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Clinical Trial Results:
Clinical Otitis Media and Pneumonia Study (COMPAS): a phase III , double-blind, randomized, controlled, multicentre study to demonstrate the efficacy of GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine (GSK1024850A) against Community Acquired Pneumonia (CAP) and Acute Otitis Media (AOM)

Summary
EudraCT number	2011-002076-16
Trial protocol	Outside EU/EEA
Global end of trial date	28 Jul 2011

Results information
Results version number	v2(current)
This version publication date	16 Oct 2020
First version publication date	15 May 2015
Other versions	v1
Version creation reason	Correction of full data set Updating the Results Summaries after a QC.

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

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Trial information

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Sponsor protocol code

109563

ISRCTN number

US NCT number

NCT00466947

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

Rue de l'Institut 89, Rixensart, Belgium,

Public contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, +44 2089904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, +44 2089904466, GSKClinicalSupportHD@gsk.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-000673-PIP01-09

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

21 Feb 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Jul 2011

Was the trial ended prematurely?

Main objective of the trial

To demonstrate the efficacy of a 3-dose primary course followed by a booster dose in the second year of life with the 10Pn-PD-DiT vaccine against likely bacterial CAP cases (B-CAP) in the entire study cohort. Likely bacterial CAP is defined as radiologically confirmed CAP cases with either alveolar consolidation/pleural effusion on the chest X-ray (CXR), or with non-alveolar infiltrates but with C-reactive protein (CRP) ≥ 40 mg/L.

Protection of trial subjects

Subjects’ safety was monitored in the study via the following measures and practice: Prior to the study: check of inclusion and exclusion criteria prior to enrolment, completed with check on gestational age, medical and pre-vaccination history of subjects; Throughout the study: regular check for exclusion criteria for further study participation, for risk factors, and for warnings, precautions and contraindications to the vaccine administered.

Background therapy

Evidence for comparator

Actual start date of recruitment

28 Jun 2007

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 13981

Country: Number of subjects enrolled

Colombia: 2483

Country: Number of subjects enrolled

Panama: 7359

Worldwide total number of subjects

23823

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

23823

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Primary outcome analysis was on 31 August 2010, when at least 535 first bacterial CAP episodes reported from 2 weeks after Dose 3 – total population: 11875 & 11863 subjects in Synflorix and Control groups; according to protocol efficacy cohort: 10295 & 10201 subjects in Synflorix and Control groups. Study end analysis was done on 23597 subjects.

Screening details

During the screening, the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing of informed consent forms by parent(s)/guardian(s).

Number of subjects started

23823

Number of subjects completed

23597

Reason: Number of subjects

Protocol deviation: 226

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer

Are arms mutually exclusive

Yes

Synflorix Group

Arm description

Subjects received 3 primary doses of Synflorix at 2, 4 and 6 months of age co-administered with Infanrix-hexa and booster dose of Synflorix at 15-18 months of age co-administered with Infanrix-IPV/Hib. All vaccines were administered intramuscularly in the right (Synflorix) or the left (Infanrix-hexa, Infanrix-IPV + Hib) thigh (primary dose) or deltoid (booster dose).

Arm type

Experimental

Investigational medicinal product name

Synflorix

Investigational medicinal product code

Other name

10Pn, 10Pn-PD-DiT, GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine, Synflorix™, GSK1024850A

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 primary doses at 2, 4 and 6 months, administered in the right thigh,and a booster dose at 15-18 months administered in the right thigh or deltoid.

Investigational medicinal product name

Infanrix-IPV + Hib

Investigational medicinal product code

Other name

Infanrix-IPV/Hib

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose administered at 15-18 months of age in the left thigh or deltoid.

Investigational medicinal product name

Infanrix Hexa

Investigational medicinal product code

Other name

DTPa-IPV-HBV / Hib, GSK Biologicals’ diphtheria-tetanus-acellular pertussis, hepatitis B virus-inactivated poliovirus and Haemophilus influenzae type b vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 primary doses at 2, 4 and 6 months administered in the left thigh.

Control Group

Arm description

Subjects received 3 doses of Engerix B at 2,4 and 6 months of age co-administered with Infanrix-IPV + Hib and 1 dose of Havrix 720 Junior co-administered with Infanrix-IPV + Hib at 15-18 months of age. All vaccine were administered in the right (Engerix B Junior, Havrix) or the left (Infanrix-IPV + Hib) thigh.

Arm type

Active comparator

Investigational medicinal product name

Engerix B Junior

Investigational medicinal product code

Other name

HBV, Engerix B

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses at 2,4 and 6 months of age, administered in the right thigh.

Investigational medicinal product name

Infanrix-IPV + Hib

Investigational medicinal product code

Other name

Infanrix-IPV/Hib

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 primary doses at 2,4 and 6 months of age, administered in in the left thigh and one booster dose at 15-18 months of age administered in the left thigh or deltoid.

Investigational medicinal product name

Havrix 720 Junior

Investigational medicinal product code

Other name

HAV, Hepatitis A vaccine (inactivated), Havrix

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 1 dose at 15-18 months of age administered in the right thigh.

Number of subjects in period 1 ^[1]	Synflorix Group	Control Group
Started	11798	11799
Completed	9302	9265
Not completed	2496	2534
Unconformity in team’s treatment	-	1
Consent withdrawn by subject	1264	1267
Physician decision	29	29
Adverse event, non-fatal	35	43
Forbidden vaccination	21	10
Subject without a legal guardian	1	-
Lost to follow-up	1137	1167
Protocol deviation	9	17

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Among the initial 23823 subjects enrolled in the study, 3 were not allocated to any groups and 2 had non-valid informed consent. In addition, analysis on the primary outcome was performed when at least 535 first bacterial CAP episodes were reported from 2 weeks after vaccine Dose 3 (31 August 2010) with 23738 subjects (11875 and 11863 in Synflorix and Control groups) and analysis at study end was performed on 23597 subjects.

Baseline characteristics

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Reporting group title

Synflorix Group

Reporting group description

Reporting group title

Control Group

Reporting group description

Reporting group values	Synflorix Group	Control Group	Total
Number of subjects	11798	11799	23597
Age categorical
Units: Subjects
In utero			0
Preterm newborn infants (gestational age < 37 wks)			0
Newborns (0-27 days)			0
Infants and toddlers (28 days-23 months)			0
Children (2-11 years)			0
Adolescents (12-17 years)			0
Adults (18-64 years)			0
From 65-84 years			0
85 years and over			0
Age continuous
Units: weeks
arithmetic mean (standard deviation)	9.2 ± 1.93	9.2 ± 1.92	-
Gender categorical
Units: Subjects
Female	5796	5767	11563
Male	6002	6032	12034

End points

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Reporting group title

Synflorix Group

Reporting group description

Reporting group title

Control Group

Reporting group description

Primary: Number of subjects with a first episode reported of bacterial community acquired pneumoniae (B-CAP)

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End point title

Number of subjects with a first episode reported of bacterial community acquired pneumoniae (B-CAP) ^[1]

End point description

A B-CAP episode was defined as a radiologically confirmed community acquired pneumoniae (CAP) episode with either alveolar consolidation/pleural effusion on the chest X-ray (CXR) or with non-alveolar infiltrates but with C reactive protein (CRP) higher than or equal to (>=) 40 milligrams per liter (mg/L). The results are presented for data lock point for the primary outcome analysis (31 August 2010), which was performed, as per protocol, when at least 535 first B-CAP episodes were reported from 2 weeks after the third vaccination dose. After analysis on primary outcome was performed, re-monitoring activities revealed ICF issues for some subjects. Therefore, a sensitivity analysis excluding 144 subjects was performed. This analysis confirmed the validity of the results for primary outcome.

End point type

Primary

End point timeframe

Any time from 2 weeks after Dose 3 up to 31 August 2010

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Synflorix Group	Control Group
Number of subjects analysed	10295	10201
Units: Subjects
Subjects with B-CAP	240	304

No statistical analyses for this end point

Primary: Time to First or Only Episode of B-CAP

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End point title

Time to First or Only Episode of B-CAP

End point description

The total time to a first episode reported of bacterial community acquired pneumoniae (B-CAP) was tabulated. A B-CAP episode was defined as a radiologically confirmed community acquired pneumoniae (CAP) episode with either alveolar consolidation/pleural effusion on the chest X-ray (CXR) or with non-alveolar infiltrates but with C reactive protein (CRP) higher than or equal to (>=) 40 milligrams per liter (mg/L). The results are presented for data lock point for the primary outcome analysis (31 August 2010), which was performed when at least 535 first B-CAP episodes were reported from 2 weeks after Dose 3 of vaccine. After analysis was performed, re-monitoring activities revealed ICF issues for some subjects. Therefore, a sensitivity analysis excluding 144 subjects was performed, which confirmed the validity of the results for primary outcome.

End point type

Primary

End point timeframe

Any time from 2 weeks after Dose 3 up to 31 August 2010

End point values	Synflorix Group	Control Group
Number of subjects analysed	10295	10201
Units: Years
number (not applicable)
Total time to first B-CAP episode	19512.99	19260.15

Vaccine Efficacy for time to first B-CAP episode

Statistical analysis description

The vaccine efficacy (VE) to prevent the first episode of B-CAP was estimated with 95% confidence interval (CI), as (1 minus the hazard ratio) times 100 obtained from a Cox regression model including the treatment group (Synflorix Group) as only regressor. Censoring occurred either at the time of the last contact, of unblinding or at 18 months of age if the booster dose was not administered or was administered at a later age.

Comparison groups

Synflorix Group v Control Group

Number of subjects included in analysis

20496

Analysis specification

Pre-specified

Analysis type

superiority ^[2]

P-value

= 0.002 ^[3]

Method

Regression, Cox

Parameter type

VE (see above)

Point estimate

22.033

Confidence interval

level

95%

sides

2-sided

lower limit

7.656

upper limit

34.172

Notes
[2] - Vaccine efficacy analysis, based on a Cox regression proportional hazard model
[3] - Statistical significance was reached if the one-sided p-value for the Wald-Test obtained from the Cox proportional hazard model calculated for the null hypothesisH0= [B-CAP VE =< 0%] (Y = Time to Event) was lower than 0.0175.

Secondary: Number of subjects with serious adverse events (SAEs)

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End point title

Number of subjects with serious adverse events (SAEs)

End point description

SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

End point type

Secondary

End point timeframe

Throughout the study (Month 0 to Month 22-25)

End point values	Synflorix Group	Control Group
Number of subjects analysed	11798	11799
Units: Subjects
Number of subjects with SAE(s)	2534	2668

No statistical analyses for this end point

Secondary: Number of subjects with any unsolicited adverse event (AE), in the Panama Subset

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End point title

Number of subjects with any unsolicited adverse event (AE), in the Panama Subset

End point description

An unsolicited AE is any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. The Panama Subset included all subjects from Panama.

End point type

Secondary

End point timeframe

Throughout the study (Month 0 to Month 22-25)

End point values	Synflorix Group	Control Group
Number of subjects analysed	3602	3612
Units: Subjects
Number of subjects with AE(s)	3530	3518

No statistical analyses for this end point

Secondary: Number of subjects with solicited local symptoms post primary vaccination in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with solicited local symptoms post primary vaccination in the Immunogenicity and Tolerability Subset

End point description

Assessed symptoms were redness, swelling and pain. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively. This outcome measure concerns solely subjects from the Synflorix Group.

End point type

Secondary

End point timeframe

Within the 4-days (Days 0–3) follow-up period across the 3 doses of the primary study vaccine administration

End point values	Synflorix Group	Control Group
Number of subjects analysed	368	0 ^[4]
Units: Subjects
Pain after vaccination with Synflorix	275
Pain after vaccination with Infanrix Hexa	270
Redness after vaccination with Synflorix	182
Redness after vaccination with Infanrix Hexa	171
Swelling after vaccination with Synflorix	141
Swelling after vaccination with Infanrix Hexa	143

Notes
[4] - The endpoint solely concerns the Synflorix Group.

No statistical analyses for this end point

Secondary: Number of subjects with solicited local symptoms post booster vaccination in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with solicited local symptoms post booster vaccination in the Immunogenicity and Tolerability Subset

End point description

End point type

Secondary

End point timeframe

Within the 4-days (Days 0–3) follow-up period following the booster vaccine administration

End point values	Synflorix Group	Control Group
Number of subjects analysed	317	0 ^[5]
Units: Subjects
Pain after vaccination with Synflorix	129
Pain after vaccination with Infanrix-IPV/Hib	131
Redness after vaccination with Synflorix	104
Redness after vaccination with Infanrix-IPV/Hib	98
Swelling after vaccination with Synflorix	74
Swelling after vaccination with Infanrix-IPV/Hib	69

Notes
[5] - The endpoint solely concerns the Synflorix Group.

No statistical analyses for this end point

Secondary: Number of subjects with solicited local symptoms post primary vaccination in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with solicited local symptoms post primary vaccination in the Immunogenicity and Tolerability Subset

End point description

End point type

Secondary

End point timeframe

Within the 4-days (Days 0–3) follow-up period across the 3 doses of the primary study vaccine administration

End point values	Synflorix Group	Control Group
Number of subjects analysed	0 ^[6]	357
Units: Subjects
Pain after vaccination with Infanrix-IPV/Hib		169
Pain after vaccination with Engerix		165
Redness after vaccination with Infanrix-IPV/Hib		118
Redness after vaccination with Engerix		109
Swelling after vaccination with Infanrix-IPV/Hib		98
Swelling after vaccination with Engerix		91

Notes
[6] - The endpoint solely concerns the Control Group.

No statistical analyses for this end point

Secondary: Number of subjects with solicited local symptoms post booster vaccination in the Immunogenicity and Tolerability Subset, for the Control Group

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End point title

Number of subjects with solicited local symptoms post booster vaccination in the Immunogenicity and Tolerability Subset, for the Control Group

End point description

Assessed symptoms were redness, swelling and pain. The Immunogenicity and Safety Tolerability Subset included 500 subjects coming from Argentina and Panama respectively. This outcome measure concerns solely subjects from the Control Group.

End point type

Secondary

End point timeframe

Within the 4-days (Days 0–3) follow-up period following the booster vaccine administration.

End point values	Synflorix Group	Control Group
Number of subjects analysed	0 ^[7]	303
Units: Subjects
Pain after vaccination with Infanrix-IPV/Hib		81
Pain after vaccination with Havrix		89
Redness after vaccination with Infanrix-IPV/Hib		81
Redness after vaccination with Havrix		73
Swelling after vaccination with Infanrix-IPV/Hib		70
Swelling after vaccination with Havrix		55

Notes
[7] - The endpoint solely concerns the Control Group.

