Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A phase IIIb randomized, open, controlled study to assess the effect of prophylactic antipyretic treatment on the rate of febrile reactions following concomitant administration of GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine with GSK Biologicals’ Infanrix hexa vaccine in children at 3, 4 and 5 months of age and GSK Biologicals’ Rotarix vaccine at 3 and 4 months of age.

    Summary
    EudraCT number
    		 2006-000559-16
    Trial protocol
    		 CZ  
    Global end of trial date
    10 Apr 2007

    Results information
    Results version number
    		 v2(current)
    This version publication date
    23 Mar 2016
    First version publication date
    28 Mar 2015
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Correction of error in solicited general symptoms

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    107017
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00370318
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline Biologicals
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    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
    26 Jul 2007
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    10 Apr 2007
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Apr 2007
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the percentage reduction in febrile reactions (rectal temperature > or = 38.0°C) when prophylactic antipyretic treatment is administered compared to no prophylactic antipyretic treatment, after primary vaccination with GSK Biologicals’ 10-valent pneumococcal conjugate vaccine and routine DTPa-HBV-IPV/Hib (Infanrix hexa) vaccination in children at 3, 4 and 5 months of age and oral live attenuated HRV (Rotarix) vaccination in children at 3 and 4 months of age.
    Protection of trial subjects
    All subjects were supervised for 30 min after vaccination/product administration with appropriate medical treatment readily available. Vaccines/products were administered by qualified and trained personnel. Vaccines/products were administered only to eligible subjects that had no contraindications to any components of the vaccines/products. Subjects were followed-up for 6 months after the last vaccination/product administration (Safety Follow-Up (FU) Phase). Adverse events specifically checked for while assessing the subjects’ safety were acute disease at the time of vaccination (acute disease being defined the presence of a mild, moderate or severe illness with or without fever defined as rectal temperature > 37.5°C; any fever >= 40.5°C (rectal temperature) or >= 40.0°C (oral/axillary/tympanic temperature) within 48 hours of vaccination, collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours of vaccination, persistent, inconsolable crying occurring within 48 hours of vaccination and lasting  3 hours, seizures with or without fever occurring within 3 days of vaccination and gastroenteritis (GE) within 7 days preceding the study vaccine administration (i.e. diarrhoea with or without vomiting).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Sep 2006
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 6 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Czech Republic: 459
    Worldwide total number of subjects
    459
    EEA total number of subjects
    459
    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)
    459
    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

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This study included an Active Phase, up to 3 months post the first study vaccination and an Safety Follow-Up Phase of up to 6 months after the last study vaccination. Withdrawal information on subjects was collected up to the end of the Active Phase, up to Month 3.

    Pre-assignment
    Screening details
    		 During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms.

    Period 1
    Period 1 title
    Overall study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 10Pn-PD-DiT/ Paracetamol Group
    Arm description
    		 Subjects were vaccinated with a 3-dose course administered at 3, 4 and 5 months of age (Study Months 0, 1 and 2) of GSK Biologicals’ pneumococcal conjugate vaccine GSK1024850A (also referred to as 10Pn-PD-DiT or 10Pn vaccine) co-administered with Infanrix™ hexa (also referred to as DTPa-HBV-IPV/Hib) and with prophylactic antipyretic treatment (rectal paracetamol or acetaminophen) under the form of suppositories of CALPOL 80 or 125, depending on the subjects’ body weight . In addition, subjects also received 2 doses of HRV vaccine (Rotarix™) and of at 3 and 4 months of age (Study Months 0 and 1).
    Arm type
    		 Experimental

    Investigational medicinal product name
    10-valent Streptococcus pneumoniae conjugate vaccine
    Investigational medicinal product code
    Other name
    10Pn, 10Pn-PD-DiT, GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine, Synflorix™, GlaxoSmithKline (GSK) Biologicals’ 1024850A vaccine,
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Three doses of the vaccine were administered intramuscularly, into the right thigh at 3, 4 and 5 months of age (Study Months 0, 1 and 2).

    Investigational medicinal product name
    Rotarix™
    Investigational medicinal product code
    Other name
    HRV, GSK Biologicals’ oral live attenuated human rotavirus vaccine.
    Pharmaceutical forms
    Powder and solvent for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    2 doses of the vaccine were administered orally at 3 and 4 months of age (Study Months 0 and 1) .

    Investigational medicinal product name
    Infanrix™ Hexa
    Investigational medicinal product code
    Other name
    DTPa-IPV-HBV/Hib, Infanrix Hexa GSK Biologicals’ diphtheria-tetanus-acellular pertussis, hepatitis B virus-inactivated poliovirus and Haemophilus influenzae typ
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses of the vaccine were administered intramuscularly in the left thigh at 3, 4 and 5 months of age (Study Months 0, 1 and 2).

    Investigational medicinal product name
    CALPOL 80
    Investigational medicinal product code
    Other name
    Paracetamol 80 mg; Acetaminophen
    Pharmaceutical forms
    Suppository
    Routes of administration
    Rectal use
    Dosage and administration details
    In subjects weighing 4.5 to < 7 kg: 3 doses administered rectally at 3, 4 and 5 months of age (Study Months 0, 1 and 2).

