	63	74	73	58	63	70	68	65	69	666
Age continuous
Units: years
arithmetic mean (standard deviation)	31.2 ± 7.0	26.5 ± 4.0	29.9 ± 6.1	31.6 ± 5.6	67.3 ± 5.6	67.8 ± 5.6	67.9 ± 4.9	67.8 ± 5.1	67.1 ± 5.6	67.6 ± 5.2	67.6 ± 4.9	67.5 ± 4.9	67.5 ± 4.9	68.1 ± 5.7	-
Sex: Female, Male
Units: Participants
FEMALE	8	7	7	9	58	54	57	58	57	57	59	58	57	58	604
MALE	4	5	5	3	43	43	43	43	44	43	44	42	44	43	449
Race/Ethnicity, Customized
Units: Subjects
AMERICAN INDIAN OR ALASKA NATIVE	0	0	0	0	1	0	0	0	0	1	0	0	0	0	2
ASIAN	0	1	0	0	0	0	0	1	0	0	0	0	1	0	3
BLACK OR AFRICAN AMERICAN	2	1	2	1	5	7	4	12	7	5	11	7	7	4	75
OTHER	0	0	0	0	0	0	3	0	0	1	0	0	1	0	5
WHITE	10	10	10	11	95	90	93	88	94	93	92	93	92	97	968

End points

Top of page

Reporting group title

Low Dose_PLAIN_A Group

Reporting group description

Subjects in Part A, aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted low dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Medium Dose_PLAIN_A Group

Reporting group description

Subjects in Part A aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted medium dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

High Dose_PLAIN_A Group

Reporting group description

Subjects in Part A aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted high dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Placebo_A Group

Reporting group description

Subjects in Part A aged 18-40 years, receiving 2 doses of placebo (Saline solution) control, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Low Dose_PLAIN_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted low dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Medium Dose_PLAIN_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted medium dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

High Dose_PLAIN_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted high dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Low Dose_AS01E_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Medium Dose_AS01E_B Group

Reporting group description

Reporting group title

High Dose_AS01E_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Low Dose_AS01B_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Medium Dose_AS01B_B Group

Reporting group description

Reporting group title

High Dose_AS01B_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Placebo_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of placebo (Saline solution) control, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Primary: Number of subjects with any solicited local symptoms after first vaccination dose

Top of page

End point title

Number of subjects with any solicited local symptoms after first vaccination dose ^[1]

End point description

Assessed solicited local AEs at injection site are pain, erythema and swelling. Any erythema/swelling was scored as injection site erythema/swelling with a diameter larger than (>) 20 millimeters (mm)

End point type

Primary

End point timeframe

During a 7-day follow-up period after first vaccination dose (i.e., on the day of vaccination [at Day 1] and 6 subsequent days)

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 scope of this endpoint analysis was descriptive, therefore no statistical analyses apply for this endpoint.

End point values	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	12	12	11	12	100	96	99	101	100	100	103	99	101	98
Units: Participants
Erythema	0	1	0	0	0	1	2	5	6	9	16	15	18	1
Pain	1	7	6	0	9	5	14	54	57	56	78	63	76	4
Swelling	0	0	0	0	0	0	2	7	7	6	10	7	9	0

No statistical analyses for this end point

Primary: Number of subjects with any solicited local symptoms after second vaccination dose

Top of page

End point title

Number of subjects with any solicited local symptoms after second vaccination dose ^[2]

End point description

End point type

Primary

End point timeframe

During a 7-day follow-up period after second vaccination dose (i.e., on the day of vaccination [at Day 61] and 6 subsequent days)

Notes
[2] - 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 scope of this endpoint analysis was descriptive, therefore no statistical analyses apply for this endpoint.

End point values	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	12	10	11	12	95	91	90	94	94	95	96	93	93	97
Units: Participants
Erythema	0	0	0	0	1	0	2	3	3	7	16	14	12	0
Pain	5	7	8	1	18	18	23	34	48	47	58	56	59	4
Swelling	0	0	0	0	0	1	2	3	3	6	10	7	10	0

No statistical analyses for this end point

Primary: Number of subjects with any solicited general symptom after first vaccination dose

Top of page

End point title

Number of subjects with any solicited general symptom after first vaccination dose ^[3]

End point description

Assessed solicited general symptoms include arthralgia, fatigue, fever [defined as temperature equal to or above 38.0 degrees Celsius (°C)], gastrointestinal symptoms [nausea, vomiting, diarrhea and/or abdominal pain], headache, myalgia and shivering.

End point type

Primary

End point timeframe

During a 7-day follow-up period after the first vaccination dose (i.e., on the day of vaccination [at Day 1] and 6 subsequent days)

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 scope of this endpoint analysis was descriptive, therefore no statistical analyses apply for this endpoint.

End point values	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	12	12	11	12	100	96	99	101	100	100	103	99	101	98
Units: Participants
Arthralgia	0	0	0	0	7	4	0	7	12	6	15	9	17	7
Fatigue	4	5	1	6	22	11	24	26	28	21	30	29	49	16
Fever	0	0	0	0	1	0	0	1	3	1	3	3	1	0
Gastrointestinal symptoms	1	2	1	1	8	8	10	8	8	9	13	7	13	10
Headache	2	4	3	2	8	7	13	20	12	17	28	27	28	8
Myalgia	0	1	1	0	4	3	1	9	8	6	19	12	18	5
Shivering	0	2	0	1	1	1	2	6	5	3	12	8	16	1

No statistical analyses for this end point

Primary: Number of subjects with any solicited general symptom after second vaccination dose

Top of page

End point title

Number of subjects with any solicited general symptom after second vaccination dose ^[4]

End point description

End point type

Primary

End point timeframe

During a 7-day follow-up period after the second vaccination dose (i.e., on the day of vaccination [at Day 61] and 6 subsequent days)

Notes
[4] - 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 scope of this endpoint analysis was descriptive, therefore no statistical analyses apply for this endpoint.

End point values	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	12	10	11	12	95	91	90	94	94	95	96	93	93	97
Units: Participants
Arthralgia	0	0	0	0	1	4	2	8	8	10	21	11	13	4
Fatigue	3	2	4	5	16	11	13	24	22	24	35	35	34	16
Fever	0	0	0	0	0	0	0	3	1	1	4	6	3	0
Gastrointestinal symptoms	1	1	2	2	4	2	7	7	5	7	11	7	9	6
Headache	2	2	3	3	11	9	8	15	18	10	33	26	18	9
Myalgia	0	0	0	0	0	2	3	6	9	11	19	12	18	2
Shivering	0	0	0	0	0	0	0	9	3	4	14	12	9	2

No statistical analyses for this end point

Primary: Number of subjects with any unsolicited adverse events (AEs) after any vaccination dose

Top of page

End point title

Number of subjects with any unsolicited adverse events (AEs) after any vaccination dose ^[5]

End point description

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and/or any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

End point type

Primary

End point timeframe

During a 30-day follow-up period (i.e., on the day of vaccination and 29 subsequent days) after any vaccination dose (across doses)

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 scope of this endpoint analysis was descriptive, therefore no statistical analyses apply for this endpoint.

End point values	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	12	12	12	12	101	97	100	101	101	100	103	100	101	101
Units: Participants	2	4	4	6	34	28	30	40	29	36	39	34	43	33

No statistical analyses for this end point

Primary: Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after first vaccine dose (Part A groups)

Top of page

End point title

Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after first vaccine dose (Part A groups) ^[6] ^[7]

End point description

Assessed hematological laboratory parameters include basophils [BASOs], eosinophils [EOSs], red blood cells [RBCs], hemoglobin [HGB], lymphocytes [LYMs], monocytes [MONOs], neutrophils [NPs], platelets [PLTs], white blood cells [WBCs]. Biochemical laboratory parameters include alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine [CR], urea nitrogen [UN] and uric acid [UA]. Categories reported when comparing Day 1 (pre-vaccination dose 1=baseline) and Day 8 hematological and biochemical laboratory results are defined as follows: <parameter>-<range at baseline>-<range at timing> (e.g. ALT-W-W). Ranges level being classified as unknown [U], below [B], within [W] or above [A] the normal ranges.

End point type

Primary

End point timeframe

At baseline and at 7 days after the first vaccine dose (Day 8)

Notes
[6] - 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 scope of this endpoint analysis was descriptive, therefore no statistical analyses apply for this endpoint.
[7] - 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: This endpoint is presented separately for Part A and Part B groups due to character limits in the Category Title field.

End point values	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group
Number of subjects analysed	12	12	11	12
Units: Participants
ALT-W-W (N=12,12,11,12)	12	12	11	12
AST-W-W (N=11,12,11,11)	11	12	11	11
AST-A-W (N=1,0,0,1)	1	0	0	1
BASOs-W-W (N=12,12,11,12)	12	12	11	12
CR-B-B (N=1,2,0,1)	0	0	0	1
CR-B-W (N=1,2,0,1)	1	2	0	0
CR-W-W (N=11,9,11,11)	11	9	11	11
CR-A-A (N=0,1,0,0)	0	1	0	0
EOSs-B-B (N=0,1,1,0)	0	1	0	0
EOSs-B-W (N=0,1,1,0)	0	0	1	0
EOSs-W-W (N=11,10,10,12)	11	10	10	12
EOSs-A-W (N=1,1,0,0)	1	1	0	0
RBCs-B-W (N=1,0,0,1)	1	0	0	1
RBCs-W-W (N=11,11,11,11)	11	11	11	11
RBCs-A-W (N=0,1,0,0)	0	1	0	0
HGB-B-B (N=1,0,0,1)	0	0	0	1
HGB-B-W (N=1,0,0,1)	1	0	0	0
HGB-W-W (N=11,12,11,11)	11	12	11	11
LYMs-B-W (0,1,0,1)	0	1	0	1
LYMs-W-W (N=12,11,11,11)	12	11	11	11
MONOs-B-W (N=0,1,0,0)	0	1	0	0
MONOs-W-W (N=12,11,11,12)	12	11	11	12
NPs-B-B (N=2,1,1,0)	0	0	1	0
NPs-B-W (N=2,1,1,0)	2	1	0	0
NPs-W-W (N=8,11,10, 12)	8	11	10	12
NPs-A-W (N=2,0,0,0)	1	0	0	0
NPs-A-A (N=2,0,0,0)	1	0	0	0
PLTs-W-W (N=12,12,11,12)	12	12	11	12
UN-W-B (N=12,12,11,12)	0	0	0	1
UN-W-W (N=12,12,11,12)	12	12	11	11
UA-B-W (N=1,0,0,0)	1	0	0	0
UA-W-W (N=11,12,11,12)	11	12	11	12
WBCs-B-B (N=2,1,1,1)	0	1	0	0
WBCs-B-W (N=2,1,1,1)	2	0	1	1
WBCs-W-W (N=8,11,10,11)	8	11	10	11
WBCs-A-W (N=2,0,0,0)	1	0	0	0
WBCs-A-A (N=2,0,0,0)	1	0	0	0

No statistical analyses for this end point

Primary: Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after first vaccine dose (Part B groups)

Top of page

End point title

Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after first vaccine dose (Part B groups) ^[8] ^[9]

End point description

End point type

Primary

End point timeframe

At baseline and at 7 days after the first vaccine dose (Day 8)

Notes
[8] - 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 scope of this endpoint analysis was descriptive, therefore no statistical analyses apply for this endpoint.
[9] - 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: This endpoint is presented separately for Part A and Part B groups due to character limits in the Category Title field.

