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    Clinical Trial Results:
    A Phase III Randomized, Double-Blind, Active-Comparator Controlled Clinical Trial to Study the Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 4, and 11 to 12 Months

    Summary
    EudraCT number
    		 2010-021491-28
    Trial protocol
    		 FI   SE   IT  
    Global end of trial date
    09 Oct 2013

    Results information
    Results version number
    		 v2(current)
    This version publication date
    15 Nov 2019
    First version publication date
    02 Aug 2015
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    V419-008
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01480258
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck, Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck, Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck, Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000394-PIP01-08
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    09 Oct 2013
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    09 Oct 2013
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Oct 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study will determine whether participants who receive V419 (PR5I) at 2, 4, and 11 to 12 months of age have an acceptable response to the vaccine. This study will also determine whether the immune response to V419 is similar to that of participants who received a licensed vaccine control. The primary hypothesis is that participants who receive PR5I at 2, 4, and 11 to 12 months have an acceptable response rate to all PR5I-contained antigens at one month after the toddler dose of PR5I.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research. The following additional measures defined for this individual study were in place for the protection of trial subjects: After each vaccination, participants were kept under observation for 30 minutes to ensure their safety. Adequate treatment provisions, including epinephrine, were available for immediate use in case of anaphylactic or anaphylactoid reactions occurring during or immediately following vaccination.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 Nov 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Finland: 919
    Country: Number of subjects enrolled
    Italy: 264
    Country: Number of subjects enrolled
    Sweden: 132
    Worldwide total number of subjects
    1315
    EEA total number of subjects
    1315
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    1315
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants from Italy and Sweden were randomized to Rotavirus Vaccine Subset 1 (Rotarix™). Participants from Finland were randomized to Rotavirus Vaccine Subset 2 (RotaTeq™).

    Pre-assignment
    Screening details
    		 1325 participants were screened. 1315 participants were randomised. 1312 participants were vaccinated. 1300 participants received the 2 doses of the infant series (period 1). 1281 participants received the toddler dose (period 2).

    Period 1
    Period 1 title
    Infant Series
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 PR5I
    Arm description
    		 Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    PR5I
    Investigational medicinal product code
    Other name
    V419 Vaxelis®
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    DTaP-HB-IPV-Hib (Diphtheria, tetanus, pertussis [acellular, component], hepatitis B [recombinant DNA], polio virus [inactivated], and Haemophilus influenza type b conjugate vaccine [adsorbed]) Vaccine 0.5 mL intramuscular injection at 2 and 4 months of age. Injection is to be administered in the upper anterolateral thigh, separate limb from the concomitant vaccine. PR5I is a liquid suspension hexavalent vaccine.

    Investigational medicinal product name
    Prevenar 13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Prevenar 13™ 0.5 mL intramuscular injection at 2 and 4 months of age. Injection is to be administered in the upper anterolateral thigh, separate limb from the concomitant vaccine.

    Investigational medicinal product name
    Rotavirus vaccine
    Investigational medicinal product code
    Other name
    Rotarix™ RotaTeq™
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Rotarix™ 1.5 mL oral dose at 2 and 4 months of age (subset 1, Italy and Sweden) or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age (subset 2, Finland)

    Arm title
    		 INFANRIX™ hexa
    Arm description
    		 Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    INFANRIX™ hexa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Combined Diphtheria-Tetanus-acellular Pertussis [DTaP], Hepatitis B [HepB], Poliovirus [IPV] and Haemophilus influenzae type b [Hib] Vaccine 0.5 mL intramuscular injection at 2 and 4 months of age. Injection is to be administered in the upper anterolateral thigh, separate limb from the concomitant vaccine. INFANRIX™ hexa is provided as 2 components (lyophilized Hib and liquid DTaP, IPV, and HepB). Prior to administration, the vaccine must be reconstituted by adding the liquid DTaPHepB-IPV component to the vial containing the Hib pellet.

    Investigational medicinal product name
    Rotavirus vaccine
    Investigational medicinal product code
    Other name
    Rotarix™ RotaTeq™
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Rotarix™ 1.5 mL oral dose at 2 and 4 months of age (subset 1, Italy and Sweden) or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age (subset 2, Finland)

    Investigational medicinal product name
    Prevenar 13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Prevenar 13™ 0.5 mL intramuscular injection at 2 and 4 months of age. Injection is to be administered in the upper anterolateral thigh, separate limb from the concomitant vaccine.

    Number of subjects in period 1
    		PR5I INFANRIX™ hexa
    Started
    656
    659
    Vaccinated
    653
    659
    Completed
    649
    651
    Not completed
    7
    8
         Consent withdrawn by subject
    1
    6
         Physician decision
    -
    1
         Not Vaccinated
    3
    -
         Adverse event, non-fatal
    1
    1
         Protocol deviation
    2
    -
    Period 2
    Period 2 title
    Interim Period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 PR5I
    Arm description
    		 Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 INFANRIX™ hexa
    Arm description
    		 Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 2
    		PR5I INFANRIX™ hexa
    Started
    649
    651
    Completed
    639
    642
    Not completed
    10
    9
         Physician decision
    1
    -
         Consent withdrawn by subject
    9
    6
         Lost to follow-up
    -
    2
         Protocol deviation
    -
    1
    Period 3
    Period 3 title
    Toddler Dose
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 PR5I
    Arm description
    		 Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Prevenar 13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Prevenar 13™ 0.5 mL intramuscular injection at 11 to 12 months of age. Injection is to be administered in the upper anterolateral thigh, separate limb from the concomitant vaccine.

