Clinical Trial Results:
A PHASE 4, RANDOMIZED, OPEN-LABEL TRIAL TO ASSESS THE IMPACT OF PROPHYLACTIC ANTIPYRETIC MEDICATION ON THE IMMUNOGENICITY OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE GIVEN WITH ROUTINE PEDIATRIC VACCINATIONS IN HEALTHY INFANTS

Due to a system error, the data reported in v1 is not correct and has been removed from public view.

Summary
EudraCT number	2010-022303-22
Trial protocol	PL
Global end of trial date	16 Jan 2013

Results information
Results version number	v2(current)
This version publication date	28 Jul 2016
First version publication date	01 Aug 2015
Other versions	v1 (removed from public view)
Version creation reason	Correction of full data set reporting periods and duplicate AEs in their data

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

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Trial information

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Sponsor protocol code

B1851047

ISRCTN number

US NCT number

NCT01392378

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

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

Public contact

Clinical Trials.gov Call Centre, Pfizer Inc., 001 8007181021, ClinicalTrials.govCallCentre@pfizer.com

Scientific contact

Clinical Trials.gov Call Centre, Pfizer Inc., 001 8007181021, ClinicalTrials.govCallCentre@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?

Analysis stage

Final

Date of interim/final analysis

26 Sep 2013

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

16 Jan 2013

Was the trial ended prematurely?

Main objective of the trial

To assess the impact of prophylactic paracetamol or ibuprofen administration on the immunogenicity of 13-valent pneumococcal conjugate vaccine (13vPnC) as measured by serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) after completion of the infant series.

Protection of trial subjects

This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed; in particular, those affording greater protection to the safety of study subjects.

Background therapy

Evidence for comparator

Actual start date of recruitment

05 Aug 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 908

Worldwide total number of subjects

908

EEA total number of subjects

908

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)

908

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

This study was conducted at 14 sites in Poland.Total 908 subjects were enrolled between 05 August 2011 to 16 January 2013. Two (2) subjects were screened but not enrolled.

Period 1 title

Infant Series

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Arm description

Subjects received open-label 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 2 months (greater than or equal to [>=]56 to less than or equal to [<=]98 days of age), 3 months (28 to 42 days after Dose 1), and 4 months (28 to 42 days after Dose 2, infant series) of age along with paracetamol at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of paracetamol.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 milliliter (mL) dose of 13vPnC at 2 months ( >= 56 to <= 98 days of age), 3 months (28 to 42 days after Dose 1), and 4 months (28 to 42 days after Dose 2, infant series) of age.

Investigational medicinal product name

INFANRIX hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received INFANRIX hexa as per manufacturer’s instructions at 2 months (>=56 to <=98 days of age), 3 months (28 to 42 days after Dose 1), and 4 months (28 to 42 days after Dose 2, infant series) of age.

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received Paracetamol suspension 15 milligram per kilogram (mg/kg) at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of paracetamol.

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Arm description

Subjects received open-label 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 2 months (>=56 to <=98 days of age), 3 months (28 to 42 days after Dose 1), and 4 months (28 to 42 days after Dose 2, infant series) of age, along with ibuprofen at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of ibuprofen.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL dose of 13vPnC at 2 months ( >= 56 to <= 98 days of age), 3 months (28 to 42 days after Dose 1),and 4 months (28 to 42 days after Dose 2, infant series) of age.

Investigational medicinal product name

INFANRIX hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received INFANRIX hexa as per manufacturer’s instructions at 2 months (>=56 to <=98 days of age), 3 months (28 to 42 days after Dose 1),and 4 months (28 to 42 days after Dose 2, infant series) of age.

Investigational medicinal product name

Ibuprofen

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received Ibuprofen suspension 10 mg/kg at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of ibuprofen.

13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Arm description

Subjects received open-label 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 2 months (>=56 to <=98 days of age), 3 months (28 to 42 days after Dose 1),and 4 months (28 to 42 days after Dose 2, infant series) of age, along with paracetamol immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of paracetamol.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL dose of 13vPnC at 2 months (>= 56 to <= 98 days of age), 3 months (28 to 42 days after Dose 1), and 4 months (28 to 42 days after Dose 2, infant series) of age.

Investigational medicinal product name

INFANRIX hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received INFANRIX hexa as per manufacturer’s instructions at 2 months (>=56 to <=98 days of age), 3 months (28 to 42 days after Dose 1),and 4 months (28 to 42 days after Dose 2, infant series) of age.

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received Paracetamol suspension 15 mg/kg immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of paracetamol.

13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Arm description

Subjects received open-label 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 2 months (>=56 to <=98 days of age), 3 months (28 to 42 days after Dose 1),and 4 months (28 to 42 days after Dose 2, infant series) of age, along with ibuprofen 10 mg/kg orally immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of ibuprofen.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL dose of 13vPnC at 2 months (>= 56 to <= 98 days of age), 3 months (28 to 42 days after Dose 1),and 4 months (28 to 42 days after Dose 2, infant series) of age.

Investigational medicinal product name

INFANRIX hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received INFANRIX hexa as per manufacturer’s instructions at 2 months (>=56 to <=98 days of age), 3 months (28 to 42 days after Dose 1),and 4 months (28 to 42 days after Dose 2, infant series) of age.

Investigational medicinal product name

Ibuprofen

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received Ibuprofen suspension 10 mg/kg immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of ibuprofen.

13vPnC + INFANRIX Hexa:Infant

Arm description

Arm type

Control

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL dose of 13vPnC at 2 months (>=56 to <=98 days of age), 3 months (28 to 42 days after Dose 1), and 4 months (28 to 42 days after Dose 2, infant series) of age.

Investigational medicinal product name

INFANRIX hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Number of subjects in period 1	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant
Started	173	176	172	177	210
Vaccinated Dose 1	173	176	172	177	210
Vaccinated Dose 2	171	174	172	177	210
Vaccinated Dose 3	170	174	172	176	210
Completed	169	174	172	175	210
Not completed	4	2	0	2	0
Withdrawal by parent	4	1	-	-	-
Adverse event	-	-	-	1	-
Protocol Violation	-	1	-	-	-
Lost to follow-up	-	-	-	1	-

Period 2 title

After Infant Series

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily:After Infant

Arm description

Included subjects who received 3 open-label doses of 13vPnC and INFANRIX hexa as per manufacturer’s instructions 28 to 42 days apart in infant series, along with paracetamol at 6 to 8 hours after vaccination and 6 to 8 hours after first dose of paracetamol.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:After Infant

Arm description

Included subjects who received 3 open-label doses of 13vPnCn and INFANRIX hexa as per manufacturer’s instructions 28 to 42 days apart in infant series, along with ibuprofen at 6 to 8 hours after vaccination and 6 to 8 hours after first dose of ibuprofen.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:After Infant

Arm description

Included subjects who received 3 open-label doses of 13vPnC and INFANRIX hexa as per manufacturer’s instructions 28 to 42 days apart in infant series, along with paracetamol immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of paracetamol.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:After Infant

Arm description

Included subjects who received 3 open-label doses of 13vPnC and INFANRIX hexa as per manufacturer’s instructions 28 to 42 days apart in infant series, along with ibuprofen immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of ibuprofen.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

13vPnC + INFANRIX Hexa:After Infant

Arm description

Included subjects who received 3 open-label doses of 13vPnC and INFANRIX hexa as per manufacturer’s instructions 28 to 42 days apart in infant series.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily:After Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:After Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:After Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:After Infant	13vPnC + INFANRIX Hexa:After Infant
Started	169	174	172	175	210
Completed	169	173	170	175	209
Not completed	0	1	2	0	1
Withdrawal by parent	-	1	1	-	1
Lost to follow-up	-	-	1	-	-

Period 3 title

Toddler Dose

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Arm description

Subjects received open-label dose of 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 11 to 12 months (366 to 425 days of age, toddler dose) of age, along with paracetamol at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of paracetamol.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL dose of 13vPnC at 11 to 12 months (366 to 425 days of age, toddler dose) of age.

Investigational medicinal product name

INFANRIX hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received INFANRIX hexa as per manufacturer’s instructions at 11 to 12 months (366 to 425 days of age, toddler dose) of age.

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received Paracetamol suspension 15 mg/kg at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of paracetamol.

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Arm description

Subjects received open-label dose of 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 11 to 12 months (366 to 425 days of age, toddler dose) of age, along with ibuprofen suspension at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of ibuprofen.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL dose of 13vPnC at 11 to 12 months (366 to 425 days of age, toddler dose) of age.

Investigational medicinal product name

INFANRIX hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received INFANRIX hexa intramuscularly as per manufacturer’s instructions at 11 to 12 months (366 to 425 days of age, toddler dose) of age.

Investigational medicinal product name

Ibuprofen

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received Ibuprofen suspension 10 mg/kg at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of ibuprofen.

13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Arm description

Subjects received open-label dose of 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 11 to 12 months (366 to 425 days of age, toddler dose) of age, along with paracetamol immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of paracetamol.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL dose of 13vPnC at 11 to 12 months (366 to 425 days of age, toddler dose) of age.

Investigational medicinal product name

INFANRIX hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received INFANRIX hexa as per manufacturer’s instructions at 11 to 12 months (366 to 425 days of age, toddler dose) of age.

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received Paracetamol suspension 15 mg/kg immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of paracetamol.

13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Arm description

Subjects received open-label dose of 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 11 to 12 months (366 to 425 days of age, toddler dose) of age, along with ibuprofen immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of ibuprofen.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL dose of 13vPnC at 11 to 12 months (366 to 425 days of age, toddler dose) of age.

Investigational medicinal product name

INFANRIX hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received INFANRIX hexa as per manufacturer’s instructions at 11 to 12 months (366 to 425 days of age, toddler dose) of age.

Investigational medicinal product name

Ibuprofen

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received Ibuprofen suspension 10 mg/kg immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of ibuprofen.

13vPnC + INFANRIX Hexa:Toddler

Arm description

Subjects received open-label dose of 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 11 to 12 months (366 to 425 days of age, toddler dose) of age.

Arm type

Control

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL dose of 13vPnC at 11 to 12 months (366 to 425 days of age, toddler dose) of age.

Investigational medicinal product name

INFANRIX hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received INFANRIX hexa as per manufacturer’s instructions at 11 to 12 months (366 to 425 days of age, toddler dose) of age.

Number of subjects in period 3	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler	13vPnC + INFANRIX Hexa:Toddler
Started	169	173	170	175	209
Completed	169	172	170	173	208
Not completed	0	1	0	2	1
Withdrawal by parent	-	1	-	1	1
Lost to follow-up	-	-	-	1	-

Baseline characteristics

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Reporting group title

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Reporting group description

Reporting group title

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Reporting group description

Reporting group title

13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Reporting group description

Subjects received open-label 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 2 months (>=56 to <=98 days of age), 3 months (28 to 42 days after Dose 1),and 4 months (28 to 42 days after Dose 2, infant series) of age, along with paracetamol immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of paracetamol.

Reporting group title

13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Reporting group description

Subjects received open-label 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 2 months (>=56 to <=98 days of age), 3 months (28 to 42 days after Dose 1),and 4 months (28 to 42 days after Dose 2, infant series) of age, along with ibuprofen 10 mg/kg orally immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of ibuprofen.

Reporting group title

13vPnC + INFANRIX Hexa:Infant

Reporting group description

Reporting group values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant	Total
Number of subjects	173	176	172	177	210	908
Age categorical
Units: Subjects
Age continuous
Units: days
arithmetic mean (standard deviation)	65.1 ± 9.5	66.5 ± 10.1	65.6 ± 9.7	66.4 ± 10.3	65.6 ± 9.4	-
Gender categorical
Units: Subjects
Female	87	89	75	79	98	428
Male	86	87	97	98	112	480

End points

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Reporting group title

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Reporting group description

Reporting group title

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Reporting group description

Reporting group title

13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Reporting group description

Subjects received open-label 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 2 months (>=56 to <=98 days of age), 3 months (28 to 42 days after Dose 1),and 4 months (28 to 42 days after Dose 2, infant series) of age, along with paracetamol immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of paracetamol.

Reporting group title

13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Reporting group description

Subjects received open-label 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 2 months (>=56 to <=98 days of age), 3 months (28 to 42 days after Dose 1),and 4 months (28 to 42 days after Dose 2, infant series) of age, along with ibuprofen 10 mg/kg orally immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of ibuprofen.

Reporting group title

13vPnC + INFANRIX Hexa:Infant

Reporting group description

Reporting group title

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily:After Infant

Reporting group description

Reporting group title

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:After Infant

Reporting group description

Reporting group title

13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:After Infant

Reporting group description

Reporting group title

13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:After Infant

Reporting group description

Reporting group title

13vPnC + INFANRIX Hexa:After Infant

Reporting group description

Included subjects who received 3 open-label doses of 13vPnC and INFANRIX hexa as per manufacturer’s instructions 28 to 42 days apart in infant series.

Reporting group title

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Reporting group description

Reporting group title

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Reporting group description

Reporting group title

13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Reporting group description

Subjects received open-label dose of 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 11 to 12 months (366 to 425 days of age, toddler dose) of age, along with paracetamol immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of paracetamol.

Reporting group title

13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Reporting group description

Subjects received open-label dose of 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 11 to 12 months (366 to 425 days of age, toddler dose) of age, along with ibuprofen immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of ibuprofen.

Reporting group title

13vPnC + INFANRIX Hexa:Toddler

Reporting group description

Subjects received open-label dose of 13vPnC and INFANRIX hexa as per manufacturer’s instructions at 11 to 12 months (366 to 425 days of age, toddler dose) of age.

Subject analysis set title

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received open-label 0.5 mL dose of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions at 2 months (greater than or equal to [>=]56 to less than or equal to [<=]98 days of age), 3 months (28 to 42 days after Dose 1), 4 months (28 to 42 days after Dose 2, infant series) and 11 to 12 months (366 to 425 days of age, toddler dose) of age, along with paracetamol suspension 15 mg/kg orally at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of paracetamol.

Subject analysis set title

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received open-label 0.5 mL dose of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions at 2 months (>=56 to <=98 days of age), 3 months (28 to 42 days after Dose 1), 4 months (28 to 42 days after Dose 2, infant series) and 11 to 12 months (366 to 425 days of age, toddler dose) of age, along with ibuprofen suspension 10 mg/kg orally at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of ibuprofen.

Subject analysis set title

13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received open-label 0.5 mL dose of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions at 2 months (>=56 to <=98 days of age), 3 months (28 to 42 days after Dose 1), 4 months (28 to 42 days after Dose 2, infant series) and 11 to 12 months (366 to 425 days of age, toddler dose) of age, along with paracetamol suspension 15 mg/kg orally immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of paracetamol.

Subject analysis set title

13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received open-label 0.5 mL dose of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions at 2 months (>=56 to <=98 days of age), 3 months (28 to 42 days after Dose 1), 4 months (28 to 42 days after Dose 2, infant series) and 11 to 12 months (366 to 425 days of age, toddler dose) of age, along with ibuprofen suspension 10 mg/kg orally immediately after vaccination, 6 to 8 hours after vaccination and 6 to 8 hours after last dose of ibuprofen.

Subject analysis set title

13vPnC + INFANRIX Hexa

Subject analysis set type

Safety analysis

Subject analysis set description

Primary: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Infant Series

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End point title

Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Infant Series

End point description

Antibody geometric least squares (LS) mean concentrations (GMCs) for 13 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F and 19A) are presented. GMC (13vPnC) and corresponding 2-sided 95 percent (%) confidence interval (CI) were evaluated. Geometric means (GMs) were calculated using all subjects with available data for the specified blood draw. Modified intent-to-treat (mITT) infant immunogenicity set: all eligible subjects who had >=1 valid,determinate assay result, 56-98 days of age at Vaccination 1, received antipyretic regimen as per randomization,may have had received additional anti-pyretic medication,had blood drawn within specified time frames,had no major protocol violations. Here ‘n’ signifies subjects with a determinate IgG concentration to the given serotype for each arm, respectively. Paracetamol and Ibuprofen have been abbreviated as PCM and IBF, respectively in the statistical analysis titles.

