Download PDF

Clinical Trial Results:
Phase 2, Randomized, Active-Controlled, Double-Blind Trial Evaluating The Safety, Tolerability, And Immunogenicity Of A 13-Valent Pneumococcal Conjugate Vaccine In Healthy Infants Given With Routine Pediatric Vaccinations In Korea

Summary
EudraCT number	2008-004769-24
Trial protocol	Outside EU/EEA
Global end of trial date	11 Dec 2009

Results information
Results version number	v1(current)
This version publication date	29 Jun 2016
First version publication date	30 Jul 2015
Other versions

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

6096A1-010

ISRCTN number

US NCT number

NCT00689351

WHO universal trial number (UTN)

Other trial identifiers

Alias ID: B1851001

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Clinical Trials.gov Call Center, Pfizer Inc, 001 8007181021, clinicaltrials.gov_inquiries@pfizer.com

Scientific contact

Clinical Trials.gov Call Center, Pfizer Inc, 001 8007181021, clinicaltrials.gov_inquiries@pfizer.com

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

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

23 Aug 2010

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

11 Dec 2009

Was the trial ended prematurely?

Main objective of the trial

To evaluate the pneumococcal immune responses induced by 13-valent pneumococcal conjugate vaccine (13vPnC) relative to the pneumococcal immune responses induced by 7 valent pneumococcal conjugate vaccine (7vPnC) when measured 1 month after the infant series. To evaluate the acceptability of the safety profile of 13vPnC as measured by the incidence rates of local reactions, systemic events, and adverse events (AEs).

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

22 Jul 2008

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Korea, Republic of: 180

Worldwide total number of subjects

180

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)

180

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

Total 180 subjects were enrolled in the study. The study was conducted in Korea, "the Republic of" which started on 22 July 2008 and completed on 11 December 2009.

Period 1 title

Infant Series

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

13vPnC: Infant Series

Arm description

Each subject was to receive 13vPnC at each of the 3 vaccination visits (2, 4, and 6month visits); Diptheria, tetanus, and acellular pertussis vaccine (DTaP) administered concomitantly with 13vPnC at 2, 4, and 6 months of age; inactivated poliovirus vaccine (IPV) and Haemophilus influenzae type b (Hib) vaccine 7 to 21 days after each dose of 13vPnC during the infant series; and hepatitis B virus vaccine (HBV) 7 to 21 days after dose 3.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

13vPnC was administered at a dose of 0.5 milliliter (mL) at 2, 4, and 6 months of age (infant series).

Investigational medicinal product name

Diphtheria, tetanus, and acellular pertussis vaccine (DTaP)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

DTap was administered intramuscularly concomitantly with 13vPnC at 2, 4, and 6 months of age in the anterolateral muscle of the right thigh according to standard vaccination practice.

Investigational medicinal product name

Inactivated poliovirus vaccine (IPV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

IPV were to be administered 7 to 21 days after each dose of 13vPnC during the infant series according to standard vaccination practice.

Investigational medicinal product name

Haemophilus influenzae type b (Hib)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Hib vaccine were to be administered 7 to 21 days after each dose of 13vPnC during the infant series according to standard vaccination practice.

Investigational medicinal product name

Hepatitis B virus vaccine (HBV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

HBV was administered 7 to 21 days after dose 3 of 13vPnC according to standard vaccination practice.

7vPnC: Infant Series

Arm description

Each subject was to receive 7vPnC at each of the 3 vaccination visits (2, 4, and 6month visits); Diptheria, tetanus, and acellular pertussis vaccine (DTaP) administered concomitantly with 7vPnC at 2, 4, and 6 months of age; inactivated poliovirus vaccine (IPV) and Haemophilus influenzae type b (Hib) vaccine 7 to 21 days after each dose of 7vPnC during the infant series; and hepatitis B virus vaccine (HBV) 7 to 21 days after dose 3.

Arm type

Active comparator

Investigational medicinal product name

7vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

7vPnC was administered at a dose of 0.5 mL at 2, 4, and 6 months of age (infant series).

Investigational medicinal product name

Diphtheria, tetanus, and acellular pertussis vaccine (DTaP)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

DTap was administered intramuscularly concomitantly with 7vPnC at 2, 4, and 6 months of age in the anterolateral muscle of the right thigh according to standard vaccination practice.

Investigational medicinal product name

Inactivated poliovirus vaccine (IPV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

IPV were to be administered 7 to 21 days after each dose of 7vPnC during the infant series according to standard vaccination practice.

Investigational medicinal product name

Haemophilus influenzae type b (Hib)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Hib vaccine were to be administered 7 to 21 days after each dose of 7vPnC during the infant series according to standard vaccination practice.

Investigational medicinal product name

Hepatitis B virus vaccine (HBV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

HBV was administered 7 to 21 days after dose 3 of 7vPnC according to standard vaccination practice.

Number of subjects in period 1	13vPnC: Infant Series	7vPnC: Infant Series
Started	91	89
Vaccinated Dose 1	88	89
Vaccinated Dose 2	86	88
Vaccinated Dose 3	85	88
Completed	85	88
Not completed	6	1
'Parent/legal guardian request '	5	-
Adverse Event	1	-
Lost to follow-up	-	1

Period 2 title

After Infant Series

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

13vPnC: After the Infant Series

Arm description

Included subjects who received 13vPnC at each of the 3 vaccination visits (2, 4, and 6month visits); Diptheria, tetanus, and acellular pertussis vaccine (DTaP) administered concomitantly with 13vPnC at 2, 4, and 6 months of age; inactivated poliovirus vaccine (IPV) and Haemophilus influenzae type b (Hib) vaccine 7 to 21 days after each dose of 13vPnC during the infant series; and hepatitis B virus vaccine (HBV) 7 to 21 days after dose 3.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

7vPnC: After the Infant Series

Arm description

Included subjects who received 7vPnC at each of the 3 vaccination visits (2, 4, and 6month visits); Diptheria, tetanus, and acellular pertussis vaccine (DTaP) administered concomitantly with 7vPnC at 2, 4, and 6 months of age; inactivated poliovirus vaccine (IPV) and Haemophilus influenzae type b (Hib) vaccine 7 to 21 days after each dose of 7vPnC during the infant series; and hepatitis B virus vaccine (HBV) 7 to 21 days after dose 3.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2	13vPnC: After the Infant Series	7vPnC: After the Infant Series
Started	85	88
Completed	84	88
Not completed	1	0
'Parent/legal guardian request '	1	-

Period 3 title

Toddler Dose

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

13vPnC: Toddler Dose

Arm description

13vPnC dose administered IM at 12 months of age (toddler dose).

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

13vPnC was administered at a dose of 0.5 mL at 12 months of age (toddler dose).

7vPnC: Toddler Dose

Arm description

7vPnC dose administered IM at 12 months of age (toddler dose).

Arm type

Active comparator

Investigational medicinal product name

7vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

7vPnC was administered at a dose of 0.5 mL at 12 months of age (toddler dose).

Number of subjects in period 3	13vPnC: Toddler Dose	7vPnC: Toddler Dose
Started	84	88
Completed	84	88

Baseline characteristics

Top of page

Reporting group title

13vPnC: Infant Series

Reporting group description

Reporting group title

7vPnC: Infant Series

Reporting group description

Reporting group values	13vPnC: Infant Series	7vPnC: Infant Series	Total
Number of subjects	91	89	180
Age categorical
Units: Subjects
Age continuous
Units: months
arithmetic mean (standard deviation)	2.1 ± 0.3	2.1 ± 0.2	-
Gender categorical
Units: Subjects
Female	45	39	84
Male	46	50	96

End points

Top of page

Reporting group title

13vPnC: Infant Series

Reporting group description

Reporting group title

7vPnC: Infant Series

Reporting group description

Reporting group title

13vPnC: After the Infant Series

Reporting group description

Reporting group title

7vPnC: After the Infant Series

Reporting group description

Reporting group title

13vPnC: Toddler Dose

Reporting group description

13vPnC dose administered IM at 12 months of age (toddler dose).