End point values	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	101	97	99	100	100	100	103	100	101	101
Units: Participants
ALT-W-U (N=100,97,99, 98,98,100,100,95,99,100)	0	0	0	1	0	0	0	0	1	1
ALT-W-W (N=100,97,99,98,98,100,100,95,99,100)	99	97	98	97	98	100	100	94	98	98
ALT-W-A (N=100,97,99,98,98,100,100,95,99,100)	1	0	1	0	0	0	0	1	0	1
ALT-A-W (N=1,0,0,2,2,0,3,5,2,1)	0	0	0	0	2	0	0	2	0	0
ALT-A-A (N=1,0,0,2,2,0,3,5,2,1)	1	0	0	2	0	0	3	3	2	1
AST-W-U (N=101,97,99,100,99,99,99,98,100,101)	0	0	0	1	0	1	2	1	1	1
AST-W-W (N=101,97,99,100,99,99,99,98,100,101)	100	97	98	98	99	98	97	97	98	99
AST-W-A (N=101,97,99,100,99,99,99,98,100,101)	1	0	1	1	0	0	0	0	1	1
AST-A-W (N=0,0,0,0,1,1,4,2,1,0)	0	0	0	0	1	1	1	1	0	0
AST-A-A(N=0,0,0,0,1,1,4,2,1,0)	0	0	0	0	0	0	3	1	1	0
BASOs-W-U(N=101,97,99,100,100,100,103,100,101,101)	0	1	0	1	4	2	0	0	0	0
BASOs-W-W(N=101,97,99,100,100,100,103,100,101,101)	100	96	99	99	96	98	103	100	101	100
BASOs-W-A(N=101,97,99,100,100,100,103,100,101,101)	1	0	0	0	0	0	0	0	0	1
CR-B-B (N=1,8,6,3,5,2,4,5,5,1)	0	5	4	3	4	0	1	3	2	0
CR-B-W (N=1,8,6,3,5,2,4,5,5,1)	1	3	2	0	1	2	3	2	3	1
CR-W-U (N=94,85,92,94,95,95,97,92,94,99)	0	0	0	0	0	0	0	0	1	1
CR-W-B (N=94,85,92,94,95,95,97,92,94,99)	1	1	1	1	1	1	1	1	5	3
CR-W-W (N=94,85,92,94,95,95,97,92,94,99)	92	83	89	92	92	93	93	90	88	95
CR-W-A (N=94,85,92,94,95,95,97,92,94,99)	1	1	2	1	2	1	3	1	0	0
CR-A-U (N=6,4,1,3,0,3,2,3,2,1)	0	0	0	1	0	0	0	0	0	0
CR-A-W (N=6,4,1,3,0,3,2,3,2,1)	2	0	0	1	0	1	0	1	0	0
CR-A-A (N=6,4,1,3,0,3,2,3,2,1)	4	4	1	1	0	2	2	2	2	1
EOSs-B-B (N=7,6,5,4,4,7,9,6,5,3)	2	3	4	0	3	5	3	4	2	2
EOSs-B-W (N=7,6,5,4,4,7,9,6,5,3)	5	3	1	3	1	2	5	2	3	1
EOSs-B-A (N=7,6,5,4,4,7,9,6,5,3)	0	0	0	1	0	0	1	0	0	0
EOSs-W-U (N=90,89,90,94,95,92,91,92,94,96)	0	1	0	1	4	2	0	0	0	0
EOSs-W-B (N=90,89,90,94,95,92,91,92,94,96)	3	1	2	2	1	1	3	5	3	5
EOSs-W-W (N=90,89,90,94,95,92,91,92,94,96)	85	86	88	91	89	88	88	86	90	90
EOSs-W-A (N=90,89,90,94,95,92,91,92,94,96)	2	1	0	0	1	1	0	1	1	1
EOSs-A-W (N=4,2,4,2,1,1,3,2,2,2)	2	1	4	1	0	0	0	0	0	2
EOSs-A-A (N=4,2,4,2,1,1,3,2,2,2)	2	1	0	1	1	1	3	2	2	0
RBCs-B-B (N=5,4,1,1,4,4,2,1,3,3)	4	3	0	1	4	3	2	1	1	2
RBCs-B-W (N=5,4,1,1,4,4,2,1,3,3)	1	1	1	0	0	1	0	0	2	1
RBCs-W-U (N=95,91,96,99,95,94,97,98,97,95)	0	1	0	1	3	2	0	0	0	0
RBCs-W-B (N=95,91,96,99,95,94,97,98,97,95)	5	1	0	0	3	3	2	1	4	1
RBCs-W-W (N=95,91,96,99,95,94,97,98,97,95)	89	89	95	98	88	89	95	96	93	94
RBCs-W-A (N=95,91,96,99,95,94,97,98,97,95)	1	0	1	0	1	0	0	1	0	0
RBCs-A-W (N=1,2,2,0,1,2,4,1,1,3)	0	1	1	0	1	0	2	1	1	0
RBCs-A-A (N=1,2,2,0,1,2,4,1,1,3)	1	1	1	0	0	2	2	0	0	3
HGB-B-U (N=10,8,1,5,7,6,4,4,9,2)	0	1	0	0	0	0	0	0	0	0
HGB-B-B (N=10,8,1,5,7,6,4,4,9,2)	9	5	1	4	7	4	4	3	5	1
HGB-B-W (N=10,8,1,5,7,6,4,4,9,2)	1	2	0	1	0	2	0	1	4	1
HGB-W-U (N=91,86,97,93,92, 94,98, 95, 91,98)	0	0	0	1	3	2	0	0	0	0
HGB-W-B (N=91,86,97,93,92, 94,98, 95, 91,98)	4	3	1	1	1	2	2	3	5	2
HGB-W-W (N=91,86,97,93,92, 94,98, 95, 91,98)	87	83	96	91	88	90	96	90	86	95
HGB-W-A (N=91,86,97,93,92, 94,98, 95, 91,98)	0	0	0	0	0	0	0	2	0	1
HGB-A-W (N=0,3,1,2,1,0,1,1,1,1)	0	2	1	1	0	0	1	0	1	1
HGB-A-A (N=0,3,1,2,1,0,1,1,1,1)	0	1	0	1	1	0	0	1	0	0
LYMs-B-B (N=2,2,0,3,3,3,4,2,1,1)	1	0	0	1	0	1	2	1	0	1
LYMs-B-W (N=2,2,0,3,3,3,4,2,1,1)	1	2	0	2	3	2	2	1	1	0
LYMs-W-U (N=99,94,99,97,96,97,99, 98,100,100)	0	1	0	1	4	2	0	0	0	0
LYMs-W-B (N=99,94,99,97,96,97,99, 98,100,100)	0	1	0	1	1	0	3	0	0	2
LYMs-W-W (N=99,94,99,97,96,97,99, 98,100,100)	99	92	99	94	90	94	96	98	100	98
LYMs-W-A (N=99,94,99,97,96,97,99, 98,100,100)	0	0	0	1	1	1	0	0	0	0
LYMs-A-W (N=0,1,0,0,1,0,0,0,0,0)	0	1	0	0	0	0	0	0	0	0
LYMs-A-A (N=0,1,0,0,1,0,0,0,0,0)	0	0	0	0	1	0	0	0	0	0
MONOs-B-U (N=4,2,3,2,1,4,5,6,4,3)	0	0	0	0	0	1	0	0	0	0
MONOs-B-B (N=4,2,3,2,1,4,5,6,4,3)	1	1	0	0	1	2	0	5	2	0
MONOs-B-W (N=4,2,3,2,1,4,5,6,4,3)	3	1	3	2	0	1	5	1	2	3
MONOs-W-U (N=97,95,96,98,99,96,98,94,97,98)	0	1	0	1	4	1	0	0	0	0
MONOs-W-B (N=97,95,96,98,99,96,98,94,97,98)	5	0	2	0	1	3	2	1	4	3
MONOs-W-W (N=97,95,96,98,99,96,98,94,97,98)	91	94	94	97	92	91	96	92	93	95
MONOs-W-A (N=97,95,96,98,99,96,98,94,97,98)	1	0	0	0	2	1	0	1	0	0
NPs-B-B (N=1,1,3,4,1,4,3,1,2,7)	1	0	2	1	1	1	2	0	1	5
NPs-B-W (N=1,1,3,4,1,4,3,1,2,7)	0	1	1	3	0	3	1	1	1	2
NPs-W-U (N=100,96,96,93,99,94,98,98,99,93)	0	1	0	1	4	2	0	0	0	0
NPs-W-B (N=100,96,96,93,99,94,98,98,99,93)	2	1	1	2	2	2	0	1	1	0
NPs-W-W (N=100,96,96,93,99,94,98,98,99,93)	98	94	95	89	92	88	98	96	96	93
NPs-W-A (N=100,96,96,93,99,94,98,98,99,93)	0	0	0	1	1	2	0	1	2	0
NPs-A-W (N=0,0,0,3,0,2,2,1,0,1)	0	0	0	2	0	2	2	1	0	1
NPs-A-A (N=0,0,0,3,0,2,2,1,0,1)	0	0	0	1	0	0	0	0	0	0
PLTs-U-U (N=0,0,1,0,0,0,0,0,0,0)	0	0	1	0	0	0	0	0	0	0
PLTs-B-B (N=3,1,3,1,2,3,2,1,2,2)	3	1	2	1	1	2	0	1	1	2
PLTs-B-W (N=3,1,3,1,2,3,2,1,2,2)	0	0	1	0	1	1	2	0	1	0
PLTs-W-U (N=97,96,95,97,98,96,101,97,98,96)	1	1	0	3	6	3	2	0	1	0
PLTs-W-B (N=97,96,95,97,98,96,101,97,98,96)	0	1	0	1	1	0	1	0	0	0
PLTs-W-W (N=97,96,95,97,98,96,101,97,98,96)	96	94	94	93	90	93	97	96	96	96
PLTs-W-A (N=97,96,95,97,98,96,101,97,98,96)	0	0	1	0	1	0	1	1	1	0
PLTs-A-W (N=1,0,0,2,0,1,0,2,1,3)	0	0	0	1	0	0	0	1	0	0
PLTs-A-A (N=1,0,0,2,0,1,0,2,1,3)	1	0	0	1	0	1	0	1	1	3
UN-B-B (N=0,0,0,1,0,0,1,0,0,0,)	0	0	0	1	0	0	1	0	0	0
UN-W-U (N=98,97,98,98,98,93,99,98,100,100)	0	0	0	1	0	0	0	0	1	1
UN-W-B (N=98,97,98,98,98,93,99,98,100,100)	0	0	0	0	0	0	1	0	0	0
UN-W-W (N=98,97,98,98,98,93,99,98,100,100)	97	96	95	95	97	93	96	96	98	98
UN-W-A (N=98,97,98,98,98,93,99,98,100,100)	1	1	3	2	1	0	2	2	1	1
UN-A-W (N=3,0,1,1,2,7,3,2,1,1)	0	0	1	0	2	5	2	2	0	1
UN-A-A (N=3,0,1,1,2,7,3,2,1,1)	3	0	0	1	0	2	1	0	1	0
UA-B-B (N=1,2,0,3,0,2,7,4,2,3)	1	0	0	3	0	1	5	3	2	2
UA-B-W (N=1,2,0,3,0,2,7,4,2,3)	0	2	0	0	0	1	2	1	0	1
UA-W-U (N=95,94,96,96,99,93,93,91,96,94)	0	0	0	1	0	0	0	0	1	1
UA-W-B (N=95,94,96,96,99,93,93,91,96,94)	0	0	0	0	0	2	1	2	0	1
UA-W-W (N=95,94,96,96,99,93,93,91,96,94)	94	91	96	93	98	90	89	88	95	89
UA-W-A (N=95,94,96,96,99,93,93,91,96,94)	1	3	0	2	1	1	3	1	0	3
UA-A-W (N=5,1,3,1,1,5,3,5,3,4)	2	1	1	0	1	2	2	2	3	2
UA-A-A (N=5,1,3,1,1,5,3,5,3,4)	3	0	2	1	0	3	1	3	0	2
WBCs-B-U (N=3,1,4,6,3,5,5,4,5,10)	0	0	0	0	0	1	0	0	0	0
WBCs-B-B (N=3,1,4,6,3,5,5,4,5,10)	1	0	2	2	2	1	3	0	1	4
WBCs-B-W (N=3,1,4,6,3,5,5,4,5,10)	2	1	2	4	1	3	2	4	4	6
WBCs-W-U (N=96,95,95,91,95,93,96,94,95,91)	0	1	0	1	4	1	0	0	0	0
WBCs-W-B (N=96,95,95,91,95,93,96,94,95,91)	2	2	3	2	1	3	1	1	0	1
WBCs-W-W (N=96,95,95,91,95,93,96,94,95,91)	94	91	91	87	89	87	95	91	93	90
WBCs-W-A (N=96,95,95,91,95,93,96,94,95,91)	0	1	1	1	1	2	0	2	2	0
WBCs-A-W (N=2,1,0,3,2,2,2,2,1,0)	1	0	0	1	1	2	1	2	1	0
WBCs-A-A (N=2,1,0,3,2,2,2,2,1,0)	1	1	0	2	1	0	1	0	0	0