End point type

Primary

End point timeframe

1 month after the infant series

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant
Number of subjects analysed	138 ^[1]	155 ^[2]	148 ^[3]	147 ^[4]	210 ^[5]
Units: microgram per milliliter (mcg/mL)
geometric mean (confidence interval 95%)
4 (n = 137, 155, 148, 146, 210)	1.64 (1.44 to 1.87)	1.99 (1.76 to 2.25)	1.48 (1.31 to 1.68)	2.07 (1.82 to 2.34)	2.02 (1.82 to 2.25)
6B (n = 136, 155, 148, 146, 210)	0.68 (0.55 to 0.83)	0.91 (0.76 to 1.1)	0.56 (0.46 to 0.68)	0.9 (0.74 to 1.09)	0.81 (0.69 to 0.96)
9V (n = 138, 155, 148, 147, 210)	1.13 (1.01 to 1.27)	1.45 (1.3 to 1.61)	1.17 (1.05 to 1.3)	1.4 (1.26 to 1.56)	1.31 (1.19 to 1.43)
14 (n = 138, 155, 148, 147, 210)	4.45 (3.76 to 5.26)	4.73 (4.04 to 5.54)	4.75 (4.04 to 5.58)	5.26 (4.48 to 6.19)	5.38 (4.7 to 6.16)
18C (n = 138, 155, 148, 147, 210)	1.47 (1.29 to 1.66)	1.73 (1.54 to 1.95)	1.25 (1.11 to 1.42)	1.75 (1.55 to 1.97)	1.54 (1.39 to 1.7)
19F (n = 138, 155, 148, 147, 210)	1.78 (1.57 to 2.02)	2.3 (2.04 to 2.59)	1.59 (1.41 to 1.8)	2.04 (1.81 to 2.31)	1.99 (1.8 to 2.2)
23F (n= 137, 155, 148, 146, 210)	0.85 (0.72 to 1)	1.19 (1.02 to 1.4)	0.73 (0.62 to 0.86)	1.07 (0.91 to 1.26)	1.04 (0.91 to 1.19)
1 (n = 138, 155, 148, 147, 210)	1.12 (0.98 to 1.27)	1.5 (1.33 to 1.69)	1.02 (0.9 to 1.16)	1.29 (1.14 to 1.47)	1.25 (1.12 to 1.38)
3 (n = 138, 155, 148, 147, 210)	0.71 (0.63 to 0.79)	0.83 (0.75 to 0.93)	0.57 (0.51 to 0.64)	0.84 (0.75 to 0.94)	0.88 (0.79 to 0.96)
5 (n = 137, 155, 148, 146, 210)	0.79 (0.69 to 0.91)	0.98 (0.86 to 1.11)	0.63 (0.55 to 0.72)	0.9 (0.78 to 1.02)	0.81 (0.73 to 0.91)
6A (n = 138, 155, 148, 146, 210)	0.97 (0.84 to 1.13)	1.25 (1.09 to 1.44)	0.85 (0.74 to 0.98)	1.22 (1.06 to 1.41)	1.1 (0.97 to 1.24)
7F (n = 138, 155, 148, 146, 210)	1.94 (1.74 to 2.16)	2.22 (2.01 to 2.46)	1.83 (1.65 to 2.03)	2.28 (2.06 to 2.53)	2.15 (1.97 to 2.34)
19A (n = 137, 155, 148, 146, 210)	2.7 (2.38 to 3.07)	3.39 (3.01 to 3.82)	2.53 (2.24 to 2.86)	3.14 (2.77 to 3.55)	3.02 (2.72 to 3.34)

Notes
[1] - Subjects who were evaluable for this measure.
[2] - Subjects who were evaluable for this measure.
[3] - Subjects who were evaluable for this measure.
[4] - Subjects who were evaluable for this measure.
[5] - Subjects who were evaluable for this measure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 4: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol (PCM) twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0856 ^[6]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

0.96

Notes
[6] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 4: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen (IBF) twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8546 ^[7]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.16

Notes
[7] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 4: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0012 ^[8]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

0.86

Notes
[8] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 4: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8414 ^[9]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.2

Notes
[9] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6B: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2412 ^[10]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

1.08

Notes
[10] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6B: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4548 ^[11]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.44

Notes
[11] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6B: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0093 ^[12]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

0.88

Notes
[12] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6B: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8414 ^[13]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.42

Notes
[13] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 9V: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1749 ^[14]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

Notes
[14] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 9V: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3121 ^[15]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.27

Notes
[15] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 9V: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1351 ^[16]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.03

Notes
[16] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 9V: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8414 ^[17]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.24

Notes
[17] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 14: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2158 ^[18]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.03

Notes
[18] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 14: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3279 ^[19]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.08

Notes
[19] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 14: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2472 ^[20]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.09

Notes
[20] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 14: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8414 ^[21]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.21

Notes
[21] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 18C: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6193 ^[22]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.12

Notes
[22] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 18C: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3121 ^[23]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.32

Notes
[23] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 18C: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group..

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0191 ^[24]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

0.96

Notes
[24] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 18C: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8414 ^[25]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.33

Notes
[25] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19F: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2412 ^[26]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.05

Notes
[26] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19F: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3121 ^[27]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.15

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.35

Notes
[27] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19F: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0135 ^[28]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

0.94

Notes
[28] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19F: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8414 ^[29]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.21

Notes
[29] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 23F: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1749 ^[30]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

Notes
[30] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 23F: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3121 ^[31]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.15

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.41

Notes
[31] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 23F: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0038 ^[32]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

0.86

Notes
[32] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 23F: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8414 ^[33]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.27

Notes
[33] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 1: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant v 13vPnC + INFANRIX Hexa:Infant

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2412 ^[34]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.06

Notes
[34] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 1: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2053 ^[35]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.02

upper limit

1.41

Notes
[35] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 1: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0241 ^[36]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

0.96

Notes
[36] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 1: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8414 ^[37]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.22

Notes
[37] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 3: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0732 ^[38]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

0.94

Notes
[38] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 3: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.609 ^[39]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.1

Notes
[39] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 3: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[40]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

0.76

Notes
[40] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 3: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8414 ^[41]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.11

Notes
[41] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 5: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7828 ^[42]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.16

Notes
[42] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 5: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant v 13vPnC + INFANRIX Hexa:Infant

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2053 ^[43]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.21

Confidence interval

level

95%

sides

2-sided

lower limit

1.02

upper limit

1.43

Notes
[43] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 5: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0093 ^[44]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

0.92

Notes
[44] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 5: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8414 ^[45]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.31

Notes
[45] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6A: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2412 ^[46]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.07

Notes
[46] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6A: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3121 ^[47]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

1.37

Notes
[47] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6A: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0135 ^[48]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

0.93

Notes
[48] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6A: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8414 ^[49]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

1.34

Notes
[49] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 7F: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2412 ^[50]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.03

Notes
[50] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 7F: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6652 ^[51]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.91

upper limit

1.18

Notes
[51] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 7F: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0275 ^[52]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

0.98

Notes
[52] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 7F: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8414 ^[53]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.21

Notes
[53] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19A: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2412 ^[54]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.06

Notes
[54] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19A: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

365

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3121 ^[55]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.32

Notes
[55] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19A: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

358

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0387 ^[56]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

0.99

Notes
[56] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19A: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8414 ^[57]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

1.22

Notes
[57] - P-values were adjusted using false discovery rate procedure.

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

Top of page

End point title

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

End point description

Percentage of subjects achieving predefined antibody threshold >=0.35 mcg/mL along with the corresponding 95% confidence interval (CI) for 13 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F and 19A) are presented. Exact 2-sided CI based on the observed proportion of subjects. mITT infant immunogenicity population. Here ‘n’ signifies subjects with a determinate IgG concentration to the given serotype for each arm, respectively.

End point type

Secondary

End point timeframe

1 month after the infant series

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant
Number of subjects analysed	138 ^[58]	155 ^[59]	148 ^[60]	147 ^[61]	210 ^[62]
Units: percentage of subjects
number (confidence interval 95%)
4 (n = 137, 155, 148, 146, 210)	96.4 (91.69 to 98.8)	97.4 (93.52 to 99.29)	96.6 (92.29 to 98.89)	97.3 (93.13 to 99.25)	98.1 (95.2 to 99.48)
6B (n = 136, 155, 148, 146, 210)	72.8 (64.5 to 80.07)	80 (72.83 to 85.99)	61.5 (53.14 to 69.36)	79.5 (71.98 to 85.69)	77.6 (71.37 to 83.07)
9V (n = 138, 155, 148, 147, 210)	94.2 (88.9 to 97.46)	99.4 (96.46 to 99.98)	95.9 (91.39 to 98.5)	95.9 (91.33 to 98.49)	96.2 (92.63 to 98.34)
14 (n = 138, 155, 148, 147, 210)	100 (97.36 to 100)	98.7 (95.42 to 99.84)	99.3 (96.29 to 99.98)	98.6 (95.17 to 99.83)	99.5 (97.38 to 99.99)
18C (n = 138, 155, 148, 147, 210)	96.4 (91.75 to 98.81)	97.4 (93.52 to 99.29)	95.3 (90.5 to 98.08)	95.9 (91.33 to 98.49)	96.7 (93.25 to 98.65)
19F (n = 138, 155, 148, 147, 210)	97.1 (92.74 to 99.2)	99.4 (96.46 to 99.98)	95.3 (90.5 to 98.08)	96.6 (92.24 to 98.89)	97.6 (94.53 to 99.22)
23F (n = 137, 155, 148, 146, 210)	86.1 (79.19 to 91.44)	90.3 (84.54 to 94.48)	74.3 (66.5 to 81.15)	88.4 (82.01 to 93.07)	88.1 (82.93 to 92.15)
1 (n = 138, 155, 148, 147, 210)	94.2 (88.9 to 97.46)	97.4 (93.52 to 99.29)	90.5 (84.64 to 94.73)	94.6 (89.56 to 97.62)	94.3 (90.23 to 97.01)
3 (n = 138, 155, 148, 147, 210)	83.3 (76.05 to 89.13)	89.7 (83.78 to 93.98)	81.1 (73.83 to 87.05)	88.4 (82.13 to 93.12)	91 (86.23 to 94.46)
5 (n = 137, 155, 148, 146, 210)	84.7 (77.53 to 90.25)	91 (85.31 to 94.97)	76.4 (68.68 to 82.94)	89.7 (83.62 to 94.13)	84.3 (78.65 to 88.93)
6A (n = 138, 155, 148, 146, 210)	86.2 (79.34 to 91.5)	92.3 (86.87 to 95.94)	83.1 (76.08 to 88.76)	91.8 (86.08 to 95.68)	91.9 (87.36 to 95.21)
7F (n = 138, 155, 148, 146, 210)	100 (97.36 to 100)	99.4 (96.46 to 99.98)	97.3 (93.22 to 99.26)	100 (97.51 to 100)	99.5 (97.38 to 99.99)
19A (n = 137, 155, 148, 146, 210)	98.5 (94.83 to 99.82)	99.4 (96.46 to 99.98)	98 (94.19 to 99.58)	99.3 (96.24 to 99.98)	100 (98.26 to 100)

Notes
[58] - Subjects who were evaluable for this measure.
[59] - Subjects who were evaluable for this measure.
[60] - Subjects who were evaluable for this measure.
[61] - Subjects who were evaluable for this measure.
[62] - Subjects who were evaluable for this measure.

No statistical analyses for this end point

Secondary: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Toddler Dose

Top of page

End point title

Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Toddler Dose

End point description

Antibody geometric LS mean concentrations (GMCs) for 13 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F and 19A) are presented. GMC (13vPnC) and corresponding 2-sided 95% CI were evaluated. Geometric means (GMs) were calculated using all subjects with available data for the specified blood draw. mITT toddler immunogenicity set: eligible subjects who had >=1 valid,determinate assay result, 56-98 days of age at Vaccination 1, received antipyretic regimen as per randomization, received all vaccinations, may have had received additional anti-pyretic medication, had blood drawn within specified time frames, had no major protocol violations. Here ‘n’ signifies subjects with a determinate IgG concentration to the given serotype for each arm respectively. Paracetamol and Ibuprofen have been abbreviated as PCM and IBF, respectively in the statistical analysis titles.

End point type

Secondary

End point timeframe

1 month after the toddler dose

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler	13vPnC + INFANRIX Hexa:Toddler
Number of subjects analysed	130 ^[63]	144 ^[64]	143 ^[65]	139 ^[66]	206 ^[67]
Units: mcg/mL
geometric mean (confidence interval 95%)
4 (n = 130, 144, 143, 139, 206)	3.07 (2.66 to 3.54)	3.43 (3 to 3.93)	2.97 (2.6 to 3.41)	3.43 (2.99 to 3.94)	3.1 (2.77 to 3.48)
6B (n = 130, 144, 143, 139, 206)	6.7 (5.76 to 7.78)	8.01 (6.94 to 9.24)	6.38 (5.53 to 7.36)	7.3 (6.31 to 8.44)	7.08 (6.28 to 7.98)
9V (n = 130, 144, 143, 139, 206)	2.15 (1.93 to 2.4)	2.23 (2.01 to 2.47)	2.17 (1.96 to 2.41)	2.12 (1.91 to 2.35)	2.16 (1.99 to 2.36)
14 (n = 130, 144, 143, 139, 206)	8.1 (7.04 to 9.31)	8.4 (7.36 to 9.59)	7.95 (6.96 to 9.08)	9.12 (7.96 to 10.43)	9.1 (8.15 to 10.17)
18C (n = 130, 144, 143, 139, 206)	1.35 (1.2 to 1.53)	1.68 (1.49 to 1.88)	1.36 (1.21 to 1.53)	1.63 (1.45 to 1.84)	1.59 (1.44 to 1.75)
19F (n = 130, 144, 143, 139, 206)	8.41 (7.17 to 9.87)	8.99 (7.72 to 10.46)	7.53 (6.47 to 8.76)	8.02 (6.88 to 9.36)	7.95 (7 to 9.02)
23F (n = 130, 144, 142, 139, 206)	2.34 (2.01 to 2.73)	2.96 (2.56 to 3.43)	2.37 (2.05 to 2.75)	2.86 (2.47 to 3.32)	2.75 (2.43 to 3.1)
1 (n = 130, 144, 143, 139, 206)	2.8 (2.47 to 3.17)	3.22 (2.85 to 3.62)	2.66 (2.36 to 3)	3.12 (2.76 to 3.52)	3.04 (2.75 to 3.35)
3 (n = 129, 144, 143, 138, 203)	0.46 (0.4 to 0.52)	0.54 (0.47 to 0.61)	0.46 (0.4 to 0.52)	0.49 (0.42 to 0.55)	0.54 (0.48 to 0.6)
5 (n = 130, 144, 143, 139, 206)	2.33 (2.07 to 2.63)	2.75 (2.46 to 3.07)	2.4 (2.15 to 2.69)	2.62 (2.33 to 2.93)	2.84 (2.59 to 3.12)
6A (n = 130, 144, 143, 139, 206)	5.12 (4.48 to 5.86)	5.73 (5.04 to 6.5)	5.27 (4.64 to 5.99)	5.36 (4.7 to 6.1)	5.52 (4.97 to 6.14)
7F (n = 130, 144, 142, 139, 206)	3.79 (3.42 to 4.19)	3.89 (3.54 to 4.28)	3.56 (3.23 to 3.92)	3.97 (3.6 to 4.38)	3.98 (3.67 to 4.31)
19A (n = 129, 144, 142, 139, 206)	7.11 (6.22 to 8.12)	7.99 (7.04 to 9.06)	7.31 (6.43 to 8.3)	7.35 (6.47 to 8.36)	7.71 (6.94 to 8.57)