Reporting group title

7vPnC: Toddler Dose

Reporting group description

7vPnC dose administered IM at 12 months of age (toddler dose).

Primary: Percentage of Subjects Achieving a Serotype-specific Immunoglobulin G (IgG) Antibody Level Greater Than or Equal to (>=) 0.35 Micrograms Per Milliliter (Mcg/mL) Measured 1 Month After the Infant Series

Top of page

End point title

Percentage of Subjects Achieving a Serotype-specific Immunoglobulin G (IgG) Antibody Level Greater Than or Equal to (>=) 0.35 Micrograms Per Milliliter (Mcg/mL) Measured 1 Month After the Infant Series ^[1]

End point description

Percentage of subjects achieving predefined antibody threshold ≥0.35 Mcg/mL along with the corresponding 95 percent (%) confidence interval (CI) was calculated for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A). Evaluable Infant Immunogenicity population: subjects who were 41 to 99 days of age (inclusive) on the day of the first vaccination, who had treatments as randomized (all expected doses) and at least 1 valid and determinate assay result for proposed analysis and no major protocol violation.

End point type

Primary

End point timeframe

1 month after the infant series (7 months of age)

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

End point values	13vPnC: Infant Series	7vPnC: Infant Series
Number of subjects analysed	83	85
Units: percentage of subjects
number (confidence interval 95%)
Serotype 4	100 (95.7 to 100)	100 (95.8 to 100)
Serotype 6B	98.8 (93.5 to 100)	100 (95.8 to 100)
Serotype 9V	100 (95.7 to 100)	100 (95.8 to 100)
Serotype 14	100 (95.7 to 100)	100 (95.8 to 100)
Serotype 18C	100 (95.7 to 100)	100 (95.8 to 100)
Serotype 19F	97.6 (95.7 to 100)	98.8 (93.6 to 100)
Serotype 23F	98.8 (91.6 to 99.7)	98.8 (93.6 to 100)
Serotype 1	100 (93.5 to 100)	2.4 (0.3 to 8.2)
Serotype 3	100 (95.7 to 100)	2.4 (0.3 to 8.2)
Serotype 5	100 (95.7 to 100)	57.5 (45.9 to 68.5)
Serotype 6A	97.6 (95.7 to 100)	72.3 (61.4 to 81.6)
Serotype 7F	100 (91.6 to 99.7)	4.8 (1.3 to 11.7)
Serotype 19A	100 (95.7 to 100)	100 (95.6 to 100)

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving a Serotype-specific IgG Antibody Level (>=) 0.35 Mcg/mL Measured 1 Month After the Toddler Dose

Top of page

End point title

Percentage of Subjects Achieving a Serotype-specific IgG Antibody Level (>=) 0.35 Mcg/mL Measured 1 Month After the Toddler Dose

End point description

Percentage of subjects achieving predefined antibody threshold ≥0.35Mcg/mL along with the corresponding 95% CI was calculated for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A). Exact 2-sided CI was based on the observed percentage of subjects. Evaluable Toddler Immunogenicity population:41-99 days old inclusive on day of first vaccination, 365-395 days old inclusive at toddler dose, had all treatments as randomized, blood drawn within specified timeframes, at least 1 valid and determinate assay result for proposed analysis, and no major protocol violations.

End point type

Secondary

End point timeframe

1 month after the toddler dose (13 months of age)

End point values	13vPnC: Toddler Dose	7vPnC: Toddler Dose
Number of subjects analysed	80	84
Units: percentage of subjects
number (confidence interval 95%)
Serotype 4	100 (95.5 to 100)	100 (95.7 to 100)
Serotype 6B	100 (95.5 to 100)	100 (95.7 to 100)
Serotype 9V	100 (95.5 to 100)	100 (95.7 to 100)
Serotype 14	98.7 (93.1 to 100)	100 (95.7 to 100)
Serotype 18C	100 (95.5 to 100)	100 (95.7 to 100)
Serotype 19F	100 (95.5 to 100)	100 (95.7 to 100)
Serotype 23F	100 (95.5 to 100)	100 (95.7 to 100)
Serotype 1	100 (95.5 to 100)	1.3 (0 to 6.9)
Serotype 3	100 (95.5 to 100)	12 (5.9 to 21)
Serotype 5	100 (95.5 to 100)	92.4 (84.2 to 97.2)
Serotype 6A	98.8 (93.2 to 100)	100 (95.7 to 100)
Serotype 7F	100 (95.4 to 100)	23.6 (13.2 to 37)
Serotype 19A	100 (95.5 to 100)	98.8 (93.5 to 100)

No statistical analyses for this end point

Other pre-specified: Geometric Mean Concentration (GMC) of Serotype-specific IgG Antibody 1 Month After the Infant Series

Top of page

End point title

Geometric Mean Concentration (GMC) of Serotype-specific IgG Antibody 1 Month After the Infant Series

End point description

Antibody GMC along with corresponding 2-sided 95% CI for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. Geometric mean concentrations (GMCs) were calculated using all subjects with available data for the specified blood draw. Evaluable Infant Immunogenicity Population.

End point type

Other pre-specified

End point timeframe

1 month after the infant series (7 months of age)

End point values	13vPnC: Infant Series	7vPnC: Infant Series
Number of subjects analysed	83	85
Units: Mcg/mL (micrograms per milliliter)
geometric mean (confidence interval 95%)
Serotype 4	5.4 (4.62 to 6.3)	6.97 (5.94 to 8.18)
Serotype 6B	5.71 (4.64 to 7.03)	4.88 (3.96 to 6.01)
Serotype 9V	3.33 (2.9 to 3.83)	3.78 (3.31 to 4.33)
Serotype 14	14.83 (12.38 to 17.77)	16.29 (13.36 to 19.85)
Serotype 18C	4.57 (3.98 to 5.24)	4.73 (4.09 to 5.47)
Serotype 19F	3.88 (3.18 to 4.72)	4.2 (3.55 to 4.96)
Serotype 23F	4.29 (3.56 to 5.16)	4.11 (3.4 to 4.98)
Serotype 1	7.44 (6.25 to 8.85)	0.02 (0.02 to 0.03)
Serotype 3	1.6 (1.35 to 1.89)	0.04 (0.03 to 0.05)
Serotype 5	5.06 (4.37 to 5.85)	0.39 (0.3 to 0.49)
Serotype 6A	5.73 (4.64 to 7.07)	0.64 (0.49 to 0.82)
Serotype 7F	6.97 (6.07 to 8)	0.04 (0.03 to 0.05)
Serotype 19A	5.94 (5.13 to 6.89)	2.65 (2.29 to 3.06)

Serotype 4

Statistical analysis description

Ratio of geometric means (13vPnC, 7vPnC).Geometric mean ratio computed from back transformation using Student t distribution for the mean difference of the measures on the log scale. CI for the ratio were back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC, 7vPnC).

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

0.97

Serotype 6B

Statistical analysis description

Ratio of geometric means (13vPnC, 7vPnC). Geometric mean ratio computed from back transformation using Student t distribution for the mean difference of the measures on the log scale. CI for the ratio were back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC, 7vPnC).

Comparison groups

7vPnC: Infant Series v 13vPnC: Infant Series

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

1.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.57

Serotype 9V

Statistical analysis description

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.07

Serotype 14

Statistical analysis description

Comparison groups

7vPnC: Infant Series v 13vPnC: Infant Series

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.19

Serotype 18C

Statistical analysis description

Ratio of geometric means (13vPnC, 7vPnC). Geometric mean ratio computed from back transformation using Student t distribution for the mean difference of the measures on the log scale. CI for the ratio were back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC, 7vPnC).