No statistical analyses for this end point

Primary: Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after second vaccine dose (Part A groups)

Top of page

End point title

Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after second vaccine dose (Part A groups) ^[10] ^[11]

End point description

Assessed hematological laboratory parameters include basophils [BASOs], eosinophils [EOSs], red blood cells [RBCs], hemoglobin [HGB], lymphocytes [LYMs], monocytes [MONOs], neutrophils [NPs], platelets [PLTs], white blood cells [WBCs]. Biochemical laboratory parameters include alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine [CR], urea nitrogen [UN] and uric acid [UA]. Categories reported when comparing Day 61 (pre-vaccination dose 2=baseline) and Day 68 hematological and biochemical laboratory results are defined as follows: <parameter>-<range at baseline>-<range at timing> (e.g. ALT-W-W). Ranges level being classified as unknown [U], below [B], within [W] or above [A] the normal ranges.

End point type

Primary

End point timeframe

At baseline and at 7 days after the second vaccine dose (Day 68)

Notes
[10] - 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 scope of this endpoint analysis was descriptive, therefore no statistical analyses apply for this endpoint.
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is presented separately for Part A and Part B groups due to character limits in the Category Title field.

End point values	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group
Number of subjects analysed	12	10	11	12
Units: Participants
ALT-W-W (N=12,10,10,12)	11	10	10	12
ALT-W-A (N=12,10,10,12)	1	0	0	0
ALT-A-W (N=0,0,1,0)	0	0	1	0
AST-W-W (N=11,10,11,12)	10	10	11	12
AST-W-A (N=11,10,11,12)	1	0	0	0
AST-A-A (N=1,0,0,0)	1	0	0	0
BASOs-U-W (N=1,0,0,0)	1	0	0	0
BASOs-W-W (N=11,10,11,12)	11	10	11	12
CR-B-B (N=0,0,0,1)	0	0	0	1
CR-W-W (N=12,9,11,10)	12	7	11	10
CR-W-A (N=12,9,11,10)	0	2	0	0
CR-A-W (N=0,1,0,1)	0	0	0	1
CR-A-A (N=0,1,0,1)	0	1	0	0
EOSs-U-W (N=1,0,0,0)	1	0	0	0
EOSs-B-B (N=0,1,1,0)	0	0	1	0
EOSs-B-W (N=0,1,1,0)	0	1	0	0
EOSs-W-B (N=11,9,10,12)	1	0	1	0
EOSs-W-W (N=11,9,10,12)	10	9	8	12
EOSs-W-A (N=11,9,10,12)	0	0	1	0
RBCs-U-B (N=1,0,0,0)	1	0	0	0
RBCs-W-B (N=11,9,11,12)	1	0	0	0
RBCs-W-W (N=11,9,11,12)	10	9	10	12
RBCs-W-A (N=11,9,11,12)	0	0	1	0
RBCs-A-A (N=0,1,0,0)	0	1	0	0
HGB-U-B (N=1,0,0,0)	1	0	0	0
HGB-B-W (N=0,0,1,0)	0	0	1	0
HGB-W-W (N=11,10,10,12)	11	10	9	12
HGB-W-A (N=11,10,10,12)	0	0	1	0
LYMs-U-W (N=1,0,0,0)	1	0	0	0
LYMs-B-W (N=0,0,0,1)	0	0	0	1
LYMs-W-W (N=11,10,11,11)	11	10	11	11
MONOs-U-W (N=1,0,0,0)	1	0	0	0
MONOs-B-W (N=0,0,1,0)	0	0	1	0
MONOs-W-W (N=11,10,10,12)	11	10	10	12
NPs-U-W (N=1,0,0,0)	1	0	0	0
NPs-B-B (N=1,0,1,0)	0	0	1	0
NPs-B-W (N=1,0,1,0)	1	0	0	0
NPs-W-B (N=10,10,10,12)	1	0	0	0
NPs-W-W (N=10,10,10,12)	9	10	10	12
PLTs-U-W (N=1,1,0,0)	1	1	0	0
PLTs-W-W (N=11,8,11,12)	11	8	11	12
PLTs-A-W (N=0,1,0,0)	0	1	0	0
UN-W-W (N=12,10,11,12)	12	10	11	12
UA-B-W (N=1,0,0,0)	1	0	0	0
UA-W-W (N=11,10,11,12)	11	10	11	12
WBCs-U-W (N=1,0,0,0)	1	0	0	0
WBCs-B-B (N=2,0,1,0)	1	0	1	0
WBCs-B-W (N=2,0,1,0)	1	0	0	0
WBCs-W-B (N=8,10,10,12)	1	0	0	0
WBCs-W-W (N=8,10,10,12)	7	10	10	12
WBCs-A-W (N=1,0,0,0)	1	0	0	0

No statistical analyses for this end point

Primary: Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after second vaccine dose (Part B groups)

Top of page

End point title

Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after second vaccine dose (Part B groups) ^[12] ^[13]

End point description

Assessed hematological laboratory parameters include basophils [BASOs], eosinophils [EOSs], red blood cells [RBCs], hemoglobin [HGB], lymphocytes [LYMs], monocytes [MONOs], neutrophils [NPs], platelets [PLTs], white blood cells [WBCs]. Biochemical laboratory parameters include alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine [CR], urea nitrogen [UN] and uric acid [UA]. Categories reported when comparing Day 61 (pre-vaccination dose 2=baseline) and Day 68 hematological and biochemical laboratory results are defined as follows: <parameter>-<range at baseline>-<range at timing> (e.g. ALT-W-W). Ranges level being classified as unknown [U], below [B], within [W] or above [A] the normal ranges.

End point type

Primary

End point timeframe

At baseline and at 7 days after the second vaccine dose (Day 68)

Notes
[12] - 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 scope of this endpoint analysis was descriptive, therefore no statistical analyses apply for this endpoint.
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is presented separately for Part A and Part B groups due to character limits in the Category Title field.