Notes
[63] - Subjects who were evaluable for this measure.
[64] - Subjects who were evaluable for this measure.
[65] - Subjects who were evaluable for this measure.
[66] - Subjects who were evaluable for this measure.
[67] - Subjects who were evaluable for this measure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 4: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.935 ^[68]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.19

Notes
[68] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 4: Ratio of IgG GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7918 ^[69]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.32

Notes
[69] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6922 ^[70]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.14

Notes
[70] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9765 ^[71]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.32

Notes
[71] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler v 13vPnC + INFANRIX Hexa:Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6915 ^[72]

Method

General linear model

Parameter type

GMC Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.15

Notes
[72] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7918 ^[73]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

1.36

Notes
[73] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4389 ^[74]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

1.09

Notes
[74] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9765 ^[75]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.24

Notes
[75] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.935 ^[76]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.14

Notes
[76] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7918 ^[77]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

1.18

Notes
[77] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.943 ^[78]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.15

Notes
[78] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9765 ^[79]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.12

Notes
[79] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5167 ^[80]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

1.06

Notes
[80] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7918 ^[81]

Method

General linear model

Parameter type

GMC Ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.1

Notes
[81] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2514 ^[82]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.04

Notes
[82] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9872 ^[83]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.19

Notes
[83] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2582 ^[84]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

Notes
[84] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7918 ^[85]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.91

upper limit

1.23

Notes
[85] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2514 ^[86]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

Notes
[86] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9765 ^[87]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.2

Notes
[87] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6915 ^[88]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.3

Notes
[88] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7918 ^[89]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.38

Notes
[89] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler v 13vPnC + INFANRIX Hexa:Toddler

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6922 ^[90]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.15

Notes
[90] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9872 ^[91]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.23

Notes
[91] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler v 13vPnC + INFANRIX Hexa:Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3609 ^[92]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.04

Notes
[92] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7918 ^[93]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

1.3

Notes
[93] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2514 ^[94]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.05

Notes
[94] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9765 ^[95]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.26

Notes
[95] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6304 ^[96]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.08

Notes
[96] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7918 ^[97]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.91

upper limit

1.24

Notes
[97] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2514 ^[98]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

1.03

Notes
[98] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9765 ^[99]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.2

Notes
[99] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2582 ^[100]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.01

Notes
[100] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9279 ^[101]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.18

Notes
[101] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2514 ^[102]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.01

Notes
[102] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9765 ^[103]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.07

Notes
[103] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1424 ^[104]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

0.96

Notes
[104] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7918 ^[105]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.12

Notes
[105] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2514 ^[106]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

0.98

Notes
[106] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9765 ^[107]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.07

Notes
[107] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6304 ^[108]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.1

Notes
[108] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7918 ^[109]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.22

Notes
[109] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6922 ^[110]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.13

Notes
[110] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9765 ^[111]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.15

Notes
[111] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6572 ^[112]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.08

Notes
[112] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7918 ^[113]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.11

Notes
[113] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2514 ^[114]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.01

Notes
[114] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9872 ^[115]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.13

Notes
[115] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6304 ^[116]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.09

Notes
[116] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7918 ^[117]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.22

Notes
[117] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6922 ^[118]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.12

Notes
[118] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9765 ^[119]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.13

Notes
[119] - P-values were adjusted using false discovery rate procedure.

Secondary: Percentage of Subjects Achieving Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Titers Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) 1 Month After the Infant Series

Top of page

End point title

Percentage of Subjects Achieving Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Titers Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) 1 Month After the Infant Series

End point description

Percentage of subjects achieving serotype-specific pneumococcal OPA titer >= LLOQ, along with the corresponding 95% CIs for 13 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F and 19A) are presented. Exact 2-sided CI based on the observed proportion of subjects. The OPA LLOQ in titers for each serotype: 1 = 1:18; 3 = 1:12; 4 = 1:21; 5 = 1:29; 6A = 1:37; 6B = 1:43; 7F = 1:210; 9V = 1:345; 14 = 1:35; 18C = 1:31; 19A = 1:18; 19F = 1:48; 23F = 1:13. mITT infant immunogenicity population. Here ‘n’ signifies subjects with a determinate IgG concentration to the given serotype for each arm respectively.

End point type

Secondary

End point timeframe

1 month after the infant series

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant
Number of subjects analysed	46 ^[120]	48 ^[121]	44 ^[122]	44 ^[123]	76 ^[124]
Units: percentage of subjects
number (confidence interval 95%)
4 (n = 37, 46, 42, 41, 61)	100 (90.5 to 100)	100 (92.3 to 100)	100 (91.6 to 100)	100 (91.4 to 100)	100 (94.1 to 100)
6B (n = 36, 45, 43, 40, 62)	94.4 (81.3 to 99.3)	88.9 (75.9 to 96.3)	88.4 (74.9 to 96.1)	92.5 (79.6 to 98.4)	96.8 (88.8 to 99.6)
9V (n = 37, 48, 42, 41, 65)	62.2 (44.8 to 77.5)	66.7 (51.6 to 79.6)	59.5 (43.3 to 74.4)	80.5 (65.1 to 91.2)	75.4 (63.1 to 85.2)
14 (n = 38, 48, 41, 41, 64)	89.5 (75.2 to 97.1)	97.9 (88.9 to 99.9)	100 (91.4 to 100)	97.6 (87.1 to 99.9)	96.9 (89.2 to 99.6)
18C (n = 37, 47, 41, 41, 62)	100 (90.5 to 100)	95.7 (85.5 to 99.5)	100 (91.4 to 100)	97.6 (87.1 to 99.9)	100 (94.2 to 100)
19F (n = 37, 46, 41, 42, 63)	97.3 (85.8 to 99.9)	87 (73.7 to 95.1)	90.2 (76.9 to 97.3)	92.9 (80.5 to 98.5)	95.2 (86.7 to 99)
23F (n = 38, 45, 42, 42, 63)	92.1 (78.6 to 98.3)	97.8 (88.2 to 99.9)	92.9 (80.5 to 98.5)	90.5 (77.4 to 97.3)	93.7 (84.5 to 98.2)
1 (n = 42, 42, 43, 44, 74)	47.6 (32 to 63.6)	42.9 (27.7 to 59)	30.2 (17.2 to 46.1)	29.5 (16.8 to 45.2)	45.9 (34.3 to 57.9)
3 (n = 41, 41, 39, 39, 69)	97.6 (87.1 to 99.9)	97.6 (87.1 to 99.9)	97.4 (86.5 to 99.9)	94.9 (82.7 to 99.4)	100 (94.8 to 100)
5 (n = 42, 43, 44, 42, 73)	92.9 (80.5 to 98.5)	90.7 (77.9 to 97.4)	86.4 (72.6 to 94.8)	92.9 (80.5 to 98.5)	86.3 (76.2 to 93.2)
6A (n = 46, 42, 39, 39, 76)	93.5 (82.1 to 98.6)	100 (91.6 to 100)	100 (91 to 100)	100 (91 to 100)	98.7 (92.9 to 100)
7F (n = 46, 42, 40, 39, 76)	100 (92.3 to 100)	100 (91.6 to 100)	100 (91.2 to 100)	97.4 (86.5 to 99.9)	100 (95.3 to 100)
19A (n = 42, 44, 41, 42, 74)	92.9 (80.5 to 98.5)	100 (92 to 100)	90.2 (76.9 to 97.3)	88.1 (74.4 to 96)	97.3 (90.6 to 99.7)

Notes
[120] - "N"(Number of subjects analyzed) signifies those subjects who were evaluable for this measure.
[121] - "N"(Number of subjects analyzed) signifies those subjects who were evaluable for this measure.
[122] - "N"(Number of subjects analyzed) signifies those subjects who were evaluable for this measure.
[123] - "N"(Number of subjects analyzed) signifies those subjects who were evaluable for this measure.
[124] - "N"(Number of subjects analyzed) signifies those subjects who were evaluable for this measure.

No statistical analyses for this end point

Secondary: Geometric Mean Titer (GMT) for Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) 1 Month After the Infant Series

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End point title

Geometric Mean Titer (GMT) for Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) 1 Month After the Infant Series

End point description

Antibody-mediated serum OPA against the 13 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F and 19A) was measured centrally using a pneumococcal OPA assay. Results were expressed as OPA titers. OPA titers were logarithmically transformed for analysis; geometric means calculated and expressed as geometric mean titers (GMTs). mITT infant immunogenicity population. Here ‘n’ signifies subjects with a determinate OPA titer to the given serotype for each arm respectively. Paracetamol and Ibuprofen have been abbreviated as PCM and IBF, respectively in the statistical analysis titles.

End point type

Secondary

End point timeframe

1 month after the infant series

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant
Number of subjects analysed	46 ^[125]	48 ^[126]	44 ^[127]	44 ^[128]	76 ^[129]
Units: titer
geometric mean (confidence interval 95%)
4 (n = 37, 46, 42, 41, 61)	1269 (961.2 to 1674.2)	1135 (885.2 to 1456.1)	1240 (955.9 to 1609.3)	1361 (1045.4 to 1771)	1086 (874.9 to 1347.9)
6B (n = 36, 45, 43, 40, 62)	794 (450.4 to 1399.6)	655 (394.6 to 1087.9)	470 (279.9 to 789.7)	663 (387.2 to 1135.1)	748 (485.6 to 1152)
9V (n = 37, 48, 42, 41, 65)	120 (52.5 to 274.2)	166 (80.5 to 343.3)	93 (43 to 203)	285 (129.8 to 623.8)	241 (129 to 448.7)
14 (n = 38, 48, 41, 41, 64)	435 (277.2 to 683.5)	622 (416 to 928.6)	650 (420.7 to 1003)	991 (642.1 to 1530.9)	951 (671.6 to 1346.3)
18C (n = 37, 47, 41, 41, 62)	1094 (777.8 to 1539.2)	853 (630 to 1154.3)	877 (634.1 to 1212.7)	1031 (745.8 to 1426.2)	1092 (838.9 to 1421.3)
19F (n = 37, 46, 41, 42, 63)	346 (219.7 to 545.4)	221 (146.8 to 331.9)	165 (106.8 to 253.4)	294 (191.8 to 450.2)	279 (196.8 to 395)
23F (n = 38, 45, 42, 42, 63)	342 (211.6 to 552.6)	441 (283.7 to 685.4)	332 (210 to 523.4)	321 (203.3 to 506.7)	366 (252.4 to 532.1)
1 (n = 42, 42, 43, 44, 74)	12 (8.7 to 17.7)	11 (7.5 to 15.4)	8 (5.5 to 11.2)	8 (5.4 to 10.9)	12 (9 to 15.5)
3 (n = 41, 41, 39, 39, 69)	72 (57.4 to 91.1)	76 (60.4 to 95.7)	56 (44.1 to 70.8)	62 (49.3 to 79.1)	87 (73.1 to 104.3)
5 (n = 42, 43, 44, 42, 73)	86 (59.7 to 122.7)	96 (67.4 to 137.3)	54 (37.7 to 76.2)	99 (69.1 to 142)	76 (57.5 to 99.2)
6A (n = 46, 42, 39, 39, 76)	1060 (784.5 to 1431.1)	1681 (1227.3 to 2302.3)	1228 (886 to 1701.9)	1281 (924 to 1775.1)	1462 (1157.1 to 1847.1)
7F (n = 46, 42, 40, 39, 76)	1766 (1387 to 2247.7)	1907 (1481 to 2454.6)	1747 (1348.6 to 2263.3)	1584 (1218.8 to 2058.9)	2125 (1761.6 to 2564.6)
19A (n = 42, 44, 41, 42, 74)	185 (127.8 to 268.3)	257 (178.5 to 368.5)	163 (112.3 to 237.9)	159 (110 to 230.9)	240 (181.9 to 318)

Notes
[125] - "N"(Number of subjects analyzed) signifies those subjects who were evaluable for this measure.
[126] - "N"(Number of subjects analyzed) signifies those subjects who were evaluable for this measure.
[127] - "N"(Number of subjects analyzed) signifies those subjects who were evaluable for this measure.
[128] - "N"(Number of subjects analyzed) signifies those subjects who were evaluable for this measure.
[129] - "N"(Number of subjects analyzed) signifies those subjects who were evaluable for this measure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 4: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant v 13vPnC + INFANRIX Hexa:Infant

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7148 ^[130]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.66

Notes
[130] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 4: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7907 ^[131]

Method

General linear model

Parameter type

GMT Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

1.45

Notes
[131] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 4: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4765 ^[132]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.6

Notes
[132] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 4: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5037 ^[133]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

1.76

Notes
[133] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6B: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9414 ^[134]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

2.17

Notes
[134] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6B: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7907 ^[135]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

1.71

Notes
[135] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6B: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.29 ^[136]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

1.23

Notes
[136] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6B: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8826 ^[137]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.44

upper limit

1.77

Notes
[137] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 9V: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5823 ^[138]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.18

upper limit

1.4

Notes
[138] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 9V: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7636 ^[139]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.27

upper limit

1.8

Notes
[139] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 9V: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2407 ^[140]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.14

upper limit

1.05

Notes
[140] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 9V: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8826 ^[141]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

3.22

Notes
[141] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 14: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0961 ^[142]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.26

upper limit

0.81

Notes
[142] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 14: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant v 13vPnC + INFANRIX Hexa:Infant

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7636 ^[143]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

1.11

Notes
[143] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 14: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.29 ^[144]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

1.19

Notes
[144] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 14: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group..

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8826 ^[145]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.82

Notes
[145] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 18C: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9925 ^[146]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.54

Notes
[146] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 18C: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7636 ^[147]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

1.17

Notes
[147] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 18C: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3929 ^[148]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.22

Notes
[148] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 18C: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8826 ^[149]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

1.43

Notes
[149] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19F: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7433 ^[150]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

2.2

Notes
[150] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19F: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7636 ^[151]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.46

upper limit

1.35

Notes
[151] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19F: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2407 ^[152]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.34

upper limit

1.03

Notes
[152] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19F: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8826 ^[153]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

1.83

Notes
[153] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 23F: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9414 ^[154]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

1.71

Notes
[154] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 23F: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7636 ^[155]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

2.14

Notes
[155] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 23F: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.738 ^[156]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.63

Notes
[156] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 23F: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8826 ^[157]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

1.58

Notes
[157] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 1: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9414 ^[158]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.65

Notes
[158] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 1: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7907 ^[159]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

1.43

Notes
[159] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 1: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2407 ^[160]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

1.04

Notes
[160] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 1: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant v 13vPnC + INFANRIX Hexa:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.267 ^[161]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

1.02

Notes
[161] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 3: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5823 ^[162]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

1.11

Notes
[162] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 3: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant v 13vPnC + INFANRIX Hexa:Infant

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7636 ^[163]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.16

Notes
[163] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 3: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0422 ^[164]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

0.86

Notes
[164] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 3: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.267 ^[165]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

0.96

Notes
[165] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 5: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8454 ^[166]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.78

Notes
[166] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 5: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7636 ^[167]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

Notes
[167] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 5: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2824 ^[168]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

1.11

Notes
[168] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 5: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5155 ^[169]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

2.06

Notes
[169] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6A: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5823 ^[170]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.06

Notes
[170] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6A: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7636 ^[171]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.7

Notes
[171] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6A: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4644 ^[172]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

1.25

Notes
[172] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 6A: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8826 ^[173]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

1.31

Notes
[173] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 7F: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5823 ^[174]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

1.13

Notes
[174] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 7F: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7636 ^[175]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.23

Notes
[175] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 7F: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3299 ^[176]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.13

Notes
[176] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 7F: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.267 ^[177]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.03

Notes
[177] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19A: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5823 ^[178]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

1.23

Notes
[178] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19A: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7907 ^[179]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.69

Notes
[179] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19A: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2742 ^[180]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

1.09

Notes
[180] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Serotype 19A: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.267 ^[181]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

1.05

Notes
[181] - P-values were adjusted using false discovery rate procedure.