    Investigational medicinal product name
    PR5I
    Investigational medicinal product code
    Other name
    V419 Vaxelis®
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    DTaP-HB-IPV-Hib (Diphtheria, tetanus, pertussis [acellular, component], hepatitis B [recombinant DNA], polio virus [inactivated], and Haemophilus influenza type b conjugate vaccine [adsorbed]) Vaccine 0.5 mL intramuscular injection at 11 to 12 months of age. Injection is to be administered in the upper anterolateral thigh, separate limb from the concomitant vaccine. PR5I is a liquid suspension hexavalent vaccine.

    Arm title
    		 INFANRIX™ hexa
    Arm description
    		 Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    INFANRIX™ hexa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Combined Diphtheria-Tetanus-acellular Pertussis [DTaP], Hepatitis B [HepB], Poliovirus [IPV] and Haemophilus influenzae type b [Hib] Vaccine 0.5 mL intramuscular injection at 11 to 12 months of age. Injection is to be administered in the upper anterolateral thigh, separate limb from the concomitant vaccine. INFANRIX™ hexa is provided as 2 components (lyophilized Hib and liquid DTaP, IPV, and HepB). Prior to administration, the vaccine must be reconstituted by adding the liquid DTaPHepB-IPV component to the vial containing the Hib pellet.

    Investigational medicinal product name
    Prevenar 13™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Prevenar 13™ 0.5 mL intramuscular injection at 11 to 12 months of age. Injection is to be administered in the upper anterolateral thigh, separate limb from the concomitant vaccine.

    Number of subjects in period 3
    		PR5I INFANRIX™ hexa
    Started
    639
    642
    Completed
    639
    642

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    PR5I
    Reporting group description
    		 Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

    Reporting group title
    INFANRIX™ hexa
    Reporting group description
    		 Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

    Reporting group values
    		 PR5I INFANRIX™ hexa Total
    Number of subjects
    		 656 659 1315
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 656 659 1315
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 0 0 0
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age Continuous
    Units: Days
        arithmetic mean (standard deviation)
    		 68 ( 10.3 ) 68.1 ( 10.5 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 323 313 636
        Male
    		 333 346 679
    Region of Enrollment
    Units: Subjects
        Finland
    		 459 460 919
        Italy
    		 132 132 264
        Sweden
    		 65 67 132

    End points

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    End points reporting groups
    Reporting group title
    PR5I
    Reporting group description
    		 Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

    Reporting group title
    INFANRIX™ hexa
    Reporting group description
    		 Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
    Reporting group title
    PR5I
    Reporting group description
    		 Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

    Reporting group title
    INFANRIX™ hexa
    Reporting group description
    		 Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
    Reporting group title
    PR5I
    Reporting group description
    		 Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

    Reporting group title
    INFANRIX™ hexa
    Reporting group description
    		 Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

    Subject analysis set title
    PR51
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

    Subject analysis set title
    INFANRIX™ hexa
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

    Primary: Acceptability of antibody (Ab) response or seroresponse rates to all antigens contained in PR5I vaccine one month after the Toddler dose of PR5I (11 to 12 months of age)

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    End point title
    		 Acceptability of antibody (Ab) response or seroresponse rates to all antigens contained in PR5I vaccine one month after the Toddler dose of PR5I (11 to 12 months of age) [1]
    End point description
    Acceptability response rates: Ab titre ≥1.0 μg/mL for Hib (polyribosylribitol phosphate, PRP); ≥10 mIU/mL for HBsAg; ≥0.1 IU/mL for diphtheria and tetanus; ≥8 (1/dil) for IPV type 1, 2 & 3, and percentage of pertussis seroresponder participants (Pertussis toxoid [PT], Filamentous haemagglutinin [FHA], Fimbriae types 2 & 3 [FIM] and Pertactin [PRN]) 1 month Post-Toddler PR51 dose. Seroresponse: (1) If pre-Dose 1 Ab concentration (cc) was <LLOQ (lower limit of quantitation), postvaccination Ab cc was ≥LLOQ, (2) If pre-Dose 1 Ab cc was ≥LLOQ, postvaccination Ab cc was ≥prevaccination levels. Analysis population: participants who met the inclusion criteria, were not protocol violators, received PR51 vaccinations within acceptable day ranges, and had a blood draw sample window of Days 28 to 51 following the Toddler dose. The analysis populations may not have been identical for each antigen-specific analysis at each post-vaccination visit.
    End point type
    Primary
    End point timeframe
    1 month after Toddler dose of PR51 (post-toddler dose)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No between-group statistical analyses were performed for this endpoint. Single-sided analyses are presented on ClinicalTrials.gov NCT01480258.
    End point values
    		 PR5I INFANRIX™ hexa
    Number of subjects analysed
    638
    0 [2]
    Units: Percentage of participants
    number (confidence interval 95%)
        Anti-PRP ≥1.0 μg/mL; n=454
    89.87 (86.72 to 92.49)
    ( to )
        Anti-HBsAg ≥10 mIU/mL; n=377
    98.14 (96.21 to 99.25)
    ( to )
        Anti-Diphtheria ≥0.1 IU/mL; n=590
    98.64 (97.35 to 99.41)
    ( to )
        Anti-Tetanus ≥0.1 IU/mL; n=589
    99.83 (99.06 to 100.00)
    ( to )
        Anti-PT seroresponse; n=566
    99.12 (97.95 to 99.71)
    ( to )
        Anti-FHA seroresponse; n=582
    97.42 (95.78 to 98.55)
    ( to )
        Anti-FIM seroresponse; n=581
    98.28 (96.86 to 99.17)
    ( to )
        Anti-PRN seroresponse; n=582
    96.91 (95.16 to 98.16)
    ( to )
        Anti-IPV1 ≥1:8 dilution; n=591
    99.32 (98.28 to 99.82)
    ( to )
        Anti-IPV2 ≥1:8 dilution; n=591
    99.83 (99.06 to 100.00)
    ( to )
        Anti-IPV3 ≥1:8 dilution; n=590
    99.49 (98.52 to 99.90)
    ( to )
    Notes
    [2] - Participants receiving INFANRIX™ hexa were excluded from the acceptability analyses.
    No statistical analyses for this end point