No statistical analyses for this end point

Secondary: Number of subjects with solicited general symptoms post primary vaccination in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with solicited general symptoms post primary vaccination in the Immunogenicity and Tolerability Subset

End point description

Assessed symptoms were fever (defined as rectal temperature equal or higher than [>=] 38 degrees Celsius [°C]). irritability/fussiness, drowsiness, and loss of appetite. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

Within the 4-days (Days 0–3) follow-up period across the 3 doses of the primary study vaccine administration

End point values	Synflorix Group	Control Group
Number of subjects analysed	368	357
Units: Subjects
Drowsiness	236	168
Fever (rectal temperature >= 38°C)	247	125
Irritability	289	206
Loss of appetite	133	80

No statistical analyses for this end point

Secondary: Number of subjects with solicited general symptoms post booster vaccination in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with solicited general symptoms post booster vaccination in the Immunogenicity and Tolerability Subset

End point description

End point type

Secondary

End point timeframe

Within the 4-days (Days 0–3) follow-up period following the booster vaccine administration

End point values	Synflorix Group	Control Group
Number of subjects analysed	317	303
Units: Subjects
Drowsiness	74	65
Fever (rectal temperature >= 38°C)	93	73
Irritability	121	95
Loss of appetite	51	46

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of clinically confirmed acute otitis media (AOM) (C-AOM), in the Panama Subset

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End point title

Number of subjects with a first episode reported of clinically confirmed acute otitis media (AOM) (C-AOM), in the Panama Subset

End point description

The Panama Subset contained all subjects enrolled in Panama.

End point type

Secondary

End point timeframe

Any time from 2 weeks after Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	3010	2979
Units: Subjects
C-AOM	204	239

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with alveolar consolidation or pleural effusion on the chest X-ray (CXR) (C-CAP)

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End point title

Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with alveolar consolidation or pleural effusion on the chest X-ray (CXR) (C-CAP)

End point description

CXR alveolar consolidation was defined as CXR with a dense, often homogeneous, confluent alveolar infiltrate that could encompass an entire lobe or segment, or a fluffy, mass-like, cloud-like density that erased heart and diaphragm borders (silhouette sign) and that often contained air bronchograms. CXR pleural effusion was defined as a fluid collecting in the pleural space around the lung, seen radiologically as a dense rim (the same density as the chest-wall muscles) interposed between the lung and the ribs.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	10211	10140
Units: Subjects
CAP with alveolar consolidation/pleural effusion	181	231

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to any bacterial pathogen, in the Panama Subset

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End point title

Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to any bacterial pathogen, in the Panama Subset

End point description

The Panama Subset contained all subjects enrolled in Panama.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	3010	2979
Units: Subjects
B-AOM	32	45

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to Streptococcus pneumoniae (S. pn.) vaccine serotypes, in the Panama Subset

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End point title

Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to Streptococcus pneumoniae (S. pn.) vaccine serotypes, in the Panama Subset

End point description

The 10 pneumococcal S. pneumoniae vaccine serotypes assessed for this outcome measure were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The Panama Subset contained all subjects enrolled in Panama.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	3010	2979
Units: Subjects
B-AOM caused by S. pn. serotypes	6	18

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to Streptococcus pneumoniae (S. pn.) cross-reactive serotypes, in the Panama Subset.

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End point title

Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to Streptococcus pneumoniae (S. pn.) cross-reactive serotypes, in the Panama Subset.

End point description

The S. pn. cross-reactive serotypes assessed for this outcome measure were the serotypes 6A, 18B, 19A and 23A. The Panama Subset contained all subjects enrolled in Panama.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	3010	2979
Units: Subjects
B-AOM caused by S. pn. cross-reactive serotypes	3	4

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to other pneumococcal serotypes, in the Panama Subset.

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End point title

Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to other pneumococcal serotypes, in the Panama Subset.

End point description

Other pneumococcal serotypes were defined for this outcome measures as non-Streptococcus pneumoniae vaccine and cross-reactive serotypes. The Panama Subset contained all subjects enrolled in Panama.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	3010	2979
Units: Subjects
B-AOM caused by other pneumococcal serotypes	3	4

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to Haemophilus influenzae (H. influenzae), in the Panama Subset

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End point title

Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to Haemophilus influenzae (H. influenzae), in the Panama Subset

End point description

The Panama Subset contained all subjects enrolled in Panama.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	3010	2979
Units: Subjects
B-AOM caused by H. influenzae	12	14

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to non-typeable Haemophilus influenzae (H. influenzae), in the Panama Subset

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End point title

Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to non-typeable Haemophilus influenzae (H. influenzae), in the Panama Subset

End point description

The Panama Subset contained all subjects enrolled in Panama

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	3010	2979
Units: Subjects
B-AOM caused by non-typeable H. influenzae	12	14

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to other AOM pathogens, in the Panama Subset

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End point title

Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to other AOM pathogens, in the Panama Subset

End point description

Other pathogens assessed included among others Moraxella catarrhalis, Group A streptococci, and Staphyloccus aureus. The Panama Subset contained all subjects enrolled in Panama.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	3010	2979
Units: Subjects
B-AOM caused by other pathogens	8	7

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with alveolar consolidation or pleural effusion on the Chest X-ray (CXR) (C-CAP) with positive respiratory viral test (RVT)

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End point title

Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with alveolar consolidation or pleural effusion on the Chest X-ray (CXR) (C-CAP) with positive respiratory viral test (RVT)

End point description

A CXR with consolidation was defined as a CXR with a dense, often homogeneous, confluent alveolar infiltrate that could encompass an entire lobe or segment, or a fluffy, mass-like, cloud-like density that erased heart and diaphragm borders (silhouette sign) and that often contained air bronchograms. Pleural effusion was defined as a fluid collecting in the pleural space around the lung, seen radiologically as a dense rim (the same density as the chest-wall muscles) interposed between the lung and the ribs.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	10211	10140
Units: Subjects
C-CAP associated with positive RVT	21	25

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with any abnormal CXR with positive respiratory viral test (RVT)

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End point title

Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with any abnormal CXR with positive respiratory viral test (RVT)

End point description

An “abnormal CXR” was defined as a CXR with either consolidation, pleural effusion and/or abnormal pulmonary alveolar or non-alveolar infiltrates on the digital CXR image. CXR with consolidation was defined as a CXR with a dense, often homogeneous, confluent alveolar infiltrate that could encompass an entire lobe or segment, or a fluffy, mass-like, cloud-like density that erased heart and diaphragm borders (silhouette sign) and that often contained air bronchograms. Pleural effusion was defined as a fluid collecting in the pleural space around the lung, seen radiologically as a dense rim (the same density as the chest-wall muscles) interposed between the lung and the ribs.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	10211	10140
Units: Subjects
CAP with abnormal CXR with positive RVT	104	112

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of bacterial community acquired pneumoniae (B-CAP) with positive respiratory viral test (RVT).

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End point title

Number of subjects with a first episode reported of bacterial community acquired pneumoniae (B-CAP) with positive respiratory viral test (RVT).

End point description

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	10211	10140
Units: Subjects
B-CAP associated with positive RVT	35	39

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of suspected community acquired pneumoniae (CAP) (S-CAP)

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End point title

Number of subjects with a first episode reported of suspected community acquired pneumoniae (CAP) (S-CAP)

End point description

An episode of S-CAP involved either any subject who was referred to have a chest X-ray (CXR) performed as part of the clinical assessment of a febrile syndrome or an acute respiratory infection (ARI), or a hospitalized child who had a CXR performed within 2 days prior to, or within the first 3 days after hospital admission, as part of the clinical assessment of a febrile syndrome or an ARI.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	10211	10140
Units: Subjects
S-CAP	2108	2237

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with any abnormal chest X-ray (CXR)

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End point title

Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with any abnormal chest X-ray (CXR)

End point description

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	10211	10140
Units: Subjects
CAP with any abnormal CXR	681	764

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of suspected community acquired pneumoniae (CAP) (S-CAP) with C reactive protein (CRP) >= cut-off, regardless of chest X-ray (CXR) reading

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End point title

Number of subjects with a first episode reported of suspected community acquired pneumoniae (CAP) (S-CAP) with C reactive protein (CRP) >= cut-off, regardless of chest X-ray (CXR) reading

End point description

A case of S-CAP involved either any subject who was referred to have a CXR performed as part of the clinical assessment of a febrile syndrome or an acute respiratory infection (ARI), or a hospitalized child who had a CXR performed within 2 days prior to, or within the first 3 days after hospital admission, as part of the clinical assessment of a febrile syndrome or an ARI. CRP cut-off values applied for this outcome measure were 40 milligrams per liter (mg/L), 80 mg/L, and 120 mg/L.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	10211	10140
Units: Subjects
S-CAP with CRP >= 40 mg/L regardless of CXR exam	425	499
S-CAP with CRP >= 80 mg/L regardless of CXR exam	175	237
S-CAP with CRP >= 120 mg/L regardless of CXR exam	85	119

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of CAP with either alveolar consolidation/pleural effusion on chest X-ray (CXR) (C-CAP) or with non-alveolar infiltrates (NAI-CAP) but with C reactive protein (CRP) >= cut-off.

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End point title

Number of subjects with a first episode reported of CAP with either alveolar consolidation/pleural effusion on chest X-ray (CXR) (C-CAP) or with non-alveolar infiltrates (NAI-CAP) but with C reactive protein (CRP) >= cut-off.

End point description

CRP cut-off values applied for this outcome measure were 80 milligrams per liter (mg/L), and 120 mg/L.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	10211	10140
Units: Subjects
C-CAP or NAI-CAP with CRP >= 80 mg/L	208	256
C-CAP or NAI-CAP with CRP >= 120 mg/L	191	240

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of vaccine-type invasive pneumococcal disease (VT-IPD).

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End point title

Number of subjects with a first episode reported of vaccine-type invasive pneumococcal disease (VT-IPD).

End point description

A VT-IPD was defined as a bacteriologically culture confirmed invasive pneumococcal disease case caused by any of the 10 pneumococcal Streptococcus pneumoniae vaccine serotypes. The 10 pneumococcal S. pneumoniae vaccine serotypes assessed for this outcome measure were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	10211	10140
Units: Subjects
VT-IPD	0	16

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of a bacteriologically confirmed invasive pneumococcal disease (Bact.-conf. ID).

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End point title

Number of subjects with a first episode reported of a bacteriologically confirmed invasive pneumococcal disease (Bact.-conf. ID).

End point description

A Bact.-conf. ID was defined as a bacteriologically culture confirmed invasive pneumococcal disease (ID) cases due to any of the 10 Streptococcus pneumoniae vaccine serotypes as identified through positive culture. The 10 pneumococcal S. pneumoniae vaccine serotypes assessed for this outcome measure were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	10211	10140
Units: Subjects
Bact.-conf. ID	6	17

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of pneumococcal invasive disease (Pneumococcal ID)

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End point title

Number of subjects with a first episode reported of pneumococcal invasive disease (Pneumococcal ID)

End point description

A Pneumococcal ID was defined as a bacteriologically culture confirmed invasive pneumococcal disease (ID) cases due to any of the 10 Streptococcus pneumoniae vaccine serotypes. The 10 pneumococcal S. pneumoniae vaccine serotypes assessed for this outcome measure were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Pneumococcal ID cases were identified through non-culture pneumococcal diagnostic tests with additional non-culture vaccine type serotyping. Tests used included rapid in-vitro diagnostic tests or Latex agglutination.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	10211	10140
Units: Subjects
Pneumococcal ID	6	17

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of Invasive Pneumococcal Disease (IPD) due to Streptococcus (S. pn.) cross-reactive pneumococcal serotypes.

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End point title

Number of subjects with a first episode reported of Invasive Pneumococcal Disease (IPD) due to Streptococcus (S. pn.) cross-reactive pneumococcal serotypes.

End point description

The S. pn. cross-reactive serotypes assessed for this outcome measure were the serotypes 19A, 6A and 9N.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	10211	10140
Units: Subjects
IPD due to S. pn. cross-reactive serotypes	2	1

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of Invasive Pneumococcal Disease (IPD) due to pneumococcal serotypes other than Streptococcus (S. pn.) vaccine and cross-reactive serotypes.

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End point title

Number of subjects with a first episode reported of Invasive Pneumococcal Disease (IPD) due to pneumococcal serotypes other than Streptococcus (S. pn.) vaccine and cross-reactive serotypes.

End point description

The serotypes assessed for this outcome measure included among others the pneumococcal serotypes 12F, 16F, 24F, 38 and 8.

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	10211	10140
Units: Subjects
IPD due to other pneumococcal serotypes	3	0

No statistical analyses for this end point

Secondary: Number of subjects with a first episode reported of invasive disease (ID) due to Haemophilus influenzae

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End point title

Number of subjects with a first episode reported of invasive disease (ID) due to Haemophilus influenzae

End point description

End point type

Secondary

End point timeframe

Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	10211	10140
Units: Subjects
ID due to Haemophilus influenzae	0	0

No statistical analyses for this end point

Secondary: Number of subjects with Streptococcus pneumoniae (S. pn.) vaccine serotypes identified in nasopharyngeal swabs, in the Carriage Subset.

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End point title

Number of subjects with Streptococcus pneumoniae (S. pn.) vaccine serotypes identified in nasopharyngeal swabs, in the Carriage Subset.

End point description

The 10 pneumococcal S. pn. vaccine serotypes assessed for this outcome measure were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. S. pn. serotypes were identified using latex agglutination and by quellung reaction with omni serum. The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.

End point type

Secondary

End point timeframe

At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	814	814
Units: Subjects
Month 5 (N=814; 814)	104	123
Month 10-13 (N=788; 784)	92	123
Month 13-16 (N=758; 762)	88	109
Month 14-17 (N=720; 738)	74	103
Month 16-19 (N=696; 690)	68	98
Month 22-25 (N=627; 639)	61	86

No statistical analyses for this end point

Secondary: Number of subjects with Streptococcus pneumoniae (S. pn.) cross-reactive serotypes identified in nasopharyngeal swabs, in the Carriage Subset.

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End point title

Number of subjects with Streptococcus pneumoniae (S. pn.) cross-reactive serotypes identified in nasopharyngeal swabs, in the Carriage Subset.

End point description

Any serotype belonging to the same serogroup as the Synflorix vaccine serotypes, but different from the vaccine serotypes, was considered for this analysis of carriage S. pn. cross-reactive serotypes. S. pn. serotypes were identified using latex agglutination and by quellung reaction with omni serum. The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.

End point type

Secondary

End point timeframe

At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	814	814
Units: Subjects
Month 5 (N=814; 814)	63	67
Month 10-13 (N=788; 784)	81	63
Month 13-16 (N=758; 762)	57	63
Month 14-17 (N=720; 738)	57	49
Month 16-19 (N=696; 690)	55	57
Month 22-25 (N=627; 639)	38	46

No statistical analyses for this end point

Secondary: Number of subjects with Streptococcus pneumoniae (S. pn.) serotypes identified in nasopharyngeal swabs other than the Synflorix vaccine and cross-reactive serotypes, in the Carriage Subset

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End point title

Number of subjects with Streptococcus pneumoniae (S. pn.) serotypes identified in nasopharyngeal swabs other than the Synflorix vaccine and cross-reactive serotypes, in the Carriage Subset

End point description

S. pn. serotypes were identified using latex agglutination and by quellung reaction with omni serum. The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.