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.18

Serotype 19F

Statistical analysis description

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.19

Serotype 23F

Statistical analysis description

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.36

Serotype 1

Statistical analysis description

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

329.44

Confidence interval

level

95%

sides

2-sided

lower limit

242.98

upper limit

446.67

Serotype 3

Statistical analysis description

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

40.79

Confidence interval

level

95%

sides

2-sided

lower limit

30.27

upper limit

54.97

Serotype 5

Statistical analysis description

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

13.12

Confidence interval

level

95%

sides

2-sided

lower limit

9.92

upper limit

17.34

Serotype 6A

Statistical analysis description

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

9.01

Confidence interval

level

95%

sides

2-sided

lower limit

6.46

upper limit

12.56

Serotype 7F

Statistical analysis description

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

165.9

Confidence interval

level

95%

sides

2-sided

lower limit

122.95

upper limit

223.85

Serotype 19A

Statistical analysis description

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

168

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

2.24

Confidence interval

level

95%

sides

2-sided

lower limit

1.83

upper limit

2.75

Other pre-specified: Geometric Mean Concentration (GMC) of Serotype-specific IgG Antibody 1 Month After the Toddler Dose

Top of page

End point title

Geometric Mean Concentration (GMC) of Serotype-specific IgG Antibody 1 Month After the Toddler Dose

End point description

End point type

Other pre-specified

End point timeframe

1 month after the Toddler Dose (13 months of age)

End point values	13vPnC: Toddler Dose	7vPnC: Toddler Dose
Number of subjects analysed	80	84
Units: Mcg/mL
geometric mean (confidence interval 95%)
Serotype 4	6.46 (5.29 to 7.9)	8.25 (6.88 to 9.89)
Serotype 6B	16.81 (14.36 to 19.68)	15.14 (11.91 to 19.25)
Serotype 9V	4.59 (3.91 to 5.38)	4.83 (4.12 to 5.67)
Serotype 14	11.51 (9.59 to 13.8)	15.64 (13.07 to 18.72)
Serotype 18C	6.86 (5.67 to 8.29)	7.44 (6.27 to 8.83)
Serotype 19F	7.75 (6.3 to 9.53)	5.35 (4.52 to 6.33)
Serotype 23F	10.95 (8.77 to 13.66)	10.44 (8.6 to 12.68)
Serotype 1	9.29 (7.65 to 11.28)	0.04 (0.03 to 0.05)
Serotype 3	1.65 (1.4 to 1.95)	0.1 (0.08 to 0.13)
Serotype 5	8.92 (7.62 to 10.45)	1.31 (1.09 to 1.56)
Serotype 6A	13.58 (11.28 to 16.36)	3.33 (2.67 to 4.14)
Serotype 7F	11.17 (9.33 to 13.37)	0.1 (0.07 to 0.14)
Serotype 19A	10.12 (8.55 to 11.98)	2.38 (2.04 to 2.78)

Serotype 4

Statistical analysis description

Ratio of geometric means (13vPnC, 7vPnC). Geometric mean ratio computed from back transformation using Student t distribution for the mean difference of the measures on the log scale. CI for the ratio were back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC, 7vPnC).

Comparison groups

7vPnC: Toddler Dose v 13vPnC: Toddler Dose

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.02

Serotype 6B

Statistical analysis description

Ratio of geometric means (13vPnC, 7vPnC). Geometric mean ratio computed from back transformation using Student t distribution for the mean difference of the measures on the log scale. CI for the ratio were back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC, 7vPnC).

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.48

Serotype 9V

Statistical analysis description

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.19

Serotype 14

Statistical analysis description

Ratio of geometric means (13vPnC, 7vPnC). Geometric mean ratio computed from back transformation using Student t distribution for the mean difference of the measures on the log scale. CI for the ratio were back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC, 7vPnC).

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

0.95

Serotype 18C

Statistical analysis description

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.19

Serotype 19F

Statistical analysis description

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

1.45

Confidence interval

level

95%

sides

2-sided

lower limit

1.11

upper limit

1.88

Serotype 23F

Statistical analysis description

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

1.05

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.4

Serotype 1

Statistical analysis description

Ratio of geometric means (13vPnC, 7vPnC). Geometric mean ratio computed from back transformation using Student t distribution for the mean difference of the measures on the log scale. CI for the ratio were back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC, 7vPnC).

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

234.33

Confidence interval

level

95%

sides

2-sided

lower limit

176.33

upper limit

311.41

Serotype 3

Statistical analysis description

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

16.63

Confidence interval

level

95%

sides

2-sided

lower limit

12.19

upper limit

22.69

Serotype 5

Statistical analysis description

Ratio of geometric means (13vPnC, 7vPnC). Geometric mean ratio computed from back transformation using Student t distribution for the mean difference of the measures on the log scale. CI for the ratio were back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC, 7vPnC).

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

6.84

Confidence interval

level

95%

sides

2-sided

lower limit

5.39

upper limit

8.67

Serotype 6A

Statistical analysis description

Ratio of geometric means (13vPnC, 7vPnC). Geometric mean ratio computed from back transformation using Student t distribution for the mean difference of the measures on the log scale. CI for the ratio were back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC, 7vPnC).

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

4.08

Confidence interval

level

95%

sides

2-sided

lower limit

3.07

upper limit

5.43

Serotype 7F

Statistical analysis description

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

110.92

Confidence interval

level

95%

sides

2-sided

lower limit

77.09

upper limit

159.59

Serotype 19A

Statistical analysis description

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

other

Method

Student t distribution

Parameter type

Ratio of geometric means

Point estimate

4.25

Confidence interval

level

95%

sides

2-sided

lower limit

3.39

upper limit

5.33

Other pre-specified: Percentage of Subjects Reporting Pre-specified Local Reactions: Infant Series Dose 1 (2 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-specified Local Reactions: Infant Series Dose 1 (2 Months of Age)

End point description

Pre-specified local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Swelling and redness were scaled as Any (swelling or redness present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (greater than [>] 7.0 cm). Subjects may be represented in more than 1 category. Safety population: All subjects who received at least 1 dose of the study vaccine. Here "n" = number of subjects reporting the specific characteristic.

End point type

Other pre-specified

End point timeframe

Within 4 days after dose 1 (2 months of age)

End point values	13vPnC: Infant Series	7vPnC: Infant Series
Number of subjects analysed	75 ^[2]	79 ^[3]
Units: percentage of subjects
number (not applicable)
Tenderness: Any (n=23,26)	31.9	34.2
Tenderness: Significant (n=6,2)	8.8	2.8
Swelling: Any (n=14,18)	19.7	24.7
Swelling: Mild (n=8,18)	11.6	24.7
Swelling: Moderate (n=7,4)	10.1	5.7
Redness: Any (n=27,22)	37.5	29.3
Redness: Mild (n=23,19)	32.9	25.3
Redness: Moderate (n=4,3)	5.8	4.3

Notes
[2] - N = Number of subjects reporting yes for at least 1 day or no for all days
[3] - N = Number of subjects reporting yes for at least 1 day or no for all days

Tenderness: Any

Statistical analysis description

Comparison between treatments for any tenderness.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.862

Method

Fisher exact

Confidence interval

Tenderness: Significant

Statistical analysis description

Comparison between treatments for significant tenderness.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.157

Method

Fisher exact

Confidence interval

Swelling: Any

Statistical analysis description

Comparison between treatments for any swelling.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.55

Method

Fisher exact

Confidence interval

Swelling: Mild

Statistical analysis description

Comparison between treatments for mild swelling.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.052

Method

Fisher exact

Confidence interval

Swelling: Moderate

Statistical analysis description

Comparison between treatments for moderate swelling.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.366

Method

Fisher exact

Confidence interval

Redness: Any

Statistical analysis description

Comparison between treatments for any redness.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.301

Method

Fisher exact

Confidence interval

Redness: Mild

Statistical analysis description

Comparison between treatments for mild redness.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.362

Method

Fisher exact

Confidence interval

Redness: Moderate

Statistical analysis description

Comparison between treatments for moderate redness.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

154

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.718

Method

Fisher exact

Confidence interval

Other pre-specified: Percentage of Subjects Reporting Pre-specified Local Reactions: Infant Series Dose 2 (4 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-specified Local Reactions: Infant Series Dose 2 (4 Months of Age)

End point description

Pre-specified local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Swelling and redness were scaled as Any (swelling or redness present); Mild (0.5 cm to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (>7.0 cm). Subjects may be represented in more than 1 category. Safety; Here "n" = number of subjects reporting the specific characteristic.