End point values	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	97	94	95	96	98	97	98	97	97	99
Units: Participants
ALT-U-W (N=1,0,0,1,0,1,1,1,2,0)	1	0	0	1	0	1	1	1	2	0
ALT-W-U (N=95,94,95,93,96,96,95,93,91,97)	0	0	0	0	0	0	0	0	0	1
ALT-W-W (N=95,94,95,93,96,96,95,93,91,97)	93	94	95	93	94	94	95	91	90	96
ALT-W-A (N=95,94,95,93,96,96,95,93,91,97)	2	0	0	0	2	2	0	2	1	0
ALT-A-W (N=1,0,0,2,2,0,2,3,4,2)	1	0	0	1	1	0	1	2	2	0
ALT-A-A (N=1,0,0,2,2,0,2,3,4,2)	0	0	0	1	1	0	1	1	2	2
AST-U-W (N=1,0,0,1,0,1,1,1,2,0)	1	0	0	1	0	1	1	1	2	0
AST-W-U (N=96,93,95,94,97,96,95,95,93,98)	0	0	0	0	0	0	0	0	0	1
AST-W-W (N=96,93,95,94,97,96,95,95,93,98)	94	93	95	93	97	94	95	93	92	97
AST-W-A (N=96,93,95,94,97,96,95,95,93,98)	2	0	0	1	0	2	0	2	1	0
AST-A-W (N=0,1,0,1,1,0,2,1,2,1)	0	1	0	0	1	0	0	0	1	0
AST-A-A (N=0,1,0,1,1,0,2,1,2,1)	0	0	0	1	0	0	2	1	1	1
BASOs-U-W (N=1,0,1,0,2,2,2,1,2,1)	1	0	1	0	2	2	2	1	2	1
BASOs-W-U (N=96,94,94,96,96,95,96,96,95,98)	1	0	0	0	1	1	0	0	0	1
BASOs-W-W (N=96,94,94,96,96,95,96,96,95,98)	95	94	94	96	95	94	96	96	95	97
CR-U-B (N=1,0,0,1,0,1,1,1,2,0)	0	0	0	0	0	0	0	0	1	0
CR-U-W (N=1,0,0,1,0,1,1,1,2,0)	1	0	0	1	0	1	0	1	1	0
CR-U-A (N=1,0,0,1,0,1,1,1,2,0)	0	0	0	0	0	0	1	0	0	0
CR-B-U (N=3,6,3,3,4,1,3,6,7,1)	0	0	0	0	0	0	0	0	0	1
CR-B-B (N=3,6,3,3,4,1,3,6,7,1)	0	4	2	2	4	1	2	3	1	0
CR-B-W (N=3,6,3,3,4,1,3,6,7,1)	3	2	1	1	0	0	1	3	6	0
CR-W-B (N=87,83,90,89,92,94,93,88,87,97	1	2	2	2	3	3	2	1	1	0
CR-W-W (N=87,83,90,89,92,94,93,88,87,97	83	81	86	87	88	90	88	86	83	96
CR-W-A (N=87,83,90,89,92,94,93,88,87,97	3	0	2	0	1	1	3	1	3	1
CR-A-W (N=6,5,2,3,2,1,1,2,1,1)	2	2	0	2	1	0	1	0	0	0
CR-A-A (N=6,5,2,3,2,1,1,2,1,1)	4	3	2	1	1	1	0	2	1	1
EOSs-U-W (N=1,0,1,0,2,2,2,1,2,1)	1	0	1	0	2	1	2	1	2	1
EOSs-U-A (N=1,0,1,0,2,2,2,1,2,1)	0	0	0	0	0	1	0	0	0	0
EOSs-B-U (N=7,5,9,6,8,5,6,8,6,8)	1	0	0	0	0	0	0	0	0	0
EOSs-B-B (N=7,5,9,6,8,5,6,8,6,8)	3	2	4	2	3	4	1	1	4	3
EOSs-B-W (N=7,5,9,6,8,5,6,8,6,8)	3	3	5	4	5	1	5	7	2	5
EOSs-W-U (N=86,87,82,87,84,88,85,87,87,88)	0	0	0	0	1	1	0	0	0	1
EOSs-W-B (N=86,87,82,87,84,88,85,87,87,88)	2	2	4	6	3	1	6	1	3	0
EOSs-W-W (N=86,87,82,87,84,88,85,87,87,88)	82	85	78	79	79	83	78	83	83	87
EOSs-W-A (N=86,87,82,87,84,88,85,87,87,88)	2	0	0	2	1	3	1	3	1	0
EOSs-A-W (N=3,2,3,3,4,2,5,1,2,2)	1	1	2	2	0	1	4	1	0	2
EOSs-A-A (N=3,2,3,3,4,2,5,1,2,2)	2	1	1	1	4	1	1	0	2	0
RBCs-U-B (N=1,0,1,0,2,2,2,1,2,1)	0	0	0	0	1	0	0	0	0	0
RBCs-U-W (N=1,0,1,0,2,2,2,1,2,1)	1	0	1	0	1	2	2	1	2	0
RBCs-U-A (N=1,0,1,0,2,2,2,1,2,1)	0	0	0	0	0	0	0	0	0	1
RBCs-B-B (N=7,2,0,2,3,4,3,0,4,1)	6	2	0	1	3	4	2	0	2	1
RBCs-B-W (N=7,2,0,2,3,4,3,0,4,1)	1	0	0	1	0	0	1	0	2	0
RBCs-W-U (N=87,91,91,93,92,89,90,94,90,96)	1	0	0	0	1	1	0	0	0	1
RBCs-W-B (N=87,91,91,93,92,89,90,94,90,96)	3	3	0	1	2	3	1	0	1	3
RBCs-W-W (N=87,91,91,93,92,89,90,94,90,96)	83	88	91	92	89	83	89	94	89	92
RBCs-W-A (N=87,91,91,93,92,89,90,94,90,96)	0	0	0	0	0	2	0	0	0	0
RBCs-A-W (N=2,1,3,1,1,2,3,2,1,1)	2	1	1	1	1	2	1	0	0	0
RBCs-A-A (N=2,1,3,1,1,2,3,2,1,1)	0	0	2	0	0	0	2	2	1	1
HGB-U-B (N=1,0,1,0,2,2,2,1,2,1)	0	0	0	0	2	0	0	0	0	0
HGB-U-W (N=1,0,1,0,2,2,2,1,2,1)	1	0	1	0	0	2	2	1	2	1
HGB-B-B (N=8,8,3,7,5,9,6,3,9,4)	7	6	2	6	3	6	5	3	8	3
HGB-B-W (N=8,8,3,7,5,9,6,3,9,4)	1	2	1	1	2	3	1	0	1	1
HGB-W-U (N=87,85,90,86,90,84,90,91,85,94)	1	0	0	0	1	1	0	0	0	1
HGB-W-B (N=87,85,90,86,90,84,90,91,85,94)	5	2	0	0	3	1	1	1	3	2
HGB-W-W (N=87,85,90,86,90,84,90,91,85,94)	81	83	89	86	86	82	89	90	82	91
HGB-W-A (N=87,85,90,86,90,84,90,91,85,94)	0	0	1	0	0	0	0	0	0	0
HGB-A-W (N=1,1,1,3,1,2,0,2,1,0)	0	1	1	2	0	2	0	1	0	0
HGB-A-A (N=1,1,1,3,1,2,0,2,1,0)	1	0	0	1	1	0	0	1	1	0
LYMs-U-W (N=1,0,1,0,2,2,2,1,2,1)	1	0	1	0	2	2	2	1	2	1
LYMs-B-B (N=2,1,4,4,4,2,3,1,1,5)	0	0	0	2	1	1	2	0	0	4
LYMs-B-W (N=2,1,4,4,4,2,3,1,1,5)	2	1	4	2	3	1	1	1	1	1
LYMs-W-U (N=93,92,90,91,91,93,93,95,94,93)	1	0	0	0	1	1	0	0	0	1
LYMs-W-B (N=93,92,90,91,91,93,93,95,94,93)	2	0	0	1	1	0	2	1	0	1
LYMs-W-W (N=93,92,90,91,91,93,93,95,94,93)	90	91	89	90	88	92	91	94	94	91
LYMs-W-A (N=93,92,90,91,91,93,93,95,94,93)	0	1	1	0	1	0	0	0	0	0
LYMs-A-W (N=1,1,0,1,1,0,0,0,0,0)	1	1	0	1	0	0	0	0	0	0
LYMs-A-A (N=1,1,0,1,1,0,0,0,0,0)	0	0	0	0	1	0	0	0	0	0
MONOs-U-B (N=1,0,1,0,2,2,2,1,2,1)	0	0	0	0	0	0	0	0	1	0
MONOs-U-W (N=1,0,1,0,2,2,2,1,2,1)	1	0	1	0	2	2	2	1	1	1
MONOs-B-B (N=5,0,4,3,4,6,4,4,5,6)	2	0	0	0	1	1	0	1	1	3
MONOs-B-W (N=5,0,4,3,4,6,4,4,5,6)	3	0	4	3	3	5	4	3	4	3
MONOs-W-U (N=89,94,90,93,92,89,92,91,90,92)	1	0	0	0	1	1	0	0	0	1
MONOs-W-B (N=89,94,90,93,92,89,92,91,90,92)	1	2	3	2	1	6	1	3	1	3
MONOs-W-W (N=89,94,90,93,92,89,92,91,90,92)	87	92	87	91	90	82	91	88	89	88
MONOs-A-W (N=2,0,0,0,0,0,0,1,0,0)	1	0	0	0	0	0	0	0	0	0
MONOs-A-A (N=2,0,0,0,0,0,0,1,0,0)	1	0	0	0	0	0	0	1	0	0
NPs-U-W (N=1,0,1,0,2,2,2,1,2,1)	1	0	1	0	2	2	2	1	2	1
NPs-B-B (N=2,1,1,3,1,3,2,1,1,2)	1	1	0	1	0	2	0	0	0	2
NPs-B-W (N=2,1,1,3,1,3,2,1,1,2)	1	0	1	2	1	1	2	1	1	0
NPs-W-U (N=94,92,93,92,95,92,94,95,93,96)	1	0	0	0	1	1	0	0	0	1
NPs-W-B (N=94,92,93,92,95,92,94,95,93,96)	0	1	3	1	1	1	2	0	4	2
NPs-W-W (N=94,92,93,92,95,92,94,95,93,96)	92	90	90	90	91	90	92	95	89	92
NPs-W-A (N=94,92,93,92,95,92,94,95,93,96)	1	1	0	1	2	0	0	0	0	1
NPs-A-W (N=0,1,0,1,0,0,0,0,1,0)	0	1	0	0	0	0	0	0	1	0
NPs-A-A (N=0,1,0,1,0,0,0,0,1,0)	0	0	0	1	0	0	0	0	0	0
PLTs-U-U (N=3,2,2,0,2,3,5,2,2,1)	1	0	0	0	0	1	0	0	0	0
PLTs-U-W (N=3,2,2,0,2,3,5,2,2,1)	2	2	2	0	2	2	5	2	2	1
PLTs-B-U (N=3,1,3,1,0,2,1,1,1,2)	0	0	1	0	0	0	0	0	0	0
PLTs-B-B (N=3,1,3,1,0,2,1,1,1,2)	3	0	1	1	0	1	0	1	0	2
PLTs-B-W (N=3,1,3,1,0,2,1,1,1,2)	0	1	1	0	0	1	1	0	1	0
PLTs-W-U (N=89,91,89,93,96,90,91,92,92,93)	1	0	0	0	1	1	1	1	0	1
PLTs-W-B (N=89,91,89,93,96,90,91,92,92,93)	0	1	0	0	1	1	1	0	0	0
PLTs-W-W (N=89,91,89,93,96,90,91,92,92,93)	88	89	88	91	92	88	87	90	89	91
PLTs-W-A (N=89,91,89,93,96,90,91,92,92,93)	0	1	1	2	2	0	2	1	3	1
PLTs-A-W (N=2,0,1,2,0,2,1,2,2,3)	1	0	0	0	0	1	1	0	1	0
PLTs-A-A (N=2,0,1,2,0,2,1,2,2,3)	1	0	1	2	0	1	0	2	1	3
UN-U-W (N=1,0,0,1,0,1,1,1,2,0)	1	0	0	1	0	1	0	1	2	0
UN-U-A (N=1,0,0,1,0,1,1,1,2,0)	0	0	0	0	0	0	1	0	0	0
UN-B-B (N=0,0,0,1,0,0,2,1,1,0)	0	0	0	1	0	0	1	0	0	0
UN-B-W (N=0,0,0,1,0,0,2,1,1,0)	0	0	0	0	0	0	1	1	1	0
UN-W-U (N=92,94,93,92,95,94,92,92,92,99)	0	0	0	0	0	0	0	0	0	1
UN-W-W (N=92,94,93,92,95,94,92,92,92,99)	91	94	93	91	95	94	91	91	91	97
UN-W-A (N=92,94,93,92,95,94,92,92,92,99)	1	0	0	1	0	0	1	1	1	1
UN-A-W (N=4,0,2,2,3,2,3,3,2,0)	1	0	2	1	3	1	2	2	2	0
UN-A-A (N=4,0,2,2,3,2,3,3,2,0)	3	0	0	1	0	1	1	1	0	0
UA-U-B (N=1,0,0,1,0,1,1,1,2,0)	0	0	0	0	0	0	0	0	1	0
UA-U-W (N=1,0,0,1,0,1,1,1,2,0)	1	0	0	1	0	1	0	1	1	0
UA-U-A (N=1,0,0,1,0,1,1,1,2,0)	0	0	0	0	0	0	1	0	0	0
UA-B-B (N=2,2,1,3,0,1,4,2,2,3)	1	2	0	3	0	1	4	2	2	2
UA-B-W (N=2,2,1,3,0,1,4,2,2,3)	1	0	1	0	0	0	0	0	0	1
UA-W-U (N=91,87,92,90,98,92,93,91,92,91)	0	0	0	0	0	0	0	0	0	1
UA-W-B (N=91,87,92,90,98,92,93,91,92,91)	0	1	1	0	0	1	1	1	0	3
UA-W-W (N=91,87,92,90,98,92,93,91,92,91)	91	86	87	89	98	91	92	87	91	83
UA-W-A (N=91,87,92,90,98,92,93,91,92,91)	0	0	4	1	0	0	0	3	1	4
UA-A-W (N=3,5,2,2,0,3,0,3,1,5)	1	2	1	2	0	2	0	2	1	4
UA-A-A (N=3,5,2,2,0,3,0,3,1,5)	2	3	1	0	0	1	0	1	0	1
WBCs-U-W (N=1,0,1,0,2,2,2,1,2,1)	1	0	1	0	2	2	2	1	2	1
WBCs-B-B (N=4,0,3,4,5,4,7,4,3,5)	2	0	1	1	1	0	1	2	1	4
WBCs-B-W (N=4,0,3,4,5,4,7,4,3,5)	2	0	2	3	4	4	6	2	2	1
WBCs-W-U (N=91,92,91,90,89,91,89,92,91,93)	1	0	0	0	1	1	0	0	0	1
WBCs-W-B (N=91,92,91,90,89,91,89,92,91,93)	3	0	2	3	3	2	1	0	3	1
WBCs-W-W (N=91,92,91,90,89,91,89,92,91,93)	86	92	89	86	83	88	88	91	88	90
WBCs-W-A (N=91,92,91,90,89,91,89,92,91,93)	1	0	0	1	2	0	0	1	0	1
WBCs-A-W (N=1,2,0,2,2,0,0,0,1,0)	0	1	0	1	2	0	0	0	1	0
WBCs-A-A (N=1,2,0,2,2,0,0,0,1,0)	1	1	0	1	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Number of subjects with any Grade 3 non-serious AEs (solicited and unsolicited) after first dose of vaccination

Top of page

End point title

Number of subjects with any Grade 3 non-serious AEs (solicited and unsolicited) after first dose of vaccination ^[14]

End point description

A Grade 3 AE is any AE assessed as severe, i.e. which prevents normal, everyday activities. In adults, such an AE would, for example, prevent attendance at work and would necessitate the administration of corrective therapy.

End point type

Primary

End point timeframe

During a 30-day follow-up period (i.e., on the day of vaccination at Day 1, and 29 subsequent days) after first dose of vaccination

Notes
[14] - 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 scope of this endpoint analysis was descriptive, therefore no statistical analyses apply for this endpoint.