End point type

Secondary

End point timeframe

At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	814	814
Units: Subjects
Month 5 (N=814; 814)	99	86
Month 10-13 (N=788; 784)	85	85
Month 13-16 (N=758; 762)	83	85
Month 14-17 (N=720; 738)	78	85
Month 16-19 (N=696; 690)	89	69
Month 22-25 (N=627; 639)	74	61

No statistical analyses for this end point

Secondary: Number of subjects with H. influenzae strains identified in nasopharyngeal swabs, in the Carriage subset

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End point title

Number of subjects with H. influenzae strains identified in nasopharyngeal swabs, in the Carriage subset

End point description

Results included samples confirmed as positive for Haemophilus influenzae (H. influenzae) or non-typeable H. influenzae (NTHi) after differentiation from H. haemolyticus by polymerase chain reaction (PCR) assay. The Carriage Subset contained a subgroup of 2,000 subjects enrolled in Panama.

End point type

Secondary

End point timeframe

At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	824	820
Units: Subjects
Month 5 (N=824; 820)	36	40
Month 10-13 (N=788;785)	45	44
Month 13-16 (N=757;762)	32	39
Month 14-17 (N=720; 737)	28	34
Month 16-19 (N=696; 690)	28	38
Month 22-25 (N=628; 640)	29	33

No statistical analyses for this end point

Secondary: Number of subjects with acquisition of new Streptococcus pneumoniae strains identified in nasopharyngeal swabs, in the Carriage Subset

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End point title

Number of subjects with acquisition of new Streptococcus pneumoniae strains identified in nasopharyngeal swabs, in the Carriage Subset

End point description

The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.

End point type

Secondary

End point timeframe

At Months 10-13, 13-16, 14-17, 16-19 and 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	788	784
Units: Subjects
Month 10-13 (N=788;784)	171	175
Month 13-16 (N=758;762)	145	165
Month 14-17 (N=720;738)	110	137
Month 16-19 (N=696;690)	126	137
Month 22-25;N=627;639)	123	124

No statistical analyses for this end point

Secondary: Number of subjects with acquisition of new Haemophilus influenzae strains identified in nasopharyngeal swabs, in the Carriage Subset.

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End point title

Number of subjects with acquisition of new Haemophilus influenzae strains identified in nasopharyngeal swabs, in the Carriage Subset.

End point description

The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.

End point type

Secondary

End point timeframe

At Months 10-13, 13-16, 14-17, 16-19 and 22-25

End point values	Synflorix Group	Control Group
Number of subjects analysed	788	785
Units: Subjects
Month 10-13 (N=788;785)	39	37
Month 13-16 (N=757;762)	27	33
Month 14-17 (N=720;737)	23	28
Month 16-19 (N=696;690)	22	32
Month 22-25 (N=628;640)	28	31

No statistical analyses for this end point

Secondary: Number of subjects with any antibiotic prescription at least once during the entire study period, in the Carriage Subset.

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End point title

Number of subjects with any antibiotic prescription at least once during the entire study period, in the Carriage Subset.

End point description

The Carriage Subset consisted in a subgroup of 2,000 subjects enrolled in Panama.

End point type

Secondary

End point timeframe

Throughout the study (Month 0 to Month 22-25)

End point values	Synflorix Group	Control Group
Number of subjects analysed	955	966
Units: Subjects
Subjects with any antibiotic prescription	611	626

No statistical analyses for this end point

Secondary: Pneumococcal antibody concentrations against pneumococcal vaccine serotypes, in the Immunogenicity and Tolerability Subset.

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End point title

Pneumococcal antibody concentrations against pneumococcal vaccine serotypes, in the Immunogenicity and Tolerability Subset.

End point description

Antibody concentrations were measured by 22F enzyme-linked Immunosorbent Assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). Serotypes assessed were the pneumococcal vaccine serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The cut-off of the assay was >= 0.05 µg/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

At Month 5, one month after the third dose of primary vaccination

End point values	Synflorix Group	Control Group
Number of subjects analysed	334	331
Units: µg/mL
geometric mean (confidence interval 95%)
ANTI-1 (N=334;312)	2.51 (2.29 to 2.75)	0.04 (0.03 to 0.04)
ANTI-4 (N=334;328)	3.26 (2.98 to 3.56)	0.03 (0.03 to 0.04)
ANTI-5 (N=334;324)	4.2 (3.86 to 4.57)	0.05 (0.04 to 0.05)
ANTI-6B (N=334;322)	1.34 (1.18 to 1.52)	0.03 (0.03 to 0.03)
ANTI-7F (N=334;330)	3.86 (3.56 to 4.19)	0.04 (0.04 to 0.05)
ANTI-9V (N=334;331)	3.15 (2.84 to 3.5)	0.04 (0.03 to 0.04)
ANTI-14 (N=334;330)	4.55 (4.07 to 5.1)	0.09 (0.08 to 0.11)
ANTI-18C (N=334;328)	5.32 (4.73 to 5.99)	0.04 (0.04 to 0.04)
ANTI-19F (N=334;327)	5.33 (4.7 to 6.06)	0.06 (0.05 to 0.07)
ANTI-23F (N=334;331)	1.99 (1.76 to 2.26)	0.04 (0.03 to 0.04)

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset

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End point title

Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset

End point description

Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The cut-off of the assay was >= 0.05 µg/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

At Month 5, one month after the third dose of primary vaccination

End point values	Synflorix Group	Control Group
Number of subjects analysed	334	326
Units: µg/mL
geometric mean (confidence interval 95%)
ANTI-6A (N=334;321)	0.32 (0.27 to 0.37)	0.03 (0.03 to 0.04)
ANTI-19A (N=334;326)	0.29 (0.25 to 0.33)	0.04 (0.04 to 0.05)

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal vaccine serotypes, in the Immunogenicity and Tolerability Subset.

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End point title

Antibody concentrations against pneumococcal vaccine serotypes, in the Immunogenicity and Tolerability Subset.

End point description

Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). Serotypes assessed were the pneumococcal vaccine serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The cut-off of the assay was >= 0.05 µg/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST)

End point values	Synflorix Group	Control Group
Number of subjects analysed	231	214
Units: µg/mL
geometric mean (confidence interval 95%)
ANTI-1, PRE (N=231;203)	0.35 (0.31 to 0.39)	0.05 (0.04 to 0.06)
ANTI-1, M1 POST-BST (N=219;196)	3.58 (3.15 to 4.07)	0.06 (0.05 to 0.06)
ANTI-1, M9 POST-BST (N=206;181)	0.65 (0.56 to 0.75)	0.06 (0.05 to 0.06)
ANTI-4, PRE (N=231;214)	0.48 (0.42 to 0.55)	0.04 (0.04 to 0.05)
ANTI-4, M1 POST-BST (N=217;204)	6.55 (5.81 to 7.38)	0.05 (0.04 to 0.05)
ANTI-4, M9 POST-BST (N=206;183)	0.87 (0.77 to 0.99)	0.04 (0.04 to 0.05)
ANTI-5, PRE (N=231;209)	0.9 (0.8 to 1.01)	0.07 (0.07 to 0.09)
ANTI-5, M1 POST-BST (N=219;199)	5.73 (5.04 to 6.5)	0.07 (0.06 to 0.08)
ANTI-5, M9 POST-BST (N=206;182)	1.19 (1.05 to 1.36)	0.09 (0.08 to 0.1)
ANTI-6B, PRE (N=229;212)	0.55 (0.47 to 0.64)	0.04 (0.03 to 0.04)
ANTI-6B, M1 POST-BST (N=217;198)	3.32 (2.92 to 3.77)	0.04 (0.03 to 0.04)
ANTI-6B, M9 POST-BST (N=206;182)	0.83 (0.71 to 0.96)	0.05 (0.04 to 0.06)
ANTI-7F, PRE (N=231;210)	0.94 (0.84 to 1.04)	0.06 (0.05 to 0.07)
ANTI-7F, M1 POST-BST (N=218;198)	5.77 (5.23 to 6.36)	0.06 (0.05 to 0.07)
ANTI-7F, M9 POST-BST (N=206;182)	1.32 (1.19 to 1.45)	0.07 (0.05 to 0.08)
ANTI-9V, PRE (N=230;214)	1.14 (1 to 1.31)	0.04 (0.04 to 0.05)
ANTI-9V, M1 POST-BST (N=218;203)	7.34 (6.51 to 8.27)	0.04 (0.04 to 0.05)
ANTI-9V, M9 POST-BST (N=206;182)	1.8 (1.59 to 2.03)	0.05 (0.04 to 0.06)
ANTI-14, PRE (N=231;214)	1.15 (1.15 to 1.35)	0.11 (0.09 to 0.13)
ANTI-14, M1 POST-BST (N=219;200)	9.31 (8.18 to 10.6)	0.12 (0.1 to 0.14)
ANTI-14, M9 POST-BST (N=206;183)	1.98 (1.74 to 2.26)	0.17 (0.14 to 0.21)
ANTI-18C, PRE (N=231;210)	0.9 (0.79 to 1.03)	0.05 (0.04 to 0.06)
ANTI-18C, M1 POST-BST (N=219;203)	16.38 (14.47 to 18.55)	0.05 (0.04 to 0.05)
ANTI-18C, M9 POST-BST (N=206;181)	2.5 (2.21 to 2.83)	0.05 (0.04 to 0.06)
ANTI-19F, PRE (N=231;206)	1.27 (1.09 to 1.48)	0.06 (0.05 to 0.07)
ANTI-19F, M1 POST-BST (N=219;198)	9.4 (8.4 to 10.52)	0.07 (0.05 to 0.08)
ANTI-19F, M9 POST-BST (N=205;181)	2.47 (2.16 to 2.84)	0.1 (0.08 to 0.12)
ANTI-23F, PRE (N=229;204)	0.62 (0.53 to 0.72)	0.04 (0.03 to 0.05)
ANTI-23F, M1 POST-BST (N=218;201)	4.02 (3.49 to 4.62)	0.04 (0.03 to 0.04)
ANTI-23F, M9 POST-BST (N=206;179)	0.92 (0.8 to 1.06)	0.05 (0.04 to 0.06)

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset

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End point title

Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset

End point description

End point type

Secondary

End point timeframe

Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST)

End point values	Synflorix Group	Control Group
Number of subjects analysed	231	214
Units: µg/mL
geometric mean (confidence interval 95%)
ANTI-6A, PRE (N=231;214)	0.22 (0.18 to 0.26)	0.04 (0.04 to 0.05)
ANTI-6A, M1 POST-BST (N=219;204)	1.14 (0.93 to 1.4)	0.04 (0.03 to 0.04)
ANTI-6A, M9 POST-BST (N=206;183)	0.31 (0.26 to 0.37)	0.05 (0.04 to 0.06)
ANTI-19A, PRE (N=229;212)	0.25 (0.21 to 0.3)	0.05 (0.05 to 0.07)
ANTI-19A, M1 POST-BST (N=218;201)	1.34 (1.11 to 1.62)	0.06 (0.05 to 0.07)
ANTI-19A, M9 POST-BST (N=206;181)	0.54 (0.46 to 0.65)	0.09 (0.07 to 0.11)

No statistical analyses for this end point

Secondary: Number of subjects with antibody concentrations against pneumococcal vaccine serotypes >= 0.20 micrograms per milliliter (µg/mL), in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with antibody concentrations against pneumococcal vaccine serotypes >= 0.20 micrograms per milliliter (µg/mL), in the Immunogenicity and Tolerability Subset

End point description

Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA). Serotypes assessed were the pneumococcal vaccine serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

At Month 5, one month after the third dose of primary vaccination

End point values	Synflorix Group	Control Group
Number of subjects analysed	334	331
Units: Subjects
ANTI-1 (N=334;312)	333	13
ANTI-4 (N=334;328)	332	11
ANTI-5 (N=334;324)	333	22
ANTI-6B (N=334;322)	311	8
ANTI-7F (N=334;330)	333	28
ANTI-9V (N=334;331)	330	19
ANTI-14 (N=334;330)	328	77
ANTI-18C (N=334;328)	330	21
ANTI-19F (N=334;327)	325	40
ANTI-23F (N=334;331)	321	15

No statistical analyses for this end point

Secondary: Number of subjects with antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A >= 0.20 micrograms per milliliter (µg/mL), in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A >= 0.20 micrograms per milliliter (µg/mL), in the Immunogenicity and Tolerability Subset

End point description

Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA). The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

At Month 5, one month after the third dose of primary vaccination

End point values	Synflorix Group	Control Group
Number of subjects analysed	334	326
Units: Subjects
ANTI-6A (N=334;321)	215	5
ANTI-19A (N=334;326)	204	18

No statistical analyses for this end point

Secondary: Number of subjects with antibody concentrations against pneumococcal vaccine serotypes >= 0.20 micrograms per milliliter (µg/mL), in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with antibody concentrations against pneumococcal vaccine serotypes >= 0.20 micrograms per milliliter (µg/mL), in the Immunogenicity and Tolerability Subset

End point description

Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA). Serotypes assessed with the pneumococcal vaccine serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST)

End point values	Synflorix Group	Control Group
Number of subjects analysed	231	214
Units: Subjects
ANTI-1, PRE (N=231;203)	164	14
ANTI-1, M1 POST-BST (N=219;196)	219	19
ANTI-1, M9 POST-BST (N=206;181)	186	14
ANTI-4, PRE (N=231;214)	190	26
ANTI-4, M1 POST-BST (N=217;204)	217	24
ANTI-4, M9 POST-BST (N=206;183)	198	15
ANTI-5, PRE (N=231;209)	218	27
ANTI-5, M1 POST-BST (N=219;199)	219	30
ANTI-5, M9 POST-BST (N=206;182)	200	34
ANTI-6B, PRE (N=229;212)	182	12
ANTI-6B, M1 POST-BST (N=217;198)	215	13
ANTI-6B, M9 POST-BST (N=206;182)	192	21
ANTI-7F, PRE (N=231;210)	222	34
ANTI-7F, M1 POST-BST (N=218;198)	218	36
ANTI-7F, M9 POST-BST (N=206;182)	205	31
ANTI-9V, PRE (N=230;214)	221	22
ANTI-9V, M1 POST-BST (N=218;203)	218	14
ANTI-9V, M9 POST-BST (N=206;182)	206	26
ANTI-14, PRE (N=231;214)	217	51
ANTI-14, M1 POST-BST (N=219;200)	219	52
ANTI-14, M9 POST-BST (N=206;183)	204	68
ANTI-18C, PRE (N=231;210)	217	22
ANTI-18C, M1 POST-BST (N=219;203)	219	21
ANTI-18C, M9 POST-BST (N=206;181)	205	18
ANTI-19F, PRE (N=231;206)	221	35
ANTI-19F, M1 POST-BST (N=219;198)	218	39
ANTI-19F, M9 POST-BST (N=205;181)	204	52
ANTI-23F, PRE (N=229;204)	198	15
ANTI-23F, M1 POST-BST (N=218;201)	216	14
ANTI-23F, M9 POST-BST (N=206;179)	196	25