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Haemophilus Influenzae Type b (Hib) Polyribosylribitol Phosphate (PRP) Antibody 1 Month After the Infant Series

Top of page

End point title

Geometric Mean Concentration (GMC) for Antigen-specific Haemophilus Influenzae Type b (Hib) Polyribosylribitol Phosphate (PRP) Antibody 1 Month After the Infant Series

End point description

Geometric LS mean concentrations (GMCs) and corresponding 2-sided 95% CIs were evaluated for Hib PRP antibody.mITT infant immunogenicity population. Paracetamol and Ibuprofen have been abbreviated as PCM and IBF, respectively in the statistical analysis titles.

End point type

Secondary

End point timeframe

1 month after the infant series

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant
Number of subjects analysed	136 ^[182]	146 ^[183]	144 ^[184]	139 ^[185]	198 ^[186]
Units: mcg/mL
geometric mean (confidence interval 95%)	0.54 (0.44 to 0.66)	0.59 (0.49 to 0.73)	0.49 (0.4 to 0.6)	0.51 (0.42 to 0.63)	0.58 (0.49 to 0.69)

Notes
[182] - Subjects who were evaluable for this measure.
[183] - Subjects who were evaluable for this measure.
[184] - Subjects who were evaluable for this measure.
[185] - Subjects who were evaluable for this measure.
[186] - Subjects who were evaluable for this measure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant v 13vPnC + INFANRIX Hexa:Infant

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.813 ^[187]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.22

Notes
[187] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

344

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.845 ^[188]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.34

Notes
[188] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

342

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.461 ^[189]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.11

Notes
[189] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

337

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.545 ^[190]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.16

Notes
[190] - P-values were adjusted using false discovery rate procedure.

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) Antibody 1 Month After the Infant Series

Top of page

End point title

Geometric Mean Concentration (GMC) for Antigen-specific Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) Antibody 1 Month After the Infant Series

End point description

Geometric LS mean concentration (GMCs) were measured in Enzyme-linked Immunosorbent Assay (ELISA) units/mL (EU/mL) and corresponding 2-sided 95% CIs were evaluated for pertussis (pertussis toxin [PT], filamentous hemagglutinin [FHA] and pertactin [PRN]) antibodies. mITT infant immunogenicity population. Paracetamol and Ibuprofen have been abbreviated as PCM and IBF, respectively in the statistical analysis titles.

End point type

Secondary

End point timeframe

1 month after the infant series

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant
Number of subjects analysed	132 ^[191]	143 ^[192]	141 ^[193]	131 ^[194]	193 ^[195]
Units: EU/mL
geometric mean (confidence interval 95%)
Pertussis PT	40.86 (36.49 to 45.76)	43.51 (39.02 to 48.51)	40.27 (36.09 to 44.93)	39.26 (35.04 to 43.98)	44.85 (40.84 to 49.25)
Pertussis FHA	46.29 (41.49 to 51.65)	40.65 (36.59 to 45.16)	41.32 (37.16 to 45.94)	35.55 (31.85 to 39.68)	48.42 (44.22 to 53.01)
Pertussis PRN	72.9 (63.26 to 84.01)	71.26 (62.18 to 81.66)	65.82 (57.38 to 75.5)	68.53 (59.44 to 79.02)	84.57 (75.21 to 95.09)

Notes
[191] - Subjects who were evaluable for this measure.
[192] - Subjects who were evaluable for this measure.
[193] - Subjects who were evaluable for this measure.
[194] - Subjects who were evaluable for this measure.
[195] - Subjects who were evaluable for this measure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Pertussis PT: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant v 13vPnC + INFANRIX Hexa:Infant

Number of subjects included in analysis

325

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.712 ^[196]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.06

Notes
[196] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Pertussis PT: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.837 ^[197]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.12

Notes
[197] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Pertussis PT: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.357 ^[198]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.04

Notes
[198] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Pertussis PT: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

324

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.19 ^[199]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.01

Notes
[199] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Pertussis FHA: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

325

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.813 ^[200]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.1

Notes
[200] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Pertussis FHA: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.136 ^[201]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

0.96

Notes
[201] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Pertussis FHA: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.104 ^[202]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

0.98

Notes
[202] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Pertussis FHA: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

324

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[203]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

0.85

Notes
[203] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Pertussis PRN: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

325

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.712 ^[204]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.04

Notes
[204] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Pertussis PRN: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.206 ^[205]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.01

Notes
[205] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Pertussis PRN: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.066 ^[206]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

0.93

Notes
[206] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Pertussis PRN: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

324

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.085 ^[207]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

0.97

Notes
[207] - P-values were adjusted using false discovery rate procedure.

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Tetanus and Diphtheria Antibody 1 Month After the Infant Series

Top of page

End point title

Geometric Mean Concentration (GMC) for Antigen-specific Tetanus and Diphtheria Antibody 1 Month After the Infant Series

End point description

Geometric LS mean concentration (GMCs) were measured in International Units/mL (IU/mL) and corresponding 2-sided 95% CIs were evaluated for tetanus and diphtheria antibodies. mITT infant immunogenicity population. Paracetamol and Ibuprofen have been abbreviated as PCM and IBF, respectively in the statistical analysis titles.

End point type

Secondary

End point timeframe

1 month after the infant series

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant
Number of subjects analysed	132 ^[208]	143 ^[209]	141 ^[210]	131 ^[211]	193 ^[212]
Units: IU/mL
geometric mean (confidence interval 95%)
Tetanus	0.73 (0.65 to 0.83)	0.7 (0.62 to 0.79)	0.69 (0.61 to 0.77)	0.6 (0.53 to 0.68)	0.82 (0.74 to 0.9)
Diphtheria	0.62 (0.56 to 0.69)	0.68 (0.61 to 0.75)	0.61 (0.55 to 0.68)	0.65 (0.59 to 0.73)	0.65 (0.6 to 0.72)

Notes
[208] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[209] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[210] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[211] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[212] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Tetanus: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant v 13vPnC + INFANRIX Hexa:Infant

Number of subjects included in analysis

325

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.712 ^[213]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.06

Notes
[213] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Tetanus: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.206 ^[214]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

Notes
[214] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Tetanus: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.104 ^[215]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

0.98

Notes
[215] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Tetanus: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

324

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[216]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

0.87

Notes
[216] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Diphtheria: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

325

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.813 ^[217]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.09

Notes
[217] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Diphtheria: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.837 ^[218]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

1.19

Notes
[218] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Diphtheria: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.534 ^[219]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.07

Notes
[219] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Diphtheria: Ratio of GMCs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

324

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.961 ^[220]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.15

Notes
[220] - P-values were adjusted using false discovery rate procedure.

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Hepatitis B Virus (HBV) Antibody 1 Month After the Infant Series

Top of page

End point title

Geometric Mean Concentration (GMC) for Antigen-specific Hepatitis B Virus (HBV) Antibody 1 Month After the Infant Series

End point description

Geometric LS mean concentration (GMCs) were measured in milli international units/mL (mIU/mL) and corresponding 2-sided 95% CIs were evaluated for hepatitis B virus (HBV) antibody. mITT infant immunogenicity population. Paracetamol and Ibuprofen have been abbreviated as PCM and IBF, respectively in the statistical analysis titles.

End point type

Secondary

End point timeframe

1 month after the infant series

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant
Number of subjects analysed	105 ^[221]	116 ^[222]	120 ^[223]	112 ^[224]	156 ^[225]
Units: mIU/mL
geometric mean (confidence interval 95%)	756.42 (589.71 to 970.26)	770.93 (608.34 to 976.98)	689.34 (546.12 to 870.11)	599.12 (470.78 to 762.43)	733.29 (597.81 to 899.46)

Notes
[221] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[222] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[223] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[224] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[225] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant v 13vPnC + INFANRIX Hexa:Infant

Number of subjects included in analysis

261

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.85 ^[226]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

1.42

Notes
[226] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

272

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.837 ^[227]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.05

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.44

Notes
[227] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.695 ^[228]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.28

Notes
[228] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

268

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.408 ^[229]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.12

Notes
[229] - P-values were adjusted using false discovery rate procedure.

Secondary: Geometric Mean Titer (GMT) for Antigen-specific Poliomyelitis Type 1, 2 and 3 Antibodies 1 Month After the Infant Series

Top of page

End point title

Geometric Mean Titer (GMT) for Antigen-specific Poliomyelitis Type 1, 2 and 3 Antibodies 1 Month After the Infant Series

End point description

Geometric LS mean concentrations (GMCs) were measured as titers and corresponding 2-sided 95% CIs were evaluated for poliomyelitis type 1, 2 and 3 antibodies. mITT infant immunogenicity population. Paracetamol and Ibuprofen have been abbreviated as PCM and IBF, respectively in the statistical analysis titles.

End point type

Secondary

End point timeframe

1 month after the infant series

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant
Number of subjects analysed	89 ^[230]	105 ^[231]	93 ^[232]	84 ^[233]	135 ^[234]
Units: titer
geometric mean (confidence interval 95%)
Poliomyelitis Type 1	68.11 (53.14 to 87.3)	66.59 (52.98 to 83.68)	67.43 (52.89 to 85.96)	70.66 (54.73 to 91.23)	72.02 (58.88 to 88.1)
Poliomyelitis Type 2	79.6 (61.54 to 102.95)	73.52 (58.01 to 93.16)	62.12 (48.3 to 79.9)	55.17 (42.33 to 71.89)	67.37 (54.67 to 83.02)
Poliomyelitis Type 3	246.22 (192.84 to 314.38)	184.03 (146.96 to 230.46)	257.92 (203.08 to 327.56)	218.85 (170.18 to 281.44)	231.02 (189.44 to 281.72)

Notes
[230] - Subjects who were evaluable for this measure.
[231] - Subjects who were evaluable for this measure.
[232] - Subjects who were evaluable for this measure.
[233] - Subjects who were evaluable for this measure.
[234] - Subjects who were evaluable for this measure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Poliomyelitis Type 1: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant v 13vPnC + INFANRIX Hexa:Infant

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.813 ^[235]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.3

Notes
[235] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Poliomyelitis Type 1: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

240

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.837 ^[236]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.25

Notes
[236] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Poliomyelitis Type 1: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.695 ^[237]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.28

Notes
[237] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Poliomyelitis Type 1: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.961 ^[238]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.36

Notes
[238] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Poliomyelitis Type 2: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.808 ^[239]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.18

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.65

Notes
[239] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Poliomyelitis Type 2: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

240

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.837 ^[240]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.5

Notes
[240] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Poliomyelitis Type 2: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.695 ^[241]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

1.28

Notes
[241] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Poliomyelitis Type 2: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.408 ^[242]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

1.15

Notes
[242] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Poliomyelitis Type 3: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.813 ^[243]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.46

Notes
[243] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Poliomyelitis Type 3: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen twice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant

Number of subjects included in analysis

240

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.343 ^[244]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

1.08

Notes
[244] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Poliomyelitis Type 3: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Paracetamol thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.695 ^[245]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.52

Notes
[245] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Poliomyelitis Type 3: Ratio of GMTs along with 2-sided 95% CI were back transformed from the difference of the LS mean of 13vPnC + INFANRIX hexa + Ibuprofen thrice daily group minus the LS mean of 13vPnC + INFANRIX hexa group.

Comparison groups

13vPnC + INFANRIX Hexa:Infant v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.925 ^[246]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.31

Notes
[246] - P-values were adjusted using false discovery rate procedure.

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Haemophilus Influenzae Type b (Hib) Polyribosylribitol Phosphate (PRP) Antibody 1 Month After the Toddler Dose

Top of page

End point title

Geometric Mean Concentration (GMC) for Antigen-specific Haemophilus Influenzae Type b (Hib) Polyribosylribitol Phosphate (PRP) Antibody 1 Month After the Toddler Dose

End point description

Geometric LS mean concentration (GMCs) were measured in mcg/mL and corresponding 2-sided 95% CIs were evaluated for Hib PRP antibody. mITT toddler immunogenicity population. Paracetamol and Ibuprofen have been abbreviated as PCM and IBF, respectively in the statistical analysis titles.

End point type

Secondary

End point timeframe

1 month after the toddler dose

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler	13vPnC + INFANRIX Hexa:Toddler
Number of subjects analysed	126 ^[247]	135 ^[248]	141 ^[249]	138 ^[250]	202 ^[251]
Units: mcg/mL
geometric mean (confidence interval 95%)	9.65 (7.74 to 12.03)	9.35 (7.55 to 11.57)	8.25 (6.69 to 10.16)	7.84 (6.35 to 9.68)	8.96 (7.53 to 10.67)

Notes
[247] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[248] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[249] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[250] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[251] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler v 13vPnC + INFANRIX Hexa:Toddler

Number of subjects included in analysis

328

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.91 ^[252]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.43

Notes
[252] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

337

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.85 ^[253]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.37

Notes
[253] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

343

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.868 ^[254]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.21

Notes
[254] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.914 ^[255]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.15

Notes
[255] - P-values were adjusted using false discovery rate procedure.

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) Antibodies 1 Month After the Toddler Dose

Top of page

End point title

Geometric Mean Concentration (GMC) for Antigen-specific Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) Antibodies 1 Month After the Toddler Dose

End point description

Geometric LS mean concentration (GMCs) were measured in EU/mL and corresponding 2-sided 95% CIs were evaluated for pertussis (pertussis toxin [PT], filamentous hemagglutinin [FHA] and pertactin [PRN]) antibodies. mITT toddler immunogenicity population. Paracetamol and Ibuprofen have been abbreviated as PCM and IBF, respectively in the statistical analysis titles.

End point type

Secondary

End point timeframe

1 month after the toddler dose

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler	13vPnC + INFANRIX Hexa:Toddler
Number of subjects analysed	123 ^[256]	137 ^[257]	141 ^[258]	136 ^[259]	199 ^[260]
Units: EU/mL
geometric mean (confidence interval 95%)
Pertussis PT	77.43 (68.12 to 88.02)	76.93 (68.13 to 86.87)	73.72 (65.4 to 83.1)	73.38 (64.96 to 82.9)	74.01 (66.91 to 81.86)
Pertussis FHA	115.55 (104.32 to 128)	117.87 (106.98 to 129.87)	123.56 (112.3 to 135.95)	108.11 (98.09 to 119.16)	117.01 (107.97 to 126.81)
Pertussis PRN	158.28 (136.3 to 183.81)	156.98 (136.24 to 180.87)	160.96 (139.98 to 185.08)	158.71 (137.67 to 182.97)	172.8 (153.64 to 194.36)

Notes
[256] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[257] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[258] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[259] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[260] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler v 13vPnC + INFANRIX Hexa:Toddler

Number of subjects included in analysis

322

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.91 ^[261]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.05

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

1.23

Notes
[261] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.85 ^[262]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

1.22

Notes
[262] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.961 ^[263]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.16

Notes
[263] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

335

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.916 ^[264]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.16

Notes
[264] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

322

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.91 ^[265]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.12

Notes
[265] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler v 13vPnC + INFANRIX Hexa:Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.909 ^[266]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

1.14

Notes
[266] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.868 ^[267]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.2

Notes
[267] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

335

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.914 ^[268]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.05

Notes
[268] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

322

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.91 ^[269]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.11

Notes
[269] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.85 ^[270]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.09

Notes
[270] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.868 ^[271]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.12

Notes
[271] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

335

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.914 ^[272]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.1

Notes
[272] - P-values were adjusted using false discovery rate procedure.

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Tetanus and Diphtheria Antibodies 1 Month After the Toddler Dose

Top of page

End point title

Geometric Mean Concentration (GMC) for Antigen-specific Tetanus and Diphtheria Antibodies 1 Month After the Toddler Dose

End point description

Geometric LS mean concentration (GMCs) were measured in IU/mL and corresponding 2-sided 95% CIs were evaluated for tetanus and diphtheria antibodies. mITT toddler immunogenicity population. Paracetamol and Ibuprofen have been abbreviated as PCM and IBF, respectively in the statistical analysis titles.