    Secondary: Non-inferiority of antibody (Ab) response rate to Haemophilus influenzae type b (PRP) one month after the 2nd dose of PR5I (4 months of age) as compared with INFANRIX hexa

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    End point title
    		 Non-inferiority of antibody (Ab) response rate to Haemophilus influenzae type b (PRP) one month after the 2nd dose of PR5I (4 months of age) as compared with INFANRIX hexa
    End point description
    Percentage of participants with an Ab titre ≥1.0 μg/mL for Hib (polyribosylribitol phosphate, PRP) measured by radioimmunoassay (RIA) 1 month post-infant dose 2 of PR5I or INFANRIX hexa. Analysis population: participants who received 2nd dose in the Infant series and had a blood draw sample window of Days 28 to 51 post-infant dose 2.
    End point type
    Secondary
    End point timeframe
    1 month after the 2nd dose (post-infant dose 2)
    End point values
    		 PR5I INFANRIX™ hexa
    Number of subjects analysed
    609
    592
    Units: Percentage of participants
        number (not applicable)
    72.86
    26.66
    Statistical analysis title
    		 Between group comparison
    Comparison groups
    PR5I v INFANRIX™ hexa
    Number of subjects included in analysis
    1201
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    P-value
    		 < 0.001 [4]
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in percentages
    Point estimate
    46.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 41.05
         upper limit
    		 51.06
    Notes
    [3] - If the lower bound of the 95% confidence interval (CI) was greater than -10% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
    [4] - Stratification by country.

    Secondary: Superiority of antibody (Ab) response rates to Haemophilus influenzae type b (PRP) one month after the 2nd dose of PR5I (4 months of age) as compared with INFANRIX hexa

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    End point title
    		 Superiority of antibody (Ab) response rates to Haemophilus influenzae type b (PRP) one month after the 2nd dose of PR5I (4 months of age) as compared with INFANRIX hexa
    End point description
    Percentage of participants with an Ab titre ≥1.0 μg/mL for Hib (polyribosylribitol phosphate, PRP) measured by RIA 1 month post-infant dose 2 of PR5I or INFANRIX hexa. Analysis population: participants who received 2nd dose in the Infant series and had a blood draw sample window of Days 28 to 51 post-infant dose 2.
    End point type
    Secondary
    End point timeframe
    1 month after the 2nd dose (post-infant dose 2)
    End point values
    		 PR5I INFANRIX™ hexa
    Number of subjects analysed
    609
    592
    Units: Percentage of participants
        number (not applicable)
    72.86
    26.66
    Statistical analysis title
    		 Between group comparison
    Comparison groups
    PR5I v INFANRIX™ hexa
    Number of subjects included in analysis
    1201
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 < 0.001
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in percentages
    Point estimate
    46.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 41.05
         upper limit
    		 51.06
    Notes
    [5] - If the lower bound of the 95% CI was greater than 0, it was concluded that PR5I group response rate was superior to INFANRIX hexa group response rate.