No statistical analyses for this end point

Secondary: Number of subjects with pneumococcal antibody concentrations against cross-reactive serotypes 6A and 19A higher >= 0.20 micrograms per milliliter (µg/mL), in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with pneumococcal antibody concentrations against cross-reactive serotypes 6A and 19A higher >= 0.20 micrograms per milliliter (µg/mL), in the Immunogenicity and Tolerability Subset

End point description

Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA). The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST)

End point values	Synflorix Group	Control Group
Number of subjects analysed	231	214
Units: Subjects
ANTI-6A, PRE (N=231;214)	119	14
ANTI-6A, M1 POST-BST (N=219;204)	187	12
ANTI-6A, M9 POST-BST (N=206;183)	129	24
ANTI-19A, PRE (N=229;212)	131	28
ANTI-19A, M1 POST-BST (N=218;201)	197	27
ANTI-19A, M9 POST-BST (N=206;181)	165	47

No statistical analyses for this end point

Secondary: Number of subjects with antibody concentrations against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 0.05 microgram per milliliter (µg/mL), in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with antibody concentrations against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 0.05 microgram per milliliter (µg/mL), in the Immunogenicity and Tolerability Subset

End point description

A seropositive subject was defined as a subject with antibody concentrations against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F => 0.05 µg/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

At Month 5, one month after the third dose of primary vaccination

End point values	Synflorix Group	Control Group
Number of subjects analysed	334	331
Units: Subjects
ANTI-1 (N=334;312)	333	88
ANTI-4 (N=334;328)	333	48
ANTI-5 (N=334;324)	334	153
ANTI-6B (N=334;322)	324	48
ANTI-7F (N=334;330)	333	116
ANTI-9V (N=334;331)	331	68
ANTI-14 (N=334;330)	333	234
ANTI-18C (N=334;328)	333	92
ANTI-19F (N=334;327)	331	176
ANTI-23F (N=334;331)	328	78

No statistical analyses for this end point

Secondary: Number of subjects with pneumococcal antibody concentrations against serotypes 6A and 19A >= 0.05 µg/mL, in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with pneumococcal antibody concentrations against serotypes 6A and 19A >= 0.05 µg/mL, in the Immunogenicity and Tolerability Subset

End point description

A seropositive subject was defined as a subject with antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A>= 0.05 µg/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

At Month 5, one month after the third dose of primary vaccination

End point values	Synflorix Group	Control Group
Number of subjects analysed	334	326
Units: Subjects
ANTI-6A (N=334;321)	306	77
ANTI-19A (N=334;326)	303	120

No statistical analyses for this end point

Secondary: Number of subjects with antibody concentrations against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 0.05 microgram per milliliter (µg/mL), in the Immunogenicity and Tolerability Subset

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End point title

End point description

End point type

Secondary

End point timeframe

Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST

End point values	Synflorix Group	Control Group
Number of subjects analysed	231	214
Units: Subjects
ANTI-1, PRE (N=231;203)	231	87
ANTI-1, M1 POST-BST (N=219;196)	219	101
ANTI-1, M9 POST-BST (N=206;181)	206	95
ANTI-4, PRE (N=231;214)	231	52
ANTI-4, M1 POST-BST (N=217;204)	217	65
ANTI-4, M9 POST-BST (N=206;183)	206	58
ANTI-5, PRE (N=231;209)	231	150
ANTI-5, M1 POST-BST (N=219;199)	219	142
ANTI-5, M9 POST-BST (N=206;182)	206	133
ANTI-6B, PRE (N=229;212)	226	60
ANTI-6B, M1 POST-BST (N=217;198)	216	54
ANTI-6B, M9 POST-BST (N=206;182)	206	72
ANTI-7F, PRE (N=231;210)	231	79
ANTI-7F, M1 POST-BST (N=218;198)	218	79
ANTI-7F, M9 POST-BST (N=206;182)	206	87
ANTI-9V, PRE (N=230;214)	230	51
ANTI-9V, M1 POST-BST (N=218;203)	218	58
ANTI-9V, M9 POST-BST (N=206;182)	206	68
ANTI-14, PRE (N=231;214)	231	157
ANTI-14, M1 POST-BST (N=219;200)	219	160
ANTI-14, M9 POST-BST (N=206;183)	206	154
ANTI-18C, PRE (N=231;210)	230	72
ANTI-18C, M1 POST-BST (N=219;203)	219	71
ANTI-18C, M9 POST-BST (N=206;181)	206	73
ANTI-19F, PRE (N=231;206)	231	71
ANTI-19F, M1 POST-BST (N=219;198)	219	85
ANTI-19F, M9 POST-BST (N=205;181)	205	93
ANTI-23F, PRE (N=229;204)	223	44
ANTI-23F, M1 POST-BST (N=218;201)	216	44
ANTI-23F, M9 POST-BST (N=206;179)	206	62

No statistical analyses for this end point

Secondary: Number of subjects with pneumococcal antibody concentrations against serotypes 6A and 19A >= 0.05 µg/mL, in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with pneumococcal antibody concentrations against serotypes 6A and 19A >= 0.05 µg/mL, in the Immunogenicity and Tolerability Subset

End point description

End point type

Secondary

End point timeframe

Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST) .

End point values	Synflorix Group	Control Group
Number of subjects analysed	231	214
Units: Subjects
ANTI-6A, PRE (N=231;214)	210	61
ANTI-6A, M1 POST-BST (N=219;204)	214	61
ANTI-6A, M9 POST-BST (N=206;183)	196	69
ANTI-19A, PRE (N=229;212)	208	76
ANTI-19A, M1 POST-BST (N=218;201)	212	83
ANTI-19A, M9 POST-BST (N=206;181)	201	89

No statistical analyses for this end point

Secondary: Titers for opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F, in the Immunogenicity and Tolerability Subset

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End point title

Titers for opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F, in the Immunogenicity and Tolerability Subset

End point description

The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

At Month 5, one month after the third dose of primary vaccination

End point values	Synflorix Group	Control Group
Number of subjects analysed	317	317
Units: Titers
geometric mean (confidence interval 95%)
OPSONO-1 (N=306;305)	139.5 (116.8 to 166.5)	4.8 (4.5 to 5.3)
OPSONO-4 (N=310;299)	771.7 (686.5 to 867.6)	5.1 (4.5 to 5.8)
OPSONO-5 (N=313;314)	224.8 (196 to 257.8)	4.5 (4.2 to 4.8)
OPSONO-6B (N=315;309)	689.7 (553.2 to 859.7)	5.4 (4.6 to 6.2)
OPSONO-7F (N=302;266)	4656.7 (4175.6 to 5193.3)	110.4 (78.8 to 154.7)
OPSONO-9V (N=312;302)	1690.4 (1489.4 to 1918.7)	14.6 (11.6 to 18.2)
OPSONO-14 (N=308;273)	908.5 (795.2 to 1038.1)	16.5 (12.9 to 21.1)
OPSONO-18C (N=308;317)	310.9 (259.4 to 372.6)	4.4 (4.1 to 4.7)
OPSONO-19F (N=304;314)	383 (308.5 to 475.5)	4.7 (4.3 to 5.2)
OPSONO-23F (N=317;282)	2167.4 (1863.4 to 2521.1)	14.5 (11 to 19.1)

No statistical analyses for this end point

Secondary: Titers for opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset

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End point title

Titers for opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset

End point description

The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

At Month 5, one month after the third dose of primary vaccination

End point values	Synflorix Group	Control Group
Number of subjects analysed	302	309
Units: Titers
geometric mean (confidence interval 95%)
OPSONO-6A (N=297;305)	156.9 (121.8 to 202.1)	5 (4.5 to 5.5)
OPSONO-19A (N=302;309)	18.2 (14.5 to 22.9)	4.1 (4 to 4.3)

No statistical analyses for this end point

Secondary: Titers for opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F, in the Immunogenicity and Tolerability Subset

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End point title

Titers for opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F, in the Immunogenicity and Tolerability Subset

End point description

The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST)

End point values	Synflorix Group	Control Group
Number of subjects analysed	221	210
Units: Titers
geometric mean (confidence interval 95%)
OPSONO-1, PRE (N=221;210)	9 (7.4 to 10.9)	4.6 (4.2 to 5)
OPSONO-1, M1 POST-BST (N=209;200)	357.5 (281.8 to 453.5)	4.8 (4.4 to 5.4)
OPSONO-1, M9 POST-BST (N=196;176)	34.4 (26.6 to 44.7)	4.6 (4.2 to 5.1)
OPSONO-4, PRE (N=208;193)	29.2 (21.2 to 40.2)	8.6 (6.4 to 11.5)
OPSONO-4, M1 POST-BST (N=207;193)	2853.5 (2365.5 to 3442.1)	8.3 (6.3 to 10.9)
OPSONO-4, M9 POST-BST (N=192;173)	165.6 (115.3 to 237.9)	8.1 (6.1 to 10.8)
OPSONO-5, PRE (N=205;204)	18.5 (15.4 to 22.3)	4.3 (4.1 to 4.6)
OPSONO-5, M1 POST-BST (N=196;187)	306.1 (252 to 371.8)	4.4 (4.1 to 4.7)
OPSONO-5, M9 POST-BST (N=192;173)	44.1 (35.5 to 54.7)	4.2 (4 to 4.4)
OPSONO-6B, PRE (N=209;197)	95.5 (70.1 to 130.1)	7.6 (6 to 9.8)
OPSONO-6B, M1 POST-BST (N=203;190)	1123.4 (939.2 to 1343.9)	7.1 (5.6 to 8.9)
OPSONO-6B, M9 POST-BST (N=178;165)	128.9 (92.7 to 179.2)	11.4 (8.3 to 15.8)
OPSONO-7F, PRE (N=217;202)	1522.8 (1338.5 to 1732.6)	979.5 (821.2 to 1168.5)
OPSONO-7F, M1 POST-BST (N=205;196)	4336.3 (3607.9 to 5211.8)	746.4 (590.7 to 943.1)
OPSONO-7F, M9 POST-BST (N=192;172)	2598 (2232 to 3024.1)	1214.3 (1011.4 to 1458)
OPSONO-9V, PRE (N=213;188)	709.4 (601.7 to 836.3)	233.7 (175.3 to 311.4)
OPSONO-9V, M1 POST-BST (N=200;189)	3763 (3317.5 to 4268.3)	250.9 (186.1 to 338.4)
OPSONO-9V, M9 POST-BST (N=194;168)	1320.3 (1153.1 to 1511.7)	337.4 (252.4 to 451)
OPSONO-14, PRE (N=205;192)	121.2 (89.7 to 163.8)	27 (18.9 to 38.5)
OPSONO-14, M1 POST-BST (N=209;188)	2659.6 (2266.2 to 3121.3)	21.7 (15 to 31.2)
OPSONO-14, M9 POST-BST (N=185;159)	330.6 (242.7 to 450.5)	27.6 (18.3 to 41.8)
OPSONO-18C, PRE (N=204;191)	15 (11.5 to 19.6)	4.8 (4.2 to 5.4)
OPSONO-18C, M1 POST-BST (N=188;187)	2426 (2041.8 to 2882.5)	5.2 (4.4 to 6)
OPSONO-18C, M9 POST-BST (N=170;164)	722 (553.6 to 941.6)	5.3 (4.4 to 6.5)
OPSONO-19F, PRE (N=218;205)	24.3 (19.6 to 30.1)	5 (4.4 to 5.7)
OPSONO-19F, M1 POST-BST (N=199;200)	657.5 (497.4 to 869.1)	5 (4.4 to 5.7)
OPSONO-19F, M9 POST-BST (N=194;170)	118 (90.6 to 153.7)	4.8 (4.3 to 5.4)
OPSONO-23F, PRE (N=215;199)	679.3 (494.3 to 933.6)	76.9 (49 to 120.6)
OPSONO-23F, M1 POST-BST (N=206;190)	4278.3 (3609.3 to 5071.3)	99.7 (62.7 to 158.6)
OPSONO-23F, M9 POST-BST (N=187;167)	999.6 (711.8 to 1403.9)	109.4 (65.7 to 182.2)

No statistical analyses for this end point

Secondary: Titers for Opsonophagocytic activity against pneumococcal serotypes 6A and 19A in the Immunogenicity and Tolerability Subset

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End point title

Titers for Opsonophagocytic activity against pneumococcal serotypes 6A and 19A in the Immunogenicity and Tolerability Subset

End point description

The cut-off of the assay was >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST)

End point values	Synflorix Group	Control Group
Number of subjects analysed	217	204
Units: Titers
geometric mean (confidence interval 95%)
OPSONO-6A, PRE (N=189;194)	43.8 (31 to 62)	7.1 (5.7 to 8.9)
OPSONO-6A, M1 POST BST (N=185;185)	277.2 (198.7 to 386.7)	7.6 (6 to 9.7)
OPSONO-6A, M9 POST-BST (N=175;156)	63.9 (44.3 to 92)	17.2 (12.1 to 24.4)
OPSONO-19A, PRE (N=217;204)	6.3 (5.3 to 7.4)	5 (4.4 to 5.6)
OPSONO-19A, M1 POST-BST (N=200;197)	132.8 (97.5 to 180.8)	5.4 (4.7 to 6.2)
OPSONO-19A, M9 POST-BST (N=187;171)	26.1 (19.5 to 35.1)	6.3 (5.3 to 7.5)

No statistical analyses for this end point

Secondary: Number of subjects with titers for opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F => 8, in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with titers for opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F => 8, in the Immunogenicity and Tolerability Subset

End point description

A seropositive subject was defined as a subject with titers for opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

At Month 5, one month after the third dose of primary vaccination

End point values	Synflorix Group	Control Group
Number of subjects analysed	317	317
Units: Subjects
OPSONO-1 (N=306;305)	280	25
OPSONO-4 (N=310;299)	306	15
OPSONO-5 (N=313;314)	303	13
OPSONO-6B (N=315;309)	286	16
OPSONO-7F (N=302;266)	302	162
OPSONO-9V (N=312;302)	311	98
OPSONO-14 (N=308;273)	306	95
OPSONO-18C (N=308;317)	290	8
OPSONO-19F (N=304;314)	277	16
OPSONO-23F (N=317;282)	311	68

No statistical analyses for this end point

Secondary: Number of subjects with titers for opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A >= 8, in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with titers for opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A >= 8, in the Immunogenicity and Tolerability Subset

End point description

A seropositive subject was defined as a subject with titers for opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

At Month 5, one month after the third dose of primary vaccination

End point values	Synflorix Group	Control Group
Number of subjects analysed	302	309
Units: Subjects
OPSONO-6A (N=297;305)	232	16
OPSONO-19A (N=302;309)	121	5

No statistical analyses for this end point

Secondary: Number of subjects with titers for opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 8, in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with titers for opsonophagocytic activity against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 8, in the Immunogenicity and Tolerability Subset