End point type

Secondary

End point timeframe

1 month after the toddler dose

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler	13vPnC + INFANRIX Hexa:Toddler
Number of subjects analysed	123 ^[273]	137 ^[274]	141 ^[275]	136 ^[276]	199 ^[277]
Units: IU/mL
geometric mean (confidence interval 95%)
Tetanus	2.54 (2.28 to 2.83)	2.5 (2.26 to 2.77)	2.6 (2.35 to 2.88)	2.29 (2.07 to 2.54)	2.66 (2.44 to 2.89)
Diphtheria	1.64 (1.49 to 1.8)	1.94 (1.77 to 2.12)	1.69 (1.54 to 1.84)	1.87 (1.71 to 2.04)	1.9 (1.77 to 2.05)

Notes
[273] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[274] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen.
[275] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen
[276] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen
[277] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

322

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.91 ^[278]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.1

Notes
[278] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.85 ^[279]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.07

Notes
[279] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.939 ^[280]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.12

Notes
[280] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

335

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.279 ^[281]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

0.98

Notes
[281] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

322

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.149 ^[282]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

0.97

Notes
[282] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.85 ^[283]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.91

upper limit

1.14

Notes
[283] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

340

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.394 ^[284]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

0.99

Notes
[284] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

335

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.916 ^[285]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.1

Notes
[285] - P-values were adjusted using false discovery rate procedure.

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Hepatitis B Virus (HBV) Antibody 1 Month After the Toddler Dose

Top of page

End point title

Geometric Mean Concentration (GMC) for Antigen-specific Hepatitis B Virus (HBV) Antibody 1 Month After the Toddler Dose

End point description

Geometric LS mean concentration (GMCs) were measured in mIU/mL and corresponding 2-sided 95% CIs were evaluated for hepatitis B virus (HBV) antibody. mITT toddler immunogenicity population. Paracetamol and Ibuprofen have been abbreviated as PCM and IBF, respectively in the statistical analysis titles. Paracetamol and Ibuprofen have been abbreviated as PCM and IBF, respectively in the statistical analysis titles.

End point type

Secondary

End point timeframe

1 month after the toddler dose

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler	13vPnC + INFANRIX Hexa:Toddler
Number of subjects analysed	119 ^[286]	131 ^[287]	133 ^[288]	133 ^[289]	191 ^[290]
Units: mIU/mL
geometric mean (confidence interval 95%)	4868.61 (3750.57 to 6319.94)	4148.04 (3234.82 to 5319.08)	4250.41 (3320.88 to 5440.13)	4263.28 (3330.93 to 5456.6)	3866.37 (3146.78 to 4750.52)

Notes
[286] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen
[287] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen
[288] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen
[289] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen
[290] - Subjects with a determinate antibody concentration to the given concomitant vaccine antigen

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler v 13vPnC + INFANRIX Hexa:Toddler

Number of subjects included in analysis

310

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.869 ^[291]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.26

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

1.76

Notes
[291] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

322

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.85 ^[292]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.48

Notes
[292] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

324

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.868 ^[293]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.52

Notes
[293] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

324

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.916 ^[294]

Method

General Linear Model

Parameter type

GMC Ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.52

Notes
[294] - P-values were adjusted using false discovery rate procedure.

Secondary: Geometric Mean Titer (GMT) for Antigen-specific Poliomyelitis Type 1, 2 and 3 Antibodies 1 Month After the Toddler Dose

Top of page

End point title

Geometric Mean Titer (GMT) for Antigen-specific Poliomyelitis Type 1, 2 and 3 Antibodies 1 Month After the Toddler Dose

End point description

Geometric LS mean concentration (GMCs) were measured as titers and corresponding 2-sided 95% CIs were evaluated for poliomyelitis type 1, 2 and 3 antibodies. mITT toddler immunogenicity population. Paracetamol and Ibuprofen have been abbreviated as PCM and IBF, respectively in the statistical analysis titles.

End point type

Secondary

End point timeframe

1 month after the toddler dose

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler	13vPnC + INFANRIX Hexa:Toddler
Number of subjects analysed	123 ^[295]	133 ^[296]	141 ^[297]	136 ^[298]	201 ^[299]
Units: titer
geometric mean (confidence interval 95%)
Poliomyelitis Type 1	399.56 (332.13 to 480.68)	426.63 (357.15 to 509.62)	443.97 (373.58 to 527.63)	415.45 (348.48 to 495.29)	406.37 (351.67 to 469.59)
Poliomyelitis Type 2	613.18 (515.3 to 729.65)	586.3 (496.01 to 693.03)	587.56 (499.47 to 691.18)	605.78 (513.44 to 714.73)	621.07 (542.07 to 711.57)
Poliomyelitis Type 3	1205.8 (1001.18 to 1452.24)	1045.57 (874.35 to 1250.32)	1210.29 (1017.32 to 1439.87)	1187.11 (994.68 to 1416.76)	1237.86 (1070.27 to 1431.7)

Notes
[295] - Subjects who were evaluable for this measure.
[296] - Subjects who were evaluable for this measure.
[297] - Subjects who were evaluable for this measure.
[298] - Subjects who were evaluable for this measure.
[299] - Subjects who were evaluable for this measure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler v 13vPnC + INFANRIX Hexa:Toddler

Number of subjects included in analysis

324

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.91 ^[300]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.24

Notes
[300] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.85 ^[301]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.05

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.32

Notes
[301] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

342

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.868 ^[302]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.37

Notes
[302] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

337

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.916 ^[303]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.28

Notes
[303] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

324

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.91 ^[304]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.23

Notes
[304] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.85 ^[305]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.17

Notes
[305] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

342

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.868 ^[306]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.17

Notes
[306] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

337

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.916 ^[307]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.21

Notes
[307] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler

Number of subjects included in analysis

324

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.91 ^[308]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.23

Notes
[308] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Twice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler

Number of subjects included in analysis

334

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.85 ^[309]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.06

Notes
[309] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+PCM Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler

Number of subjects included in analysis

342

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.939 ^[310]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.23

Notes
[310] - P-values were adjusted using false discovery rate procedure.

13vPnC+INFANRIX+IBF Thrice vs 13vPnC+INFANRIX

Statistical analysis description

Comparison groups

13vPnC + INFANRIX Hexa:Toddler v 13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler

Number of subjects included in analysis

337

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.916 ^[311]

Method

General Linear Model

Parameter type

GMT Ratio

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.21

Notes
[311] - P-values were adjusted using false discovery rate procedure.

Secondary: Percentage of Subjects Achieving Pre-specified Criteria for the Concomitant Antigens Contained in INFANRIX Hexa 1 Month After the Infant Series

Top of page

End point title

Percentage of Subjects Achieving Pre-specified Criteria for the Concomitant Antigens Contained in INFANRIX Hexa 1 Month After the Infant Series

End point description

Percentage of subjects achieving pre-specified criteria for concomitant antigens contained in INFANRIX hexa (Hib polyribosylribitol phosphate [PRP] >=0.15 mcg/mL; Hib PRP >=1 mcg/mL; Pertussis PT >=14.6 EU/mL, FHA >=16.1 EU/mL, PRN >=24.0 EU/mL; Tetanus >=0.1 IU/mL; Diphtheria >=0.1 IU/mL; HBV >=10 mIU/mL; Poliomyelitis Type 1, 2, 3 >=1:8 titer) along with the corresponding 95% CIs were presented. Exact 2-sided CI based on the observed proportion of subjects. Pre-specified criteria for pertussis was the level that 95% of the subjects achieved in 13vPnC + INFANRIX hexa group. mITT infant immunogenicity population. Here ‘n’ signifies subjects with a determinate antibody concentration or titer to the given concomitant vaccine antigen for each arm respectively.

End point type

Secondary

End point timeframe

1 month after the infant series

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant
Number of subjects analysed	136 ^[312]	146 ^[313]	144 ^[314]	139 ^[315]	198 ^[316]
Units: percentage of subjects
number (confidence interval 95%)
Hib PRP >=0.15 mcg/mL (n= 136, 146, 144, 139, 198)	87.5 (80.7 to 92.5)	84.2 (77.3 to 89.7)	86.1 (79.4 to 91.3)	85.6 (78.7 to 91)	87.9 (82.5 to 92.1)
Hib PRP >=1 mcg/mL (n = 136, 146, 144, 139, 198)	33.8 (25.9 to 42.4)	37 (29.2 to 45.4)	27.1 (20 to 35.1)	28.1 (20.8 to 36.3)	33.8 (27.3 to 40.9)
Pertussis PT >=14.6 EU/mL (n= 132,143,141,131,193)	93.2 (87.5 to 96.8)	97.2 (93 to 99.2)	91.5 (85.6 to 95.5)	90.8 (84.5 to 95.2)	95.3 (91.3 to 97.8)
Pertussis FHA >=16.1 EU/mL (n=132,143,141,131,193)	96.2 (91.4 to 98.8)	92.3 (86.7 to 96.1)	93.6 (88.2 to 97)	88.5 (81.8 to 93.4)	95.3 (91.3 to 97.8)
Pertussis PRN >=24.0 EU/mL (n=132,143,141,131,193)	90.9 (84.7 to 95.2)	87.4 (80.8 to 92.4)	88.7 (82.2 to 93.4)	89.3 (82.7 to 94)	95.3 (91.3 to 97.8)
Tetanus >=0.1 IU/mL (n = 132,143,141,131,193)	100 (97.2 to 100)	100 (97.5 to 100)	100 (97.4 to 100)	98.5 (94.6 to 99.8)	99.5 (97.1 to 100)
Diphtheria >=0.1 IU/mL (n = 132,143,141,131,193)	100 (97.2 to 100)	98.6 (95 to 99.8)	99.3 (96.1 to 100)	97.7 (93.5 to 99.5)	99.5 (97.1 to 100)
HBV >= 10mIU/mL (n = 105,116,120,112,156)	100 (96.5 to 100)	99.1 (95.3 to 100)	99.2 (95.4 to 100)	99.1 (95.1 to 100)	98.7 (95.4 to 99.8)
PoliomyelitisType1 >=1:8titer (n=89,105,93,84,135)	97.8 (92.1 to 99.7)	98.1 (93.3 to 99.8)	97.8 (92.4 to 99.7)	100 (95.7 to 100)	99.3 (95.9 to 100)
PoliomyelitisType2 >=1:8titer (n=89,105,93,84,135)	95.5 (88.9 to 98.8)	98.1 (93.3 to 99.8)	95.7 (89.4 to 98.8)	96.4 (89.9 to 99.3)	95.6 (90.6 to 98.4)
PoliomyelitisType3 >=1:8titer (n=89,105,93,84,135)	100 (95.9 to 100)	100 (96.5 to 100)	98.9 (94.2 to 100)	98.8 (93.5 to 100)	99.3 (95.9 to 100)

Notes
[312] - Subjects who were evaluable for this measure.
[313] - Subjects who were evaluable for this measure.
[314] - Subjects who were evaluable for this measure.
[315] - Subjects who were evaluable for this measure.
[316] - Subjects who were evaluable for this measure.

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving Pre-specified Criteria for the Concomitant Antigens Contained in INFANRIX Hexa 1 Month After the Toddler Dose

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End point title

Percentage of Subjects Achieving Pre-specified Criteria for the Concomitant Antigens Contained in INFANRIX Hexa 1 Month After the Toddler Dose

End point description

Percentage of subjects achieving pre-specified criteria for concomitant antigens contained in INFANRIX hexa (Hib polyribosylribitol phosphate [PRP] >=0.15 mcg/mL; Hib PRP >=1 mcg/mL; Pertussis PT >=14.8 EU/mL, FHA >=46.5 EU/mL, PRN >=43.5 EU/mL; Tetanus >=0.1 IU/mL; Diphtheria >=0.1 IU/mL; HBV >=10 mIU/mL; Poliomyelitis Type 1, 2, 3 >=1:8 titer) along with the corresponding 95% CIs were presented. Exact 2-sided CI based on the observed proportion of subjects. Pre-specified criteria for pertussis was the level that 95% of the subjects achieved in 13vPnC + INFANRIX hexa group. mITT toddler immunogenicity population. Here ‘n’ signifies subjects with a determinate antibody concentration or titer to the given concomitant vaccine antigen for each arm respectively.

End point type

Secondary

End point timeframe

1 month after the toddler dose

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler	13vPnC + INFANRIX Hexa:Toddler
Number of subjects analysed	126 ^[317]	137 ^[318]	141 ^[319]	138 ^[320]	202 ^[321]
Units: percentage of subjects
number (confidence interval 95%)
Hib PRP >=0.15 mcg/mL (n= 126, 135, 141, 138, 202)	100 (97.1 to 100)	99.3 (95.9 to 100)	100 (97.4 to 100)	100 (97.4 to 100)	100 (98.2 to 100)
Hib PRP >=1 mcg/mL (n = 126, 135, 141, 138, 202)	95.2 (89.9 to 98.2)	96.3 (91.6 to 98.8)	95.7 (91 to 98.4)	95.7 (90.8 to 98.4)	95 (91.1 to 97.6)
Pertussis PT >=14.8 EU/mL (n= 123,137,141,136,199)	97.6 (93 to 99.5)	99.3 (96 to 100)	98.6 (95 to 99.8)	100 (97.3 to 100)	95.5 (91.6 to 97.9)
Pertussis FHA >=46.5 EU/mL (n=123,137,141,136,199)	91.1 (84.6 to 95.5)	94.9 (89.8 to 97.9)	93.6 (88.2 to 97)	92.6 (86.9 to 96.4)	95.5 (91.6 to 97.9)
Pertussis PRN >=43.5 EU/mL (n=123,137,141,136,199)	91.9 (85.6 to 96)	94.9 (89.8 to 97.9)	94.3 (89.1 to 97.5)	94.1 (88.7 to 97.4)	95.5 (91.6 to 97.9)
Tetanus >=0.1 IU/mL (n = 123,137,141,136,199)	100 (97 to 100)	100 (97.3 to 100)	100 (97.4 to 100)	100 (97.3 to 100)	100 (98.2 to 100)
Diphtheria >=0.1 IU/mL (n = 123,137,141,136,199)	100 (97 to 100)	100 (97.3 to 100)	100 (97.4 to 100)	100 (97.3 to 100)	100 (98.2 to 100)
HBV >= 10 mIU/mL (n = 119,131,133,133,191)	100 (96.9 to 100)	98.5 (94.6 to 99.8)	100 (97.3 to 100)	100 (97.3 to 100)	99.5 (97.1 to 100)
Poliomyelitis 1 >=1:8titer (n=123,133,141,136,201)	99.2 (95.6 to 100)	100 (97.3 to 100)	100 (97.4 to 100)	100 (97.3 to 100)	99.5 (97.3 to 100)
Poliomyelitis 2 >=1:8titer (n=123,133,141,136,201)	100 (97 to 100)	100 (97.3 to 100)	100 (97.4 to 100)	100 (97.3 to 100)	100 (98.2 to 100)
Poliomyelitis 3 >=1:8titer (n=123,133,141,136,201)	100 (97 to 100)	100 (97.3 to 100)	100 (97.4 to 100)	100 (97.3 to 100)	100 (98.2 to 100)

Notes
[317] - Subjects who were evaluable for this measure.
[318] - Subjects who were evaluable for this measure.
[319] - Subjects who were evaluable for this measure.
[320] - Subjects who were evaluable for this measure.
[321] - Subjects who were evaluable for this measure.