    Secondary: Non-inferiority Ab response rates to PR5I antigens one month after the Toddler dose of PR5I (11 to 12 months of age) as compared with INFANRIX hexa

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    End point title
    		 Non-inferiority Ab response rates to PR5I antigens one month after the Toddler dose of PR5I (11 to 12 months of age) as compared with INFANRIX hexa
    End point description
    Percentage of participants with pre-specified Ab titre for PRP, HBsAg, diphtheria, tetanus, IPV1, 2 & 3, and percentage of pertussis seroresponder participants (PT, FHA, FIM and PRN) 1 month post-toddler dose were calculated based on the method by Miettinen and Nurminen stratified by country. Seroresponse was defined: (1) If pre-Dose 1 Ab cc was <LLOQ, post-vaccination Ab cc was ≥LLOQ, (2) If pre-Dose 1 Ab cc was ≥LLOQ, post-vaccination Ab cc was ≥pre-vaccination levels. Due to the timing of the occurrence of protocol violation or the availability of each antigen serology testing result, the analysis populations may not have been identical for each antigen-specific analysis at each post-vaccination visit. Analysis population: participants who met the inclusion criteria, were not protocol violators, received vaccinations within acceptable day ranges, and had a blood draw sample window of Days 28 to 51 following the Toddler dose.
    End point type
    Secondary
    End point timeframe
    1 month after Toddler dose (post-toddler dose)
    End point values
    		 PR5I INFANRIX™ hexa
    Number of subjects analysed
    638
    642
    Units: Percentage of participants
    number (not applicable)
        Anti-PRP ≥1.0 μg/mL; n=454, n=478
    89.80
    91.06
        Anti-HBsAg ≥10 mIU/mL; n=377, n=391
    98.14
    98.73
        Anti-Diphtheria ≥0.1 IU/mL; n=590, n=578
    98.62
    99.83
        Anti-Tetanus ≥0.1 IU/mL; n=589, n=577
    99.83
    100.00
        Anti-PT seroresponse; n=566, n=561
    99.11
    99.64
        Anti-FHA seroresponse; n=582, n=571
    97.40
    99.13
        Anti-PRN seroresponse; n=582, n=572
    96.86
    98.28
        Anti-IPV1 ≥1:8 dilution; n=591, n=580
    99.32
    99.83
        Anti-IPV2 ≥1:8 dilution; n=591, n=579
    99.83
    100.00
        Anti-IPV3 ≥1:8 dilution; n=590, n=579
    99.49
    99.65
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of PRP
    Comparison groups
    PR5I v INFANRIX™ hexa
    Number of subjects included in analysis
    1280
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    P-value
    		 < 0.001 [7]
    Method
    		 Miettinen & Nurminen with stratification
    Parameter type
    		 Difference in percentages
    Point estimate
    -1.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.13
         upper limit
    		 2.52
    Notes
    [6] - The estimate of the difference between PR5I & INFANRIX hexa groups in PRP response rate (based on Ab titre ≥1.0 μg/mL) was calculated with its 1-sided P-value & 2-sided 95% CI. If the lower bound of the 95% CI was greater than -10% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
    [7] - Statistical method was based on the Miettinen & Nurminen method stratified by country.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of HBsAg
    Comparison groups
    PR5I v INFANRIX™ hexa
    Number of subjects included in analysis
    1280
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [8]
    P-value
    		 < 0.001 [9]
    Method
    		 Miettinen & Nurminen with stratification
    Parameter type
    		 Difference in percentages
    Point estimate
    -0.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.66
         upper limit
    		 1.35
    Notes
    [8] - The estimate of the difference between PR5I & INFANRIX hexa groups in HBsAg response rate (based on Ab titre ≥10 mIU/mL) was calculated with its 1-sided P-value & 2-sided 95% CI. If the lower bound of the 95% CI was greater than -10% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
    [9] - Statistical method was based on the Miettinen & Nurminen method stratified by country.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of diptheria
    Comparison groups
    PR5I v INFANRIX™ hexa
    Number of subjects included in analysis
    1280
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [10]
    P-value
    		 < 0.001 [11]
    Method
    		 Miettinen & Nurminen with stratification
    Parameter type
    		 Difference in percentages
    Point estimate
    -1.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.54
         upper limit
    		 -0.22
    Notes
    [10] - The estimate of the difference between PR5I & INFANRIX hexa groups in Diphtheria response rate (based on Ab titre ≥0.1 IU/mL) was calculated with its 1-sided P-value & 2-sided 95% CI. If the lower bound of the 95% CI was greater than -10% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
    [11] - Statistical method was based on the Miettinen & Nurminen method stratified by country.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of tetanus
    Comparison groups
    PR5I v INFANRIX™ hexa
    Number of subjects included in analysis
    1280
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [12]
    P-value
    		 < 0.001 [13]
    Method
    		 Miettinen & Nurminen with stratification
    Parameter type
    		 Difference in percentages
    Point estimate
    -0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.95
         upper limit
    		 0.5
    Notes
    [12] - The estimate of the difference between PR5I & INFANRIX hexa groups in Tetanus response rate (based on Ab titre ≥0.1 IU/mL) was calculated with its 1-sided P-value & 2-sided 95% CI. If the lower bound of the 95% CI was greater than -5% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
    [13] - Statistical method was based on the Miettinen & Nurminen method stratified by country.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of PT
    Comparison groups
    PR5I v INFANRIX™ hexa
    Number of subjects included in analysis
    1280
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [14]
    P-value
    		 < 0.001 [15]
    Method
    		 Miettinen & Nurminen with stratification
    Parameter type
    		 Difference in percentages
    Point estimate
    -0.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.75
         upper limit
    		 0.49
    Notes
    [14] - The estimate of the difference between PR5I & INFANRIX hexa groups in the percentage of seroresponder participants for PT was calculated with its 1-sided P-value & 2-sided 95% CI. If the lower bound of the 95% CI was greater than -10% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
    [15] - Statistical method was based on the Miettinen & Nurminen method stratified by country.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of FHA
    Comparison groups
    PR5I v INFANRIX™ hexa
    Number of subjects included in analysis
    1280
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [16]
    P-value
    		 < 0.001 [17]
    Method
    		 Miettinen & Nurminen with stratification
    Parameter type
    		 Difference in percentages
    Point estimate
    -1.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.47
         upper limit
    		 -0.26
    Notes
    [16] - The estimate of the difference between PR5I & INFANRIX hexa groups in the percentage of seroresponder participants for FHA was calculated with its 1-sided P-value & 2-sided 95% CI. If the lower bound of the 95% CI was greater than -10% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
    [17] - Statistical method was based on the Miettinen & Nurminen method stratified by country.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of PRN
    Comparison groups
    PR5I v INFANRIX™ hexa
    Number of subjects included in analysis
    1280
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [18]
    P-value
    		 < 0.001 [19]
    Method
    		 Miettinen & Nurminen with stratification
    Parameter type
    		 Difference in percentages
    Point estimate
    -1.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.42
         upper limit
    		 0.39
    Notes
    [18] - The estimate of the difference between PR5I & INFANRIX hexa groups in the percentage of seroresponder participants for PRN was calculated with its 1-sided P-value & 2-sided 95% CI. If the lower bound of the 95% CI was greater than -10% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
    [19] - Statistical method was based on the Miettinen & Nurminen method stratified by country.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of IPV1
    Comparison groups
    PR5I v INFANRIX™ hexa
    Number of subjects included in analysis
    1280
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [20]
    P-value
    		 < 0.001 [21]
    Method
    		 Miettinen & Nurminen with stratification
    Parameter type
    		 Difference in percentages
    Point estimate
    -0.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.59
         upper limit
    		 0.34
    Notes
    [20] - The estimate of the difference between PR5I & INFANRIX hexa groups in IPV1 response rate (based on Ab titre ≥8 (1/dil)) was calculated with its 1-sided P-value & 2-sided 95% CI. If the lower bound of the 95% CI was greater than -5% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
    [21] - Statistical method was based on the Miettinen & Nurminen method stratified by country.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of IPV2
    Comparison groups
    PR5I v INFANRIX™ hexa
    Number of subjects included in analysis
    1280
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [22]
    P-value
    		 < 0.001 [23]
    Method
    		 Miettinen & Nurminen with stratification
    Parameter type
    		 Difference in percentages
    Point estimate
    -0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.96
         upper limit
    		 0.49
    Notes
    [22] - The estimate of the difference between PR5I & INFANRIX hexa groups in IPV2 response rate (based on Ab titre ≥8 (1/dil)) was calculated with its 1-sided P-value & 2-sided 95% CI. If the lower bound of the 95% CI was greater than -5% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
    [23] - Statistical method was based on the Miettinen & Nurminen method stratified by country.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of IPV3
    Comparison groups
    PR5I v INFANRIX™ hexa
    Number of subjects included in analysis
    1280
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [24]
    P-value
    		 < 0.001 [25]
    Method
    		 Miettinen & Nurminen with stratification
    Parameter type
    		 Difference in percentages
    Point estimate
    -0.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0.82
    Notes
    [24] - The estimate of the difference between PR5I & INFANRIX hexa groups in IPV3 response rate (based on Ab titre ≥8 (1/dil)) was calculated with its 1-sided P-value & 2-sided 95% CI. If the lower bound of the 95% CI was greater than -5% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
    [25] - Statistical method was based on the Miettinen & Nurminen method stratified by country.