    Investigational medicinal product name
    CALPOL 125
    Investigational medicinal product code
    Other name
    Paracetamol 125 mg; Acetaminophen
    Pharmaceutical forms
    Suppository
    Routes of administration
    Rectal use
    Dosage and administration details
    In subjects weighing >= 7 kg: 3 doses administered rectally at 3, 4 and 5 months of age (Study Months 0, 1 and 2).

    Arm title
    		 10Pn-PD-DiT Group
    Arm description
    		 Subjects were vaccinated with a 3-dose course administered at 3, 4 and 5 months of age (Study Months 0, 1 and 2) of GSK Biologicals’ pneumococcal conjugate vaccine GSK1024850A (also referred to as 10Pn-PD-DiT or 10Pn vaccine) co-administered with Infanrix™ hexa (also referred to as DTPa-HBV-IPV/Hib). Subjects also received 2 doses of HRV vaccine (Rotarix™) without prophylactic antipyretic treatment at 3 and 4 months of age (Study Months 0 and 1).
    Arm type
    		 Experimental

    Investigational medicinal product name
    10-valent Streptococcus pneumoniae conjugate vaccine
    Investigational medicinal product code
    Other name
    10Pn, 10Pn-PD-DiT, GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine, Synflorix™, GlaxoSmithKline (GSK) Biologicals’ 1024850A vaccine,
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Three doses of the vaccine were administered intramuscularly, into the right thigh at 3, 4 and 5 months of age (Study Months 0, 1 and 2).

    Investigational medicinal product name
    Rotarix™
    Investigational medicinal product code
    Other name
    HRV, GSK Biologicals’ oral live attenuated human rotavirus vaccine.
    Pharmaceutical forms
    Powder and solvent for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    2 doses of the vaccine were administered orally at 3 and 4 months of age (Study Months 0 and 1) .

    Investigational medicinal product name
    Infanrix™ Hexa
    Investigational medicinal product code
    Other name
    DTPa-IPV-HBV/Hib, Infanrix Hexa GSK Biologicals’ diphtheria-tetanus-acellular pertussis, hepatitis B virus-inactivated poliovirus and Haemophilus influenzae typ
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses of the vaccine were administered intramuscularly in the left thigh at 3, 4 and 5 months of age (Study Months 0, 1 and 2).

    Number of subjects in period 1
    		10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Started
    226
    233
    Completed
    224
    232
    Not completed
    2
    1
         Consent withdrawn by subject
    1
    -
         Adverse event, non-fatal
    1
    -
         Migrated/moved from study area
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    10Pn-PD-DiT/ Paracetamol Group
    Reporting group description
    		 Subjects were vaccinated with a 3-dose course administered at 3, 4 and 5 months of age (Study Months 0, 1 and 2) of GSK Biologicals’ pneumococcal conjugate vaccine GSK1024850A (also referred to as 10Pn-PD-DiT or 10Pn vaccine) co-administered with Infanrix™ hexa (also referred to as DTPa-HBV-IPV/Hib) and with prophylactic antipyretic treatment (rectal paracetamol or acetaminophen) under the form of suppositories of CALPOL 80 or 125, depending on the subjects’ body weight . In addition, subjects also received 2 doses of HRV vaccine (Rotarix™) and of at 3 and 4 months of age (Study Months 0 and 1).

    Reporting group title
    10Pn-PD-DiT Group
    Reporting group description
    		 Subjects were vaccinated with a 3-dose course administered at 3, 4 and 5 months of age (Study Months 0, 1 and 2) of GSK Biologicals’ pneumococcal conjugate vaccine GSK1024850A (also referred to as 10Pn-PD-DiT or 10Pn vaccine) co-administered with Infanrix™ hexa (also referred to as DTPa-HBV-IPV/Hib). Subjects also received 2 doses of HRV vaccine (Rotarix™) without prophylactic antipyretic treatment at 3 and 4 months of age (Study Months 0 and 1).

    Reporting group values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group Total
    Number of subjects
    		 226 233 459
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: weeks
        arithmetic mean (standard deviation)
    		 12.2 ( 2.06 ) 12.3 ( 2.21 ) -
    Gender categorical
    Units: Subjects
        Female
    		 114 109 223
        Male
    		 112 124 236

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    10Pn-PD-DiT/ Paracetamol Group
    Reporting group description
    		 Subjects were vaccinated with a 3-dose course administered at 3, 4 and 5 months of age (Study Months 0, 1 and 2) of GSK Biologicals’ pneumococcal conjugate vaccine GSK1024850A (also referred to as 10Pn-PD-DiT or 10Pn vaccine) co-administered with Infanrix™ hexa (also referred to as DTPa-HBV-IPV/Hib) and with prophylactic antipyretic treatment (rectal paracetamol or acetaminophen) under the form of suppositories of CALPOL 80 or 125, depending on the subjects’ body weight . In addition, subjects also received 2 doses of HRV vaccine (Rotarix™) and of at 3 and 4 months of age (Study Months 0 and 1).

    Reporting group title
    10Pn-PD-DiT Group
    Reporting group description
    		 Subjects were vaccinated with a 3-dose course administered at 3, 4 and 5 months of age (Study Months 0, 1 and 2) of GSK Biologicals’ pneumococcal conjugate vaccine GSK1024850A (also referred to as 10Pn-PD-DiT or 10Pn vaccine) co-administered with Infanrix™ hexa (also referred to as DTPa-HBV-IPV/Hib). Subjects also received 2 doses of HRV vaccine (Rotarix™) without prophylactic antipyretic treatment at 3 and 4 months of age (Study Months 0 and 1).