No statistical analyses for this end point

Secondary: Percentage of Subjects Reporting Fever Within 4 Days: Infant Series Dose 1

Top of page

End point title

Percentage of Subjects Reporting Fever Within 4 Days: Infant Series Dose 1

End point description

Subjects' core (rectal) temperature was collected for 4 days after each vaccination using an electronic diary. Subjects' temperature was collected at 6 to 8 hours after vaccination, 6 to 8 hours following that and coincidentally with antipyretic administration for groups receiving antipyretics. Temperature was recorded at bedtime daily for 3 following days (Day 2 to Day 4) and at any time during the 3 days when fever was suspected. The highest temperature for each day was recorded in the e-diary. Incidences of fever were presented in following categories: >=38 but <=39 degree Celsius (degree C), greater than (>) 39 but <=40 degree C and >40 degree C.Safety analysis set Dose 1: subjects who received Dose 1 of 13vPnC/INFANRIX hexa in infant series, had Adverse Event (AE) or temperature data. Here ‘n’ signifies subjects reporting yes for >=1 day or no for all days for specified event for each arm respectively.

End point type

Secondary

End point timeframe

Within 4 days after infant series Dose 1

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant
Number of subjects analysed	149 ^[322]	157 ^[323]	147 ^[324]	155 ^[325]	187 ^[326]
Units: percentage of subjects
number (not applicable)
Fever >=38, <=39 degree C (n= 149,157,147,155,187)	32.9	45.2	18.4	34.2	41.7
Fever >39, <=40 degree C (n = 138,145,137,146,170)	1.4	1.4	0.7	0.7	1.2
Fever >40 degree C (n = 138,145,137,146,170)	0	0	0	0	0

Notes
[322] - Subjects reported yes for greater than or equal to (>=) 1 day or no for all days.
[323] - Subjects reported yes for greater than or equal to (>=) 1 day or no for all days.
[324] - Subjects reported yes for greater than or equal to (>=) 1 day or no for all days.
[325] - Subjects reported yes for greater than or equal to (>=) 1 day or no for all days.
[326] - Subjects reported yes for greater than or equal to (>=) 1 day or no for all days.

No statistical analyses for this end point

Secondary: Percentage of Subjects Reporting Fever Within 4 Days: Infant Series Dose 2

Top of page

End point title

Percentage of Subjects Reporting Fever Within 4 Days: Infant Series Dose 2

End point description

Subjects' rectal temperature was collected for 4 days after each vaccination using an electronic diary. Subjects' temperature was collected at 6 to 8 hours after vaccination, 6 to 8 hours following that and coincidentally with antipyretic administration for groups receiving antipyretics. Temperature was recorded at bedtime daily for 3 following days (Day 2 to Day 4) and at any time during the 3 days when fever was suspected. The highest temperature for each day was recorded in the e-diary. Incidences of fever were presented in following categories: >=38 but <=39 degree C, >39 but <=40 degree C and >40 degree C. Safety analysis set Dose 2: subjects who received Dose 2 of 13vPnC/INFANRIX hexa in infant series and had AE or temperature data available. Here, ‘n’ signifies subjects reporting yes for >=1 day or no for all days for specified event for each arm respectively.

End point type

Secondary

End point timeframe

Within 4 days after infant series Dose 2

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant
Number of subjects analysed	141 ^[327]	152 ^[328]	140 ^[329]	159 ^[330]	181 ^[331]
Units: percentage of subjects
number (not applicable)
Fever >=38, <=39 degree C (n= 141,152,140,159,181)	26.2	42.8	21.4	44	39.8
Fever >39, <=40 degree C (n = 133,140,134,145,164)	1.5	0.7	1.5	1.4	3.7
Fever >40 degree C (n = 131,140,133,144,164)	0	0	0	0	0

Notes
[327] - Subjects reported yes for greater than or equal to (>=) 1 day or no for all days.
[328] - Subjects reported yes for greater than or equal to (>=) 1 day or no for all days.
[329] - Subjects reported yes for greater than or equal to (>=) 1 day or no for all days.
[330] - Subjects reported yes for greater than or equal to (>=) 1 day or no for all days.
[331] - Subjects reported yes for greater than or equal to (>=) 1 day or no for all days.

No statistical analyses for this end point

Secondary: Percentage of Subjects Reporting Fever Within 4 Days: Infant Series Dose 3

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End point title

Percentage of Subjects Reporting Fever Within 4 Days: Infant Series Dose 3

End point description

Subjects' rectal temperature was collected for 4 days after each vaccination using an electronic diary. Subjects' temperature was collected at 6 to 8 hours after vaccination, 6 to 8 hours following that and coincidentally with antipyretic administration for groups receiving antipyretics. Temperature was recorded at bedtime daily for 3 following days (Day 2 to Day 4) and at any time during the 3 days when fever was suspected. The highest temperature for each day was recorded in the e-diary. Incidences of fever were presented in following categories: >=38 but <=39 degree C, >39 but <=40 degree C and >40 degree C. Report of fever >40 degrees C after 13vPnC Infant Series Dose 3 was confirmed as data entry error.Safety analysis set Dose 3: subjects who received Dose 3 of 13vPnC/INFANRIX hexa in infant series and had AE or temperature data available.Here,‘n' signifies subjects reporting yes for >=1 day or no for all days for specified event for each arm respectively.

End point type

Secondary

End point timeframe

Within 4 days after infant series Dose 3

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant
Number of subjects analysed	136 ^[332]	146 ^[333]	135 ^[334]	141 ^[335]	175 ^[336]
Units: percentage of subjects
number (not applicable)
Fever >=38, <=39 degree C (n= 136,146,135,141,175)	22.1	30.8	17	33.3	29.7
Fever >39, <=40 degree C (n = 129,137,125,136,167)	1.6	2.9	0.8	1.5	1.8
Fever >40 degree C (n = 128,136,126,135,166)	0	0	0.8	0	0

Notes
[332] - Subjects reported yes for greater than or equal to (>=) 1 day or no for all days.
[333] - Subjects reported yes for greater than or equal to (>=) 1 day or no for all days.
[334] - Subjects reported yes for greater than or equal to (>=) 1 day or no for all days.
[335] - Subjects reported yes for greater than or equal to (>=) 1 day or no for all days.
[336] - Subjects reported yes for greater than or equal to (>=) 1 day or no for all days.

No statistical analyses for this end point

Secondary: Percentage of Subjects Reporting Fever Within 4 Days: Toddler Dose

Top of page

End point title

Percentage of Subjects Reporting Fever Within 4 Days: Toddler Dose

End point description

Subjects' rectal temperature was collected for 4 days after each vaccination using an electronic diary. Subjects' temperature was collected at 6 to 8 hours after vaccination, 6 to 8 hours following that and coincidentally with antipyretic administration for groups receiving antipyretics. Temperature was recorded at bedtime daily for 3 following days (Day 2 to Day 4) and at any time during the 3 days when fever was suspected. The highest temperature for each day was recorded in the e-diary. Incidences of fever were presented in following categories: >=38 but <=39 degree C, >39 but <=40 degree C and >40 degree C.Safety analysis set toddler dose: subjects who receive toddler dose of 13vPnC or INFANRIX hexa and had AE or temperature data available.Here,‘n’ signifies subjects reporting yes for >=1 day or no for all days for specified event for each arm, respectively.

End point type

Secondary

End point timeframe

Within 4 days after toddler dose

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler	13vPnC + INFANRIX Hexa:Toddler
Number of subjects analysed	133 ^[337]	140 ^[338]	134 ^[339]	144 ^[340]	162 ^[341]
Units: percentage of subjects
number (not applicable)
Fever >=38, <=39 degree C (n= 133,140,134,144,162)	31.6	37.1	37.3	50	30.2
Fever >39, <=40 degree C (n = 128,127,118,123,150)	5.5	7.1	4.2	5.7	2
Fever >40 degree C (n = 123,125,117,122,150)	0	0	0	0	0

Notes
[337] - Subjects reported yes for greater than or is equal to (>=) 1 day or no for all days.
[338] - Subjects reported yes for greater than or is equal to (>=) 1 day or no for all days.
[339] - Subjects reported yes for greater than or is equal to (>=) 1 day or no for all days.
[340] - Subjects reported yes for greater than or is equal to (>=) 1 day or no for all days.
[341] - Subjects reported yes for greater than or is equal to (>=) 1 day or no for all days.

No statistical analyses for this end point

Secondary: Number of Subjects With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): Infant Series

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End point title

Number of Subjects With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): Infant Series

End point description

An AE was any untoward medical occurrence in a subject who received vaccine without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent events for infant series were events between infant series Dose 1 and up to 1 month (28 to 42 days) after infant series that were absent before treatment or that worsened relative to pre-treatment state. Reported non-SAEs included AEs other than SAEs collected using electronic diary (fever, systematic assessment) and events spontaneously collected on case report form at each visit (non-systematic assessment).Safety analysis set Dose 1 included all subjects who receive Dose 1 of 13vPnC or INFANRIX hexa in infant series and had AE or temperature data available.

End point type

Secondary

End point timeframe

Baseline up to 1 Month (28 to 42 days) after infant series.

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Infant	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Infant	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Infant	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Infant	13vPnC + INFANRIX Hexa:Infant
Number of subjects analysed	173	176	172	177	210
Units: subjects
number (not applicable)
Non-SAEs	57	71	67	72	80
SAEs	7	3	11	8	10

No statistical analyses for this end point

Secondary: Number of Subjects With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): After the Infant Series

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End point title

Number of Subjects With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): After the Infant Series

End point description

An AE was any untoward medical occurrence in a subject who received vaccine without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent events after the infant series were events between 1 month (28 to 42 days) after infant series to toddler dose that were absent before treatment or that worsened relative to pre-treatment state. Reported non-SAEs included AEs other than SAEs spontaneously collected on case report form (non-systematic assessment). Safety analysis set Dose 3 included all subjects who receive Dose 3 of 13vPnC or INFANRIX hexa in infant series and had AE or temperature data available.

End point type

Secondary

End point timeframe

1 Month (28 to 42 days) after infant series Dose 3 up to toddler dose

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily	13vPnC + INFANRIX Hexa
Number of subjects analysed	170	174	172	176	210
Units: subjects
number (not applicable)
Non-SAEs	3	6	3	4	8
SAEs	6	14	10	11	9

No statistical analyses for this end point

Secondary: Number of Subjects With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): Toddler Dose

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End point title

Number of Subjects With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): Toddler Dose

End point description

An AE was any untoward medical occurrence in a subject who received vaccine without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent events for toddler dose were events between toddler dose and up to 1 month (28 to 42 days) after toddler dose that were absent before treatment or that worsened relative to pre-treatment state. Reported non-SAEs included AEs other than SAEs collected using electronic diary (fever, systematic assessment) and events spontaneously collected on case report form at each visit (non-systematic assessment).Safety analysis set toddler dose included all subjects who receive toddler dose of 13vPnC or INFANRIX hexa and had AE or temperature data available.

End point type

Secondary

End point timeframe

Toddler dose up to 1 Month (28 to 42 days) after toddler dose

End point values	13vPnC + INFANRIX Hexa + Paracetamol Twice Daily: Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily:Toddler	13vPnC + INFANRIX Hexa + Paracetamol Thrice Daily:Toddler	13vPnC + INFANRIX Hexa + Ibuprofen Thrice Daily:Toddler	13vPnC + INFANRIX Hexa:Toddler
Number of subjects analysed	169	173	170	175	209
Units: subjects
number (not applicable)
Non-SAEs	47	57	52	76	50
SAEs	3	2	1	1	1

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

AEs/SAEs: recorded from signing of informed consent form to completion of study. Subjects recorded pre-specified AEs in electronic diary: fever (up to 4 days after each vaccine dose).

Adverse event reporting additional description

Safety population: subjects who received at least 1 dose of study vaccine. SAEs and AEs were grouped by system organ class and summarized. AEs included AEs collected in electronic diary (fever, systematic assessment) and events collected on case report form at each visit (nonsystematic assessment).

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

0.0

Reporting group title

13vPnC+ INFANRIX Hexa +Paracetamol Twice Daily -Infant Series

Reporting group description

Subjects who received 3 open-label doses (0.5 mL each) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions 28 to 42 days apart in infant series, along with paracetamol suspension 15 mg/kg orally at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of paracetamol, assessed from Infant series Dose 1 through the blood draw 28 to 42 days post infant series.

Reporting group title

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily -Infant Series

Reporting group description

Subjects who received 3 open-label doses (0.5 mL each) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions 28 to 42 days apart, along with ibuprofen suspension 10 mg/kg orally at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of ibuprofen, assessed from Infant series Dose 1 through the blood draw 28 to 42 days post infant series.

Reporting group title

13vPnC+INFANRIX Hexa+Paracetamol Thrice Daily -Infant Series

Reporting group description

Subjects who received 3 open-label doses (0.5 mL each) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions 28 to 42 days apart, along with paracetamol suspension 15 mg/kg orally immediately after each vaccination, 6 to 8 hours after each vaccination and 6 to 8 hours after last dose of paracetamol, assessed from Infant series Dose 1 through the blood draw 28 to 42 days post infant series.

Reporting group title

13vPnC+ INFANRIX Hexa+ Ibuprofen Thrice Daily -Infant Series

Reporting group description

Subjects who received 3 open-label doses (0.5 mL each) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions 28 to 42 days apart, along with ibuprofen suspension 10 mg/kg orally immediately after each vaccination, 6 to 8 hours after each vaccination and 6 to 8 hours after last dose of ibuprofen, assessed from Infant series Dose 1 through the blood draw 28 to 42 days post infant series.

Reporting group title

13vPnC + INFANRIX Hexa - Infant Series

Reporting group description

Subjects who received 3 open-label doses (0.5 mL each) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions 28 to 42 days apart, assessed from Infant series Dose 1 through the blood draw 28 to 42 days post infant series (Inf Ser).

Reporting group title

13vPnC +INFANRIX Hexa +Paracetamol Twice Daily -After Inf Ser

Reporting group description

Subjects who received 3 open-label doses (0.5 mL each) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions 28 to 42 days apart in infant series (Inf Ser), along with paracetamol suspension 15 mg/kg orally at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of paracetamol, assessed after the infant series blood draw up to toddler dose.

Reporting group title

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily -After Inf Ser

Reporting group description

Subjects who received 3 open-label doses (0.5 mL each) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions 28 to 42 days apart in infant series (Inf Ser), along with ibuprofen suspension 10 mg/kg orally at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of ibuprofen, assessed after the infant series blood draw up to toddler dose.

Reporting group title

13vPnC+INFANRIX Hexa +Paracetamol Thrice Daily -After Inf Ser

Reporting group description

Subjects who received 3 open-label doses (0.5 mL each) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions 28 to 42 days apart in infant series (Inf Ser), along with paracetamol suspension 15 mg/kg orally immediately after each vaccination, 6 to 8 hours after each vaccination and 6 to 8 hours after last dose of paracetamol, assessed after the infant series blood draw up to toddler dose.

Reporting group title

13vPnC +INFANRIX Hexa +Ibuprofen Thrice Daily -After Inf Ser

Reporting group description

Subjects who received 3 open-label doses (0.5 mL each) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions 28 to 42 days apart in infant series (Inf Ser), along with ibuprofen suspension 10 mg/kg orally immediately after each vaccination, 6 to 8 hours after each vaccination and 6 to 8 hours after last dose of ibuprofen, assessed after the infant series blood draw up to toddler dose.

Reporting group title

13vPnC + INFANRIX Hexa - After Infant Series

Reporting group description

Reporting group title

13vPnC +INFANRIX Hexa + Paracetamol Twice Daily -Toddler Dose

Reporting group description

Subjects who received 3 open-label doses (0.5 mL each) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions 28 to 42 days apart in infant series and toddler dose (0.5 mL) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions at 366 to 425 days of age, along with paracetamol suspension 15 mg/kg orally at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of paracetamol, assessed from the toddler dose through the blood draw 28 to 42 days post toddler dose.

Reporting group title

13vPnC +INFANRIX Hexa + Ibuprofen Twice Daily -Toddler Dose

Reporting group description

Subjects who received 3 open-label doses (0.5 mL each) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions 28 to 42 days apart in infant series and toddler dose (0.5 mL) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions at 366 to 425 days of age, along with ibuprofen suspension 10 mg/kg orally at 6 to 8 hours after each vaccination and 6 to 8 hours after first dose of ibuprofen, assessed from the toddler dose through the blood draw 28 to 42 days post toddler dose.