End point type

Other pre-specified

End point timeframe

Within 4 days after dose 2 (4 months of age)

End point values	13vPnC: Infant Series	7vPnC: Infant Series
Number of subjects analysed	62 ^[4]	68 ^[5]
Units: percentage of subjects
number (not applicable)
Tenderness: Any (n=23,24)	38.3	37.5
Tenderness: Significant (n=0,3)	0	5
Swelling: Any (n=22,18)	35.5	28.6
Swelling: Mild (n=18,15)	29.5	24.6
Swelling: Moderate (n=4,4)	7.1	6.6
Redness: Any (n=20,25)	32.8	38.5
Redness: Mild (n=18,24)	29.5	36.9
Redness: Moderate (n=4,3)	7.1	5.1

Notes
[4] - N = Number of subjects reporting yes for at least 1 day or no for all days
[5] - N = Number of subjects reporting yes for at least 1 day or no for all days

Tenderness: Any

Statistical analysis description

Comparison between treatments for any tenderness.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

> 0.99

Method

Fisher exact

Confidence interval

Tenderness: Significant

Statistical analysis description

Comparison between treatments for significant tenderness.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.245

Method

Fisher exact

Confidence interval

Swelling: Any

Statistical analysis description

Comparison between treatments for any swelling.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.447

Method

Fisher exact

Confidence interval

Swelling: Mild

Statistical analysis description

Comparison between treatments for mild swelling.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.684

Method

Fisher exact

Confidence interval

Swelling: Moderate

Statistical analysis description

Comparison between treatments for moderate swelling.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

> 0.99

Method

Fisher exact

Confidence interval

Redness: Any

Statistical analysis description

Comparison between treatments for any redness.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.578

Method

Fisher exact

Confidence interval

Redness: Mild

Statistical analysis description

Comparison between treatments for mild redness.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.451

Method

Fisher exact

Confidence interval

Redness: Moderate

Statistical analysis description

Comparison between treatments for moderate redness.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.712

Method

Fisher exact

Confidence interval

Other pre-specified: Percentage of Subjects Reporting Pre-specified Local Reactions: Infant Series Dose 3 (6 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-specified Local Reactions: Infant Series Dose 3 (6 Months of Age)

End point description

Pre-specified local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Swelling and redness were scaled as Any (swelling or redness present); Mild (0.5 cm to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (>7.0 cm). Subjects may be represented in more than 1 category. Safety; Here "n" = number of subjects reporting the specific characteristic.

End point type

Other pre-specified

End point timeframe

Within 4 days after dose 3 (6 months of age)

End point values	13vPnC: Infant Series	7vPnC: Infant Series
Number of subjects analysed	66 ^[6]	64 ^[7]
Units: percentage of subjects
number (not applicable)
Tenderness: Any (n=15,16)	23.4	27.1
Tenderness: Significant (n=0,1)	0	1.9
Swelling: Any (n=18,14)	27.7	23.3
Swelling: Mild (n=13,13)	21	22
Swelling: Moderate (n=7,4)	11.3	7
Redness: Any (n=19,16)	30.2	26.2
Redness: Mild (n=12,15)	20	25
Redness: Moderate (n=7,3)	11.5	5.6

Notes
[6] - N = Number of subjects reporting yes for at least 1 day or no for all days
[7] - N = Number of subjects reporting yes for at least 1 day or no for all days

Tenderness: Any

Statistical analysis description

Comparison between treatments for any tenderness.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.681

Method

Fisher exact

Confidence interval

Tenderness: Significant

Statistical analysis description

Comparison between treatments for significant tenderness.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.482

Method

Fisher exact

Confidence interval

Swelling: Any

Statistical analysis description

Comparison between treatments for any swelling.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.683

Method

Fisher exact

Confidence interval

Swelling: Mild

Statistical analysis description

Comparison between treatments for mild swelling.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

> 0.99

Method

Fisher exact

Confidence interval

Swelling: Moderate

Statistical analysis description

Comparison between treatments for moderate swelling.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.533

Method

Fisher exact

Confidence interval

Redness: Any

Statistical analysis description

Comparison between treatments for any redness.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.692

Method

Fisher exact

Confidence interval

Redness: Mild

Statistical analysis description

Comparison between treatments for mild redness.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.662

Method

Fisher exact

Confidence interval

Redness: Moderate

Statistical analysis description

Comparison between treatments for moderate redness.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.331

Method

Fisher exact

Confidence interval

Other pre-specified: Percentage of Subjects Reporting Pre-specified Local Reactions: Toddler Dose (12 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-specified Local Reactions: Toddler Dose (12 Months of Age)

End point description

Pre-specified local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Swelling and redness were scaled as Any (swelling or redness present); Mild (0.5 cm to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (>7.0 cm). Subjects may be represented in more than 1 category. Safety; Here "n" = number of participants reporting the specific characteristic.

End point type

Other pre-specified

End point timeframe

Within 4 days after toddler dose (12 months of age)

End point values	13vPnC: Toddler Dose	7vPnC: Toddler Dose
Number of subjects analysed	57 ^[8]	57 ^[9]
Units: percentage of subjects
number (not applicable)
Tenderness: Any (n=19,14)	33.9	25.9
Tenderness: Significant (n=3,1)	5.9	2
Swelling: Any (n=11,10)	22.4	18.9
Swelling: Mild (n=4,7)	8.2	13.5
Swelling: Moderate (n=9,4)	18.4	7.8
Swelling: Severe (n=1,0)	2	0
Redness: Any (n=15,12)	28.8	22.2
Redness: Mild (n=9,10)	17.6	18.5
Redness: Moderate (n=8,3)	16	6

Notes
[8] - N = Number of subjects reporting yes for at least 1 day or no for all days
[9] - N = Number of subjects reporting yes for at least 1 day or no for all days

Tenderness: Any

Statistical analysis description

Comparison between treatments for any tenderness.

Comparison groups

7vPnC: Toddler Dose v 13vPnC: Toddler Dose

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.409

Method

Fisher exact

Confidence interval

Tenderness: Significant

Statistical analysis description

Comparison between treatments for significant tenderness.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.617

Method

Fisher exact

Confidence interval

Swelling: Any

Statistical analysis description

Comparison between treatments for any swelling.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.807

Method

Fisher exact

Confidence interval

Swelling: Mild

Statistical analysis description

Comparison between treatments for mild swelling.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.527

Method

Fisher exact

Confidence interval

Swelling: Moderate

Statistical analysis description

Comparison between treatments for moderate swelling.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.144

Method

Fisher exact

Confidence interval

Swelling: Severe

Statistical analysis description

Comparison between treatments for severe swelling.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.495

Method

Fisher exact

Confidence interval

Redness: Any

Statistical analysis description

Comparison between treatments for any redness.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.506

Method

Fisher exact

Confidence interval

Redness: Mild

Statistical analysis description

Comparison between treatments for mild redness.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

other

P-value

> 0.99

Method

Fisher exact

Confidence interval

Redness: Moderate

Statistical analysis description

Comparison between treatments for moderate redness.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2

Method

Fisher exact

Confidence interval

Other pre-specified: Percentage of Subjects Reporting Pre-specified Systemic Events: Infant Series Dose 1 (2 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-specified Systemic Events: Infant Series Dose 1 (2 Months of Age)

End point description

Pre-specified systemic events (any fever ≥ 38 degrees Celsius [C], decreased appetite, irritability, increased sleep, and decreased sleep) were reported using an electronic diary. Subjects may be represented in more than 1 category. Safety; Here "n" = number of subjects reporting the event.