    Secondary: Non-inferiority of Rotavirus response (geometric mean titer, GMT) one month after the 2nd dose of Rotarix (4 months of age) administered concomitantly with PR5I versus INFANRIX hexa

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    End point title
    		 Non-inferiority of Rotavirus response (geometric mean titer, GMT) one month after the 2nd dose of Rotarix (4 months of age) administered concomitantly with PR5I versus INFANRIX hexa
    End point description
    Antibody titres expressed in units/mL were measured for Rotavirus IgA by Enzyme Immunoassay (EIA), 1 month after the 2nd dose of Rotarix, administered concomitantly with PR5I or INFANRIX hexa (Post-Dose 2). The 95% CI for GMT was based on the t-distribution of the natural log-transformed antibody titer. Analysis population: participants who received dose 2 of Rotarix.
    End point type
    Secondary
    End point timeframe
    1 month after the 2nd dose of Rotarix, administered concomitantly with PR5I or INFANRIX hexa (Post-Dose 2)
    End point values
    		 PR5I INFANRIX™ hexa
    Number of subjects analysed
    160
    171
    Units: Titre (units/mL)
        geometric mean (confidence interval 95%)
    96.41 (71.69 to 129.65)
    122.24 (92.48 to 161.58)
    Statistical analysis title
    		 Between group comparison
    Comparison groups
    PR5I v INFANRIX™ hexa
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [26]
    P-value
    		 = 0.011
    Method
    		 ANCOVA
    Parameter type
    		 Geometric Mean Titre (GMT) ratio
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.2
    Notes
    [26] - The estimate for anti-rotavirus IgA GMT ratio (PR5I group/INFANRIX hexa group) was calculated with its 1-sided P-value and 2-sided 95% CI. If the lower bound of the 95% CI for GMT ratio was greater than 0.50 (non-inferiority margin), it was concluded that the Rotarix antigen response in the PR5I group was not inferior to the Rotarix antigen response in the INFANRIX hexa group.