End point values	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	12	12	12	12	101	97	100	101	101	100	103	100	101	101
Units: Participants
Any adverse event	1	0	0	0	1	1	4	3	7	1	7	6	8	4
General adverse event	1	0	0	0	1	1	3	2	5	0	2	3	4	4
Local adverse event	0	0	0	0	0	0	2	1	2	1	6	3	4	0

No statistical analyses for this end point

Primary: Number of subjects with any Grade 3 non-serious AEs (solicited and unsolicited) after second dose of vaccination

Top of page

End point title

Number of subjects with any Grade 3 non-serious AEs (solicited and unsolicited) after second dose of vaccination ^[15]

End point description

End point type

Primary

End point timeframe

During a 30-day follow-up period (i.e., on the day of vaccination at Day 61, and 29 subsequent days) after second dose of 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 scope of this endpoint analysis was descriptive, therefore no statistical analyses apply for this endpoint.

End point values	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	12	10	11	12	98	95	95	96	98	97	98	97	97	99
Units: Participants
Any adverse event	1	0	0	0	1	0	2	5	3	5	8	7	3	0
General adverse event	1	0	0	0	1	0	2	4	2	2	5	5	1	0
Local adverse event	0	0	0	0	0	0	0	1	1	3	4	2	2	0

No statistical analyses for this end point

Primary: Number of subjects with any Serious Adverse Events (SAEs) up to 30 days after the second vaccination

Top of page

End point title

Number of subjects with any Serious Adverse Events (SAEs) up to 30 days after the second vaccination ^[16]

End point description

A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity.

End point type

Primary

End point timeframe

From first vaccination (Day 1) up to 30 days post second vaccination (Day 91)

Notes
[16] - 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 scope of this endpoint analysis was descriptive, therefore no statistical analyses apply for this endpoint.

End point values	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	12	12	12	12	101	97	100	101	101	100	103	100	101	101
Units: Participants	0	0	0	0	6	0	1	4	2	1	1	3	5	1

No statistical analyses for this end point

Primary: Number of subjects with any potential immune-mediated diseases (pIMDs) up to 30 days after the second vaccination (Part B groups)

Top of page

End point title

Number of subjects with any potential immune-mediated diseases (pIMDs) up to 30 days after the second vaccination (Part B groups) ^[17] ^[18]

End point description

pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.

End point type

Primary

End point timeframe

From first vaccination (Day 1) up to 30 days post second vaccination (Day 91)

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 scope of this endpoint analysis was descriptive, therefore no statistical analyses apply for this endpoint.
[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: This endpoint is presented separately for Part A and Part B groups due to character limits in the Category Title field.

End point values	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	101	97	100	101	101	100	103	100	101	101
Units: Participants	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of subjects with any SAEs, up the end of follow-up period (Month 14) - Part B groups

Top of page

End point title

Number of subjects with any SAEs, up the end of follow-up period (Month 14) - Part B groups ^[19]

End point description

A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject.

End point type

Secondary

End point timeframe

From Day 1 up to the end of follow-up period (Month 14)

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: This endpoint is presented separately for Part A and Part B groups due to character limits in the Category Title field.

End point values	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	101	97	100	101	101	100	103	100	101	101
Units: Participants	13	3	5	8	6	11	9	5	9	9

No statistical analyses for this end point

Secondary: Number of subjects reporting pIMDs up to the end of follow-up period (Month 14) - Part B groups

Top of page

End point title

Number of subjects reporting pIMDs up to the end of follow-up period (Month 14) - Part B groups ^[20]

End point description

pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.

End point type

Secondary

End point timeframe

From Day 1 up to the end of follow-up period (Month 14)

Notes
[20] - 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: This endpoint is presented separately for Part A and Part B groups due to character limits in the Category Title field.

End point values	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	101	97	100	101	101	100	103	100	101	101
Units: Participants	1	0	0	0	1	1	0	0	0	1

No statistical analyses for this end point

Secondary: Number of subjects with at least one RSV-confirmed Respiratory Tract Infection (RTI) episode post-vaccination reported during RTI surveillance - Part B groups

Top of page

End point title

Number of subjects with at least one RSV-confirmed Respiratory Tract Infection (RTI) episode post-vaccination reported during RTI surveillance - Part B groups ^[21]

End point description

The number of subjects with at least one RTI case is provided by group. Reported categories are RSV+ (= RTI episode tested as RSV positive by quantitative reverse transcription polymerase chain reaction (qRT-PCR) on nasal/throat swab) and RSV- (= RTI episode tested as RSV negative by qRT-PCR on nasal/throat swab).

End point type

Secondary

End point timeframe

During the RSV seasons (from October 2019 to March 2020)

Notes
[21] - 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: This endpoint is presented separately for Part A and Part B groups due to character limits in the Category Title field.

End point values	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	101	97	100	101	101	100	103	100	101	101
Units: Participants
RSV+	1	2	0	0	0	0	0	2	0	3
RSV-	19	12	20	14	17	22	20	16	13	11

No statistical analyses for this end point

Secondary: Humoral immune response with respect to components of the investigational vaccine in terms of neutralizing antibody titers against RSV-serotype A (Part A groups)

Top of page

End point title

Humoral immune response with respect to components of the investigational vaccine in terms of neutralizing antibody titers against RSV-serotype A (Part A groups) ^[22]

End point description

Serological assays for the determination of functional antibodies against RSV-A were performed by neutralization assay. Anti RSV-A neutralizing antibody titers are given as geometric mean titers (GMTs) and expressed as Estimated Dose: serum dilution giving a 60% reduction of the signal compared to a control without serum (ED60).

End point type

Secondary

End point timeframe

At pre-vaccination (Day 1), 30 days post-Dose 1 (Day 31), on the day of second vaccination (Day 61) and 30 days post-Dose 2 (Day 91)

Notes
[22] - 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: This endpoint is presented separately for Part A and Part B groups due to character limits in the Category Title field.

End point values	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group
Number of subjects analysed	11	11	12	12
Units: Titers
geometric mean (confidence interval 95%)
D1 (N=11,11,12,12)	1019 (634.6 to 1636.1)	846.2 (481.7 to 1486.4)	673.6 (325.3 to 1394.7)	620.7 (365.1 to 1055.1)
D31 (N=11,8,11,12)	7658.4 (4329.7 to 13546.2)	11741.8 (4883.6 to 28231.5)	8136.9 (5066.1 to 13069.1)	789.1 (518.6 to 1200.9)
D61 (N=11,9,11,12)	4659.8 (2090 to 10389.1)	5895.8 (2791.9 to 12450.5)	4761.5 (2687.7 to 8435.5)	586.5 (333.1 to 1032.7)
D91 (N=11,9,11,12)	6237.8 (3648.1 to 10665.9)	5457.5 (2532.9 to 11758.7)	3651 (1949.6 to 6837.2)	787.9 (495.5 to 1252.6)

No statistical analyses for this end point

Secondary: Humoral immune response with respect to components of the investigational vaccine in terms of neutralizing antibody titers against RSV-serotype A (Part B groups)

Top of page

End point title

Humoral immune response with respect to components of the investigational vaccine in terms of neutralizing antibody titers against RSV-serotype A (Part B groups) ^[23]

End point description

End point type

Secondary

End point timeframe

At pre-vaccination (Day 1), 30 days post-Dose 1 (Day 31), on the day of second vaccination (Day 61) and 30 days post-Dose 2 (Day 91)

Notes
[23] - 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: This endpoint is presented separately for Part A and Part B groups due to character limits in the Category Title field.

End point values	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	101	96	99	100	101	100	102	100	101	100
Units: Titers
geometric mean (confidence interval 95%)
Day 1 (N=101,96,99,100,101,100,102,100,101,100)	1015.5 (865 to 1192.2)	1146.5 (931.6 to 1411)	976.7 (837.7 to 1138.8)	960.9 (801 to 1152.7)	966.4 (822.9 to 1134.8)	961.9 (809.5 to 1143)	981.6 (832.7 to 1157.2)	1023 (879.2 to 1190.2)	1035.7 (864.5 to 1240.7)	837.4 (701.3 to 999.9)
Day 31 (N=93,90,90,92,97,94,95,95,93,92)	5422.6 (4395 to 6690.5)	7371 (5922.5 to 9173.8)	9403.1 (7471.2 to 11834.4)	5258.5 (4351.8 to 6354.1)	6509.4 (5306.8 to 7984.4)	9350.9 (7606 to 11496.1)	6026.1 (4960.9 to 7320.1)	6899.5 (5767.8 to 8253.2)	8527.7 (7107.9 to 10231)	751.7 (625.2 to 903.9)
Day 61 (N=95,90,92,93,100,95,94,97,98,96)	5657.9 (4736 to 6759.1)	6490.8 (5190.3 to 8117.1)	7907.4 (6253.9 to 9998.2)	5019.4 (4281.5 to 5884.5)	6201.9 (5106.3 to 7532.6)	6681.7 (5498.4 to 8119.8)	5048.9 (4184.4 to 6092)	5902.1 (5023.4 to 6934.4)	7201.4 (6000.4 to 8642.8)	903.4 (750.8 to 1087.1)
Day 91 (N=88,84,87,84,91,87,85,93,92,93)	3936.2 (3281.9 to 4720.9)	5632.1 (4559.2 to 6957.5)	5956.1 (4881.4 to 7267.4)	3924.7 (3266 to 4716.2)	4770 (3904.6 to 5827.4)	5175.5 (4273.1 to 6268.5)	4435.9 (3654.7 to 5384.1)	4850.5 (4096.8 to 5742.8)	5980.6 (4988 to 7170.7)	772.4 (646.2 to 923.3)

No statistical analyses for this end point

Secondary: Humoral immune response with respect to components of the investigational vaccine in terms of RSVPreF3-specific Immunoglobulin G (IgG) antibody concentrations (Part A groups)

Top of page

End point title

Humoral immune response with respect to components of the investigational vaccine in terms of RSVPreF3-specific Immunoglobulin G (IgG) antibody concentrations (Part A groups) ^[24]

End point description

The detection and the quantification of total IgG antibodies directed against RSVPreF3 in human serum samples were based on an indirect enzyme-linked immunosorbent assay (ELISA). Anti RSVPreF3 antibody concentration is given in geometric mean concentration (GMC) and is expressed in ELISA Laboratory Units per milliliter (ELU/mL).

End point type

Secondary

End point timeframe

At pre-vaccination (Day 1), 30 days post-Dose 1 (Day 31), on the day of second vaccination (Day 61) and 30 days post-Dose 2 (Day 91)

Notes
[24] - 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: This endpoint is presented separately for Part A and Part B groups due to character limits in the Category Title field.

End point values	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group
Number of subjects analysed	11	11	12	12
Units: Titers
geometric mean (confidence interval 95%)
D1 (N=11,11,12,12)	8330.7 (5561.5 to 12478.9)	7699.5 (5326 to 11130.8)	7439.1 (5808.6 to 9527.2)	6524.8 (4828.2 to 8817.6)
D31 (N=11,8,11,12)	69843.3 (38345.8 to 127212.8)	97848.5 (65057.1 to 147168)	96645.4 (62880.7 to 148540.5)	6601 (4888.4 to 8913.6)
D61 (N=11,9,11,12)	50590.1 (27310.9 to 93711.7)	58980.8 (38982.8 to 89237.7)	56380.6 (38602.6 to 82346.1)	6242.4 (4473 to 8711.7)
D91 (N=11,9,11,12)	54900 (33635.4 to 89608.2)	54884.7 (37768.6 to 79757.3)	55444.4 (38128.6 to 80624)	6246 (4375.8 to 8915.7)

No statistical analyses for this end point

Secondary: Humoral immune response with respect to components of the investigational vaccine in terms of RSVPreF3-specific Immunoglobulin G (IgG) antibody concentrations (Part B groups)

Top of page

End point title

Humoral immune response with respect to components of the investigational vaccine in terms of RSVPreF3-specific Immunoglobulin G (IgG) antibody concentrations (Part B groups) ^[25]

End point description

End point type

Secondary

End point timeframe

At pre-vaccination (Day 1), 30 days post-Dose 1 (Day 31), on the day of second vaccination (Day 61) and 30 days post-Dose 2 (Day 91)

Notes
[25] - 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: This endpoint is presented separately for Part A and Part B groups due to character limits in the Category Title field.