End point type

Other pre-specified

End point timeframe

Within 4 days after dose 1 (2 months of age)

End point values	13vPnC: Infant Series	7vPnC: Infant Series
Number of subjects analysed	83 ^[10]	86 ^[11]
Units: percentage of subjects
number (not applicable)
Fever ≥38 degrees C but ≤39 degrees C (n=11,9)	15.9	12.5
Decreased appetite (n=23,22)	32.4	28.9
Irritability (n=38,56)	49.4	70.9
Increased sleep (n=37,30)	49.3	39
Decreased sleep (n=28,38)	37.8	50

Notes
[10] - N = Number of subjects reporting yes for at least 1 day or no for all days
[11] - N = Number of subjects reporting yes for at least 1 day or no for all days

Fever ≥38 degrees C but ≤39 degrees C

Statistical analysis description

Comparison between treatments for fever ≥38 degrees C but but less than or equal to (≤)39 degrees C.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.633

Method

Fisher exact

Confidence interval

Decreased appetite

Statistical analysis description

Comparison between treatments for decreased appetite.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.721

Method

Fisher exact

Confidence interval

Irritability

Statistical analysis description

Comparison between treatments for irritability.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.009

Method

Fisher exact

Confidence interval

Increased sleep

Statistical analysis description

Comparison between treatments for increased sleep.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.253

Method

Fisher exact

Confidence interval

Decreased sleep

Statistical analysis description

Comparison between treatments for decreased sleep.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.143

Method

Fisher exact

Confidence interval

Other pre-specified: Percentage of Subjects Reporting Pre-specified Systemic Events: Infant Series Dose 2 (4 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-specified Systemic Events: Infant Series Dose 2 (4 Months of Age)

End point description

End point type

Other pre-specified

End point timeframe

Within 4 days after dose 2 (4 months of age)

End point values	13vPnC: Infant Series	7vPnC: Infant Series
Number of subjects analysed	64 ^[12]	72 ^[13]
Units: percentage of subjects
number (not applicable)
Fever ≥38 degrees C but ≤39 degrees C (n=6,8)	10.9	13.1
Decreased appetite (n=16,28)	27.1	44.4
Irritability (n=25,36)	40.3	53.7
Increased sleep (n=17,16)	28.8	26.2
Decreased sleep (n=18,27)	30	40.9

Notes
[12] - N = Number of subjects reporting yes for at least 1 day or no for all days
[13] - N = Number of subjects reporting yes for at least 1 day or no for all days

Fever ≥38 degrees C but ≤39 degrees C

Statistical analysis description

Comparison between treatments for fever ≥38 degrees C but ≤39 degrees C.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.781

Method

Fisher exact

Confidence interval

Decreased appetite

Statistical analysis description

Comparison between treatments for decreased appetite.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.06

Method

Fisher exact

Confidence interval

Irritability

Statistical analysis description

Comparison between treatments for irritability.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.159

Method

Fisher exact

Confidence interval

Increased sleep

Statistical analysis description

Comparison between treatments for increased sleep.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.839

Method

Fisher exact

Confidence interval

Decreased sleep

Statistical analysis description

Comparison between treatments for decreased sleep.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.264

Method

Fisher exact

Confidence interval

Other pre-specified: Percentage of Subjects Reporting Pre-specified Systemic Events: Infant Series Dose 3 (6 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-specified Systemic Events: Infant Series Dose 3 (6 Months of Age)

End point description

End point type

Other pre-specified

End point timeframe

Within 4 days after dose 3 (6 months of age)

End point values	13vPnC: Infant Series	7vPnC: Infant Series
Number of subjects analysed	65 ^[14]	64 ^[15]
Units: percentage of subjects
number (not applicable)
Fever ≥38 degrees C but ≤39 degrees C (n=8,5)	13.6	9.3
Fever >39 degrees C but ≤40 degrees C (n=0,1)	0	2
Decreased appetite (n=14,16)	23	28.1
Irritability (n=13,25)	21	41.7
Increased sleep (n=18,12)	29.5	21.1
Decreased sleep (n=10,17)	16.4	29.3

Notes
[14] - N = Number of subjects reporting yes for at least 1 day or no for all days
[15] - N = Number of subjects reporting yes for at least 1 day or no for all days

Fever ≥38 degrees C but ≤39 degrees C

Statistical analysis description

Comparison between treatments for fever ≥38 degrees C but ≤39 degrees C.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.563

Method

Fisher exact

Confidence interval

Fever >39 degrees C but ≤40 degrees C

Statistical analysis description

Comparison between treatments for fever >39 degrees C but ≤40 degrees C.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.468

Method

Fisher exact

Confidence interval

Decreased appetite

Statistical analysis description

Comparison between treatments for decreased appetite.

Comparison groups

7vPnC: Infant Series v 13vPnC: Infant Series

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.535

Method

Fisher exact

Confidence interval

Irritability

Statistical analysis description

Comparison between treatments for irritability.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.019

Method

Fisher exact

Confidence interval

Increased sleep

Statistical analysis description

Comparison between treatments for increased sleep.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.398

Method

Fisher exact

Confidence interval

Decreased sleep

Statistical analysis description

Comparison between treatments for decreased sleep.

Comparison groups

13vPnC: Infant Series v 7vPnC: Infant Series

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.125

Method

Fisher exact

Confidence interval

Other pre-specified: Percentage of Subjects Reporting Pre-specified Systemic Events: Toddler Dose (12 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-specified Systemic Events: Toddler Dose (12 Months of Age)

End point description

End point type

Other pre-specified

End point timeframe

Within 4 days after toddler dose (12 months of age)

End point values	13vPnC: Toddler Dose	7vPnC: Toddler Dose
Number of subjects analysed	64 ^[16]	65 ^[17]
Units: percentage of subjects
number (not applicable)
Fever ≥38 degrees C but ≤39 degrees C (n=7,10)	13.7	19.6
Fever >39 degrees C but ≤40 degrees C (n=1,0)	2	0
Decreased appetite (n=13,15)	22.8	27.8
Irritability (n=18,21)	30.5	37.5
Increased sleep (n=11,8)	21.2	15.4
Decreased sleep (n=11,20)	20.4	34.5

Notes
[16] - N = Number of subjects reporting yes for at least 1 day or no for all days
[17] - N = Number of subjects reporting yes for at least 1 day or no for all days

Fever ≥38 degrees C but ≤39 degrees C

Statistical analysis description

Comparison between treatments for fever ≥38 degrees C but ≤39 degrees C.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.596

Method

Fisher exact

Confidence interval

Fever >39 degrees C but ≤40 degrees C

Statistical analysis description

Comparison between treatments for fever >39 degrees C but ≤40 degrees C.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other

P-value

> 0.99

Method

Fisher exact

Confidence interval

Decreased appetite

Statistical analysis description

Comparison between treatments for decreased appetite.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.633

Method

Fisher exact

Confidence interval

Irritability

Statistical analysis description

Comparison between treatments for irritability.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.439

Method

Fisher exact

Confidence interval

Increased sleep

Statistical analysis description

Comparison between treatments for increased sleep.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.613

Method

Fisher exact

Confidence interval

Decreased sleep

Statistical analysis description

Comparison between treatments for decreased sleep.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.138

Method

Fisher exact

Confidence interval

Adverse events

Top of page

Timeframe for reporting adverse events

Baseline through 1 Month after last study vaccination (13 Months). Local reactions and systemic events assessed within 4 days of dose: Infant Series Dose 1=2 months of age; Dose 2=4 months of age; Dose 3=6 months of age; Toddler Dose=12 months of age.