End point description

End point type

Secondary

End point timeframe

Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST)

End point values	Synflorix Group	Control Group
Number of subjects analysed	221	210
Units: Subjects
OPSONO-1, PRE (N=221;210)	58	9
OPSONO-1, M1 POST-BST (N=209;200)	195	14
OPSONO-1, M9 POST-BST (N=196;176)	127	10
OPSONO-4, PRE (N=208;193)	108	25
OPSONO-4, M1 POST-BST (N=207;193)	206	26
OPSONO-4, M9 POST-BST (N=192;173)	147	22
OPSONO-5, PRE (N=205;204)	138	7
OPSONO-5, M1 POST-BST (N=196;187)	194	10
OPSONO-5, M9 POST-BST (N=192;173)	157	3
OPSONO-6B, PRE (N=209;197)	162	27
OPSONO-6B, M1 POST-BST (N=203;190)	200	23
OPSONO-6B, M9 POST-BST (N=178;165)	146	35
OPSONO-7F, PRE (N=217;202)	217	197
OPSONO-7F, M1 POST-BST (N=205;196)	203	185
OPSONO-7F, M9 POST-BST (N=192;172)	192	169
OPSONO-9V, PRE (N=213;188)	212	159
OPSONO-9V, M1 POST-BST (N=200;189)	200	157
OPSONO-9V, M9 POST-BST (N=194;168)	194	148
OPSONO-14, PRE (N=205;192)	158	73
OPSONO-14, M1 POST-BST (N=209;188)	208	61
OPSONO-14, M9 POST-BST (N=185;159)	160	57
OPSONO-18C, PRE (N=204;191)	86	8
OPSONO-18C, M1 POST-BST (N=188;187)	187	11
OPSONO-18C, M9 POST-BST (N=170;164)	165	10
OPSONO-19F, PRE (N=218;205)	150	14
OPSONO-19F, M1 POST-BST (N=199;200)	186	13
OPSONO-19F, M9 POST-BST (N=194;170)	168	11
OPSONO-23F, PRE (N=215;199)	190	94
OPSONO-23F, M1 POST-BST (N=206;190)	205	97
OPSONO-23F, M9 POST-BST (N=187;167)	167	85

No statistical analyses for this end point

Secondary: Number of subjects with titers for opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A >= 8, in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with titers for opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A >= 8, in the Immunogenicity and Tolerability Subset

End point description

A seropositive subject was a subject with titers for opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A >= 8. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST).

End point values	Synflorix Group	Control Group
Number of subjects analysed	217	204
Units: Subjects
OPSONO-6A, PRE (N=189;194)	99	24
OPSONO-6A, M1 POST BST (N=185;185)	150	26
OPSONO-6A, M9 POST-BST (N=175;156)	104	50
OPSONO-19A, PRE (N=217;204)	32	14
OPSONO-19A, M1 POST-BST (N=200;197)	161	20
OPSONO-19A, M9 POST-BST (N=187;171)	108	32

No statistical analyses for this end point

Secondary: Concentrations of antibodies against protein D (ANTI-PD), in the Immunogenicity and Tolerability Subset

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End point title

Concentrations of antibodies against protein D (ANTI-PD), in the Immunogenicity and Tolerability Subset

End point description

ANTI-PD concentrations are expressed as geometric mean concentrations (GMCs), in enzyme-linked immunosorbent assay (ELISA) unit per milliliter (EL.U/mL). The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

At Month 5, one month after the third dose of primary vaccination

End point values	Synflorix Group	Control Group
Number of subjects analysed	334	325
Units: EL.U/mL
geometric mean (confidence interval 95%)
ANTI-PD	2455.2 (2248.3 to 2681.1)	101.2 (91.3 to 112.2)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against protein D (ANTI-PD), in the Immunogenicity and Tolerability Subset

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End point title

Concentrations of antibodies against protein D (ANTI-PD), in the Immunogenicity and Tolerability Subset

End point description

End point type

Secondary

End point timeframe

Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 Post-BST and M9 POST-BST)

End point values	Synflorix Group	Control Group
Number of subjects analysed	230	211
Units: EL.U/mL
geometric mean (confidence interval 95%)
ANTI-PD, PRE (N=230;211)	638.6 (556.2 to 733.2)	103.1 (90.5 to 117.5)
ANTI-PD, M1 POST BST (N=218;195)	2787 (2435.9 to 3188.7)	92.4 (82.6 to 103.3)
ANTI-PD, M9 POST-BST (N=206;182)	824.1 (704.2 to 964.4)	94.5 (84.4 to 105.8)

No statistical analyses for this end point

Secondary: Number of subjects with anti-protein D (ANTI-PD) antibody concentrations >= 100 enzyme-linked immunosorbent assay units per milliliter ( EL.U/mL), in the Immunogenicity and Tolerability Subset

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End point title

Number of subjects with anti-protein D (ANTI-PD) antibody concentrations >= 100 enzyme-linked immunosorbent assay units per milliliter ( EL.U/mL), in the Immunogenicity and Tolerability Subset

End point description

A seropositive subject was defined as a subject with ANTI-PD antibody concentrations >= 100 EL.U/mL. The Immunogenicity and Tolerability Subset included 500 subjects coming from Argentina and Panama respectively.

End point type

Secondary

End point timeframe

At Month 5, one month after the third dose of primary vaccination

End point values	Synflorix Group	Control Group
Number of subjects analysed	334	325
Units: Subjects
ANTI-PD	333	141

No statistical analyses for this end point

Secondary: Number of subjects with anti-protein D (ANTI-PD) antibody concentrations >= 100 enzyme-linked immunosorbent assay units per milliliter ( EL.U/mL), in the Immunogenicity and Tolerability Subset.

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End point title

Number of subjects with anti-protein D (ANTI-PD) antibody concentrations >= 100 enzyme-linked immunosorbent assay units per milliliter ( EL.U/mL), in the Immunogenicity and Tolerability Subset.

End point description

End point type

Secondary

End point timeframe

Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 Post-BST and M9 Post-BST)

End point values	Synflorix Group	Control Group
Number of subjects analysed	230	211
Units: Subjects
ANTI-PD, PRE (N=230;211)	223	96
ANTI-PD, M1 POST BST (N=218;195)	218	83
ANTI-PD, M9 POST-BST (N=206;182)	198	84

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

SAEs and unsolicited AEs: Throughout the study (Months 0 to 22-25). Solicited symptoms: 4-day (Days 0–3) follow-up period across the 3 doses of primary study vaccine course/ 4-day (Days 0–3) follow-up period post booster vaccination

Adverse event reporting additional description

SAEs reports were collected based on the Total Vaccinated cohort. Reports for unsolicited and solicited AEs were collected based on the TVC, from the Panama Subset and from the Immunogenicity and Tolerability Subset, respectively. Occurrences of AEs (all/related) was not available and is encoded as equal to the number of subjects affected.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

15.1

Reporting group title

Control Group

Reporting group description

Subjects received 3 doses of Engerix at 2,4 and 6 months of age co-administered with Infanrix-IPV/Hib and 1 dose of Havrix co-administered with Infanrix-IPV/Hib at 15-18 months of age. All vaccine were administered in the right (Engerix, Havrix) or the left (Infanrix-IPV/Hib) thigh.

Reporting group title

Synflorix Group

Reporting group description

Subjects received 3 primary doses of Synflorix at 2, 4 and 6 months of age co-administered with Infanrix-hexa and booster dose of Synflorix at 15-18 months of age co-administered with Infanrix-IPV/Hib. All vaccines were administered intramuscularly in the right (Synflorix) or the left (Infanrix-hexa, Infanrix-IPV/Hib) thigh (primary dose) or deltoid (booster dose).