End point values	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	101	96	99	100	101	100	102	100	101	100
Units: ELU/mL
geometric mean (confidence interval 95%)
Day 1 (N=101,96,99,100,101,100,102,100,101,100)	7500.2 (6582.4 to 8545.9)	7209.7 (6150.9 to 8450.7)	7134.9 (6377.7 to 7982)	6760.5 (5913.7 to 7728.5)	7438 (6544.6 to 8453.4)	6685.4 (5827 to 7670.4)	7468.5 (6544 to 8523.5)	7245.5 (6265.8 to 8378.3)	6655.4 (5862.2 to 7555.9)	6543.8 (5663 to 7561.6)
Day 31 (N=93,90,90,92,97,94,95,95,93,92)	53994 (46566.7 to 62605.8)	71618.4 (60729.6 to 84459.5)	90933.2 (79096.2 to 104541.6)	53598.9 (47062.7 to 61043)	63823.4 (55601.6 to 73261)	83462.5 (70906.1 to 98242.3)	59026.1 (51236.4 to 68000)	70524 (60825.4 to 81769.1)	78831.2 (68382.5 to 90876.4)	6593.4 (5672 to 7664.4)
Day 61 (N=95,90,93,93,100,95,94,97,98,96)	47594.2 (41241.9 to 54924.8)	56855.4 (47655.2 to 67831.7)	70294.1 (61103.1 to 80867.5)	41543.8 (36864.7 to 46816.8)	51209.9 (44850.5 to 58470.9)	62543.2 (52975.1 to 73839.3)	45679.1 (39722.6 to 52528.7)	54342.7 (47099 to 62700.5)	61577.7 (53431.3 to 70966.1)	6307.9 (5453.8 to 7295.9)
Day 91 (N=88,84,87,84,91,87,85,93,92,93)	42523.7 (36905 to 48997.8)	54711.2 (47013.5 to 63669.2)	60955.2 (53029.7 to 70065.1)	42504.6 (38044.3 to 47487.9)	52846.4 (47105.8 to 59286.7)	59624.5 (51680 to 68790.2)	53779.9 (47588.5 to 60776.8)	57314.9 (51038.1 to 64363.6)	61433.7 (54066.2 to 69805)	6748.7 (5804.1 to 7847.1)

No statistical analyses for this end point

Secondary: Descriptive statistics of the frequency of RSVPreF3 specific cluster of differentiation 4+ (CD4+) T cells expressing at least 2 markers (Part A groups)

Top of page

End point title

Descriptive statistics of the frequency of RSVPreF3 specific cluster of differentiation 4+ (CD4+) T cells expressing at least 2 markers (Part A groups) ^[26]

End point description

Among markers expressed were interleukin-2 (IL2), cluster of 40 ligand (CD40L), tumor necrosis factor alpha (TNF α) and interferon gamma (IFN γ), in vitro upon stimulation with RSVPreF3 peptide preparations. Reported statistics at each time point during which blood sample were collected for cell-mediated immunity, are geometric mean and inter-quartile range.

End point type

Secondary

End point timeframe

At pre-vaccination (Day 1), 30 days post-Dose 1 (Day 31), on the day of second vaccination (Day 61) and 30 days post-Dose 2 (Day 91)

Notes
[26] - 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: This endpoint is presented separately for Part A and Part B groups due to character limits in the Category Title field.

End point values	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group
Number of subjects analysed	11	11	10	12
Units: Cells per million CD4+ T Cells
median (inter-quartile range (Q1-Q3))
D1 (N=11,11,10,11)	400.0 (348 to 791)	272.0 (163 to 570)	317.5 (184 to 628)	393.0 (333 to 680)
D31 (N=9,8,10,11)	1649.0 (864 to 2604)	2302.5 (1545 to 2725)	1773.5 (1318 to 2124)	303.0 (90 to 416)
D61 (N=10,8,9,11)	1271.0 (519 to 1679)	1515.0 (1129 to 2159)	1066.0 (764 to 1502)	263.0 (184 to 459)
D91 (N=10,8,9,12)	1006.5 (872 to 1779)	1221.0 (924 to 1518)	1487.0 (1005 to 1664)	374.5 (295 to 588)

No statistical analyses for this end point

Secondary: Descriptive statistics of the frequency of RSVPreF3 specific cluster of differentiation 4+ (CD4+) T cells expressing at least 2 markers (Part B groups)

Top of page

End point title

Descriptive statistics of the frequency of RSVPreF3 specific cluster of differentiation 4+ (CD4+) T cells expressing at least 2 markers (Part B groups) ^[27]

End point description

End point type

Secondary

End point timeframe

At pre-vaccination (Day 1), 30 days post-Dose 1 (Day 31), on the day of second vaccination (Day 61) and 30 days post-Dose 2 (Day 91)

Notes
[27] - 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: This endpoint is presented separately for Part A and Part B groups due to character limits in the Category Title field.

End point values	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	Low Dose_AS01E_B Group	Medium Dose_AS01E_B Group	High Dose_AS01E_B Group	Low Dose_AS01B_B Group	Medium Dose_AS01B_B Group	High Dose_AS01B_B Group	Placebo_B Group
Number of subjects analysed	83	79	84	82	82	83	88	87	86	86
Units: Cells per million CD4+ T Cells
median (inter-quartile range (Q1-Q3))
Day 1 (N=82,77,84,82,82,83,80,87,86,84)	208.5 (84 to 351)	166.0 (75 to 291)	225.5 (109 to 327)	209.5 (127 to 338)	188.0 (103 to 326)	192.0 (67 to 381)	187.5 (91 to 325.5)	185.0 (82 to 294)	206.0 (98 to 351)	178.0 (100.5 to 293.5)
Day 31 (N=76,68,76,76,73,75,77,80,76,77)	979.5 (639.5 to 1422.5)	1089.5 (786 to 1812.5)	1052.0 (674.5 to 1798)	1594.0 (916 to 2360)	1297.0 (881 to 2321)	1466.0 (787 to 2116)	1952.0 (1353 to 2953)	1690.5 (1162.5 to 2691.5)	1742.5 (1088 to 2360.5)	176.0 (85 to 297)
Day 61 (N=83,79,82,77,81,79,88,86,84,86)	688.0 (430 to 1076)	737.0 (437 to 1309)	770.0 (479 to 1235)	1086.0 (663 to 1621)	1020.0 (603 to 1405)	934.0 (598 to 1517)	1228.5 (777.5 to 1832.5)	1315.0 (887 to 1728)	1078.0 (781 to 1631)	183.0 (61 to 311)
Day 91 (N=79,79,82,74,80,78,78,83,80,84)	888.0 (650 to 1318)	1034.0 (670 to 1598)	1081.5 (769 to 1569)	1732.0 (1163 to 2149)	1603.5 (1087 to 2284)	1496.0 (1179 to 2072)	1966.0 (1339 to 2700)	1558.0 (1263 to 2353)	2096.5 (1441.5 to 2760.5)	190.5 (100.5 to 308)

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Solicited AEs:during the 7-day follow-up period after each dose. Unsolicited AEs:during the 30-day follow-up period after any dose. SAEs:during the whole study period, from Day 1 till Day 91 for Part A groups and till Month 14 for Part B groups.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

Low Dose_PLAIN_A Group

Reporting group description

Subjects in Part A, aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted low dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Medium Dose_PLAIN_A Group

Reporting group description

Subjects in Part A aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted medium dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

High Dose_PLAIN_A Group

Reporting group description

Subjects in Part A aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted high dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Placebo_A Group

Reporting group description

Subjects in Part A aged 18-40 years, receiving 2 doses of placebo (Saline solution) control, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Low Dose_PLAIN_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted low dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Medium Dose_PLAIN_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted medium dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

High Dose_PLAIN_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted high dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

High Dose_AS01E_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Medium Dose_AS01E_B Group

Reporting group description

Reporting group title

Low Dose_AS01E_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

High Dose_AS01B_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Medium Dose_AS01B_B Group

Reporting group description

Reporting group title

Low Dose_AS01B_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Reporting group title

Placebo_B Group

Reporting group description

Subjects in Part B aged 60-80 years, receiving 2 doses of placebo (Saline solution) control, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Low Dose_PLAIN_A Group

Medium Dose_PLAIN_A Group

High Dose_PLAIN_A Group

Placebo_A Group

Low Dose_PLAIN_B Group

Medium Dose_PLAIN_B Group

High Dose_PLAIN_B Group

High Dose_AS01E_B Group

Medium Dose_AS01E_B Group

Low Dose_AS01E_B Group

High Dose_AS01B_B Group

Medium Dose_AS01B_B Group

Low Dose_AS01B_B Group

Placebo_B Group

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 12 (0.00%)

13 / 101 (12.87%)

3 / 97 (3.09%)

5 / 100 (5.00%)

11 / 100 (11.00%)

6 / 101 (5.94%)

8 / 101 (7.92%)

9 / 101 (8.91%)

5 / 100 (5.00%)

9 / 103 (8.74%)

9 / 101 (8.91%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Anal cancer

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 100 (1.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Breast cancer

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

2 / 101 (1.98%)

1 / 101 (0.99%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

1 / 101 (0.99%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Clear cell renal cell carcinoma

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

1 / 101 (0.99%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hormone receptor positive breast cancer

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 101 (0.99%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Invasive ductal breast carcinoma

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 101 (0.99%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lung carcinoma cell type unspecified stage IV

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 101 (0.99%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Malignant peritoneal neoplasm

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 101 (0.99%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Prostate cancer

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 100 (1.00%)

0 / 101 (0.00%)

2 / 100 (2.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Sarcoma uterus

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 101 (0.99%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Uterine cancer

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Aortic aneurysm rupture

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

1 / 97 (1.03%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Shock haemorrhagic

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

1 / 97 (1.03%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Thrombophlebitis superficial

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 100 (1.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (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

Chest pain

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 100 (1.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Death

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

1 / 97 (1.03%)

1 / 100 (1.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 101 (0.99%)

0 / 100 (0.00%)

1 / 103 (0.97%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Reproductive system and breast disorders

Cervical dysplasia

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rectocele

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Asthma

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Chronic obstructive pulmonary disease

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 100 (1.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

2 / 101 (1.98%)

1 / 101 (0.99%)

0 / 100 (0.00%)

1 / 103 (0.97%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory distress

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

1 / 103 (0.97%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Psychiatric disorders

Alcohol abuse

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 100 (1.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bipolar disorder

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 101 (0.99%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Major depression

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 101 (0.99%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Acetabulum fracture

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 101 (0.99%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Chest injury

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Femur fracture

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 101 (0.99%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Head injury

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Jaw fracture

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Meniscus injury

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 101 (0.99%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Patella fracture

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

1 / 97 (1.03%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rib fracture

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

1 / 101 (0.99%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Skin laceration

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Subdural haematoma

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 100 (1.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Upper limb fracture

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Acute myocardial infarction

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

1 / 100 (1.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

1 / 103 (0.97%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Arrhythmia

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (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%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

1 / 101 (0.99%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Atrioventricular block complete

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac arrest

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

1 / 103 (0.97%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Cardio-respiratory arrest

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

1 / 97 (1.03%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Cardiomyopathy

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ventricular extrasystoles

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 100 (1.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ventricular tachycardia

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Cerebrovascular accident

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 101 (0.99%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cervicobrachial syndrome

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

1 / 100 (1.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Encephalitis autoimmune

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypoaesthesia

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ischaemic stroke

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

1 / 97 (1.03%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Loss of consciousness

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Iron deficiency anaemia

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

1 / 100 (1.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ear and labyrinth disorders