Adverse event reporting additional description

An Adverse Event (AE) term may be reported as both serious and non-serious AE, but are distinct events.AE may=serious for 1 subject and=non-serious for another subject or may have experienced both a serious and non-serious episode of the same event. LR & SE to be assessed only for infant series and toddler dose groups. For MedDRA V 0.0 is captured.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

0.0

Reporting group title

Infant Series 13vPnC

Reporting group description

Each subject was to receive 13vPnC 0.5 mL dose administered IM at each of the 3 vaccination visits (2, 4, and 6-month visits). DTaP was to be administered concomitantly with 13vPnC at 2, 4, and 6 months of age. In addition, IPV and Hib vaccine were to be administered 7 to 21 days after each dose of 13vPnC during the infant series, and HBV was administered 7 to 21 days after dose 3.

Reporting group title

Infant Series 7vPnC

Reporting group description

Each subject was to receive 7vPnC 0.5 mL dose administered IM at at each of the 3 vaccination visits (2, 4, and 6-month visits). DTaP was to be administered concomitantly with 7vPnC at 2, 4, and 6 months of age. In addition, IPV and Hib vaccine were to be administered 7 to 21 days after each dose of 7vPnC during the infant series, HBV was administered 7 to 21 days after dose 3.

Reporting group title

After the Infant Series 13vPnC

Reporting group description

Reporting group title

After the Infant Series 7vPnC

Reporting group description

Reporting group title

Toddler Dose 13vPnC

Reporting group description

13vPnC 0.5mL dose administered IM at 12 months of age (toddler dose).

Reporting group title

Toddler Dose 7vPnC

Reporting group description

7vPnC 0.5mL dose administered IM at 12 months of age (toddler dose).