Reporting group title

13vPnC +INFANRIX Hexa +Paracetamol Thrice Daily -Toddler Dose

Reporting group description

Subjects who received 3 open-label doses (0.5 mL each) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions 28 to 42 days apart in infant series and toddler dose (0.5 mL) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions at 366 to 425 days of age, along with paracetamol suspension 15 mg/kg orally immediately after each vaccination, 6 to 8 hours after each vaccination and 6 to 8 hours after last dose of paracetamol, assessed from the toddler dose through the blood draw 28 to 42 days post toddler dose.

Reporting group title

13vPnC +INFANRIX Hexa +Ibuprofen Thrice Daily -Toddler Dose

Reporting group description

Subjects who received 3 open-label doses (0.5 mL each) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions 28 to 42 days apart in infant series and toddler dose (0.5 mL) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions at 366 to 425 days of age, along with ibuprofen suspension 15 mg/kg orally immediately after each vaccination, 6 to 8 hours after each vaccination and 6 to 8 hours after last dose of ibuprofen, assessed from the toddler dose through the blood draw 28 to 42 days post toddler dose.

Reporting group title

13vPnC + INFANRIX Hexa - Toddler Dose

Reporting group description

Subjects who received 3 open-label doses (0.5 mL each) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions 28 to 42 days apart in infant series and toddler dose (0.5 mL) of 13vPnC intramuscularly and INFANRIX hexa intramuscularly as per manufacturer’s instructions at 366 to 425 days of age, assessed from the toddler dose through the blood draw 28 to 42 days post toddler dose.

13vPnC+ INFANRIX Hexa +Paracetamol Twice Daily -Infant Series

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily -Infant Series

13vPnC+INFANRIX Hexa+Paracetamol Thrice Daily -Infant Series

13vPnC+ INFANRIX Hexa+ Ibuprofen Thrice Daily -Infant Series

13vPnC + INFANRIX Hexa - Infant Series

13vPnC +INFANRIX Hexa +Paracetamol Twice Daily -After Inf Ser

13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily -After Inf Ser

13vPnC+INFANRIX Hexa +Paracetamol Thrice Daily -After Inf Ser

13vPnC +INFANRIX Hexa +Ibuprofen Thrice Daily -After Inf Ser

13vPnC + INFANRIX Hexa - After Infant Series

13vPnC +INFANRIX Hexa + Paracetamol Twice Daily -Toddler Dose

13vPnC +INFANRIX Hexa + Ibuprofen Twice Daily -Toddler Dose

13vPnC +INFANRIX Hexa +Paracetamol Thrice Daily -Toddler Dose

13vPnC +INFANRIX Hexa +Ibuprofen Thrice Daily -Toddler Dose

13vPnC + INFANRIX Hexa - Toddler Dose

Total subjects affected by serious adverse events

subjects affected / exposed

7 / 173 (4.05%)

3 / 176 (1.70%)

11 / 172 (6.40%)

8 / 177 (4.52%)

10 / 210 (4.76%)

6 / 170 (3.53%)

14 / 174 (8.05%)

10 / 172 (5.81%)

11 / 176 (6.25%)

9 / 210 (4.29%)

3 / 169 (1.78%)

2 / 173 (1.16%)

1 / 170 (0.59%)

1 / 175 (0.57%)

1 / 209 (0.48%)

number of deaths (all causes)

number of deaths resulting from adverse events

Injury, poisoning and procedural complications

Head injury

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

1 / 210 (0.48%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

2 / 169 (1.18%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Thermal burn

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

1 / 174 (0.57%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Exposure to toxic agent

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

1 / 172 (0.58%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Congenital, familial and genetic disorders

Ventricular septal defect

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

1 / 210 (0.48%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Movement disorder

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

1 / 170 (0.59%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Stomatitis

subjects affected / exposed

1 / 173 (0.58%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrooesophageal reflux disease

subjects affected / exposed

0 / 173 (0.00%)

1 / 176 (0.57%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

1 / 172 (0.58%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Diarrhoea haemorrhagic

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

1 / 210 (0.48%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Diarrhoea

subjects affected / exposed

0 / 173 (0.00%)

1 / 176 (0.57%)

0 / 172 (0.00%)

0 / 177 (0.00%)

1 / 210 (0.48%)

0 / 170 (0.00%)

1 / 174 (0.57%)

1 / 172 (0.58%)

2 / 176 (1.14%)

3 / 210 (1.43%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Constipation

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

1 / 172 (0.58%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rectal haemorrhage

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

1 / 172 (0.58%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Hyperbilirubinaemia

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

1 / 172 (0.58%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Bronchitis chronic

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

1 / 176 (0.57%)

1 / 210 (0.48%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

Dermatitis

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

1 / 170 (0.59%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

1 / 173 (0.58%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Breath holding

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

1 / 209 (0.48%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Infections and infestations

Gastroenteritis

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

1 / 177 (0.56%)

1 / 210 (0.48%)

2 / 170 (1.18%)

4 / 174 (2.30%)

0 / 172 (0.00%)

1 / 176 (0.57%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

1 / 170 (0.59%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 4

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pharyngitis

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

1 / 175 (0.57%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Upper respiratory tract infection

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

1 / 172 (0.58%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

2 / 174 (1.15%)

0 / 172 (0.00%)

1 / 176 (0.57%)

0 / 210 (0.00%)

0 / 169 (0.00%)

1 / 173 (0.58%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Viral infection

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

1 / 169 (0.59%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

1 / 173 (0.58%)

2 / 176 (1.14%)

1 / 172 (0.58%)

2 / 177 (1.13%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

1 / 172 (0.58%)

2 / 176 (1.14%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 2

0 / 1

0 / 2

0 / 0

0 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

2 / 173 (1.16%)

0 / 176 (0.00%)

3 / 172 (1.74%)

2 / 177 (1.13%)

2 / 210 (0.95%)

1 / 170 (0.59%)

1 / 174 (0.57%)

2 / 172 (1.16%)

2 / 176 (1.14%)

1 / 210 (0.48%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 4

0 / 2

0 / 1

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pertussis

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

1 / 210 (0.48%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Otitis media acute

subjects affected / exposed

1 / 173 (0.58%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

1 / 176 (0.57%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Otitis media

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

1 / 210 (0.48%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

1 / 176 (0.57%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nasopharyngitis

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

1 / 177 (0.56%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lower respiratory tract infection

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

1 / 177 (0.56%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Laryngitis

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

1 / 172 (0.58%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

1 / 172 (0.58%)

0 / 176 (0.00%)

1 / 210 (0.48%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Exanthema subitum

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

1 / 172 (0.58%)

0 / 177 (0.00%)

0 / 210 (0.00%)

1 / 170 (0.59%)

0 / 174 (0.00%)

1 / 172 (0.58%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchopneumonia

subjects affected / exposed

2 / 173 (1.16%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

1 / 210 (0.48%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchitis

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

1 / 172 (0.58%)

2 / 177 (1.13%)

0 / 210 (0.00%)

0 / 170 (0.00%)

1 / 174 (0.57%)

0 / 172 (0.00%)

2 / 176 (1.14%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchiolitis

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

1 / 172 (0.58%)

0 / 177 (0.00%)

1 / 210 (0.48%)

0 / 170 (0.00%)

0 / 174 (0.00%)

1 / 172 (0.58%)

1 / 176 (0.57%)

1 / 210 (0.48%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bacterial infection

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

1 / 174 (0.57%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ear infection

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

1 / 174 (0.57%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis Escherichia coli

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

1 / 176 (0.57%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis rotavirus

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

3 / 174 (1.72%)

1 / 172 (0.58%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyelonephritis

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

1 / 210 (0.48%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory tract infection

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

1 / 170 (0.59%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

0 / 210 (0.00%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory tract infection viral

subjects affected / exposed

0 / 173 (0.00%)

0 / 176 (0.00%)

0 / 172 (0.00%)

0 / 177 (0.00%)

0 / 210 (0.00%)

0 / 170 (0.00%)

0 / 174 (0.00%)

0 / 172 (0.00%)

0 / 176 (0.00%)

1 / 210 (0.48%)

0 / 169 (0.00%)

0 / 173 (0.00%)

0 / 170 (0.00%)

0 / 175 (0.00%)