Vertigo

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Constipation

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 100 (1.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pancreatitis

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 100 (1.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small intestinal obstruction

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 101 (0.99%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Upper gastrointestinal haemorrhage

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

1 / 103 (0.97%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Biliary colic

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 101 (0.99%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cholecystitis

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 100 (1.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (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%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 101 (0.99%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

1 / 103 (0.97%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Back pain

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

1 / 100 (1.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

2 / 103 (1.94%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Cervical spinal stenosis

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 101 (0.99%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intervertebral disc protrusion

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lumbar spinal stenosis

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Muscular weakness

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 100 (1.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Osteoarthritis

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

1 / 101 (0.99%)

0 / 100 (0.00%)

1 / 103 (0.97%)

1 / 101 (0.99%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pain in extremity

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

1 / 101 (0.99%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Spondylolisthesis

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (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 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 101 (0.99%)

0 / 101 (0.00%)

1 / 100 (1.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Arthritis bacterial

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

1 / 101 (0.99%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Arthritis infective

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

1 / 103 (0.97%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bacteraemia

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

1 / 103 (0.97%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

COVID-19

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 100 (1.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Device related infection

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 100 (1.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

1 / 101 (0.99%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

1 / 101 (0.99%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Postoperative wound infection

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

1 / 103 (0.97%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal cord abscess

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

1 / 103 (0.97%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal cord infection

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

1 / 103 (0.97%)

0 / 101 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Staphylococcal infection

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

1 / 103 (0.97%)

0 / 101 (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

Diabetes mellitus

subjects affected / exposed

0 / 12 (0.00%)

0 / 101 (0.00%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

1 / 101 (0.99%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hyperkalaemia

subjects affected / exposed

0 / 12 (0.00%)

1 / 101 (0.99%)

0 / 97 (0.00%)

0 / 100 (0.00%)

0 / 101 (0.00%)

0 / 100 (0.00%)

0 / 103 (0.00%)

0 / 101 (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	Low Dose_PLAIN_A Group	Medium Dose_PLAIN_A Group	High Dose_PLAIN_A Group	Placebo_A Group	Low Dose_PLAIN_B Group	Medium Dose_PLAIN_B Group	High Dose_PLAIN_B Group	High Dose_AS01E_B Group	Medium Dose_AS01E_B Group	Low Dose_AS01E_B Group	High Dose_AS01B_B Group	Medium Dose_AS01B_B Group	Low Dose_AS01B_B Group	Placebo_B Group
Total subjects affected by non serious adverse events
subjects affected / exposed	9 / 12 (75.00%)	10 / 12 (83.33%)	9 / 12 (75.00%)	10 / 12 (83.33%)	62 / 101 (61.39%)	54 / 97 (55.67%)	61 / 100 (61.00%)	83 / 100 (83.00%)	80 / 101 (79.21%)	77 / 101 (76.24%)	93 / 101 (92.08%)	88 / 100 (88.00%)	91 / 103 (88.35%)	54 / 101 (53.47%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Monoclonal gammopathy
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Basal cell carcinoma
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Benign anorectal neoplasm
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Large intestine benign neoplasm
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Lipoma
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Squamous cell carcinoma
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	2 / 103 (1.94%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	1	0	2	1
Haematoma
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Phlebitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
General disorders and administration site conditions
Injection site pain
subjects affected / exposed	6 / 12 (50.00%)	9 / 12 (75.00%)	8 / 12 (66.67%)	1 / 12 (8.33%)	23 / 101 (22.77%)	19 / 97 (19.59%)	31 / 100 (31.00%)	65 / 100 (65.00%)	63 / 101 (62.38%)	60 / 101 (59.41%)	82 / 101 (81.19%)	78 / 100 (78.00%)	81 / 103 (78.64%)	8 / 101 (7.92%)
occurrences all number	6	14	14	1	27	23	37	103	105	89	137	120	136	8
Fatigue
subjects affected / exposed	5 / 12 (41.67%)	5 / 12 (41.67%)	4 / 12 (33.33%)	7 / 12 (58.33%)	29 / 101 (28.71%)	20 / 97 (20.62%)	29 / 100 (29.00%)	36 / 100 (36.00%)	39 / 101 (38.61%)	41 / 101 (40.59%)	53 / 101 (52.48%)	47 / 100 (47.00%)	45 / 103 (43.69%)	24 / 101 (23.76%)
occurrences all number	7	7	5	11	39	22	37	46	51	51	83	64	66	32
Chills
subjects affected / exposed	0 / 12 (0.00%)	2 / 12 (16.67%)	0 / 12 (0.00%)	1 / 12 (8.33%)	2 / 101 (1.98%)	1 / 97 (1.03%)	2 / 100 (2.00%)	6 / 100 (6.00%)	7 / 101 (6.93%)	11 / 101 (10.89%)	19 / 101 (18.81%)	19 / 100 (19.00%)	21 / 103 (20.39%)	3 / 101 (2.97%)
occurrences all number	0	2	0	1	2	1	2	7	8	15	25	20	26	3
Injection site swelling
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	4 / 100 (4.00%)	11 / 100 (11.00%)	9 / 101 (8.91%)	8 / 101 (7.92%)	14 / 101 (13.86%)	9 / 100 (9.00%)	17 / 103 (16.50%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	1	4	12	10	10	19	14	20	0
Hangover
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Pyrexia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	1 / 97 (1.03%)	0 / 100 (0.00%)	2 / 100 (2.00%)	4 / 101 (3.96%)	3 / 101 (2.97%)	6 / 101 (5.94%)	8 / 100 (8.00%)	6 / 103 (5.83%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	1	1	0	2	4	4	6	9	7	1
Influenza like illness
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	2 / 101 (1.98%)	3 / 101 (2.97%)	2 / 100 (2.00%)	2 / 103 (1.94%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	2	3	2	2	0
Injection site pruritus
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	3 / 100 (3.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	1 / 101 (0.99%)	3 / 101 (2.97%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0	1	1	3	0	0	0
Injection site warmth
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	3 / 101 (2.97%)	2 / 101 (1.98%)	1 / 100 (1.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	3	2	2	1	0
Malaise
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	2 / 100 (2.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	1 / 101 (0.99%)	1 / 100 (1.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	2	0	1	1	1	1	0
Feeling hot
subjects affected / exposed	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	0 / 100 (0.00%)	2 / 100 (2.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	2 / 103 (1.94%)	0 / 101 (0.00%)
occurrences all number	0	1	0	0	0	1	0	2	1	0	0	0	2	0
Injection site haemorrhage
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	2 / 101 (1.98%)	1 / 100 (1.00%)	0 / 103 (0.00%)	2 / 101 (1.98%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	2	2	0	2
Injection site bruising
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	1	0	0	1
Peripheral swelling
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	1 / 103 (0.97%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	1	1
Chest discomfort
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1
Feeling cold
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	1	0	0
Oedema peripheral
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Swelling
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	0
Inflammation
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1	0	0	0
Injection site reaction
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1	0	0	0
Pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	1
Asthenia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	1	0
Axillary pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Chest pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Impaired healing
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Injection site induration
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Injection site movement impairment
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Injection site paraesthesia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Immune system disorders
Allergy to arthropod bite
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Hypersensitivity
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Reaction to preservatives
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Seasonal allergy
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	0
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Benign prostatic hyperplasia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Breast pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Erectile dysfunction
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Pelvic pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	2 / 97 (2.06%)	1 / 100 (1.00%)	3 / 100 (3.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	3 / 101 (2.97%)	1 / 100 (1.00%)	4 / 103 (3.88%)	1 / 101 (0.99%)
occurrences all number	0	1	0	0	1	2	1	3	1	0	3	1	4	1
Cough
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	2 / 97 (2.06%)	2 / 100 (2.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	2 / 101 (1.98%)	1 / 101 (0.99%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	2	2	1	0	2	1	1	0	0
Nasal congestion
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	2 / 100 (2.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	1	0	0	0	0
Dysphonia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	2 / 100 (2.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	0	1	0
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0	0	0	0
Rhinorrhoea
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0	0	0
Nasal discharge discolouration
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Sneezing
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Productive cough
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Lower respiratory tract congestion
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Paranasal sinus hypersecretion
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Pulmonary mass
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Respiratory disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Rhinitis allergic
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Rhonchi
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Sinus congestion
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Asthma
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Epistaxis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Insomnia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	2 / 101 (1.98%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	1	0	0	0
Cardiac murmur
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Haemoglobin decreased
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Neutrophil count decreased
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
White blood cell count decreased
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Basophil count increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Heart rate irregular
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Injury, poisoning and procedural complications
Joint dislocation
subjects affected / exposed	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Arthropod bite
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	2 / 101 (1.98%)	1 / 97 (1.03%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	2 / 101 (1.98%)
occurrences all number	0	0	0	0	2	1	0	0	0	1	0	0	1	2
Procedural pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	2 / 101 (1.98%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	0	0	1	2
Contusion
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	2 / 101 (1.98%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	2	0	0	0
Muscle strain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	1	0	0	0	0
Foot fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0	0	0	0
Skin laceration
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	1	0	0	0
Ligament sprain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Back injury
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Hand fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Limb injury
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Tendon rupture
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Arthropod sting
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Bone contusion
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Patella fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Post procedural inflammation
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Thermal burn
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Tooth fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Upper limb fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Congenital, familial and genetic disorders
Dermoid cyst
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	1
Palpitations
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Nervous system disorders
Headache
subjects affected / exposed	3 / 12 (25.00%)	5 / 12 (41.67%)	5 / 12 (41.67%)	5 / 12 (41.67%)	16 / 101 (15.84%)	14 / 97 (14.43%)	17 / 100 (17.00%)	24 / 100 (24.00%)	25 / 101 (24.75%)	28 / 101 (27.72%)	38 / 101 (37.62%)	38 / 100 (38.00%)	45 / 103 (43.69%)	13 / 101 (12.87%)
occurrences all number	4	6	6	7	19	18	21	29	32	36	48	54	61	17
Dizziness
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	2 / 101 (1.98%)	0 / 97 (0.00%)	1 / 100 (1.00%)	1 / 100 (1.00%)	2 / 101 (1.98%)	0 / 101 (0.00%)	0 / 101 (0.00%)	2 / 100 (2.00%)	2 / 103 (1.94%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	2	0	1	2	2	0	0	2	2	1
Dysgeusia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	0	0	1	0	0
Paraesthesia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0	0
Sciatica
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0	0	0
Nerve compression
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Sinus headache
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Blood and lymphatic system disorders
Leukopenia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Neutropenia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Leukocytosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Lymphadenopathy
subjects affected / exposed	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	1	0	0	0	0	0
Lymphocytosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Thrombocytopenia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	3 / 100 (3.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	2 / 101 (1.98%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0	0	0	2	0	0	0
Vertigo
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	1	1	0	0
External ear pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Deafness
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Ear discomfort
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Ear disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Eye disorders
Blepharitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Conjunctivitis allergic
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	1	0
Gastrointestinal disorders
Enteritis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorder
subjects affected / exposed	2 / 12 (16.67%)	2 / 12 (16.67%)	2 / 12 (16.67%)	3 / 12 (25.00%)	11 / 101 (10.89%)	9 / 97 (9.28%)	14 / 100 (14.00%)	15 / 100 (15.00%)	11 / 101 (10.89%)	13 / 101 (12.87%)	19 / 101 (18.81%)	12 / 100 (12.00%)	18 / 103 (17.48%)	13 / 101 (12.87%)
occurrences all number	2	3	3	3	13	10	17	16	13	15	22	15	24	16
Diarrhoea
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	2 / 97 (2.06%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	3 / 101 (2.97%)
occurrences all number	0	0	0	0	0	2	0	0	0	1	0	0	0	3
Constipation
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	2 / 97 (2.06%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	2 / 101 (1.98%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	2	0	0	0	3	0	0	1	1
Gastritis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	2 / 101 (1.98%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	2	0	0	1	0	0
Toothache
subjects affected / exposed	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	0 / 100 (0.00%)	2 / 100 (2.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	1	0	0	0	0	1	0	2	0	0	0	0	0	0
Faeces soft
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	2 / 101 (1.98%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Vomiting
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Dyspepsia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	1	0
Flatulence
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	1	0
Dry mouth
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Nausea
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Palatal disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Abdominal discomfort
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Abdominal pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Aphthous ulcer
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Cheilitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Eructation
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Gastric disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Large intestine polyp
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Lip swelling
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Pancreatic cyst
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Abdominal pain upper
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Skin and subcutaneous tissue disorders
Erythema
subjects affected / exposed	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	1 / 97 (1.03%)	4 / 100 (4.00%)	14 / 100 (14.00%)	9 / 101 (8.91%)	7 / 101 (6.93%)	24 / 101 (23.76%)	20 / 100 (20.00%)	24 / 103 (23.30%)	1 / 101 (0.99%)
occurrences all number	0	1	0	0	1	1	4	16	9	8	30	29	33	1
Rash
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	3 / 101 (2.97%)	0 / 97 (0.00%)	1 / 100 (1.00%)	1 / 100 (1.00%)	1 / 101 (0.99%)	1 / 101 (0.99%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	3	0	2	1	1	1	0	1	0	0
Urticaria
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	2 / 101 (1.98%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	3 / 101 (2.97%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	1	2	0	0	0	0	0	3	0	0	0
Dermatitis contact
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	1	0
Ecchymosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0	0	0
Hyperhidrosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	0	0	0	0
Pruritus
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	2 / 101 (1.98%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Hidradenitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Blister
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Dermatitis allergic
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Eczema
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Intertrigo
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Photosensitivity reaction
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Skin hyperpigmentation
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Skin lesion
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Cold sweat
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Night sweats
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Rash pruritic
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Nephrolithiasis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Dysuria
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	9 / 101 (8.91%)	8 / 97 (8.25%)	4 / 100 (4.00%)	18 / 100 (18.00%)	19 / 101 (18.81%)	14 / 101 (13.86%)	24 / 101 (23.76%)	19 / 100 (19.00%)	28 / 103 (27.18%)	11 / 101 (10.89%)
occurrences all number	0	0	0	0	10	10	4	19	23	17	31	23	37	14
Myalgia
subjects affected / exposed	0 / 12 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)	0 / 12 (0.00%)	5 / 101 (4.95%)	6 / 97 (6.19%)	5 / 100 (5.00%)	15 / 100 (15.00%)	12 / 101 (11.88%)	14 / 101 (13.86%)	32 / 101 (31.68%)	22 / 100 (22.00%)	28 / 103 (27.18%)	9 / 101 (8.91%)
occurrences all number	0	1	1	0	5	7	6	17	17	17	36	24	39	9
Back pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	2 / 100 (2.00%)	1 / 100 (1.00%)	1 / 101 (0.99%)	2 / 101 (1.98%)	4 / 101 (3.96%)	3 / 100 (3.00%)	1 / 103 (0.97%)	3 / 101 (2.97%)
occurrences all number	0	0	0	0	0	0	3	1	1	2	4	3	1	4
Neck pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	2 / 100 (2.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	2 / 101 (1.98%)	1 / 100 (1.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	2	2	1	0
Pain in extremity
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	1 / 103 (0.97%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	1	0	1	0	0	0	1	0	1	1
Tendonitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	1 / 97 (1.03%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0	1	1
Osteoarthritis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	0 / 100 (0.00%)	1 / 100 (1.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	1	0	0	0	0	0
Bursitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	1	0	0	0
Arthritis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1
Muscular weakness
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	0
Pain in jaw
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1
Joint effusion
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Groin pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Osteoporosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Rotator cuff syndrome
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Joint range of motion decreased
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Joint swelling
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Muscle discomfort
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Muscle spasms
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Fibromyalgia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Infections and infestations
Tonsillitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	0 / 12 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)	3 / 12 (25.00%)	3 / 101 (2.97%)	3 / 97 (3.09%)	4 / 100 (4.00%)	3 / 100 (3.00%)	4 / 101 (3.96%)	3 / 101 (2.97%)	6 / 101 (5.94%)	2 / 100 (2.00%)	4 / 103 (3.88%)	2 / 101 (1.98%)
occurrences all number	0	1	1	3	3	3	4	3	5	3	6	2	5	2
Urinary tract infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	2 / 97 (2.06%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	2 / 101 (1.98%)	1 / 100 (1.00%)	2 / 103 (1.94%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	2	2	0	0	1	2	1	2	1
Nasopharyngitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	2 / 100 (2.00%)	1 / 101 (0.99%)	2 / 101 (1.98%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	2	1	2	0	0	1	0
Bronchitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	4 / 97 (4.12%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	2 / 101 (1.98%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	4	0	0	0	2	0	0	0	0
Rhinitis
subjects affected / exposed	0 / 12 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	2 / 101 (1.98%)	0 / 101 (0.00%)	2 / 100 (2.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	1	1	0	1	0	0	0	0	2	0	2	1	0
Tooth abscess
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	2 / 100 (2.00%)	0 / 103 (0.00%)	2 / 101 (1.98%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	2	0	2
Gastroenteritis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	2 / 101 (1.98%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	1	0	2
Respiratory tract infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	2 / 101 (1.98%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	2	0	1	0	0	0	1	0	1	0
Sinusitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	2 / 103 (1.94%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	2	0
Viral infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	1	0	0	0
Tooth infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	1	0	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	1	1
Cystitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	2	2	0
Laryngitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	1	0	0
Otitis externa
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	0	0	0	0
Herpes zoster
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	0	0	0
Wound infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	1
Paronychia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Sialoadenitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	1 / 97 (1.03%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Cellulitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Chronic sinusitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Dermatophytosis of nail
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Fungal skin infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Hordeolum
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Pharyngitis
subjects affected / exposed	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0	0	0	0	0	0
Pulpitis dental
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Vulvovaginitis streptococcal
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Body tinea
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Folliculitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Gastroenteritis norovirus
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Gastroenteritis viral
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	1 / 101 (0.99%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Gingivitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Herpes simplex
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Oral herpes
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Pharyngitis streptococcal
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 101 (0.99%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Pneumonia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Tracheitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Bacterial infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Furuncle
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Otitis media
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Metabolism and nutrition disorders
Hyperlipidaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Hypoferritinaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Hypomagnesaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Dehydration
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hyperglycaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 101 (0.00%)	0 / 97 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 101 (0.99%)	0 / 101 (0.00%)	0 / 101 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