Serious adverse events	Infant Series 13vPnC	Infant Series 7vPnC	After the Infant Series 13vPnC	After the Infant Series 7vPnC	Toddler Dose 13vPnC	Toddler Dose 7vPnC
Total subjects affected by serious adverse events
subjects affected / exposed	8 / 88 (9.09%)	9 / 89 (10.11%)	9 / 88 (10.23%)	12 / 89 (13.48%)	3 / 84 (3.57%)	3 / 88 (3.41%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Nervous system disorders
Convulsion
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Soft tissue inflammation
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	1 / 88 (1.14%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hepatitis
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchiolitis
subjects affected / exposed	2 / 88 (2.27%)	4 / 89 (4.49%)	1 / 88 (1.14%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 4	0 / 1	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	3 / 88 (3.41%)	1 / 89 (1.12%)	1 / 88 (1.14%)	1 / 89 (1.12%)	1 / 84 (1.19%)	1 / 88 (1.14%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 1	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 88 (0.00%)	2 / 89 (2.25%)	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	1 / 88 (1.14%)	1 / 89 (1.12%)	1 / 84 (1.19%)	1 / 88 (1.14%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopneumonia
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	3 / 88 (3.41%)	2 / 89 (2.25%)	1 / 84 (1.19%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Kawasaki's disease
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media acute
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 88 (1.14%)	3 / 89 (3.37%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Herpangina
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 88 (1.14%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Adenovirus infection
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Exanthema subitum
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hand-foot-and-mouth
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rhinitis
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	1 / 88 (1.14%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Infant Series 13vPnC	Infant Series 7vPnC	After the Infant Series 13vPnC	After the Infant Series 7vPnC	Toddler Dose 13vPnC	Toddler Dose 7vPnC
Total subjects affected by non serious adverse events
subjects affected / exposed	78 / 88 (88.64%)	75 / 89 (84.27%)	18 / 88 (20.45%)	19 / 89 (21.35%)	35 / 84 (41.67%)	41 / 88 (46.59%)
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	8 / 88 (9.09%)	4 / 89 (4.49%)	0 / 88 (0.00%)	1 / 89 (1.12%)	3 / 84 (3.57%)	2 / 88 (2.27%)
occurrences all number	8	4	0	1	3	2
Injection site erythema
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Injection site induration
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Irritability
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Fever ≥ 38 degrees C but ≤ 39 degrees C: Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[1]	11 / 69 (15.94%)	9 / 72 (12.50%)	0 / 88 (0.00%)	0 / 89 (0.00%)	7 / 51 (13.73%)	10 / 51 (19.61%)
occurrences all number	11	9	0	0	7	10
Fever ≥ 38 degrees C but ≤ 39 degrees C: Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[2]	6 / 55 (10.91%)	8 / 61 (13.11%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	6	8	0	0	0	0
Fever ≥ 38 degrees C but ≤ 39 degrees C: Infant Series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[3]	8 / 59 (13.56%)	5 / 54 (9.26%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	8	5	0	0	0	0
Fever > 39 degrees C but ≤ 40 degrees C: Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[4]	0 / 67 (0.00%)	0 / 70 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 50 (2.00%)	0 / 49 (0.00%)
occurrences all number	0	0	0	0	1	0
Fever > 39 degrees C but ≤ 40 degrees C: Infant Series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[5]	0 / 58 (0.00%)	1 / 51 (1.96%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Decreased appetite: Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[6]	23 / 71 (32.39%)	22 / 76 (28.95%)	0 / 88 (0.00%)	0 / 89 (0.00%)	13 / 57 (22.81%)	15 / 54 (27.78%)
occurrences all number	23	22	0	0	13	15
Decreased appetite: Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[7]	16 / 59 (27.12%)	28 / 63 (44.44%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	16	28	0	0	0	0
Decreased appetite: Infant Series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[8]	14 / 61 (22.95%)	16 / 57 (28.07%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	14	16	0	0	0	0
Irritability: Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[9]	38 / 77 (49.35%)	56 / 79 (70.89%)	0 / 88 (0.00%)	0 / 89 (0.00%)	18 / 59 (30.51%)	21 / 56 (37.50%)
occurrences all number	38	56	0	0	18	21
Irritability: Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[10]	25 / 62 (40.32%)	36 / 67 (53.73%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	25	36	0	0	0	0
Irritability: Infant Series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[11]	13 / 62 (20.97%)	25 / 60 (41.67%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	13	25	0	0	0	0
Increased sleep: Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[12]	37 / 75 (49.33%)	30 / 77 (38.96%)	0 / 88 (0.00%)	0 / 89 (0.00%)	11 / 52 (21.15%)	8 / 52 (15.38%)
occurrences all number	37	30	0	0	11	8
Increased sleep: Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[13]	17 / 59 (28.81%)	16 / 61 (26.23%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	17	16	0	0	0	0
Increased sleep: Infant Series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[14]	18 / 61 (29.51%)	12 / 57 (21.05%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	18	12	0	0	0	0
Decreased sleep: Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[15]	28 / 74 (37.84%)	38 / 76 (50.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	11 / 54 (20.37%)	20 / 58 (34.48%)
occurrences all number	28	38	0	0	11	20
Decreased sleep: Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[16]	18 / 60 (30.00%)	27 / 66 (40.91%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	18	27	0	0	0	0
Decreased sleep: Infant Series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[17]	10 / 61 (16.39%)	17 / 58 (29.31%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	10	17	0	0	0	0
Immune system disorders
Atopy
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Reproductive system and breast disorders
Perineal fistula
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	2	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
subjects affected / exposed	16 / 88 (18.18%)	16 / 89 (17.98%)	1 / 88 (1.14%)	2 / 89 (2.25%)	5 / 84 (5.95%)	0 / 88 (0.00%)
occurrences all number	18	20	1	2	5	0
Cough
subjects affected / exposed	11 / 88 (12.50%)	17 / 89 (19.10%)	2 / 88 (2.27%)	0 / 89 (0.00%)	2 / 84 (2.38%)	1 / 88 (1.14%)
occurrences all number	12	21	2	0	2	1
Productive cough
subjects affected / exposed	3 / 88 (3.41%)	2 / 89 (2.25%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	3	2	0	0	0	0
Nasal congestion
subjects affected / exposed	2 / 88 (2.27%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	3	1	0	0	0	0
Dyspnoea
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Grunting
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Wheezing
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 84 (1.19%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	1	0
Asthma
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 84 (1.19%)	0 / 88 (0.00%)
occurrences all number	0	0	0	0	1	0
Upper airway obstruction
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 84 (1.19%)	0 / 88 (0.00%)
occurrences all number	0	0	0	0	1	0
Psychiatric disorders
Insomnia
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Investigations
Urine output decreased
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Weight decreased
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Alanine aminotransferase increased
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	0	1	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	0	1	0	0	0
Injury, poisoning and procedural complications
Concussion
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Joint dislocation
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Joint sprain
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Mouth injury
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	0	0	1	0	0
Congenital, familial and genetic disorders
Hydrocele
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	0	1	0	0	0
Cardiac disorders
Supraventricular tachycardia
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Blood and lymphatic system disorders
Iron deficiency anaemia
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 88 (1.14%)	4 / 89 (4.49%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	0	1	4	0	0
Ear and labyrinth disorders
Middle ear effusion
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Otorrhoea
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Eye disorders
Conjunctivitis
subjects affected / exposed	4 / 88 (4.55%)	2 / 89 (2.25%)	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 84 (1.19%)	0 / 88 (0.00%)
occurrences all number	4	2	0	0	1	0
Dacryostenosis acquired
subjects affected / exposed	2 / 88 (2.27%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	2	0	0	0	0	0
Blepharitis
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Entropion
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Eye discharge
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	10 / 88 (11.36%)	10 / 89 (11.24%)	3 / 88 (3.41%)	0 / 89 (0.00%)	1 / 84 (1.19%)	1 / 88 (1.14%)
occurrences all number	12	11	3	0	1	1
Vomiting
subjects affected / exposed	2 / 88 (2.27%)	3 / 89 (3.37%)	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	3	4	0	1	0	0
Constipation
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	1 / 88 (1.14%)
occurrences all number	0	1	0	0	0	1
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Intussusception
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Regurgitation
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Anal fissure
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	0	0	1	0	0
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	8 / 88 (9.09%)	8 / 89 (8.99%)	2 / 88 (2.27%)	4 / 89 (4.49%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	8	9	2	4	0	0
Eczema
subjects affected / exposed	7 / 88 (7.95%)	3 / 89 (3.37%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	7	3	0	0	0	0
Dermatitis diaper
subjects affected / exposed	4 / 88 (4.55%)	2 / 89 (2.25%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	5	2	0	0	0	0
Rash
subjects affected / exposed	1 / 88 (1.14%)	6 / 89 (6.74%)	2 / 88 (2.27%)	0 / 89 (0.00%)	0 / 84 (0.00%)	1 / 88 (1.14%)
occurrences all number	1	6	2	0	0	1
Dermatitis
subjects affected / exposed	2 / 88 (2.27%)	3 / 89 (3.37%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	2	3	0	0	0	0
Urticaria
subjects affected / exposed	0 / 88 (0.00%)	3 / 89 (3.37%)	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	3	0	1	0	0
Heat rash
subjects affected / exposed	2 / 88 (2.27%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	1 / 88 (1.14%)
occurrences all number	2	0	0	0	0	1
Rash papular
subjects affected / exposed	1 / 88 (1.14%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	1	0	0	0	0
Skin erosion
subjects affected / exposed	1 / 88 (1.14%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	1	0	0	0	0
Dermal cyst
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Dermatitis allergic
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Eczema infantile
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Intertrigo
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Rash erythematous
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Rash vesicular
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Tenderness (any): Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[18]	23 / 72 (31.94%)	26 / 76 (34.21%)	0 / 88 (0.00%)	0 / 89 (0.00%)	19 / 56 (33.93%)	14 / 54 (25.93%)
occurrences all number	23	26	0	0	19	14
Tenderness (any); Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[19]	23 / 60 (38.33%)	24 / 64 (37.50%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	23	24	0	0	0	0
Tenderness (any): Infant Series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[20]	15 / 64 (23.44%)	16 / 59 (27.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	15	16	0	0	0	0
Tenderness (significant): Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[21]	6 / 68 (8.82%)	2 / 72 (2.78%)	0 / 88 (0.00%)	0 / 89 (0.00%)	3 / 51 (5.88%)	1 / 50 (2.00%)
occurrences all number	6	2	0	0	3	1
Tenderness (significant): Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[22]	0 / 55 (0.00%)	3 / 60 (5.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	3	0	0	0	0
Tenderness (significant): Infant Series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[23]	0 / 58 (0.00%)	1 / 54 (1.85%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Swelling (any): Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[24]	14 / 71 (19.72%)	18 / 73 (24.66%)	0 / 88 (0.00%)	0 / 89 (0.00%)	11 / 49 (22.45%)	10 / 53 (18.87%)
occurrences all number	14	18	0	0	11	10
Swelling (any): Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[25]	22 / 62 (35.48%)	18 / 63 (28.57%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	22	18	0	0	0	0
Swelling (any): Infant Series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[26]	18 / 65 (27.69%)	14 / 60 (23.33%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	18	14	0	0	0	0
Swelling (mild): Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[27]	8 / 69 (11.59%)	18 / 73 (24.66%)	0 / 88 (0.00%)	0 / 89 (0.00%)	4 / 49 (8.16%)	7 / 52 (13.46%)
occurrences all number	8	18	0	0	4	7
Swelling (mild): Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[28]	18 / 61 (29.51%)	15 / 61 (24.59%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	18	15	0	0	0	0
Swelling (mild): Infant Series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[29]	13 / 62 (20.97%)	13 / 59 (22.03%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	13	13	0	0	0	0
Swelling (moderate): Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[30]	7 / 69 (10.14%)	4 / 70 (5.71%)	0 / 88 (0.00%)	0 / 89 (0.00%)	9 / 49 (18.37%)	4 / 51 (7.84%)
occurrences all number	7	4	0	0	9	4
Swelling (moderate): Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[31]	4 / 56 (7.14%)	4 / 61 (6.56%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	4	4	0	0	0	0
Swelling (moderate): Infant Series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[32]	7 / 62 (11.29%)	4 / 57 (7.02%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	7	4	0	0	0	0
Swelling (severe): Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[33]	0 / 67 (0.00%)	0 / 70 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	1	0
Redness (any): Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[34]	27 / 72 (37.50%)	22 / 75 (29.33%)	0 / 88 (0.00%)	0 / 89 (0.00%)	15 / 52 (28.85%)	12 / 54 (22.22%)
occurrences all number	27	22	0	0	15	12
Redness (any): Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[35]	20 / 61 (32.79%)	25 / 65 (38.46%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	20	25	0	0	0	0
Redness (any): Infant Series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[36]	19 / 63 (30.16%)	16 / 61 (26.23%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	19	16	0	0	0	0
Redness (mild): Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[37]	23 / 70 (32.86%)	19 / 75 (25.33%)	0 / 88 (0.00%)	0 / 89 (0.00%)	9 / 51 (17.65%)	10 / 54 (18.52%)
occurrences all number	23	19	0	0	9	10
Redness (mild): Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[38]	18 / 61 (29.51%)	24 / 65 (36.92%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	18	24	0	0	0	0
Redness (mild): Infant Series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[39]	12 / 60 (20.00%)	15 / 60 (25.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	12	15	0	0	0	0
Redness (moderate): Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[40]	4 / 69 (5.80%)	3 / 70 (4.29%)	0 / 88 (0.00%)	0 / 89 (0.00%)	8 / 50 (16.00%)	3 / 50 (6.00%)
occurrences all number	4	3	0	0	8	3
Redness (moderate): Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[41]	4 / 56 (7.14%)	3 / 59 (5.08%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	4	3	0	0	0	0
Redness (moderate): Infant Series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[42]	7 / 61 (11.48%)	3 / 54 (5.56%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	7	3	0	0	0	0
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	24 / 88 (27.27%)	30 / 89 (33.71%)	3 / 88 (3.41%)	4 / 89 (4.49%)	7 / 84 (8.33%)	10 / 88 (11.36%)
occurrences all number	37	51	3	5	7	10
Bronchiolitis
subjects affected / exposed	17 / 88 (19.32%)	9 / 89 (10.11%)	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 84 (1.19%)	0 / 88 (0.00%)
occurrences all number	27	12	0	0	1	0
Nasopharyngitis
subjects affected / exposed	11 / 88 (12.50%)	17 / 89 (19.10%)	3 / 88 (3.41%)	0 / 89 (0.00%)	3 / 84 (3.57%)	9 / 88 (10.23%)
occurrences all number	13	20	3	0	3	10
Bronchitis
subjects affected / exposed	10 / 88 (11.36%)	10 / 89 (11.24%)	2 / 88 (2.27%)	1 / 89 (1.12%)	1 / 84 (1.19%)	2 / 88 (2.27%)
occurrences all number	12	16	3	1	1	2
Gastroenteritis
subjects affected / exposed	12 / 88 (13.64%)	7 / 89 (7.87%)	0 / 88 (0.00%)	0 / 89 (0.00%)	4 / 84 (4.76%)	2 / 88 (2.27%)
occurrences all number	12	9	0	0	4	2
Otitis media acute
subjects affected / exposed	9 / 88 (10.23%)	5 / 89 (5.62%)	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 84 (0.00%)	4 / 88 (4.55%)
occurrences all number	13	5	0	1	0	4
Pharyngotonsillitis
subjects affected / exposed	4 / 88 (4.55%)	1 / 89 (1.12%)	1 / 88 (1.14%)	1 / 89 (1.12%)	1 / 84 (1.19%)	3 / 88 (3.41%)
occurrences all number	8	1	1	1	1	3
Acute tonsillitis
subjects affected / exposed	1 / 88 (1.14%)	2 / 89 (2.25%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	1 / 88 (1.14%)
occurrences all number	1	2	0	0	0	1
Otitis media
subjects affected / exposed	1 / 88 (1.14%)	2 / 89 (2.25%)	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 84 (1.19%)	0 / 88 (0.00%)
occurrences all number	1	2	0	0	1	0
Pharyngitis
subjects affected / exposed	1 / 88 (1.14%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 84 (1.19%)	2 / 88 (2.27%)
occurrences all number	1	1	0	0	1	2
Pneumonia
subjects affected / exposed	2 / 88 (2.27%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	1 / 88 (1.14%)
occurrences all number	2	0	0	0	0	1
Varicella
subjects affected / exposed	2 / 88 (2.27%)	0 / 89 (0.00%)	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	2	0	1	0	0	0
Acute sinusitis
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Bronchopneumonia
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Candidiasis
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Croup infectious
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Diarrhoea infectious
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Herpangina
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	1 / 89 (1.12%)	1 / 84 (1.19%)	2 / 88 (2.27%)
occurrences all number	0	1	0	1	1	2
Hordeolum
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Oral candidiasis
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	1 / 88 (1.14%)	0 / 89 (0.00%)	1 / 84 (1.19%)	1 / 88 (1.14%)
occurrences all number	1	0	1	0	1	1
Rhinitis
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 84 (1.19%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	1	0
Sinusitis
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 88 (0.00%)	1 / 89 (1.12%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	0	1	0	0	0	0
Viral diarrhoea
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0
Viral rash
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 84 (1.19%)	2 / 88 (2.27%)
occurrences all number	0	0	0	0	1	2
Laryngitis
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 84 (1.19%)	0 / 88 (0.00%)
occurrences all number	0	0	0	0	1	0
Periorbital cellulit
subjects affected / exposed	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	1 / 84 (1.19%)	0 / 88 (0.00%)
occurrences all number	0	0	0	0	1	0
Metabolism and nutrition disorders
Hypophagia
subjects affected / exposed	1 / 88 (1.14%)	0 / 89 (0.00%)	0 / 88 (0.00%)	0 / 89 (0.00%)	0 / 84 (0.00%)	0 / 88 (0.00%)
occurrences all number	1	0	0	0	0	0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