    Primary: Number of subjects reported with core fever (rectal temperature) ≥ 38.0 degrees Celsius (°C)

    		 Close Top of page
    End point title
    		 Number of subjects reported with core fever (rectal temperature) ≥ 38.0 degrees Celsius (°C)
    End point description
    End point type
    Primary
    End point timeframe
    Within 4 days (Day 0-3) after each vaccination, across doses
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    226
    233
    Units: Subjects
        Fever ≥ 38.0°C
    94
    154
    Statistical analysis title
    		 Difference between groups in percentage
    Statistical analysis description
    Analysis aimed at demonstrating the superiority in terms of post-immunization core fever >= 38.0°C of 10Pn-PD-DiT vaccine when co-admininistered with paracetamol compared to the 10Pn-PD-DiT vaccine when administered without such co-administration. Towards this analysis, standardized asymptotic 95% confidence interval (CI) for the groups difference [10Pn-PD-DiT/Paracetamol Group minus 10Pn-PD-DiT Group] in percentages of subjects reported with core fever >= 38.0°C was computed.
    Comparison groups
    10Pn-PD-DiT/ Paracetamol Group v 10Pn-PD-DiT Group
    Number of subjects included in analysis
    459
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    Method
    Parameter type
    		 Difference in percentage
    Point estimate
    24.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 15.49
         upper limit
    		 33.11
    Notes
    [1] - Superiority was demonstrated if the lower limit (LL) computed standardized asymptotic 95% CI was above 0%

    Secondary: Number of subjects reported with core fever (rectal temperature) > 39.0°C

    		 Close Top of page
    End point title
    		 Number of subjects reported with core fever (rectal temperature) > 39.0°C
    End point description
    End point type
    Secondary
    End point timeframe
    Within 4 days (Day 0-3) after at least one vaccination, across doses
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    226
    233
    Units: Subjects
        Fever (rectal temperature) > 39.0°C
    4
    17
    No statistical analyses for this end point

    Secondary: Number of subjects reported with any and Grade 3 solicited local symptoms

    		 Close Top of page
    End point title
    		 Number of subjects reported with any and Grade 3 solicited local symptoms
    End point description
    Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any occurrence of the specified symptom regardless of intensity. Grade 3 pain was defined as cried when limb was moved/spontaneously painful. Grade 3 redness/swelling was defined as redness/swelling > 30 millimetres from injection site.
    End point type
    Secondary
    End point timeframe
    Within 4 days after each vaccination, across doses
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    226
    233
    Units: Subjects
        Any pain
    69
    101
        Grade 3 pain
    2
    10
        Any redness
    134
    143
        Grade 3 redness
    6
    10
        Any swelling
    89
    102
        Grade 3 swelling
    18
    23
    No statistical analyses for this end point

    Secondary: Number of subjects reported with any and Grade 3 solicited general symptoms

    		 Close Top of page
    End point title
    		 Number of subjects reported with any and Grade 3 solicited general symptoms
    End point description
    Solicited general symptoms assessed were diarrhea, drowsiness, fever (rectal temperature >= 38.5°C), irritability, loss of appetite and vomiting. Any was defined as any occurrence of the specified symptom regardless of intensity and relation to vaccination. Any for diarrhea was defined as 3 looser than normal stools/day and any for vomiting was defined as one episode of vomiting/day. Grade 3 diarrhea was defined as 6 or more looser stools/day. Grade 3 drowsiness was defined as drowsiness that prevented normal activity. Grade 3 fever was defined as rectal temperature >40.0°C. Grade 3 irritability was defined as crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite was defined as not eating at all. Grade 3 vomiting was defined as 3 or more episodes of vomiting/day.
    End point type
    Secondary
    End point timeframe
    Within 4 days after each vaccination, across doses
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    226
    233
    Units: Subjects
        Any diarrhea
    34
    31
        Grade 3 diarrhea
    8
    5
        Any drowsiness
    137
    155
        Grade 3 drowsiness
    0
    5
        Any fever (rectal temperature >=38.0°C))
    94
    154
        Grade 3 fever (rectal temperature > 40.0°C)
    1
    0
        Any irritability
    139
    166
        Grade 3 irritability
    2
    8
        Any loss of appetite
    49
    68
        Grade 3 loss of appetite
    0
    0
        Any vomiting
    30
    15
        Grade 3 vomiting
    6
    2
    No statistical analyses for this end point

    Secondary: Number of subjects reported with unsolicited adverse events (AEs)

    		 Close Top of page
    End point title
    		 Number of subjects reported with unsolicited adverse events (AEs)
    End point description
    End point type
    Secondary
    End point timeframe
    Within 31 days (Day 0-30) after each vaccination, across doses
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    226
    233
    Units: Subjects
        Subject(s) with AE(s)
    100
    114
    No statistical analyses for this end point

    Secondary: Number of subjects reported with serious adverse events (SAEs) during the Active Phase of the study

    		 Close Top of page
    End point title
    		 Number of subjects reported with serious adverse events (SAEs) during the Active Phase of the study
    End point description
    End point type
    Secondary
    End point timeframe
    During the Active Phase of the study, from Month 0 to Month 3)
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    226
    233
    Units: Subjects
        Subject(s) with SAE(s)
    8
    6
    No statistical analyses for this end point