0 / 209 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	13vPnC+ INFANRIX Hexa +Paracetamol Twice Daily -Infant Series	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily -Infant Series	13vPnC+INFANRIX Hexa+Paracetamol Thrice Daily -Infant Series	13vPnC+ INFANRIX Hexa+ Ibuprofen Thrice Daily -Infant Series	13vPnC + INFANRIX Hexa - Infant Series	13vPnC +INFANRIX Hexa +Paracetamol Twice Daily -After Inf Ser	13vPnC + INFANRIX Hexa + Ibuprofen Twice Daily -After Inf Ser	13vPnC+INFANRIX Hexa +Paracetamol Thrice Daily -After Inf Ser	13vPnC +INFANRIX Hexa +Ibuprofen Thrice Daily -After Inf Ser	13vPnC + INFANRIX Hexa - After Infant Series	13vPnC +INFANRIX Hexa + Paracetamol Twice Daily -Toddler Dose	13vPnC +INFANRIX Hexa + Ibuprofen Twice Daily -Toddler Dose	13vPnC +INFANRIX Hexa +Paracetamol Thrice Daily -Toddler Dose	13vPnC +INFANRIX Hexa +Ibuprofen Thrice Daily -Toddler Dose	13vPnC + INFANRIX Hexa - Toddler Dose
Total subjects affected by non serious adverse events
subjects affected / exposed	57 / 173 (32.95%)	71 / 176 (40.34%)	67 / 172 (38.95%)	72 / 177 (40.68%)	80 / 210 (38.10%)	3 / 170 (1.76%)	6 / 174 (3.45%)	3 / 172 (1.74%)	4 / 176 (2.27%)	8 / 210 (3.81%)	47 / 169 (27.81%)	57 / 173 (32.95%)	52 / 170 (30.59%)	76 / 175 (43.43%)	50 / 209 (23.92%)
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	2 / 173 (1.16%)	6 / 176 (3.41%)	5 / 172 (2.91%)	2 / 177 (1.13%)	2 / 210 (0.95%)	0 / 170 (0.00%)	1 / 174 (0.57%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	1 / 169 (0.59%)	3 / 173 (1.73%)	1 / 170 (0.59%)	3 / 175 (1.71%)	2 / 209 (0.96%)
occurrences all number	2	7	5	2	2	0	1	0	0	0	1	3	1	3	2
Vaccination site swelling
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	1 / 209 (0.48%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Vaccination site nodule
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Irritability
subjects affected / exposed	1 / 173 (0.58%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Crying
subjects affected / exposed	1 / 173 (0.58%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Adverse drug reaction
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Fever ≥38°C but ≤39°C Dose 1
Additional description: Dose 1: Subjects affected and occurrences for SE is same as data collected through ediaries 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]	49 / 149 (32.89%)	71 / 157 (45.22%)	27 / 147 (18.37%)	53 / 155 (34.19%)	78 / 187 (41.71%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	42 / 133 (31.58%)	52 / 140 (37.14%)	50 / 134 (37.31%)	72 / 144 (50.00%)	49 / 162 (30.25%)
occurrences all number	49	71	27	53	78	0	0	0	0	0	42	52	50	72	49
Fever >39°C but ≤40°C Dose 1
Additional description: Dose 1: Subjects affected and occurrences for SE is same as data collected through ediaries 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]	2 / 138 (1.45%)	2 / 145 (1.38%)	1 / 137 (0.73%)	1 / 146 (0.68%)	2 / 170 (1.18%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	7 / 128 (5.47%)	9 / 127 (7.09%)	5 / 118 (4.24%)	7 / 123 (5.69%)	3 / 150 (2.00%)
occurrences all number	2	2	1	1	2	0	0	0	0	0	7	9	5	7	3
Fever ≥38°C but ≤39°C Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE is same as data collected through ediaries 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]	37 / 141 (26.24%)	65 / 152 (42.76%)	30 / 140 (21.43%)	70 / 159 (44.03%)	72 / 181 (39.78%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	37	65	30	70	72	0	0	0	0	0	0	0	0	0	0
Fever >39°C but ≤40°C Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE is same as data collected through ediaries 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]	2 / 133 (1.50%)	1 / 140 (0.71%)	2 / 134 (1.49%)	2 / 145 (1.38%)	6 / 164 (3.66%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	2	1	2	2	6	0	0	0	0	0	0	0	0	0	0
Fever ≥38°C but ≤39°C Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE is same as data collected through ediaries 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]	30 / 136 (22.06%)	45 / 146 (30.82%)	23 / 135 (17.04%)	47 / 141 (33.33%)	52 / 175 (29.71%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	30	45	23	47	52	0	0	0	0	0	0	0	0	0	0
Fever >39°C but ≤40°C Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE is same as data collected through ediaries 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]	2 / 129 (1.55%)	4 / 137 (2.92%)	1 / 125 (0.80%)	2 / 136 (1.47%)	3 / 167 (1.80%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	2	4	1	2	3	0	0	0	0	0	0	0	0	0	0
Fever >40°C Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE is same as data collected through ediaries 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]	0 / 128 (0.00%)	0 / 136 (0.00%)	1 / 126 (0.79%)	0 / 135 (0.00%)	0 / 166 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Immune system disorders
Food allergy
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	1 / 176 (0.57%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Milk allergy
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	0 / 172 (0.00%)	0 / 177 (0.00%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0
Reproductive system and breast disorders
Breast enlargement
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	1 / 176 (0.57%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Genital labial adhesions
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	1 / 210 (0.48%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Cough
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	1 / 172 (0.58%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0
Rhinitis allergic
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	1 / 172 (0.58%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Psychiatric disorders
Psychomotor retardation
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	1 / 174 (0.57%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Apathy
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Investigations
Cardiac murmur
subjects affected / exposed	0 / 173 (0.00%)	2 / 176 (1.14%)	3 / 172 (1.74%)	1 / 177 (0.56%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	1 / 210 (0.48%)	1 / 169 (0.59%)	3 / 173 (1.73%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	2	3	1	1	0	0	0	0	1	1	3	0	0	0
Weight increased
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	1 / 173 (0.58%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	1 / 209 (0.48%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Head injury
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	1 / 173 (0.58%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0
Thermal burn
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	1 / 169 (0.59%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	1 / 209 (0.48%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
Mouth injury
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Congenital, familial and genetic disorders
Keratosis follicular
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	1 / 210 (0.48%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Patent ductus arteriosus
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	1 / 172 (0.58%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Hydrocele
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Atrial septal defect
subjects affected / exposed	1 / 173 (0.58%)	0 / 176 (0.00%)	1 / 172 (0.58%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Nervous system disorders
Hypertonia
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Hypotonia
subjects affected / exposed	1 / 173 (0.58%)	0 / 176 (0.00%)	1 / 172 (0.58%)	1 / 177 (0.56%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	1	0	1	1	1	0	0	0	0	0	0	0	0	0	0
Neuromyopathy
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	1 / 172 (0.58%)	1 / 177 (0.56%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	1	1	1	0	0	0	0	0	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	1 / 172 (0.58%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	1 / 209 (0.48%)
occurrences all number	0	1	1	0	0	0	0	0	0	0	0	0	0	0	1
Iron deficiency anaemia
subjects affected / exposed	2 / 173 (1.16%)	0 / 176 (0.00%)	1 / 172 (0.58%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	2	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Eye disorders
Conjunctivitis
subjects affected / exposed	1 / 173 (0.58%)	3 / 176 (1.70%)	7 / 172 (4.07%)	5 / 177 (2.82%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	1 / 169 (0.59%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	1 / 209 (0.48%)
occurrences all number	1	4	7	5	0	0	0	0	0	0	1	0	0	0	1
Dacryostenosis acquired
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	1 / 172 (0.58%)	1 / 177 (0.56%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	1	2	1	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	1 / 173 (0.58%)	2 / 176 (1.14%)	5 / 172 (2.91%)	4 / 177 (2.26%)	2 / 210 (0.95%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	3 / 169 (1.78%)	1 / 173 (0.58%)	1 / 170 (0.59%)	5 / 175 (2.86%)	2 / 209 (0.96%)
occurrences all number	1	2	5	4	2	0	0	0	0	0	3	1	1	5	2
Gingival pain
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	1 / 209 (0.48%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1
Stomatitis
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	1 / 169 (0.59%)	0 / 173 (0.00%)	3 / 170 (1.76%)	0 / 175 (0.00%)	1 / 209 (0.48%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	3	0	1
Teething
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	2 / 177 (1.13%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	1 / 209 (0.48%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	1
Toothache
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	1 / 170 (0.59%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Inguinal hernia
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	1 / 170 (0.59%)	1 / 174 (0.57%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	1 / 172 (0.58%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	1 / 172 (0.58%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0
Vomiting
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Intestinal haemorrhage
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Haematochezia
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Flatulence
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Dyspepsia
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0
Dyschezia
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Constipation
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	1 / 172 (0.58%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Aphthous stomatitis
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	3 / 172 (1.74%)	1 / 177 (0.56%)	2 / 210 (0.95%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	3	1	2	0	0	0	0	0	0	0	0	0	0
Abdominal pain
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	0 / 172 (0.00%)	1 / 177 (0.56%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	1	0	1	1	0	0	0	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Dermatitis
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	1 / 175 (0.57%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Dermatitis allergic
subjects affected / exposed	3 / 173 (1.73%)	1 / 176 (0.57%)	1 / 172 (0.58%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	1 / 174 (0.57%)	0 / 172 (0.00%)	0 / 176 (0.00%)	1 / 210 (0.48%)	0 / 169 (0.00%)	0 / 173 (0.00%)	2 / 170 (1.18%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	3	1	1	1	0	0	1	0	0	1	0	0	2	0	0
Dermatitis atopic
subjects affected / exposed	2 / 173 (1.16%)	2 / 176 (1.14%)	1 / 172 (0.58%)	1 / 177 (0.56%)	4 / 210 (1.90%)	1 / 170 (0.59%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	2 / 169 (1.18%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	2	2	1	1	4	1	0	0	0	0	2	0	0	0	0
Dermatitis diaper
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	1 / 172 (0.58%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	1 / 169 (0.59%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	1	1	1	0	0	0	0	0	0	1	0	0	0	0
Rash
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	0 / 172 (0.00%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	1 / 210 (0.48%)	0 / 169 (0.00%)	0 / 173 (0.00%)	1 / 170 (0.59%)	1 / 175 (0.57%)	0 / 209 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	1	0	0	1	1	0
Rash papular
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	2 / 175 (1.14%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Rash pruritic
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	1 / 209 (0.48%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Skin discolouration
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	1 / 209 (0.48%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Petechiae
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	1 / 210 (0.48%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Cafe au lait spots
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	1 / 210 (0.48%)	1 / 170 (0.59%)	0 / 174 (0.00%)	0 / 172 (0.00%)	1 / 176 (0.57%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	1	0	0	0	0	0	0
Dermatitis contact
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Eczema
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Seborrhoeic dermatitis
subjects affected / exposed	1 / 173 (0.58%)	2 / 176 (1.14%)	1 / 172 (0.58%)	1 / 177 (0.56%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	1	2	1	1	1	0	0	0	0	0	0	0	0	0	0
Skin depigmentation
subjects affected / exposed	1 / 173 (0.58%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Urticaria
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	0 / 172 (0.00%)	0 / 177 (0.00%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0
Renal and urinary disorders
Hypercalciuria
subjects affected / exposed	1 / 173 (0.58%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	1 / 174 (0.57%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Vesicoureteric reflux
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	1 / 172 (0.58%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Foot deformity
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	1 / 174 (0.57%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Muscle tightness
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Infections and infestations
Bronchitis
subjects affected / exposed	9 / 173 (5.20%)	8 / 176 (4.55%)	11 / 172 (6.40%)	9 / 177 (5.08%)	5 / 210 (2.38%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	1 / 210 (0.48%)	2 / 169 (1.18%)	0 / 173 (0.00%)	3 / 170 (1.76%)	5 / 175 (2.86%)	2 / 209 (0.96%)
occurrences all number	9	8	12	9	5	0	0	0	0	1	2	0	3	5	2
Coxsackie viral infection
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	1 / 169 (0.59%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Ear infection
subjects affected / exposed	1 / 173 (0.58%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	1 / 169 (0.59%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Exanthema subitum
subjects affected / exposed	0 / 173 (0.00%)	4 / 176 (2.27%)	1 / 172 (0.58%)	0 / 177 (0.00%)	2 / 210 (0.95%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	2 / 169 (1.18%)	1 / 173 (0.58%)	4 / 170 (2.35%)	0 / 175 (0.00%)	1 / 209 (0.48%)
occurrences all number	0	4	1	0	2	0	0	0	0	0	2	1	4	0	1
Gastroenteritis
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	1 / 170 (0.59%)	1 / 175 (0.57%)	1 / 209 (0.48%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	1	1	1
Gastroenteritis viral
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	1 / 170 (0.59%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Laryngitis
subjects affected / exposed	1 / 173 (0.58%)	2 / 176 (1.14%)	3 / 172 (1.74%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	2 / 209 (0.96%)
occurrences all number	1	2	3	1	0	0	0	0	0	0	0	0	0	0	2
Nasopharyngitis
subjects affected / exposed	11 / 173 (6.36%)	6 / 176 (3.41%)	10 / 172 (5.81%)	8 / 177 (4.52%)	18 / 210 (8.57%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	1 / 210 (0.48%)	1 / 169 (0.59%)	2 / 173 (1.16%)	4 / 170 (2.35%)	2 / 175 (1.14%)	1 / 209 (0.48%)
occurrences all number	14	7	11	9	21	0	0	0	0	1	1	2	4	2	1
Otitis media
subjects affected / exposed	1 / 173 (0.58%)	1 / 176 (0.57%)	0 / 172 (0.00%)	0 / 177 (0.00%)	2 / 210 (0.95%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	1 / 176 (0.57%)	0 / 210 (0.00%)	0 / 169 (0.00%)	1 / 173 (0.58%)	0 / 170 (0.00%)	1 / 175 (0.57%)	0 / 209 (0.00%)
occurrences all number	1	1	0	0	2	0	0	0	1	0	0	1	0	1	0
Otitis media acute
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	1 / 169 (0.59%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0
Pharyngitis
subjects affected / exposed	4 / 173 (2.31%)	6 / 176 (3.41%)	5 / 172 (2.91%)	4 / 177 (2.26%)	3 / 210 (1.43%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	1 / 169 (0.59%)	2 / 173 (1.16%)	5 / 170 (2.94%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	4	6	5	4	3	0	0	0	0	0	1	2	5	0	0
Respiratory tract infection
subjects affected / exposed	4 / 173 (2.31%)	7 / 176 (3.98%)	4 / 172 (2.33%)	5 / 177 (2.82%)	3 / 210 (1.43%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	1 / 173 (0.58%)	0 / 170 (0.00%)	6 / 175 (3.43%)	2 / 209 (0.96%)
occurrences all number	4	7	4	6	3	0	0	0	0	0	0	1	0	6	2
Rhinitis
subjects affected / exposed	3 / 173 (1.73%)	7 / 176 (3.98%)	11 / 172 (6.40%)	10 / 177 (5.65%)	9 / 210 (4.29%)	0 / 170 (0.00%)	0 / 174 (0.00%)	1 / 172 (0.58%)	0 / 176 (0.00%)	0 / 210 (0.00%)	2 / 169 (1.18%)	4 / 173 (2.31%)	5 / 170 (2.94%)	3 / 175 (1.71%)	5 / 209 (2.39%)
occurrences all number	3	7	11	11	10	0	0	1	0	0	2	4	5	3	5
Tonsillitis
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	1 / 170 (0.59%)	0 / 175 (0.00%)	1 / 209 (0.48%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1
Upper respiratory tract infection
subjects affected / exposed	15 / 173 (8.67%)	12 / 176 (6.82%)	14 / 172 (8.14%)	17 / 177 (9.60%)	12 / 210 (5.71%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	7 / 169 (4.14%)	7 / 173 (4.05%)	3 / 170 (1.76%)	4 / 175 (2.29%)	7 / 209 (3.35%)
occurrences all number	16	12	15	19	15	0	0	0	0	0	7	7	3	4	7
Varicella
subjects affected / exposed	1 / 173 (0.58%)	2 / 176 (1.14%)	0 / 172 (0.00%)	3 / 177 (1.69%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	1 / 170 (0.59%)	1 / 175 (0.57%)	0 / 209 (0.00%)
occurrences all number	1	2	0	3	1	0	0	0	0	0	0	0	1	1	0
Viral infection
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	1 / 169 (0.59%)	0 / 173 (0.00%)	1 / 170 (0.59%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0
Viral upper respiratory tract infection
subjects affected / exposed	2 / 173 (1.16%)	1 / 176 (0.57%)	0 / 172 (0.00%)	0 / 177 (0.00%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	1 / 175 (0.57%)	0 / 209 (0.00%)
occurrences all number	3	1	0	0	1	0	0	0	0	0	0	0	0	1	0
Urinary tract infection
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	3 / 172 (1.74%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	1	3	0	0	0	0	0	0	0	0	0	0	0	0
Pneumonia
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	1 / 177 (0.56%)	2 / 210 (0.95%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	1	2	0	0	0	0	0	0	0	0	0	0
Cystitis
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctivitis infective
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Candidiasis
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Bronchopneumonia
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Anal abscess
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Impetigo
subjects affected / exposed	1 / 173 (0.58%)	0 / 176 (0.00%)	0 / 172 (0.00%)	0 / 177 (0.00%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Oral candidiasis
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	2 / 172 (1.16%)	1 / 177 (0.56%)	1 / 210 (0.48%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	3	1	2	0	0	0	0	0	0	0	0	0	0
Lower respiratory tract infection
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	0 / 172 (0.00%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0
Metabolism and nutrition disorders
Calcium metabolism disorder
subjects affected / exposed	0 / 173 (0.00%)	0 / 176 (0.00%)	0 / 172 (0.00%)	1 / 177 (0.56%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Weight gain poor
subjects affected / exposed	0 / 173 (0.00%)	1 / 176 (0.57%)	0 / 172 (0.00%)	0 / 177 (0.00%)	0 / 210 (0.00%)	0 / 170 (0.00%)	0 / 174 (0.00%)	0 / 172 (0.00%)	0 / 176 (0.00%)	0 / 210 (0.00%)	0 / 169 (0.00%)	0 / 173 (0.00%)	0 / 170 (0.00%)	0 / 175 (0.00%)	0 / 209 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed 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.

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Were there any global substantial amendments to the protocol? Yes

20 Jun 2012

1-The Adverse Event Reporting section was updated in line with standards. 2-A section was added on medication errors.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A PHASE 4, RANDOMIZED, OPEN-LABEL TRIAL TO ASSESS THE IMPACT OF PROPHYLACTIC ANTIPYRETIC MEDICATION ON THE IMMUNOGENICITY OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE GIVEN WITH ROUTINE PEDIATRIC VACCINATIONS IN HEALTHY INFANTS

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Infant Series

Primary: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Infant Series

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

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

Secondary: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Toddler Dose

Secondary: Percentage of Subjects Achieving Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Titers Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) 1 Month After the Infant Series

Secondary: Percentage of Subjects Achieving Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Titers Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) 1 Month After the Infant Series

Secondary: Geometric Mean Titer (GMT) for Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) 1 Month After the Infant Series

Secondary: Geometric Mean Titer (GMT) for Serotype-specific Pneumococcal Opsonophagocytic Activity (OPA) 1 Month After the Infant Series

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Haemophilus Influenzae Type b (Hib) Polyribosylribitol Phosphate (PRP) Antibody 1 Month After the Infant Series

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Haemophilus Influenzae Type b (Hib) Polyribosylribitol Phosphate (PRP) Antibody 1 Month After the Infant Series

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) Antibody 1 Month After the Infant Series

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) Antibody 1 Month After the Infant Series

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Tetanus and Diphtheria Antibody 1 Month After the Infant Series

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Tetanus and Diphtheria Antibody 1 Month After the Infant Series

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Hepatitis B Virus (HBV) Antibody 1 Month After the Infant Series

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Hepatitis B Virus (HBV) Antibody 1 Month After the Infant Series

Secondary: Geometric Mean Titer (GMT) for Antigen-specific Poliomyelitis Type 1, 2 and 3 Antibodies 1 Month After the Infant Series

Secondary: Geometric Mean Titer (GMT) for Antigen-specific Poliomyelitis Type 1, 2 and 3 Antibodies 1 Month After the Infant Series

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Haemophilus Influenzae Type b (Hib) Polyribosylribitol Phosphate (PRP) Antibody 1 Month After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Haemophilus Influenzae Type b (Hib) Polyribosylribitol Phosphate (PRP) Antibody 1 Month After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) Antibodies 1 Month After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) Antibodies 1 Month After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Tetanus and Diphtheria Antibodies 1 Month After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Tetanus and Diphtheria Antibodies 1 Month After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Hepatitis B Virus (HBV) Antibody 1 Month After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Hepatitis B Virus (HBV) Antibody 1 Month After the Toddler Dose

Secondary: Geometric Mean Titer (GMT) for Antigen-specific Poliomyelitis Type 1, 2 and 3 Antibodies 1 Month After the Toddler Dose

Secondary: Geometric Mean Titer (GMT) for Antigen-specific Poliomyelitis Type 1, 2 and 3 Antibodies 1 Month After the Toddler Dose

Secondary: Percentage of Subjects Achieving Pre-specified Criteria for the Concomitant Antigens Contained in INFANRIX Hexa 1 Month After the Infant Series

Secondary: Percentage of Subjects Achieving Pre-specified Criteria for the Concomitant Antigens Contained in INFANRIX Hexa 1 Month After the Infant Series

Secondary: Percentage of Subjects Achieving Pre-specified Criteria for the Concomitant Antigens Contained in INFANRIX Hexa 1 Month After the Toddler Dose

Secondary: Percentage of Subjects Achieving Pre-specified Criteria for the Concomitant Antigens Contained in INFANRIX Hexa 1 Month After the Toddler Dose

Secondary: Percentage of Subjects Reporting Fever Within 4 Days: Infant Series Dose 1

Secondary: Percentage of Subjects Reporting Fever Within 4 Days: Infant Series Dose 1

Secondary: Percentage of Subjects Reporting Fever Within 4 Days: Infant Series Dose 2

Secondary: Percentage of Subjects Reporting Fever Within 4 Days: Infant Series Dose 2

Secondary: Percentage of Subjects Reporting Fever Within 4 Days: Infant Series Dose 3

Secondary: Percentage of Subjects Reporting Fever Within 4 Days: Infant Series Dose 3

Secondary: Percentage of Subjects Reporting Fever Within 4 Days: Toddler Dose

Secondary: Percentage of Subjects Reporting Fever Within 4 Days: Toddler Dose

Secondary: Number of Subjects With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): Infant Series

Secondary: Number of Subjects With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): Infant Series

Secondary: Number of Subjects With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): After the Infant Series

Secondary: Number of Subjects With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): After the Infant Series

Secondary: Number of Subjects With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): Toddler Dose

Secondary: Number of Subjects With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs): Toddler Dose

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A PHASE 4, RANDOMIZED, OPEN-LABEL TRIAL TO ASSESS THE IMPACT OF PROPHYLACTIC ANTIPYRETIC MEDICATION ON THE IMMUNOGENICITY OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE GIVEN WITH ROUTINE PEDIATRIC VACCINATIONS IN HEALTHY INFANTS