    Secondary: Number of participants who experienced an adverse event (AE) from Day 1 to Day 15 after any vaccination

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    End point title
    		 Number of participants who experienced an adverse event (AE) from Day 1 to Day 15 after any vaccination
    End point description
    Injection-site and systemic AEs were reported daily on the Vaccination Report Card (VRC) by the parent(s) or legal representative from Day 1 (D1) to D15 after each vaccination. Solicited injection site and systemic AEs were reported daily from D1 to D5 after each vaccination. AEs at injection sites were always considered as vaccine-related (V-related) (Injection-Site Reactions [ISRs]). The investigator had to assess whether systemic AEs were related or not to the vaccine. All AEs (related and unrelated) are displayed here. Analysis population: all randomized participants who received at least 1 vaccination and who had safety follow-up.
    End point type
    Secondary
    End point timeframe
    Solicited AEs: up to 5 days (Days 1-5 after any vaccination); unsolicited AEs: up to 15 days (Day 1-15 after any vaccination)
    End point values
    		 PR51 INFANRIX™ hexa
    Number of subjects analysed
    653
    659
    Units: Percentage of participants
    number (not applicable)
        At least 1 ISR or systemic AE (D1-D15)
    99.5
    99.2
        At least 1 V-related ISR or systemic AE (D1-D15)
    99.5
    98.8
        At least 1 ISR (D1-D15)
    90.8
    88.2
        At least 1 solicited ISR (D1-D5)
    90.4
    87.9
        At least 1 systemic AE (D1-D15)
    99.1
    98.9
        At least 1 V-related systemic AE (D1-D15)
    99.1
    98.3
        At least 1 solicited systemic AE (D1-D5)
    99.1
    98.3
        At least 1 V-related solicited systemic AE (D1-D5)
    99.1
    98.2
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of ISR or systemic AE
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [27]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 1.4
    Notes
    [27] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate an overall trend and not any specific difference. If 0.0 was excluded from the 95% CI, the trend could not be ruled out.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of V-related ISR or systemic AE
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [28]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 2
    Notes
    [28] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate an overall trend and not any specific difference. If 0.0 was excluded from the 95% CI, the trend could not be ruled out.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of at least 1 ISR
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [29]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    2.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 6
    Notes
    [29] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate an overall trend and not any specific difference. If 0.0 was excluded from the 95% CI, the trend could not be ruled out.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of at least 1 solicited ISR
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [30]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    2.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 5.9
    Notes
    [30] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate an overall trend and not any specific difference. If 0.0 was excluded from the 95% CI, the trend could not be ruled out.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of at least 1 systemic AE
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [31]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 1.4
    Notes
    [31] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate an overall trend and not any specific difference. If 0.0 was excluded from the 95% CI, the trend could not be ruled out.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of at least 1 vaccine-related systemic AE
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [32]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 2.2
    Notes
    [32] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate an overall trend and not any specific difference. If 0.0 was excluded from the 95% CI, the trend could not be ruled out.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of at least 1 solicited systemic AE
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [33]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 2.2
    Notes
    [33] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate an overall trend and not any specific difference. If 0.0 was excluded from the 95% CI, the trend could not be ruled out.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of at least 1 vaccine-related solicited systemic AE
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [34]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 2.3
    Notes
    [34] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate an overall trend and not any specific difference. If 0.0 was excluded from the 95% CI, the trend could not be ruled out.

    Secondary: Percentage of participants reporting solicited ISRs from D1 to D5 after any vaccination

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    End point title
    		 Percentage of participants reporting solicited ISRs from D1 to D5 after any vaccination
    End point description
    Adverse events at injection sites were always considered as related to vaccine (Injection-Site Reactions [ISRs]). Solicited ISRs were defined as injection-site erythema, injection-site pain, and injection-site swelling occurring from D1 to D5 after vaccination. Analysis population: all randomised participants who received at least 1 vaccination and who had safety follow-up.
    End point type
    Secondary
    End point timeframe
    Up to 5 days (Day 1 to Day 5 following vaccination)
    End point values
    		 PR51 INFANRIX™ hexa
    Number of subjects analysed
    653
    659
    Units: Percentage of participants
    number (not applicable)
        Injection-site erythema
    68.6
    60.4
        Injection-site pain
    73.4
    70.0
        Injection-site swelling
    56.8
    49.3
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of injection-site erythema
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [35]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    8.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3
         upper limit
    		 13.3
    Notes
    [35] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate whether an overall trend of risk differences existed. If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of injection-site pain
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [36]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    3.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 8.3
    Notes
    [36] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate whether an overall trend of risk differences existed. If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of injection-site swelling
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [37]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    7.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.1
         upper limit
    		 12.9
    Notes
    [37] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate whether an overall trend of risk differences existed. If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