    Secondary: Number of subjects reported with serious adverse events (SAEs) throughout the entire study

    		 Close Top of page
    End point title
    		 Number of subjects reported with serious adverse events (SAEs) throughout the entire study
    End point description
    End point type
    Secondary
    End point timeframe
    During the entire study period, from Month 0 to Month 8, up to 6 months after the last study vaccine dose
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    226
    233
    Units: Subjects
        Subject(s) with SAE(s)
    20
    17
    No statistical analyses for this end point

    Secondary: Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL

    		 Close Top of page
    End point title
    		 Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL
    End point description
    Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were measured by 22F-inhibition Enzyme-Linked ImmunoSorbent Assay (ELISA). Seroprotection and seropositivity cut-offs for the assay were >= 0.20 and 0.05 μg/mL, respectively.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of pneumococcal vaccination.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    208
    227
    Units: Subjects
        Anti-1 ≥ 0.2 μg/mL, at M3 (N=207; 226)
    202
    224
        Anti-4 ≥ 0.2 μg/mL, at M3 (N=206; 226)
    205
    225
        Anti-5 ≥ 0.2 μg/mL, at M3 (N=207; 227)
    206
    226
        Anti-6B ≥ 0.2 μg/mL, at M3 (N=206; 225)
    128
    170
        Anti-7F ≥ 0.2 μg/mL, at M3 (N=208; 227)
    206
    226
        Anti-9V ≥ 0.2 μg/mL, at M3 (N=204; 225)
    200
    222
        Anti-14 ≥ 0.2 μg/mL, at M3 (N=207; 225)
    206
    224
        Anti-18C ≥ 0.2 μg/mL, at M3 (N=208; 227)
    199
    226
        Anti-19F ≥ 0.2 μg/mL, at M3 (N=208; 227)
    203
    227
        Anti-23F ≥ 0.2 μg/mL, at M3 (N=204; 225)
    164
    196
    No statistical analyses for this end point

    Secondary: Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F)

    		 Close Top of page
    End point title
    		 Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F)
    End point description
    Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were measured by 22F-inhibition Enzyme-Linked ImmunoSorbent Assay (ELISA). Seropositivity cut-off for the assay was >= 0.05 μg/mL.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of pneumococcal vaccination.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    208
    227
    Units: μg/mL
    geometric mean (confidence interval 95%)
        Anti-1, M3, (N=207; 226)
    0.92 (0.83 to 1.03)
    1.45 (1.31 to 1.61)
        Anti-4, M3, (N=206; 226)
    1.33 (1.18 to 1.5)
    2.13 (1.91 to 2.37)
        Anti-5, M3, (N=207; 227)
    1.42 (1.28 to 1.58)
    2.04 (1.85 to 2.25)
        Anti-6B, M3, (N=206; 225)
    0.26 (0.22 to 0.31)
    0.46 (0.38 to 0.54)
        Anti-7F, M3, (N=208; 227)
    1.57 (1.43 to 1.72)
    2.16 (1.96 to 2.37)
        Anti-9V, M3, (N=204; 225)
    1.03 (0.92 to 1.15)
    1.48 (1.34 to 1.64)
        Anti-14, M3, (N=207; 225)
    2.3 (2.05 to 2.58)
    3.57 (3.16 to 4.03)
        Anti-18C, M3, (N=208; 227)
    1.19 (1.03 to 1.38)
    2.65 (2.37 to 2.98)
        Anti-19F, M3, (N=208; 227)
    3.46 (3.01 to 3.98)
    5.59 (4.99 to 6.26)
        Anti-23F, M3, (N=204; 225)
    0.49 (0.42 to 0.59)
    0.76 (0.64 to 0.9)
    No statistical analyses for this end point

    Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F

    		 Close Top of page
    End point title
    		 Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F
    End point description
    OPA titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seropositivity cut-off for the assay was ≥ 8.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of pneumococcal vaccination
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    164
    176
    Units: Titers
    geometric mean (confidence interval 95%)
        Opsono-1 (N=164;176)
    10.3 (8.3 to 12.8)
    23.7 (18.2 to 31)
        Opsono-4 (N=163;175)
    788.3 (691.8 to 898.4)
    744.6 (649.2 to 854.2)
        Opsono-5 (N=159;171)
    32.2 (25.9 to 40)
    72.5 (59.9 to 87.7)
        Opsono-6B (N=157;162)
    386.7 (270 to 554)
    684.8 (523.9 to 895.3)
        Opsono-7F (N=158;170)
    2458.2 (2096 to 2883)
    2345.3 (1970.7 to 2791.2)
        Opsono-9V (N=154;169)
    1658.1 (1438.3 to 1911.4)
    1230.3 (1026.8 to 1474)
        Opsono-14 (N=160;175)
    897.6 (753.2 to 1069.6)
    1161.6 (985 to 1369.8)
        Opsono-18C (N=157;170)
    135 (106.6 to 171)
    202.2 (170.4 to 240)
        Opsono-19F (N=155;165)
    244.6 (187.4 to 319.4)
    369.5 (295.6 to 461.9)
        Opsono-23F (N=160;170)
    1163.6 (885.4 to 1529.2)
    1497.2 (1215 to 1845.1)
    No statistical analyses for this end point

    Secondary: Antibody concentrations against pneumococcal serotypes 6A and 19A (Anti-6A and 19A)