Serious adverse events	Control Group	Synflorix Group
Total subjects affected by serious adverse events
subjects affected / exposed	2668 / 11799 (22.61%)	2534 / 11798 (21.48%)
number of deaths (all causes)	26	19
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia
subjects affected / exposed	2 / 11799 (0.02%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acute myeloid leukaemia
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Brain neoplasm
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Hepatoblastoma
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Histiocytosis haematophagic
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nephroblastoma
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neuroblastoma
subjects affected / exposed	2 / 11799 (0.02%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Retinoblastoma bilateral
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Capillary fragility
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Extremity necrosis
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Flushing
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haematoma
subjects affected / exposed	2 / 11799 (0.02%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypovolaemic shock
subjects affected / exposed	3 / 11799 (0.03%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Kawasaki’s disease
subjects affected / exposed	3 / 11799 (0.03%)	9 / 11798 (0.08%)
occurrences causally related to treatment / all	0 / 3	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0
Phlebitis
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Shock
subjects affected / exposed	4 / 11799 (0.03%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Surgical and medical procedures
Finger amputation
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Therapeutic hypothermia
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Toe amputation
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Cephalhaematoma
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Crying
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Effusion
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Electrocution
subjects affected / exposed	2 / 11799 (0.02%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 2
Hypothermia
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	31 / 11799 (0.26%)	24 / 11798 (0.20%)
occurrences causally related to treatment / all	0 / 31	0 / 24
deaths causally related to treatment / all	0 / 0	0 / 0
Sudden death
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Sudden infant death syndrome
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Systemic inflammatory response syndrome
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Food allergy
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypersensitivity
subjects affected / exposed	6 / 11799 (0.05%)	5 / 11798 (0.04%)
occurrences causally related to treatment / all	0 / 6	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Immunodeficiency
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Milk allergy
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Selective iga immunodeficiency
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Social circumstances
Alcohol use
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Physical abuse
subjects affected / exposed	2 / 11799 (0.02%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Balanoposthitis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Genital lesion
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute lung injury
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Acute pulmonary oedema
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 1
Acute respiratory failure
subjects affected / exposed	2 / 11799 (0.02%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Allergic bronchitis
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Apnoea
subjects affected / exposed	1 / 11799 (0.01%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Apnoeic attack
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Apparent life threatening event
subjects affected / exposed	3 / 11799 (0.03%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	1 / 3	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Asphyxia
subjects affected / exposed	3 / 11799 (0.03%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 2	0 / 2
Aspiration
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Asthma
subjects affected / exposed	83 / 11799 (0.70%)	82 / 11798 (0.70%)
occurrences causally related to treatment / all	0 / 83	0 / 82
deaths causally related to treatment / all	0 / 0	0 / 0
Asthmatic crisis
subjects affected / exposed	210 / 11799 (1.78%)	192 / 11798 (1.63%)
occurrences causally related to treatment / all	0 / 210	0 / 192
deaths causally related to treatment / all	0 / 0	0 / 0
Atelectasis
subjects affected / exposed	5 / 11799 (0.04%)	10 / 11798 (0.08%)
occurrences causally related to treatment / all	0 / 5	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchial hyperreactivity
subjects affected / exposed	14 / 11799 (0.12%)	16 / 11798 (0.14%)
occurrences causally related to treatment / all	0 / 14	0 / 16
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchial obstruction
subjects affected / exposed	141 / 11799 (1.20%)	127 / 11798 (1.08%)
occurrences causally related to treatment / all	0 / 141	0 / 127
deaths causally related to treatment / all	0 / 1	0 / 0
Bronchospasm
subjects affected / exposed	9 / 11799 (0.08%)	6 / 11798 (0.05%)
occurrences causally related to treatment / all	0 / 9	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Epistaxis
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infantile asthma
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	4 / 11799 (0.03%)	6 / 11798 (0.05%)
occurrences causally related to treatment / all	0 / 4	0 / 6
deaths causally related to treatment / all	0 / 2	0 / 1
Laryngeal oedema
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lung disorder
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Obstructive airways disorder
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	3 / 11799 (0.03%)	8 / 11798 (0.07%)
occurrences causally related to treatment / all	0 / 3	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 1
Pneumonia aspiration
subjects affected / exposed	3 / 11799 (0.03%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	4 / 11799 (0.03%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	2 / 11799 (0.02%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Respiratory disorder
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	6 / 11799 (0.05%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 6	0 / 4
deaths causally related to treatment / all	0 / 3	0 / 0
Sleep apnoea syndrome
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Wheezing
subjects affected / exposed	42 / 11799 (0.36%)	48 / 11798 (0.41%)
occurrences causally related to treatment / all	0 / 42	0 / 48
deaths causally related to treatment / all	0 / 0	0 / 0
Dermatitis allergic
subjects affected / exposed	1 / 11799 (0.01%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Agitation
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Binge eating
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Breath holding
subjects affected / exposed	6 / 11799 (0.05%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 6	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Psychomotor retardation
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholangitis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic failure
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Hepatitis acute
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Acid base balance abnormal
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Aspiration bronchial
subjects affected / exposed	3 / 11799 (0.03%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 3	0 / 2
Injury, poisoning and procedural complications
Abdominal injury
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Accidental exposure
subjects affected / exposed	8 / 11799 (0.07%)	10 / 11798 (0.08%)
occurrences causally related to treatment / all	0 / 8	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Accidental overdose
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Accidental poisoning
subjects affected / exposed	3 / 11799 (0.03%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Animal bite
subjects affected / exposed	2 / 11799 (0.02%)	5 / 11798 (0.04%)
occurrences causally related to treatment / all	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Arthropod bite
subjects affected / exposed	1 / 11799 (0.01%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Arthropod sting
subjects affected / exposed	5 / 11799 (0.04%)	6 / 11798 (0.05%)
occurrences causally related to treatment / all	0 / 5	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Back injury
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Burns first degree
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Burns second degree
subjects affected / exposed	8 / 11799 (0.07%)	6 / 11798 (0.05%)
occurrences causally related to treatment / all	0 / 8	0 / 6
deaths causally related to treatment / all	0 / 1	0 / 0
Carbon monoxide poisoning
subjects affected / exposed	1 / 11799 (0.01%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Chemical injury
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Chemical poisoning
subjects affected / exposed	21 / 11799 (0.18%)	24 / 11798 (0.20%)
occurrences causally related to treatment / all	0 / 21	0 / 24
deaths causally related to treatment / all	0 / 0	0 / 0
Chest injury
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Contusion
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Craniocerebral injury
subjects affected / exposed	36 / 11799 (0.31%)	39 / 11798 (0.33%)
occurrences causally related to treatment / all	0 / 36	0 / 39
deaths causally related to treatment / all	0 / 0	0 / 1
Electric shock
subjects affected / exposed	1 / 11799 (0.01%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Electrical burn
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Extradural haematoma
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Eye burns
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eye injury
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eyelid injury
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Face injury
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	5 / 11799 (0.04%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Foreign body
subjects affected / exposed	15 / 11799 (0.13%)	16 / 11798 (0.14%)
occurrences causally related to treatment / all	0 / 15	0 / 16
deaths causally related to treatment / all	0 / 0	0 / 0
Fracture
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gingival injury
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hand fracture
subjects affected / exposed	3 / 11799 (0.03%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Head injury
subjects affected / exposed	74 / 11799 (0.63%)	75 / 11798 (0.64%)
occurrences causally related to treatment / all	0 / 74	0 / 75
deaths causally related to treatment / all	0 / 0	0 / 0
Herbal toxicity
subjects affected / exposed	2 / 11799 (0.02%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	2 / 11799 (0.02%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Injury
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Laceration
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Limb crushing injury
subjects affected / exposed	2 / 11799 (0.02%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Limb traumatic amputation
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lower limb fracture
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Mouth injury
subjects affected / exposed	2 / 11799 (0.02%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple injuries
subjects affected / exposed	33 / 11799 (0.28%)	26 / 11798 (0.22%)
occurrences causally related to treatment / all	0 / 33	0 / 26
deaths causally related to treatment / all	0 / 1	0 / 0
Near drowning
subjects affected / exposed	3 / 11799 (0.03%)	6 / 11798 (0.05%)
occurrences causally related to treatment / all	0 / 3	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Open fracture
subjects affected / exposed	2 / 11799 (0.02%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Open wound
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonitis chemical
subjects affected / exposed	3 / 11799 (0.03%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Poisoning
subjects affected / exposed	2 / 11799 (0.02%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Postoperative fever
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Procedural haemorrhage
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	2 / 11799 (0.02%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Skull fracture
subjects affected / exposed	5 / 11799 (0.04%)	6 / 11798 (0.05%)
occurrences causally related to treatment / all	0 / 5	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Tendon injury
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Thermal burn
subjects affected / exposed	36 / 11799 (0.31%)	25 / 11798 (0.21%)
occurrences causally related to treatment / all	0 / 36	0 / 25
deaths causally related to treatment / all	0 / 0	0 / 1
Tibia fracture
subjects affected / exposed	2 / 11799 (0.02%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tongue injury
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tooth fracture
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Toxicity to various agents
subjects affected / exposed	12 / 11799 (0.10%)	12 / 11798 (0.10%)
occurrences causally related to treatment / all	0 / 12	0 / 12
deaths causally related to treatment / all	0 / 0	0 / 0
Traumatic haematoma
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	4 / 11799 (0.03%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Vulvovaginal injury
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Wound
subjects affected / exposed	5 / 11799 (0.04%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Wound dehiscence
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital, familial and genetic disorders
Cerebral palsy
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Coarctation of the aorta
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital absence of bile ducts
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital oral malformation
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital syphilis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cystic fibrosis
subjects affected / exposed	0 / 11799 (0.00%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Dermoid cyst
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Heart disease congenital
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Laryngomalacia
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Meningomyelocele
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Porencephaly
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Pyloric stenosis
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Retinoblastoma
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sickle cell anaemia
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sickle cell anaemia with crisis
subjects affected / exposed	2 / 11799 (0.02%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal muscular atrophy
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thalassaemia sickle cell
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Cardiac failure
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 1
Cardiac failure congestive
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardio-respiratory arrest
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 2
Cyanosis
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intracardiac mass
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Ventricular arrhythmia
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Nervous system disorders
Ataxia
subjects affected / exposed	2 / 11799 (0.02%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Brain injury
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Brain oedema
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Cerebrospinal fistula
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cns ventriculitis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Convulsion
subjects affected / exposed	25 / 11799 (0.21%)	28 / 11798 (0.24%)
occurrences causally related to treatment / all	0 / 25	0 / 28
deaths causally related to treatment / all	0 / 0	0 / 0
Dystonia
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	2 / 11799 (0.02%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Extrapyramidal disorder
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile convulsion
subjects affected / exposed	135 / 11799 (1.14%)	95 / 11798 (0.81%)
occurrences causally related to treatment / all	0 / 135	0 / 95
deaths causally related to treatment / all	0 / 0	0 / 0
Grand mal convulsion
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Guillain-barre syndrome
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoxic-ischaemic encephalopathy
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Infantile spasms
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intracranial pressure increased
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Myoclonic epilepsy
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Post-traumatic epilepsy
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Presyncope
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Status epilepticus
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Viith nerve paralysis
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	9 / 11799 (0.08%)	5 / 11798 (0.04%)
occurrences causally related to treatment / all	0 / 9	0 / 5
deaths causally related to treatment / all	0 / 1	0 / 0
Coagulopathy
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	4 / 11799 (0.03%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Haemolysis
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Disseminated intravascular coagulation
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Haemolytic anaemia
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemolytic uraemic syndrome
subjects affected / exposed	1 / 11799 (0.01%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhagic disorder
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypersplenism
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypochromic anaemia
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Idiopathic thrombocytopenic purpura
subjects affected / exposed	2 / 11799 (0.02%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Iron deficiency anaemia
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Leukaemoid reaction
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphadenitis
subjects affected / exposed	19 / 11799 (0.16%)	12 / 11798 (0.10%)
occurrences causally related to treatment / all	0 / 19	0 / 12
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphadenopathy
subjects affected / exposed	2 / 11799 (0.02%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombocytopenic purpura
subjects affected / exposed	2 / 11799 (0.02%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Conjunctivitis
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Conjunctivitis allergic
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ulcerative keratitis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal adhesions
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal distension
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal mass
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	5 / 11799 (0.04%)	8 / 11798 (0.07%)
occurrences causally related to treatment / all	0 / 5	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Acute abdomen
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Appendix disorder
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Constipation
subjects affected / exposed	10 / 11799 (0.08%)	11 / 11798 (0.09%)
occurrences causally related to treatment / all	0 / 10	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	53 / 11799 (0.45%)	63 / 11798 (0.53%)
occurrences causally related to treatment / all	0 / 53	0 / 63
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea haemorrhagic
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dyspepsia
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enteritis
subjects affected / exposed	20 / 11799 (0.17%)	15 / 11798 (0.13%)
occurrences causally related to treatment / all	0 / 20	0 / 15
deaths causally related to treatment / all	0 / 0	0 / 0
Faecaloma
subjects affected / exposed	3 / 11799 (0.03%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Food poisoning
subjects affected / exposed	1 / 11799 (0.01%)	5 / 11798 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis
subjects affected / exposed	4 / 11799 (0.03%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis erosive
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorder
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	2 / 11799 (0.02%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	3 / 11799 (0.03%)	6 / 11798 (0.05%)
occurrences causally related to treatment / all	0 / 3	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Gingival bleeding
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haematochezia
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ileus
subjects affected / exposed	3 / 11799 (0.03%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Ileus paralytic
subjects affected / exposed	23 / 11799 (0.19%)	33 / 11798 (0.28%)
occurrences causally related to treatment / all	0 / 23	0 / 33
deaths causally related to treatment / all	0 / 0	0 / 0
Infantile colic
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	3 / 11799 (0.03%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Inguinal hernia, obstructive
subjects affected / exposed	3 / 11799 (0.03%)	5 / 11798 (0.04%)
occurrences causally related to treatment / all	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal haemorrhage
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	2 / 11799 (0.02%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal perforation
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intussusception
subjects affected / exposed	11 / 11799 (0.09%)	14 / 11798 (0.12%)
occurrences causally related to treatment / all	0 / 11	0 / 14
deaths causally related to treatment / all	0 / 1	0 / 0
Malabsorption
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Mallory-weiss syndrome
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Stomatitis
subjects affected / exposed	6 / 11799 (0.05%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 6	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	1 / 11799 (0.01%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
subjects affected / exposed	37 / 11799 (0.31%)	42 / 11798 (0.36%)
occurrences causally related to treatment / all	0 / 37	0 / 42
deaths causally related to treatment / all	0 / 0	0 / 0
Multi-organ failure
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Skin and subcutaneous tissue disorders
Acute haemorrhagic oedema of infancy
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Angioedema
subjects affected / exposed	3 / 11799 (0.03%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cutaneous loxoscelism
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dermatitis bullous
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dermatitis contact
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dermatitis diaper
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dermatitis exfoliative
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dermatosis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Erythema multiforme
subjects affected / exposed	2 / 11799 (0.02%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhagic urticaria
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Heat rash
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Henoch-schonlein purpura
subjects affected / exposed	3 / 11799 (0.03%)	5 / 11798 (0.04%)
occurrences causally related to treatment / all	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Rash
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Rash scarlatiniform
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin oedema
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urticaria
subjects affected / exposed	15 / 11799 (0.13%)	10 / 11798 (0.08%)
occurrences causally related to treatment / all	0 / 15	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Glomerulonephritis acute
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Haematuria
subjects affected / exposed	4 / 11799 (0.03%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nephrotic syndrome
subjects affected / exposed	3 / 11799 (0.03%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Oliguria
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Prerenal failure
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelocaliectasis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal failure acute
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Endocrine disorders
Hyperadrenalism
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypothyroidism
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthritis
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Compartment syndrome
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Connective tissue disorder
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dactylitis
subjects affected / exposed	2 / 11799 (0.02%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Periostitis
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sacroiliitis
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Synovitis
subjects affected / exposed	2 / 11799 (0.02%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Tenosynovitis
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Torticollis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Trigger finger
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Abdominal wall abscess
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Abscess
subjects affected / exposed	9 / 11799 (0.08%)	11 / 11798 (0.09%)
occurrences causally related to treatment / all	0 / 9	0 / 11
deaths causally related to treatment / all	0 / 1	0 / 0
Abscess limb
subjects affected / exposed	16 / 11799 (0.14%)	10 / 11798 (0.08%)
occurrences causally related to treatment / all	0 / 16	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Abscess neck
subjects affected / exposed	8 / 11799 (0.07%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 8	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Abscess of eyelid
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acarodermatitis
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Acquired immunodeficiency syndrome
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acute sinusitis
subjects affected / exposed	3 / 11799 (0.03%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Adenoiditis
subjects affected / exposed	4 / 11799 (0.03%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Adenovirus infection
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Amoebiasis
subjects affected / exposed	2 / 11799 (0.02%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Amoebic dysentery
subjects affected / exposed	3 / 11799 (0.03%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	3 / 11799 (0.03%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Appendicitis perforated
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Arthritis bacterial
subjects affected / exposed	2 / 11799 (0.02%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Ascariasis
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atypical pneumonia
subjects affected / exposed	12 / 11799 (0.10%)	14 / 11798 (0.12%)
occurrences causally related to treatment / all	0 / 12	0 / 14
deaths causally related to treatment / all	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	6 / 11799 (0.05%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 6	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Bacterial diarrhoea
subjects affected / exposed	2 / 11799 (0.02%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	2 / 11799 (0.02%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Breast abscess
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchiolitis
subjects affected / exposed	518 / 11799 (4.39%)	473 / 11798 (4.01%)
occurrences causally related to treatment / all	0 / 518	0 / 473
deaths causally related to treatment / all	0 / 1	0 / 1
Bronchitis
subjects affected / exposed	129 / 11799 (1.09%)	124 / 11798 (1.05%)
occurrences causally related to treatment / all	0 / 129	0 / 124
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchopneumonia
subjects affected / exposed	95 / 11799 (0.81%)	106 / 11798 (0.90%)
occurrences causally related to treatment / all	0 / 95	0 / 106
deaths causally related to treatment / all	0 / 1	0 / 0
Bullous impetigo
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Burn infection
subjects affected / exposed	1 / 11799 (0.01%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cat scratch disease
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	46 / 11799 (0.39%)	45 / 11798 (0.38%)
occurrences causally related to treatment / all	0 / 46	0 / 45
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis of male external genital organ
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis orbital
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colostomy infection
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Conjunctivitis bacterial
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Conjunctivitis chlamydial
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Conjunctivitis infective
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Croup infectious
subjects affected / exposed	7 / 11799 (0.06%)	10 / 11798 (0.08%)
occurrences causally related to treatment / all	0 / 7	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Cytomegalovirus hepatitis
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dengue fever
subjects affected / exposed	15 / 11799 (0.13%)	18 / 11798 (0.15%)
occurrences causally related to treatment / all	0 / 15	0 / 18
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea infectious
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Dysentery
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ear infection
subjects affected / exposed	2 / 11799 (0.02%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Empyema
subjects affected / exposed	2 / 11799 (0.02%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Encephalitis viral
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enteritis infectious
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enterococcal sepsis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia urinary tract infection
subjects affected / exposed	2 / 11799 (0.02%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Exanthema subitum
subjects affected / exposed	4 / 11799 (0.03%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
External ear cellulitis
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Fungal skin infection
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	497 / 11799 (4.21%)	553 / 11798 (4.69%)
occurrences causally related to treatment / all	0 / 497	0 / 553
deaths causally related to treatment / all	0 / 0	0 / 2
Gastroenteritis adenovirus
subjects affected / exposed	3 / 11799 (0.03%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis bacterial
subjects affected / exposed	9 / 11799 (0.08%)	8 / 11798 (0.07%)
occurrences causally related to treatment / all	0 / 9	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	49 / 11799 (0.42%)	38 / 11798 (0.32%)
occurrences causally related to treatment / all	0 / 49	0 / 38
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis shigella
subjects affected / exposed	8 / 11799 (0.07%)	8 / 11798 (0.07%)
occurrences causally related to treatment / all	0 / 8	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	9 / 11799 (0.08%)	9 / 11798 (0.08%)
occurrences causally related to treatment / all	0 / 9	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0
Giardiasis
subjects affected / exposed	3 / 11799 (0.03%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gingivitis
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hantaviral infection
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Herpangina
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes simplex
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes virus infection
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Impetigo
subjects affected / exposed	4 / 11799 (0.03%)	10 / 11798 (0.08%)
occurrences causally related to treatment / all	0 / 4	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Infected bites
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infected cyst
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Infected fistula
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infectious mononucleosis
subjects affected / exposed	4 / 11799 (0.03%)	5 / 11798 (0.04%)
occurrences causally related to treatment / all	0 / 4	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Infective pulmonary exacerbation of cystic fibrosis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza
subjects affected / exposed	2 / 11799 (0.02%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Klebsiella bacteraemia
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Klebsiella sepsis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Laryngitis
subjects affected / exposed	14 / 11799 (0.12%)	9 / 11798 (0.08%)
occurrences causally related to treatment / all	0 / 14	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0
Lobar pneumonia
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lung infection
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lymph node abscess
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Mastoiditis
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Meningitis
subjects affected / exposed	2 / 11799 (0.02%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Meningitis aseptic
subjects affected / exposed	2 / 11799 (0.02%)	6 / 11798 (0.05%)
occurrences causally related to treatment / all	0 / 2	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Meningitis meningococcal
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Meningitis pneumococcal
subjects affected / exposed	2 / 11799 (0.02%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0
Meningitis viral
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myiasis
subjects affected / exposed	4 / 11799 (0.03%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nasal abscess
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nasopharyngitis
subjects affected / exposed	3 / 11799 (0.03%)	6 / 11798 (0.05%)
occurrences causally related to treatment / all	0 / 3	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Necrotising fasciitis
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nosocomial infection
subjects affected / exposed	3 / 11799 (0.03%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Oral candidiasis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oral herpes
subjects affected / exposed	2 / 11799 (0.02%)	11 / 11798 (0.09%)
occurrences causally related to treatment / all	0 / 2	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Otitis externa
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Otitis media
subjects affected / exposed	8 / 11799 (0.07%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 8	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Otitis media acute
subjects affected / exposed	16 / 11799 (0.14%)	16 / 11798 (0.14%)
occurrences causally related to treatment / all	0 / 16	0 / 16
deaths causally related to treatment / all	0 / 0	0 / 0
Paronychia
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Parotitis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Periorbital cellulitis
subjects affected / exposed	16 / 11799 (0.14%)	12 / 11798 (0.10%)
occurrences causally related to treatment / all	0 / 16	0 / 12
deaths causally related to treatment / all	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	4 / 11799 (0.03%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Pertussis
subjects affected / exposed	16 / 11799 (0.14%)	19 / 11798 (0.16%)
occurrences causally related to treatment / all	0 / 16	0 / 19
deaths causally related to treatment / all	0 / 0	0 / 1
Pharyngeal abscess
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	13 / 11799 (0.11%)	5 / 11798 (0.04%)
occurrences causally related to treatment / all	0 / 13	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Pharyngotonsillitis
subjects affected / exposed	2 / 11799 (0.02%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumococcal sepsis
subjects affected / exposed	2 / 11799 (0.02%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumocystis jiroveci infection
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	557 / 11799 (4.72%)	478 / 11798 (4.05%)
occurrences causally related to treatment / all	0 / 557	0 / 478
deaths causally related to treatment / all	0 / 6	0 / 3
Pneumonia adenoviral
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia influenza
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia pneumococcal
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia respiratory syncytial viral
subjects affected / exposed	5 / 11799 (0.04%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia viral
subjects affected / exposed	9 / 11799 (0.08%)	8 / 11798 (0.07%)
occurrences causally related to treatment / all	0 / 9	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Postoperative wound infection
subjects affected / exposed	1 / 11799 (0.01%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pseudomembranous colitis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary sepsis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Pyelonephritis
subjects affected / exposed	6 / 11799 (0.05%)	11 / 11798 (0.09%)
occurrences causally related to treatment / all	0 / 6	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	1 / 11799 (0.01%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pyoderma
subjects affected / exposed	8 / 11799 (0.07%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 8	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Pyomyositis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus bronchiolitis
subjects affected / exposed	5 / 11799 (0.04%)	6 / 11798 (0.05%)
occurrences causally related to treatment / all	0 / 5	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus bronchitis
subjects affected / exposed	6 / 11799 (0.05%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 6	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	2 / 11799 (0.02%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory tract infection viral
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rhinitis
subjects affected / exposed	7 / 11799 (0.06%)	5 / 11798 (0.04%)
occurrences causally related to treatment / all	0 / 7	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Roseola
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Salmonellosis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Scarlet fever
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	14 / 11799 (0.12%)	11 / 11798 (0.09%)
occurrences causally related to treatment / all	0 / 14	0 / 11
deaths causally related to treatment / all	0 / 4	0 / 0
Sepsis syndrome
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Septic shock
subjects affected / exposed	7 / 11799 (0.06%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 7	0 / 4
deaths causally related to treatment / all	0 / 5	0 / 3
Shigella infection
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	5 / 11799 (0.04%)	9 / 11798 (0.08%)
occurrences causally related to treatment / all	0 / 5	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0
Skin candida
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin infection
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal bacteraemia
subjects affected / exposed	1 / 11799 (0.01%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal scalded skin syndrome
subjects affected / exposed	0 / 11799 (0.00%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal sepsis
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal skin infection
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Streptococcal sepsis
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	14 / 11799 (0.12%)	8 / 11798 (0.07%)
occurrences causally related to treatment / all	0 / 14	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Systemic candida
subjects affected / exposed	1 / 11799 (0.01%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Thyroglossal cyst infection
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	3 / 11799 (0.03%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Tooth abscess
subjects affected / exposed	0 / 11799 (0.00%)	2 / 11798 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Tracheitis
subjects affected / exposed	7 / 11799 (0.06%)	8 / 11798 (0.07%)
occurrences causally related to treatment / all	0 / 7	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Typhoid fever
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	11 / 11799 (0.09%)	15 / 11798 (0.13%)
occurrences causally related to treatment / all	0 / 11	0 / 15
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	93 / 11799 (0.79%)	76 / 11798 (0.64%)
occurrences causally related to treatment / all	0 / 93	0 / 76
deaths causally related to treatment / all	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Varicella
subjects affected / exposed	18 / 11799 (0.15%)	10 / 11798 (0.08%)
occurrences causally related to treatment / all	0 / 18	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Viral infection
subjects affected / exposed	11 / 11799 (0.09%)	12 / 11798 (0.10%)
occurrences causally related to treatment / all	0 / 11	0 / 12
deaths causally related to treatment / all	0 / 0	0 / 0
Viral pharyngitis
subjects affected / exposed	7 / 11799 (0.06%)	9 / 11798 (0.08%)
occurrences causally related to treatment / all	0 / 7	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0
Viral rash
subjects affected / exposed	4 / 11799 (0.03%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Viral sepsis
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Viral tonsillitis
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vulvovaginitis
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Wound infection
subjects affected / exposed	3 / 11799 (0.03%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Cow’s milk intolerance
subjects affected / exposed	1 / 11799 (0.01%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dehydration
subjects affected / exposed	438 / 11799 (3.71%)	463 / 11798 (3.92%)
occurrences causally related to treatment / all	0 / 438	0 / 463
deaths causally related to treatment / all	0 / 1	0 / 2
Diabetes mellitus
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic ketoacidosis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Electrolyte imbalance
subjects affected / exposed	5 / 11799 (0.04%)	8 / 11798 (0.07%)
occurrences causally related to treatment / all	0 / 5	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Failure to thrive
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Feeding disorder neonatal
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Food intolerance
subjects affected / exposed	3 / 11799 (0.03%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	0 / 11799 (0.00%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	5 / 11799 (0.04%)	4 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 5	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 0
Lactose intolerance
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Malnutrition
subjects affected / exposed	4 / 11799 (0.03%)	3 / 11798 (0.03%)
occurrences causally related to treatment / all	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolic acidosis
subjects affected / exposed	0 / 11799 (0.00%)	1 / 11798 (0.01%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Type 1 diabetes mellitus
subjects affected / exposed	1 / 11799 (0.01%)	0 / 11798 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