    Secondary: Percentage of participants reporting unsolicited ISRs from D1 to D15 after any vaccination

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    End point title
    		 Percentage of participants reporting unsolicited ISRs from D1 to D15 after any vaccination
    End point description
    Adverse events at injection sites were always considered as related to vaccine (Injection-Site Reactions [ISRs]). Unsolicited ISRs occurring from Day 1 (D1) to D15 after any vaccination were reported daily on the VRC by the parent(s) or legal representative. Unsolicited ISRs with incidence ≥1% are reported below. Analysis population: all randomised participants who received at least 1 vaccination and who had safety follow-up.
    End point type
    Secondary
    End point timeframe
    From D1 to D15 after any vaccination
    End point values
    		 PR51 INFANRIX™ hexa
    Number of subjects analysed
    653
    659
    Units: Percentage of participants
    number (not applicable)
        Injection-site bruising
    0.9
    2.0
        Injection-site haemorrhage
    1.8
    1.8
        Injection-site induration
    15.8
    13.2
        Injection-site nodule
    1.1
    0.8
        Injection-site warmth
    2.3
    1.2
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of injection-site bruising
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [38]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.5
         upper limit
    		 0.3
    Notes
    [38] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate an overall trend and not any specific difference. If 0.0 was excluded from the 95% CI, the trend could not be ruled out.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of injection-site haemorrhage
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [39]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 1.6
    Notes
    [39] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate an overall trend and not any specific difference. If 0.0 was excluded from the 95% CI, the trend could not be ruled out.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of injection-site induration
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    2.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 6.4
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of injection-site nodule
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [40]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 1.5
    Notes
    [40] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate an overall trend and not any specific difference. If 0.0 was excluded from the 95% CI, the trend could not be ruled out.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of injection-site warmth
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [41]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 2.7
    Notes
    [41] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate an overall trend and not any specific difference. If 0.0 was excluded from the 95% CI, the trend could not be ruled out.

    Secondary: Percentage of participants reporting solicited adverse events (AEs) from D1 to D5 after any vaccination

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    End point title
    		 Percentage of participants reporting solicited adverse events (AEs) from D1 to D5 after any vaccination
    End point description
    Solicited systemic AEs were defined as crying, decreased appetite, irritability, pyrexia (rectal temperature ≥38.0°C), somnolence, and vomiting occurring from D1 to D5 after vaccination. The investigator had to assess whether these systemic AEs were related or not to the vaccines. All (related and unrelated) are displayed here. Analysis population: all randomised participants who received at least 1 vaccination and who had safety follow-up.
    End point type
    Secondary
    End point timeframe
    Up to 5 days (from D1 to D5 after any vaccination)
    End point values
    		 PR51 INFANRIX™ hexa
    Number of subjects analysed
    653
    659
    Units: Percentage of participants
    number (not applicable)
        Crying
    89.3
    87.1
        Decreased appetite
    65.8
    62.2
        Irritability
    91.6
    89.4
        Pyrexia
    73.8
    67.4
        Somnolence
    86.1
    80.3
        Vomiting
    32.8
    31.0
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of crying
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [42]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 5.7
    Notes
    [42] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate whether an overall trend of risk differences existed. If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of decreased appetite
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [43]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    3.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 8.8
    Notes
    [43] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of irritability
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [44]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 5.4
    Notes
    [44] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of pyrexia
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [45]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    6.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.5
         upper limit
    		 11.3
    Notes
    [45] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of somnolence
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [46]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    5.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.7
         upper limit
    		 9.8
    Notes
    [46] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate an overall trend and not any specific difference. If 0.0 was excluded from the 95% CI, the trend could not be ruled out.
    Statistical analysis title
    		 Between group comparison
    Statistical analysis description
    Between group comparison of vomiting
    Comparison groups
    PR51 v INFANRIX™ hexa
    Number of subjects included in analysis
    1312
    Analysis specification
    Pre-specified
    Analysis type
    		 other [47]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.2
         upper limit
    		 6.9
    Notes
    [47] - The risk differences between groups (PR5I group – INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to approximately 11 months. Serious AEs and deaths were collected for the duration of the study; unsolicited AEs were collected from D1 to D15 after each hexavalent vaccination, solicited AEs were collected D1 to D5 after each hexavalent vaccination
    Adverse event reporting additional description
    Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.0
    Reporting groups
    Reporting group title
    PR5I
    Reporting group description
    		 Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

    Reporting group title
    INFANRIX™ hexa
    Reporting group description
    		 Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

    Serious adverse events
    		 PR5I INFANRIX™ hexa
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 653 (0.92%)
    10 / 659 (1.52%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Congenital, familial and genetic disorders
    Heart disease congenital
         subjects affected / exposed
    1 / 653 (0.15%)
    0 / 659 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vitello-intestinal duct remnant
         subjects affected / exposed
    0 / 653 (0.00%)
    1 / 659 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Kawasaki's disease
         subjects affected / exposed
    0 / 653 (0.00%)
    1 / 659 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    0 / 653 (0.00%)
    1 / 659 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Idiopathic thrombocytopenic purpura
         subjects affected / exposed
    1 / 653 (0.15%)
    0 / 659 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 653 (0.15%)
    1 / 659 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 653 (0.15%)
    0 / 659 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    1 / 653 (0.15%)
    0 / 659 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injection site abscess
         subjects affected / exposed
    0 / 653 (0.00%)
    1 / 659 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    0 / 653 (0.00%)
    1 / 659 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 653 (0.00%)
    1 / 659 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 653 (0.00%)
    1 / 659 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus bronchiolitis
         subjects affected / exposed
    0 / 653 (0.00%)
    1 / 659 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal infection
         subjects affected / exposed
    0 / 653 (0.00%)
    1 / 659 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 653 (0.15%)
    1 / 659 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 653 (0.15%)
    0 / 659 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2.5%
    Non-serious adverse events
    		 PR5I INFANRIX™ hexa
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    650 / 653 (99.54%)
    653 / 659 (99.09%)
    Nervous system disorders
    Somnolence
         subjects affected / exposed
    562 / 653 (86.06%)
    529 / 659 (80.27%)
         occurrences all number
    1168
    1118
    General disorders and administration site conditions
    Crying
         subjects affected / exposed
    583 / 653 (89.28%)
    574 / 659 (87.10%)
         occurrences all number
    1422
    1305
    Injection site bruising
         subjects affected / exposed
    13 / 653 (1.99%)
    23 / 659 (3.49%)
         occurrences all number
    15
    24
    Injection site erythema
         subjects affected / exposed
    485 / 653 (74.27%)
    450 / 659 (68.29%)
         occurrences all number
    1625
    1490
    Injection site haemorrhage
         subjects affected / exposed
    17 / 653 (2.60%)
    17 / 659 (2.58%)
         occurrences all number
    21
    20
    Injection site induration
         subjects affected / exposed
    119 / 653 (18.22%)
    107 / 659 (16.24%)
         occurrences all number
    266
    246
    Injection site pain
         subjects affected / exposed
    496 / 653 (75.96%)
    493 / 659 (74.81%)
         occurrences all number
    1778
    1656
    Injection site swelling
         subjects affected / exposed
    406 / 653 (62.17%)
    373 / 659 (56.60%)
         occurrences all number
    1179
    1083
    Irritability
         subjects affected / exposed
    598 / 653 (91.58%)
    589 / 659 (89.38%)
         occurrences all number
    1518
    1446
    Pyrexia
         subjects affected / exposed
    490 / 653 (75.04%)
    452 / 659 (68.59%)
         occurrences all number
    875
    768
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    20 / 653 (3.06%)
    10 / 659 (1.52%)
         occurrences all number
    23
    11
    Constipation
         subjects affected / exposed
    22 / 653 (3.37%)
    16 / 659 (2.43%)
         occurrences all number
    25
    18
    Diarrhoea
         subjects affected / exposed
    76 / 653 (11.64%)
    70 / 659 (10.62%)
         occurrences all number
    95
    84
    Flatulence
         subjects affected / exposed
    29 / 653 (4.44%)
    25 / 659 (3.79%)
         occurrences all number
    32
    29
    Vomiting
         subjects affected / exposed
    220 / 653 (33.69%)
    211 / 659 (32.02%)
         occurrences all number
    324
    319
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    30 / 653 (4.59%)
    24 / 659 (3.64%)
         occurrences all number
    31
    29
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    35 / 653 (5.36%)
    36 / 659 (5.46%)
         occurrences all number
    39
    39
    Otitis media
         subjects affected / exposed
    24 / 653 (3.68%)
    15 / 659 (2.28%)
         occurrences all number
    26
    15
    Rhinitis
         subjects affected / exposed
    34 / 653 (5.21%)
    41 / 659 (6.22%)
         occurrences all number
    39
    44
    Upper respiratory tract infection
         subjects affected / exposed
    41 / 653 (6.28%)
    43 / 659 (6.53%)
         occurrences all number
    45
    48
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    431 / 653 (66.00%)
    411 / 659 (62.37%)
         occurrences all number
    731
    694

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Apr 2011
    Amendment 1:The primary reasons for this amendment was (1) to designate that a subset of participants would receive Rotarix™ concomitantly with PR5I or INFANRIX hexa, while another subset of participants would receive RotaTeq™ concomitantly with PR5I or INFANRIX hexa; (2) revise the power statement for the secondary hypothesis for Rotarix™ immunogenicity; and (3) indicate that RotaTeq™ was to be administered at 2, 4, and 5 months of age.
    13 May 2011
    Amendment 2: The primary reason for this amendment was to designate that RotaTeq™ was to be supplied centrally by Merck.
    20 Jan 2012
    Amendment 3: The primary reason for this amendment was to allow the first dose of RotaTeq™ to be given in Finland prior to Visit 1 outside the study.
    26 Apr 2013
    Amendment 5: The primary reason for this amendment was to revise the statistical analysis plan.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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