    		 Close Top of page
    End point title
    		 Antibody concentrations against pneumococcal serotypes 6A and 19A (Anti-6A and 19A)
    End point description
    Anti-6A and 19A antibody concentrations were measured by 22F-inhibition Enzyme-Linked ImmunoSorbent Assay (ELISA).
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of pneumococcal vaccination.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    205
    224
    Units: μg/mL
    geometric mean (confidence interval 95%)
        Anti-6A (N=204;224)
    0.07 (0.06 to 0.08)
    0.12 (0.1 to 0.15)
        Anti-19A (N=205;223)
    0.12 (0.1 to 0.14)
    0.19 (0.17 to 0.23)
    No statistical analyses for this end point

    Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A

    		 Close Top of page
    End point title
    		 Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A
    End point description
    OPA titers against pneumococcal serotypes 6A and 19A (Opsono-6A and 19A) were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seropositivity cut-off for the assay was ≥ 8.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of pneumococcal vaccination
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    160
    172
    Units: Titers
    geometric mean (confidence interval 95%)
        Opsono-6A (N=153;165)
    49.3 (34.8 to 69.9)
    61.4 (43.7 to 86.1)
        Opsono-19A (N=160;172)
    6.3 (5.2 to 7.8)
    7.9 (6.3 to 10)
    No statistical analyses for this end point

    Secondary: Concentrations of antibodies against protein D (Anti-PD)

    		 Close Top of page
    End point title
    		 Concentrations of antibodies against protein D (Anti-PD)
    End point description
    The seropositivity cut-off for the assay was ≥ 100 Enzyme-Linked ImmunoSorbent Assay (ELISA). units per millilitre.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of pneumococcal vaccination.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    207
    222
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Anti-PD
    985.4 (872.9 to 1112.4)
    1599.1 (1434.6 to 1782.5)
    No statistical analyses for this end point

    Secondary: Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.05 μg/mL

    		 Close Top of page
    End point title
    		 Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.05 μg/mL
    End point description
    Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were measured by 22F-inhibition Enzyme-Linked ImmunoSorbent Assay (ELISA). Seropositivity cut-off for the assay was >= 0.05 μg/mL.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of pneumococcal vaccination.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    208
    227
    Units: Subjects
        Anti-1 (N=207; 226)
    207
    226
        Anti-4 (N=206; 226)
    205
    226
        Anti-5 (N=207; 227)
    207
    227
        Anti-6B (N=206; 225)
    179
    209
        Anti-7F (N=208; 227)
    208
    227
        Anti-9V (N=204; 225)
    204
    225
        Anti-14 (N=207; 225)
    207
    225
        Anti-18C (N=208; 227)
    204
    227
        Anti-19F (N=208; 227)
    208
    227
        Anti-23F (N=204; 225)
    192
    212
    No statistical analyses for this end point

    Secondary: Number of subjects with opsonophagocytic activity titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 8

    		 Close Top of page
    End point title
    		 Number of subjects with opsonophagocytic activity titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 8
    End point description
    The seropositivity cut-off of the assay was ≥ 8.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of pneumococcal vaccination.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    164
    176
    Units: Subjects
        Opsono-1 ≥ 8 (N=164;176)
    57
    97
        Opsono-4 ≥ 8 (N=163;175)
    163
    175
        Opsono-5 ≥ 8 (N=159;171)
    127
    159
        Opsono-6B ≥ 8N=157;162)
    129
    151
        Opsono-7F ≥ 8 (N=158;170)
    158
    169
        Opsono-9V ≥ 8 (N=154;169)
    154
    168
        Opsono-14 ≥ 8 (N=160;175)
    158
    174
        Opsono-18C ≥ 8 (N=157;170)
    144
    167
        Opsono-19F ≥ 8 (N=155;165)
    142
    156
        Opsono-23F ≥ 8 (N=160;170)
    150
    166
    No statistical analyses for this end point

    Secondary: Number of subjects with antibody concentrations against pneumococcal serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.05 μg/mL

    		 Close Top of page
    End point title
    		 Number of subjects with antibody concentrations against pneumococcal serotypes 6A and 19A (Anti-6A and 19A) ≥ 0.05 μg/mL
    End point description
    Anti-6A and 19A antibody concentrations were measured by 22F-inhibition Enzyme-Linked ImmunoSorbent Assay (ELISA).
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of pneumococcal vaccination.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    205
    224
    Units: Subjects
        Anti-6A, (N=204;224)
    120
    162
        Anti-19A (N=205;223)
    164
    193
    No statistical analyses for this end point

    Secondary: Number of subjects with opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A (Opsono-6A and 19A) ≥ 8

    		 Close Top of page
    End point title
    		 Number of subjects with opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A (Opsono-6A and 19A) ≥ 8
    End point description
    The seropositivity cut-off of the assay was ≥ 8.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of pneumococcal vaccination.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    160
    172
    Units: Subjects
        Opsono-6A, (N=153;165)
    92
    107
        Opsono-19A, (N=160;172)
    19
    30
    No statistical analyses for this end point

    Secondary: Number of subjects with concentrations of antibodies against protein D (Anti-PD)>= 100 Enzyme-Linked ImmunoSorbent Assay (ELISA) units per millilitre (EL.U/mL)

    		 Close Top of page
    End point title
    		 Number of subjects with concentrations of antibodies against protein D (Anti-PD)>= 100 Enzyme-Linked ImmunoSorbent Assay (ELISA) units per millilitre (EL.U/mL)
    End point description
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of pneumococcal vaccination.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    207
    222
    Units: Subjects
        Anti-PD
    205
    222
    No statistical analyses for this end point