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

Non-serious adverse events	Control Group	Synflorix Group
Total subjects affected by non serious adverse events
subjects affected / exposed	3518 / 11799 (29.82%)	3530 / 11798 (29.92%)
Injury, poisoning and procedural complications
Head injury
subjects affected / exposed ^[1]	406 / 3612 (11.24%)	454 / 3602 (12.60%)
occurrences all number	406	454
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed ^[2]	1378 / 3612 (38.15%)	1411 / 3602 (39.17%)
occurrences all number	1378	1411
General disorders and administration site conditions
Injection site pain
subjects affected / exposed ^[3]	201 / 3612 (5.56%)	384 / 3602 (10.66%)
occurrences all number	201	384
Pyrexia
subjects affected / exposed ^[4]	1916 / 3612 (53.05%)	2272 / 3602 (63.08%)
occurrences all number	1916	2272
Irritability
subjects affected / exposed ^[5]	372 / 3612 (10.30%)	458 / 3602 (12.72%)
occurrences all number	372	458
Injection site erythema
subjects affected / exposed ^[6]	172 / 3612 (4.76%)	260 / 3602 (7.22%)
occurrences all number	172	260
Drowsiness - Primary vaccination
Additional description: Solicited general AE collected in subjects in the Immunogenicity and Tolerability Subset post primary vaccination, across doses
alternative assessment type: Systematic
subjects affected / exposed ^[7]	168 / 357 (47.06%)	236 / 368 (64.13%)
occurrences all number	168	236
Fever - Primary vaccination
Additional description: Solicited general AE - Fever = rectal temperature >= 38.0°C - collected in subjects in the Immunogenicity and Tolerability Subset post primary vaccination, across doses
alternative assessment type: Systematic
subjects affected / exposed ^[8]	125 / 357 (35.01%)	247 / 368 (67.12%)
occurrences all number	125	247
Irritability - Primary vaccination
Additional description: Solicited general AE collected in subjects in the Immunogenicity and Tolerability Subset post primary vaccination, across doses
alternative assessment type: Systematic
subjects affected / exposed ^[9]	206 / 357 (57.70%)	289 / 368 (78.53%)
occurrences all number	206	289
Loss of appetite - Primary vaccination
Additional description: Solicited general AE collected in subjects in the Immunogenicity and Tolerability Subset post primary vaccination
alternative assessment type: Systematic
subjects affected / exposed ^[10]	80 / 357 (22.41%)	133 / 368 (36.14%)
occurrences all number	80	133
Drowsiness - Booster vaccination
Additional description: Solicited general AE collected in subjects in the Immunogenicity and Tolerability Subset post booster vaccination
alternative assessment type: Systematic
subjects affected / exposed ^[11]	65 / 303 (21.45%)	74 / 317 (23.34%)
occurrences all number	65	74
Fever - Booster vaccination
Additional description: Solicited general AE - Fever = rectal temperature >= 38.0°C - collected in subjects in the Immunogenicity and Tolerability Subset post booster vaccination
alternative assessment type: Systematic
subjects affected / exposed ^[12]	73 / 303 (24.09%)	93 / 317 (29.34%)
occurrences all number	73	93
Irritability - Booster vaccination
Additional description: Solicited general AE collected in subjects in the Immunogenicity and Tolerability Subset post booster vaccination
alternative assessment type: Systematic
subjects affected / exposed ^[13]	95 / 303 (31.35%)	121 / 317 (38.17%)
occurrences all number	95	121
Loss of appetite - Booster vaccination
Additional description: Solicited general AE collected in subjects in the Immunogenicity and Tolerability Subset post booster vaccination
alternative assessment type: Systematic
subjects affected / exposed ^[14]	46 / 303 (15.18%)	51 / 317 (16.09%)
occurrences all number	46	51
Pain – Primary Vaccination
Additional description: Solicited local AE collected in subjects in the Immunogenicity and Tolerability Subset post primary vaccination, across all doses and all vaccines
alternative assessment type: Systematic
subjects affected / exposed ^[15]	177 / 357 (49.58%)	282 / 368 (76.63%)
occurrences all number	177	282
Redness – Primary Vaccination
Additional description: Solicited local AE collected in subjects in the Immunogenicity and Tolerability Subset post primary vaccination, across all doses and all vaccines
alternative assessment type: Systematic
subjects affected / exposed ^[16]	135 / 357 (37.82%)	194 / 368 (52.72%)
occurrences all number	135	194
Swelling – Primary Vaccination
Additional description: Solicited local AE collected in subjects in the Immunogenicity and Tolerability Subset post primary vaccination, across all doses and all vaccines
alternative assessment type: Systematic
subjects affected / exposed ^[17]	109 / 357 (30.53%)	158 / 368 (42.93%)
occurrences all number	109	158
Pain – Booster Vaccination
Additional description: Solicited local AE collected in subjects in the Immunogenicity and Tolerability Subset post booster vaccination, across all doses and all vaccines
alternative assessment type: Systematic
subjects affected / exposed ^[18]	98 / 303 (32.34%)	140 / 317 (44.16%)
occurrences all number	98	140
Redness – Booster Primary Vaccination
Additional description: Solicited local AE collected in subjects in the Immunogenicity and Tolerability Subset post booster vaccination, across all doses and all vaccines
alternative assessment type: Systematic
subjects affected / exposed ^[19]	102 / 303 (33.66%)	117 / 317 (36.91%)
occurrences all number	102	117
Swelling – Booster Primary Vaccination
Additional description: Solicited local AE collected in subjects in the Immunogenicity and Tolerability Subset post primary vaccination, across all doses and all vaccines
alternative assessment type: Systematic
subjects affected / exposed ^[20]	85 / 303 (28.05%)	86 / 317 (27.13%)
occurrences all number	85	86
Immune system disorders
Hypersensitivity
subjects affected / exposed ^[21]	328 / 3612 (9.08%)	315 / 3602 (8.75%)
occurrences all number	328	315
Eye disorders
Conjunctivitis
subjects affected / exposed ^[22]	575 / 3612 (15.92%)	598 / 3602 (16.60%)
occurrences all number	575	598
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed ^[23]	1794 / 3612 (49.67%)	1905 / 3602 (52.89%)
occurrences all number	1794	1905
Vomiting
subjects affected / exposed ^[24]	506 / 3612 (14.01%)	520 / 3602 (14.44%)
occurrences all number	506	520
Constipation
subjects affected / exposed ^[25]	257 / 3612 (7.12%)	279 / 3602 (7.75%)
occurrences all number	257	279
Stomatitis
subjects affected / exposed ^[26]	202 / 3612 (5.59%)	174 / 3602 (4.83%)
occurrences all number	202	174
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed ^[27]	582 / 3612 (16.11%)	596 / 3602 (16.55%)
occurrences all number	582	596
Cough
subjects affected / exposed ^[28]	510 / 3612 (14.12%)	499 / 3602 (13.85%)
occurrences all number	510	499
Asthmatic crisis
subjects affected / exposed ^[29]	313 / 3612 (8.67%)	288 / 3602 (8.00%)
occurrences all number	313	288
Bronchial hyperreactivity
subjects affected / exposed ^[30]	297 / 3612 (8.22%)	322 / 3602 (8.94%)
occurrences all number	297	322
Skin and subcutaneous tissue disorders
Dermatitis
subjects affected / exposed ^[31]	464 / 3612 (12.85%)	468 / 3602 (12.99%)
occurrences all number	464	468
Dermatitis diaper
subjects affected / exposed ^[32]	316 / 3612 (8.75%)	293 / 3602 (8.13%)
occurrences all number	316	293
Dermatitis atopic
subjects affected / exposed ^[33]	296 / 3612 (8.19%)	332 / 3602 (9.22%)
occurrences all number	296	332
Rash
subjects affected / exposed ^[34]	220 / 3612 (6.09%)	220 / 3602 (6.11%)
occurrences all number	220	220
Prurigo
subjects affected / exposed ^[35]	199 / 3612 (5.51%)	179 / 3602 (4.97%)
occurrences all number	199	179
Dermatitis allergic
subjects affected / exposed ^[36]	196 / 3612 (5.43%)	163 / 3602 (4.53%)
occurrences all number	196	163
Infections and infestations
Nasopharyngitis
subjects affected / exposed ^[37]	3326 / 3612 (92.08%)	3338 / 3602 (92.67%)
occurrences all number	3326	3338
Gastroenteritis
subjects affected / exposed ^[38]	1281 / 3612 (35.47%)	1310 / 3602 (36.37%)
occurrences all number	1281	1310
Bronchiolitis
subjects affected / exposed ^[39]	1123 / 3612 (31.09%)	1119 / 3602 (31.07%)
occurrences all number	1123	1119
Pharyngitis
subjects affected / exposed ^[40]	958 / 3612 (26.52%)	950 / 3602 (26.37%)
occurrences all number	958	950
Viral infection
subjects affected / exposed ^[41]	738 / 3612 (20.43%)	714 / 3602 (19.82%)
occurrences all number	738	714
Pharyngotonsillitis
subjects affected / exposed ^[42]	682 / 3612 (18.88%)	672 / 3602 (18.66%)
occurrences all number	682	672
Rhinitis
subjects affected / exposed ^[43]	516 / 3612 (14.29%)	542 / 3602 (15.05%)
occurrences all number	516	542
Impetigo
subjects affected / exposed ^[44]	474 / 3612 (13.12%)	497 / 3602 (13.80%)
occurrences all number	474	497
Bronchitis
subjects affected / exposed ^[45]	410 / 3612 (11.35%)	486 / 3602 (13.49%)
occurrences all number	410	486
Pyoderma
subjects affected / exposed ^[46]	368 / 3612 (10.19%)	350 / 3602 (9.72%)
occurrences all number	368	350
Tonsillitis
subjects affected / exposed ^[47]	242 / 3612 (6.70%)	232 / 3602 (6.44%)
occurrences all number	242	232
Pneumonia
subjects affected / exposed ^[48]	238 / 3612 (6.59%)	217 / 3602 (6.02%)
occurrences all number	238	217
Urinary tract infection
subjects affected / exposed ^[49]	228 / 3612 (6.31%)	202 / 3602 (5.61%)
occurrences all number	228	202
Influenza
subjects affected / exposed ^[50]	175 / 3612 (4.84%)	206 / 3602 (5.72%)
occurrences all number	175	206
Metabolism and nutrition disorders
Malnutrition
subjects affected / exposed ^[51]	545 / 3612 (15.09%)	556 / 3602 (15.44%)
occurrences all number	545	556
Overweight
subjects affected / exposed ^[52]	422 / 3612 (11.68%)	416 / 3602 (11.55%)
occurrences all number	422	416
Dehydration
subjects affected / exposed ^[53]	207 / 3612 (5.73%)	182 / 3602 (5.05%)
occurrences all number	207	182