13 May 2020

This Protocol Amendment 1 outlines measures that may be applicable during special circumstances (e.g., Coronavirus disease 2019 [COVID-19] pandemic). The purpose of the amendment is to protect subject’s welfare and safety, and as far as possible ensure the potential benefit to the subject and promote data integrity. A new section has been added (Section 5.10) to provide guidance on adapting study procedures during special circumstances, such as COVID-19 pandemic.

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

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

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of subjects with any solicited local symptoms after first vaccination dose

Primary: Number of subjects with any solicited local symptoms after first vaccination dose

Primary: Number of subjects with any solicited local symptoms after second vaccination dose

Primary: Number of subjects with any solicited local symptoms after second vaccination dose

Primary: Number of subjects with any solicited general symptom after first vaccination dose

Primary: Number of subjects with any solicited general symptom after first vaccination dose

Primary: Number of subjects with any solicited general symptom after second vaccination dose

Primary: Number of subjects with any solicited general symptom after second vaccination dose

Primary: Number of subjects with any unsolicited adverse events (AEs) after any vaccination dose

Primary: Number of subjects with any unsolicited adverse events (AEs) after any vaccination dose

Primary: Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after first vaccine dose (Part A groups)

Primary: Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after first vaccine dose (Part A groups)

Primary: Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after first vaccine dose (Part B groups)

Primary: Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after first vaccine dose (Part B groups)

Primary: Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after second vaccine dose (Part A groups)

Primary: Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after second vaccine dose (Part A groups)

Primary: Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after second vaccine dose (Part B groups)

Primary: Number of subjects presenting change from baseline in hematology and biochemistry with respect of normal laboratory ranges, after second vaccine dose (Part B groups)

Primary: Number of subjects with any Grade 3 non-serious AEs (solicited and unsolicited) after first dose of vaccination

Primary: Number of subjects with any Grade 3 non-serious AEs (solicited and unsolicited) after first dose of vaccination

Primary: Number of subjects with any Grade 3 non-serious AEs (solicited and unsolicited) after second dose of vaccination

Primary: Number of subjects with any Grade 3 non-serious AEs (solicited and unsolicited) after second dose of vaccination

Primary: Number of subjects with any Serious Adverse Events (SAEs) up to 30 days after the second vaccination

Primary: Number of subjects with any Serious Adverse Events (SAEs) up to 30 days after the second vaccination

Primary: Number of subjects with any potential immune-mediated diseases (pIMDs) up to 30 days after the second vaccination (Part B groups)

Primary: Number of subjects with any potential immune-mediated diseases (pIMDs) up to 30 days after the second vaccination (Part B groups)

Secondary: Number of subjects with any SAEs, up the end of follow-up period (Month 14) - Part B groups

Secondary: Number of subjects with any SAEs, up the end of follow-up period (Month 14) - Part B groups

Secondary: Number of subjects reporting pIMDs up to the end of follow-up period (Month 14) - Part B groups

Secondary: Number of subjects reporting pIMDs up to the end of follow-up period (Month 14) - Part B groups

Secondary: Number of subjects with at least one RSV-confirmed Respiratory Tract Infection (RTI) episode post-vaccination reported during RTI surveillance - Part B groups

Secondary: Number of subjects with at least one RSV-confirmed Respiratory Tract Infection (RTI) episode post-vaccination reported during RTI surveillance - Part B groups

Secondary: Humoral immune response with respect to components of the investigational vaccine in terms of neutralizing antibody titers against RSV-serotype A (Part A groups)

Secondary: Humoral immune response with respect to components of the investigational vaccine in terms of neutralizing antibody titers against RSV-serotype A (Part A groups)

Secondary: Humoral immune response with respect to components of the investigational vaccine in terms of neutralizing antibody titers against RSV-serotype A (Part B groups)

Secondary: Humoral immune response with respect to components of the investigational vaccine in terms of neutralizing antibody titers against RSV-serotype A (Part B groups)

Secondary: Humoral immune response with respect to components of the investigational vaccine in terms of RSVPreF3-specific Immunoglobulin G (IgG) antibody concentrations (Part A groups)

Secondary: Humoral immune response with respect to components of the investigational vaccine in terms of RSVPreF3-specific Immunoglobulin G (IgG) antibody concentrations (Part A groups)

Secondary: Humoral immune response with respect to components of the investigational vaccine in terms of RSVPreF3-specific Immunoglobulin G (IgG) antibody concentrations (Part B groups)

Secondary: Humoral immune response with respect to components of the investigational vaccine in terms of RSVPreF3-specific Immunoglobulin G (IgG) antibody concentrations (Part B groups)

Secondary: Descriptive statistics of the frequency of RSVPreF3 specific cluster of differentiation 4+ (CD4+) T cells expressing at least 2 markers (Part A groups)

Secondary: Descriptive statistics of the frequency of RSVPreF3 specific cluster of differentiation 4+ (CD4+) T cells expressing at least 2 markers (Part A groups)

Secondary: Descriptive statistics of the frequency of RSVPreF3 specific cluster of differentiation 4+ (CD4+) T cells expressing at least 2 markers (Part B groups)

Secondary: Descriptive statistics of the frequency of RSVPreF3 specific cluster of differentiation 4+ (CD4+) T cells expressing at least 2 markers (Part B groups)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information