    Secondary: Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T)

    		 Close Top of page
    End point title
    		 Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T)
    End point description
    The seroprotection cut-off for the assay was ≥ 0.1 IU/mL.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of Infanrix™ hexa vaccine.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    206
    225
    Units: IU/mL
    geometric mean (confidence interval 95%)
        Anti-D
    2.67 (2.417 to 2.95)
    3.561 (3.294 to 3.849)
        Anti-T
    1.639 (1.474 to 1.822)
    2.669 (2.434 to 2.927)
    No statistical analyses for this end point

    Secondary: Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations

    		 Close Top of page
    End point title
    		 Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations
    End point description
    The seroprotection cut-off for the assay was ≥ 0.15 µg/mL.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of Infanrix™ hexa vaccine.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    207
    224
    Units: µg/mL
    geometric mean (confidence interval 95%)
        Anti-PRP
    2.278 (1.883 to 2.755)
    4.264 (3.673 to 4.951)
    No statistical analyses for this end point

    Secondary: Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations

    		 Close Top of page
    End point title
    		 Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations
    End point description
    The seropositivity cut-off for the assay was ≥ 5 Enzyme-Linked ImmunoSorbent Assay (ELISA) units per millimiter (EL.U/mL).
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of Infanrix™ hexa vaccine.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    206
    225
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Anti-PT (N=205;224)
    39.3 (36.5 to 42.3)
    42.3 (39.2 to 45.7)
        Anti-FHA (N=204;224)
    148 (134.5 to 162.8)
    166.2 (151.9 to 181.8)
        Anti-PRN (N=206;225)
    59 (52.1 to 66.8)
    78 (70.5 to 86.2)
    No statistical analyses for this end point

    Secondary: Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations

    		 Close Top of page
    End point title
    		 Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations
    End point description
    The seroprotection cut-off for the assay was ≥ 10 mIU/mL.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of Infanrix™ hexa vaccine.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    50
    66
    Units: mIU/mL
    geometric mean (confidence interval 95%)
        Anti-HBs
    254.2 (171.6 to 376.6)
    306.6 (218.6 to 430.1)
    No statistical analyses for this end point

    Secondary: Anti-polio types 1, 2 and 3 titers

    		 Close Top of page
    End point title
    		 Anti-polio types 1, 2 and 3 titers
    End point description
    The seroprotection cut-off for the assay was ≥ 8.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of Infanrix™ hexa vaccine.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    20
    25
    Units: Titers
    geometric mean (confidence interval 95%)
        Anti-Polio 1 (N=20;25)
    215.3 (135.4 to 342.1)
    142.7 (78.7 to 258.8)
        Anti-Polio 2 (N=19;23)
    171.7 (91.1 to 323.7)
    108.6 (59.8 to 197.3)
        Anti-Polio 3 (N=17;23)
    409.1 (222.2 to 753.4)
    284.3 (165.9 to 487.1)
    No statistical analyses for this end point

    Secondary: Number of subjects with anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 5 EL.U/mL

    		 Close Top of page
    End point title
    		 Number of subjects with anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 5 EL.U/mL
    End point description
    The seropositivity cut-off for the assay was ≥ 5 Enzyme-Linked ImmunoSorbent Assay (ELISA) units per millimiter (EL.U/mL).
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of Infanrix™ hexa vaccine.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    206
    225
    Units: Subjects
        Anti-PT (N=205;224)
    205
    224
        Anti-FHA (N=204;224)
    204
    224
        Anti-PRN (N=206;225)
    205
    224
    No statistical analyses for this end point

    Secondary: Number of subjects with anti-D and anti-T antibody concentrations ≥ 0.1 IU/mL.

    		 Close Top of page
    End point title
    		 Number of subjects with anti-D and anti-T antibody concentrations ≥ 0.1 IU/mL.
    End point description
    The seroprotection cut-off for the assay was ≥ 0.1 IU/mL.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of Infanrix™ hexa vaccine.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    206
    225
    Units: Subjects
        Anti-D
    206
    225
        Anti-T
    206
    225
    No statistical analyses for this end point

    Secondary: Number of subjects with anti-PRP antibody concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL.

    		 Close Top of page
    End point title
    		 Number of subjects with anti-PRP antibody concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL.
    End point description
    The seroprotection cut-offs for the assay were ≥ 0.15 µg/mL and ≥1.0 µg/mL.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of Infanrix™ hexa vaccine.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    207
    224
    Units: Subjects
        Anti-PRP ≥ 0.15 µg/mL
    199
    224
        Anti-PRP ≥ 1.0 µg/mL
    153
    205
    No statistical analyses for this end point

    Secondary: Number of subjects with anti-HBs antibody concentrations ≥10 mIU/mL.