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[17] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[18] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[19] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[20] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[21] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[22] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[23] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[24] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[25] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[26] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[27] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[28] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[29] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[30] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[31] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[32] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[33] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[34] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[35] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[36] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[37] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[38] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[39] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[40] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[41] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[42] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[43] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[44] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[45] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[46] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[47] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[48] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[49] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[50] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[51] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[52] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.
[53] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Assessment for this event was done in subjects with available results.

More information

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Were there any global substantial amendments to the protocol? Yes

26 Nov 2007

The following changes were implemented in this Amendment 1. Firstly, study centres in Colombia were added. Secondly, a new subset (‘Additional immuno’ subset) of subjects in Panama was added for further exploration after study end of the correlation between protection against of Acute Otitis Media (AOM) episodes caused by (non-typeable) H. influenzae and results of the measurement and characterization of responses induced by the protein D carrier protein. Thirdly, the Reference Laboratory was changed from Instituto Malbrán in Argentina to Eurofins in the United States, which implied adaptations to the laboratory procedures. Fourthly, an appendix was added about the background of AOM severity scales and their application in the study.

20 Mar 2008

The following changes were implemented in this Amendment 2. Firstly, in Colombia, two doses of HRV (Rotarix) vaccine would be offered to all subjects within the first six months of life to provide additional benefit. Secondly, in Panama, subjects who were part of the ‘Carriage’ subset were also given the opportunity to participate in the ‘Additional immuno’ subset. However, subjects who were part of the ‘Immunogenicity and Tolerability’ subset would not be invited to participate in the ‘Additional immuno’ subset as already four blood samples were to be collected from these subjects. Thirdly, for preterm infants the gestation period had been defined. Fourth, in case subjects would by mistake receive a vaccine with antigens common to the antigens contained in the study or co-administered vaccines outside of the context of the study, the investigator would need to evaluate whether the subject could still continue participation in the study. Therefore this criterion was added to the exclusion criteria for further study participation. Fifth, for subjects in the ‘Additional immuno’ subset, a visit was removed from the list of study procedures and the detailed description of study procedures. Sixth, new validated temperature monitoring devices had been provided to the investigational sites. Although the temperature monitoring process described in protocol still covered the use of these new devices, the related section was updated with the mandatory text of the current protocol document standard to avoid confusion. Seventh, the classification of the CXR was aligned throughout the protocol and with the Radiology workbook. Eighth, additional minor changes and clarifications were implemented.

25 Nov 2008

This protocol amendment - Amendment 3 – was developed in reply to questions from local authorities. Firstly, the recruitment period was extended to 18 months. Secondly, subjects diagnosed to be at high risk for Invasive pneumococcal disease (IPD) were excluded from the study in case a specific local vaccination program was available. Thirdly, the informed consent process for minor parents (<18 years of age) was specified. Fourth, additional minor changes and clarifications were implemented.

11 May 2009

This protocol amendment – Amendment 4 – was developed in reply to questions from local authorities. Additions were, 1) in the exclusion criteria for further study participation the criteria for high risk for pneumococcal disease were specified and 2) clarification on how to proceed in case of diagnosis of a high risk condition for pneumococcal infection was added.

14 Dec 2009

Changes were implemented in the protocol Amendment 5 towards taking into account that the number of AOM cases reported to that date was much lower than anticipated. To be able to perform the interim analysis to evaluate the efficacy of the 10Pn-PD-DiT/Synflorix vaccine to prevent the first episodes of B-CAP regardless of the number of cases of C-AOM that would be reached, it was decided to evaluate the vaccine efficacy (VE) to prevent the first episodes of B-CAP as the only primary objective, and to evaluate the VE to prevent the first episodes of C-AOM as a secondary objective instead of a co-primary objective. The number of B-CAP cases needed to perform the interim analysis was adjusted accordingly.

09 Sep 2010

This protocol Amendment 6 was developed for the following reasons. Firstly, as the observed incidence of B-CAP was lower than the expected incidence, the number of cases needed to perform the final analysis would not be reached in the near future and might never be reached based on extrapolation of the accrual of B-CAP cases. As this study had been designed to determine VE against pneumonia, which is a major burden in Latin America and the rest of the world, results should be reported in a timely manner. Therefore GSK Biologicals decided to amend the protocol to re-define the study end based on the outcome of the planned interim analysis. Secondly, in addition, clarifications to the objectives and endpoints were implemented and wordings were corrected to align with the change in the primary objective implemented in previous amendment dated 14 December 2009). Thirdly, contact details for the emergency code break were updated.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of subjects with a first episode reported of bacterial community acquired pneumoniae (B-CAP)

Primary: Number of subjects with a first episode reported of bacterial community acquired pneumoniae (B-CAP)

Primary: Time to First or Only Episode of B-CAP

Primary: Time to First or Only Episode of B-CAP

Secondary: Number of subjects with serious adverse events (SAEs)

Secondary: Number of subjects with serious adverse events (SAEs)

Secondary: Number of subjects with any unsolicited adverse event (AE), in the Panama Subset

Secondary: Number of subjects with any unsolicited adverse event (AE), in the Panama Subset

Secondary: Number of subjects with solicited local symptoms post primary vaccination in the Immunogenicity and Tolerability Subset

Secondary: Number of subjects with solicited local symptoms post primary vaccination in the Immunogenicity and Tolerability Subset

Secondary: Number of subjects with solicited local symptoms post booster vaccination in the Immunogenicity and Tolerability Subset

Secondary: Number of subjects with solicited local symptoms post booster vaccination in the Immunogenicity and Tolerability Subset

Secondary: Number of subjects with solicited local symptoms post primary vaccination in the Immunogenicity and Tolerability Subset

Secondary: Number of subjects with solicited local symptoms post primary vaccination in the Immunogenicity and Tolerability Subset

Secondary: Number of subjects with solicited local symptoms post booster vaccination in the Immunogenicity and Tolerability Subset, for the Control Group

Secondary: Number of subjects with solicited local symptoms post booster vaccination in the Immunogenicity and Tolerability Subset, for the Control Group

Secondary: Number of subjects with solicited general symptoms post primary vaccination in the Immunogenicity and Tolerability Subset

Secondary: Number of subjects with solicited general symptoms post primary vaccination in the Immunogenicity and Tolerability Subset

Secondary: Number of subjects with solicited general symptoms post booster vaccination in the Immunogenicity and Tolerability Subset

Secondary: Number of subjects with solicited general symptoms post booster vaccination in the Immunogenicity and Tolerability Subset

Secondary: Number of subjects with a first episode reported of clinically confirmed acute otitis media (AOM) (C-AOM), in the Panama Subset

Secondary: Number of subjects with a first episode reported of clinically confirmed acute otitis media (AOM) (C-AOM), in the Panama Subset

Secondary: Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with alveolar consolidation or pleural effusion on the chest X-ray (CXR) (C-CAP)

Secondary: Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with alveolar consolidation or pleural effusion on the chest X-ray (CXR) (C-CAP)

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to any bacterial pathogen, in the Panama Subset

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to any bacterial pathogen, in the Panama Subset

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to Streptococcus pneumoniae (S. pn.) vaccine serotypes, in the Panama Subset

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to Streptococcus pneumoniae (S. pn.) vaccine serotypes, in the Panama Subset

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to Streptococcus pneumoniae (S. pn.) cross-reactive serotypes, in the Panama Subset.

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to Streptococcus pneumoniae (S. pn.) cross-reactive serotypes, in the Panama Subset.

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to other pneumococcal serotypes, in the Panama Subset.

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to other pneumococcal serotypes, in the Panama Subset.

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to Haemophilus influenzae (H. influenzae), in the Panama Subset

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to Haemophilus influenzae (H. influenzae), in the Panama Subset

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to non-typeable Haemophilus influenzae (H. influenzae), in the Panama Subset

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to non-typeable Haemophilus influenzae (H. influenzae), in the Panama Subset

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to other AOM pathogens, in the Panama Subset

Secondary: Number of subjects with a first episode reported of bacteriologically confirmed acute otitis media (AOM) (B-AOM) due to other AOM pathogens, in the Panama Subset

Secondary: Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with alveolar consolidation or pleural effusion on the Chest X-ray (CXR) (C-CAP) with positive respiratory viral test (RVT)

Secondary: Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with alveolar consolidation or pleural effusion on the Chest X-ray (CXR) (C-CAP) with positive respiratory viral test (RVT)

Secondary: Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with any abnormal CXR with positive respiratory viral test (RVT)

Secondary: Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with any abnormal CXR with positive respiratory viral test (RVT)

Secondary: Number of subjects with a first episode reported of bacterial community acquired pneumoniae (B-CAP) with positive respiratory viral test (RVT).

Secondary: Number of subjects with a first episode reported of bacterial community acquired pneumoniae (B-CAP) with positive respiratory viral test (RVT).

Secondary: Number of subjects with a first episode reported of suspected community acquired pneumoniae (CAP) (S-CAP)

Secondary: Number of subjects with a first episode reported of suspected community acquired pneumoniae (CAP) (S-CAP)

Secondary: Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with any abnormal chest X-ray (CXR)

Secondary: Number of subjects with a first episode reported of community acquired pneumoniae (CAP) with any abnormal chest X-ray (CXR)

Secondary: Number of subjects with a first episode reported of suspected community acquired pneumoniae (CAP) (S-CAP) with C reactive protein (CRP) >= cut-off, regardless of chest X-ray (CXR) reading

Secondary: Number of subjects with a first episode reported of suspected community acquired pneumoniae (CAP) (S-CAP) with C reactive protein (CRP) >= cut-off, regardless of chest X-ray (CXR) reading

Secondary: Number of subjects with a first episode reported of CAP with either alveolar consolidation/pleural effusion on chest X-ray (CXR) (C-CAP) or with non-alveolar infiltrates (NAI-CAP) but with C reactive protein (CRP) >= cut-off.

Secondary: Number of subjects with a first episode reported of CAP with either alveolar consolidation/pleural effusion on chest X-ray (CXR) (C-CAP) or with non-alveolar infiltrates (NAI-CAP) but with C reactive protein (CRP) >= cut-off.

Secondary: Number of subjects with a first episode reported of vaccine-type invasive pneumococcal disease (VT-IPD).

Secondary: Number of subjects with a first episode reported of vaccine-type invasive pneumococcal disease (VT-IPD).

Secondary: Number of subjects with a first episode reported of a bacteriologically confirmed invasive pneumococcal disease (Bact.-conf. ID).

Secondary: Number of subjects with a first episode reported of a bacteriologically confirmed invasive pneumococcal disease (Bact.-conf. ID).

Secondary: Number of subjects with a first episode reported of pneumococcal invasive disease (Pneumococcal ID)

Secondary: Number of subjects with a first episode reported of pneumococcal invasive disease (Pneumococcal ID)

Secondary: Number of subjects with a first episode reported of Invasive Pneumococcal Disease (IPD) due to Streptococcus (S. pn.) cross-reactive pneumococcal serotypes.

Secondary: Number of subjects with a first episode reported of Invasive Pneumococcal Disease (IPD) due to Streptococcus (S. pn.) cross-reactive pneumococcal serotypes.

Secondary: Number of subjects with a first episode reported of Invasive Pneumococcal Disease (IPD) due to pneumococcal serotypes other than Streptococcus (S. pn.) vaccine and cross-reactive serotypes.

Secondary: Number of subjects with a first episode reported of Invasive Pneumococcal Disease (IPD) due to pneumococcal serotypes other than Streptococcus (S. pn.) vaccine and cross-reactive serotypes.

Secondary: Number of subjects with a first episode reported of invasive disease (ID) due to Haemophilus influenzae

Secondary: Number of subjects with a first episode reported of invasive disease (ID) due to Haemophilus influenzae

Secondary: Number of subjects with Streptococcus pneumoniae (S. pn.) vaccine serotypes identified in nasopharyngeal swabs, in the Carriage Subset.

Secondary: Number of subjects with Streptococcus pneumoniae (S. pn.) vaccine serotypes identified in nasopharyngeal swabs, in the Carriage Subset.

Secondary: Number of subjects with Streptococcus pneumoniae (S. pn.) cross-reactive serotypes identified in nasopharyngeal swabs, in the Carriage Subset.

Secondary: Number of subjects with Streptococcus pneumoniae (S. pn.) cross-reactive serotypes identified in nasopharyngeal swabs, in the Carriage Subset.

Secondary: Number of subjects with Streptococcus pneumoniae (S. pn.) serotypes identified in nasopharyngeal swabs other than the Synflorix vaccine and cross-reactive serotypes, in the Carriage Subset

Secondary: Number of subjects with Streptococcus pneumoniae (S. pn.) serotypes identified in nasopharyngeal swabs other than the Synflorix vaccine and cross-reactive serotypes, in the Carriage Subset

Secondary: Number of subjects with H. influenzae strains identified in nasopharyngeal swabs, in the Carriage subset