06 Jan 2009

Amendment 5 was issued approximately 6 months after the study start. It provided for an interim analysis to be conducted after all subjects had completed the infant series. The statistical analysis plan (SAP) was amended at the same time to include the interim analysis. Amendment 5 also permitted rotavirus vaccine to be administered at any time during the study, rather than only during protocol-specified time frames.

13 Jul 2009

Amendment 6, issued approximately 6 months later, rescinded this provision, because all subjects concerned had already received rotavirus vaccines, which were reported as protocol deviations if they were administered outside of the protocol-specified time frames

Were there any global interruptions to the trial? No

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

None reported

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

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

Clinical trials

Clinical Trial Results: Phase 2, Randomized, Active-Controlled, Double-Blind Trial Evaluating The Safety, Tolerability, And Immunogenicity Of A 13-Valent Pneumococcal Conjugate Vaccine In Healthy Infants Given With Routine Pediatric Vaccinations In Korea

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects Achieving a Serotype-specific Immunoglobulin G (IgG) Antibody Level Greater Than or Equal to (>=) 0.35 Micrograms Per Milliliter (Mcg/mL) Measured 1 Month After the Infant Series

Primary: Percentage of Subjects Achieving a Serotype-specific Immunoglobulin G (IgG) Antibody Level Greater Than or Equal to (>=) 0.35 Micrograms Per Milliliter (Mcg/mL) Measured 1 Month After the Infant Series

Secondary: Percentage of Subjects Achieving a Serotype-specific IgG Antibody Level (>=) 0.35 Mcg/mL Measured 1 Month After the Toddler Dose

Secondary: Percentage of Subjects Achieving a Serotype-specific IgG Antibody Level (>=) 0.35 Mcg/mL Measured 1 Month After the Toddler Dose

Other pre-specified: Geometric Mean Concentration (GMC) of Serotype-specific IgG Antibody 1 Month After the Infant Series

Other pre-specified: Geometric Mean Concentration (GMC) of Serotype-specific IgG Antibody 1 Month After the Infant Series

Other pre-specified: Geometric Mean Concentration (GMC) of Serotype-specific IgG Antibody 1 Month After the Toddler Dose

Other pre-specified: Geometric Mean Concentration (GMC) of Serotype-specific IgG Antibody 1 Month After the Toddler Dose

Other pre-specified: Percentage of Subjects Reporting Pre-specified Local Reactions: Infant Series Dose 1 (2 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-specified Local Reactions: Infant Series Dose 1 (2 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-specified Local Reactions: Infant Series Dose 2 (4 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-specified Local Reactions: Infant Series Dose 2 (4 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-specified Local Reactions: Infant Series Dose 3 (6 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-specified Local Reactions: Infant Series Dose 3 (6 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-specified Local Reactions: Toddler Dose (12 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-specified Local Reactions: Toddler Dose (12 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-specified Systemic Events: Infant Series Dose 1 (2 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-specified Systemic Events: Infant Series Dose 1 (2 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-specified Systemic Events: Infant Series Dose 2 (4 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-specified Systemic Events: Infant Series Dose 2 (4 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-specified Systemic Events: Infant Series Dose 3 (6 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-specified Systemic Events: Infant Series Dose 3 (6 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-specified Systemic Events: Toddler Dose (12 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-specified Systemic Events: Toddler Dose (12 Months of Age)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Phase 2, Randomized, Active-Controlled, Double-Blind Trial Evaluating The Safety, Tolerability, And Immunogenicity Of A 13-Valent Pneumococcal Conjugate Vaccine In Healthy Infants Given With Routine Pediatric Vaccinations In Korea