    		 Close Top of page
    End point title
    		 Number of subjects with anti-HBs antibody concentrations ≥10 mIU/mL.
    End point description
    The seroprotection cut-off for the assay was ≥ 10 mIU/mL.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of Infanrix™ hexa vaccine.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    50
    66
    Units: Subjects
        Anti-HBs
    48
    64
    No statistical analyses for this end point

    Secondary: Number of subjects with anti-polio type 1, 2 and 3 titers ≥ 8

    		 Close Top of page
    End point title
    		 Number of subjects with anti-polio type 1, 2 and 3 titers ≥ 8
    End point description
    The seroprotection cut-off for the assay was ≥ 8.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of Infanrix™ hexa vaccine.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    20
    25
    Units: Subjects
        Anti-Polio 1 (N=20;25)
    20
    25
        Anti-Polio 2 (N=19;23)
    19
    23
        Anti-Polio 3 (N=17;23)
    17
    23
    No statistical analyses for this end point

    Secondary: Number of vaccine responders as regards antibodies against pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (PRN)

    		 Close Top of page
    End point title
    		 Number of vaccine responders as regards antibodies against pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (PRN)
    End point description
    A vaccine responder to PT/FHA/PRN was defined as a subject with the appearance of antibodies against PT/FHA/PRN in subjects who were initially seronegative for anti-PT/FHA/PRN antibodies (i.e., subjects with anti-PT/FHA/PRN antibody concentrations < 5 EL.U/mL), or at least the maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (i.e., subjects with anti-PT/FHA/PRN antibody concentrations ≥ 5 EL.U/mL).
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), one month after Dose 3 of Infanrix™ hexa vaccine
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    201
    221
    Units: Subjects
        Anti-PT (N=196;213)
    194
    207
        Anti-FHA (N=197;216)
    192
    213
        Anti-PRN (N=201;221)
    185
    211
    No statistical analyses for this end point

    Secondary: Anti-rotavirus (anti-RV) Immunoglobulin A (IgA) antibody concentrations

    		 Close Top of page
    End point title
    		 Anti-rotavirus (anti-RV) Immunoglobulin A (IgA) antibody concentrations
    End point description
    The seropositivity cut-off for the assay was ≥ 20 U/mL.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), 2 months after Dose 2 of Rotarix™ vaccine.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    191
    210
    Units: U/mL
    geometric mean (confidence interval 95%)
        Anti-RV IgA
    162.7 (126.6 to 208.9)
    187.9 (149.4 to 236.3)
    No statistical analyses for this end point

    Secondary: Number of subjects with anti-RV IgA antibody concentrations >= 20 U/mL

    		 Close Top of page
    End point title
    		 Number of subjects with anti-RV IgA antibody concentrations >= 20 U/mL
    End point description
    The seropositivity cut-off for the assay was ≥ 20 U/mL.
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), 2 months after Dose 2 of Rotarix™ vaccine.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    191
    210
    Units: Subjects
        Anti-RV IgA
    156
    179
    No statistical analyses for this end point

    Secondary: Number of seroconverted subjects as regards anti-RV IgA antibodies

    		 Close Top of page
    End point title
    		 Number of seroconverted subjects as regards anti-RV IgA antibodies
    End point description
    A seroconverted subject as regards anti-RV IgA antibodies was defined as a subject with the appearance of anti-RV IgA antibody concentrations ≥ 20 U/mL in subjects initially seronegative for anti-RV IgA antibodies (i.e. subjects with anti-RV IgA antibodies concentrations < 20 U/mL).
    End point type
    Secondary
    End point timeframe
    At Month 3 (M3), 2 months after Dose 2 of Rotarix™ vaccine.
    End point values
    		 10Pn-PD-DiT/ Paracetamol Group 10Pn-PD-DiT Group
    Number of subjects analysed
    176
    193
    Units: Subjects
        Anti-R IgA
    142
    163
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Solicited symptoms:4-day follow-up periods after vaccination (Days 0- 3), across doses; Unsolicited AEs: 31-day follow-up periods after vaccination (Days 0-30), across doses; SAEs:Entire study period (Months 0-8).
    Adverse event reporting additional description
    The occurrence of reported AEs (all/related) was not available and is encoded as equal to the number of subjects affected.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    10.0
    Reporting groups
    Reporting group title
    10Pn-PD-DiT/Paracetamol Group
    Reporting group description
    		 Subjects were vaccinated with a 3-dose course administered at 3, 4 and 5 months of age (Study Months 0, 1 and 2) of GSK Biologicals’ pneumococcal conjugate vaccine GSK1024850A (also referred to as 10Pn-PD-DiT or 10Pn vaccine) co-administered with Infanrix™ hexa (also referred to as DTPa-HBV-IPV/Hib) and with prophylactic antipyretic treatment (rectal paracetamol or acetaminophen) under the form of suppositories of CALPOL 80 or 125, depending on the subjects’ body weight . In addition, subjects also received 2 doses of HRV vaccine (Rotarix™) and of at 3 and 4 months of age (Study Months 0 and 1).

    Reporting group title
    10Pn-PD-DiT Group
    Reporting group description
    		 Subjects were vaccinated with a 3-dose course administered at 3, 4 and 5 months of age (Study Months 0, 1 and 2) of GSK Biologicals’ pneumococcal conjugate vaccine GSK1024850A (also referred to as 10Pn-PD-DiT or 10Pn vaccine) co-administered with Infanrix™ hexa (also referred to as DTPa-HBV-IPV/Hib). Subjects also received 2 doses of HRV vaccine (Rotarix™) without prophylactic antipyretic treatment at 3 and 4 months of age (Study Months 0 and 1).

    Serious adverse events
    		 10Pn-PD-DiT/Paracetamol Group 10Pn-PD-DiT Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    20 / 226 (8.85%)
    17 / 233 (7.30%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Head injury
         subjects affected / exposed
    2 / 226 (0.88%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Accidental exposure
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    1 / 226 (0.44%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Circulatory collapse
         subjects affected / exposed
    1 / 226 (0.44%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Epilepsy
         subjects affected / exposed
    1 / 226 (0.44%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Milk allergy
         subjects affected / exposed
    1 / 226 (0.44%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Enteritis
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchitis chronic
         subjects affected / exposed
    1 / 226 (0.44%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Psychomotor retardation
         subjects affected / exposed
    1 / 226 (0.44%)
    0 / 233 (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
    Bronchitis
         subjects affected / exposed
    4 / 226 (1.77%)
    4 / 233 (1.72%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Exanthema subitum
         subjects affected / exposed
    1 / 226 (0.44%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 226 (0.44%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngitis
         subjects affected / exposed
    1 / 226 (0.44%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 226 (0.44%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear infection
         subjects affected / exposed
    1 / 226 (0.44%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis viral
         subjects affected / exposed
    1 / 226 (0.44%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 226 (0.44%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paronychia
         subjects affected / exposed
    1 / 226 (0.44%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 226 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    1 / 226 (0.44%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 226 (0.44%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Weight gain poor
         subjects affected / exposed
    1 / 226 (0.44%)
    2 / 233 (0.86%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 226 (0.44%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 10Pn-PD-DiT/Paracetamol Group 10Pn-PD-DiT Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    139 / 226 (61.50%)
    166 / 233 (71.24%)
    General disorders and administration site conditions
    Pain
    alternative assessment type: Systematic
         subjects affected / exposed
    69 / 226 (30.53%)
    101 / 233 (43.35%)
         occurrences all number
    69
    101
    Redness
    alternative assessment type: Systematic
         subjects affected / exposed
    134 / 226 (59.29%)
    143 / 233 (61.37%)
         occurrences all number
    134
    143
    Swelling
    alternative assessment type: Systematic
         subjects affected / exposed
    89 / 226 (39.38%)
    102 / 233 (43.78%)
         occurrences all number
    89
    102
    Diarrhea
    alternative assessment type: Systematic
         subjects affected / exposed
    34 / 226 (15.04%)
    31 / 233 (13.30%)
         occurrences all number
    34
    31
    Drowsiness
    alternative assessment type: Systematic
         subjects affected / exposed
    137 / 226 (60.62%)
    155 / 233 (66.52%)
         occurrences all number
    137
    155
    Fever (rectal temperature >=38.0°C)
    alternative assessment type: Systematic
         subjects affected / exposed
    94 / 226 (41.59%)
    154 / 233 (66.09%)
         occurrences all number
    94
    154
    Irritability
    alternative assessment type: Systematic
         subjects affected / exposed
    139 / 226 (61.50%)
    166 / 233 (71.24%)
         occurrences all number
    139
    166
    Loss of appetite
    alternative assessment type: Systematic
         subjects affected / exposed
    49 / 226 (21.68%)
    68 / 233 (29.18%)
         occurrences all number
    49
    68
    Vomiting
    alternative assessment type: Systematic
         subjects affected / exposed
    30 / 226 (13.27%)
    15 / 233 (6.44%)
         occurrences all number
    30
    15
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    15 / 226 (6.64%)
    20 / 233 (8.58%)
         occurrences all number
    15
    20
    Nasopharyngitis
         subjects affected / exposed
    15 / 226 (6.64%)
    19 / 233 (8.15%)
         occurrences all number
    15
    19
    Pharyngitis
         subjects affected / exposed
    18 / 226 (7.96%)
    16 / 233 (6.87%)
         occurrences all number
    18
    16
    Rhinitis
         subjects affected / exposed
    10 / 226 (4.42%)
    14 / 233 (6.01%)
         occurrences all number
    10
    14

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Jul 2006
    The protocol was amended on 20-July-2006 (Amendment 1). This Amendment 1 was written in response to comments given by the Czech Republic Ethics Committee (changes concerned the exclusion criteria and contra-indication sections). Furthermore, the post-licensure surveillance of Prevenar™ in the United States had shown a decrease and an increase in invasive pneumococcal disease caused by the cross-reactive vaccine serotypes 6A and 19A, respectively. Therefore it was of interest to document the immune responses (ELISA and OPA) to these cross-reactive vaccine serotypes.
    23 Nov 2006
    The protocol was amended on 23-November-2006 (Amendment 3). The Pneumococcal Otitis Efficacy Trial (POET) (GSK Biologicals’ identifier 347414/010; Protocol & Results posting on GSK Clinical Trial Register: http://www.gsk-clinicalstudyregister.com/study/347414/010?study_ids=347414 ) using the experimental 11-valent PD-conjugate vaccine (11Pn-PD) demonstrated a statistically significant and clinically relevant protective effect of the 11Pn-PD vaccine on acute otitis media (AOM). To provide a basis for the AOM efficacy of the 10Pn-PD-DiT vaccine, an immunological comparison between the 10Pn-PD-DIT vaccine and the 11Pn-PD vaccine tested in the POET trial based on a non-inferiority approach using OPA geometric mean titers (GMT) ratios and a clinical limit of 2.5, was included in the protocol. Furthermore to avoid confusion regarding the total number of enrolled subjects and the number of subjects in the randomized OPA subset, clarifications were added to the immunological read-outs table and the study design.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat Apr 27 02:19:05 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA