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    Clinical Trial Results:
    A phase III, randomized, open-label, multicenter clinical trial to assess the immunogenicity and safety of GSK Biologicals’ Herpes Zoster vaccine GSK1437173A when co-administered with Pneumovax 23 in adults aged 50 years and older.

    Summary
    EudraCT number
    		 2012-005314-19
    Trial protocol
    		 EE  
    Global end of trial date
    22 Jun 2017

    Results information
    Results version number
    		 v2(current)
    This version publication date
    05 May 2021
    First version publication date
    08 Jul 2017
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Results have been amended to account for consistency with other registries.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    116889
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02045836
    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 Disclosure Advisor, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Disclosure Advisor, GlaxoSmithKline Biologicals, 44 2089904466, 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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    21 Mar 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Jun 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the vaccine response rate (VRR) to the HZ/su vaccine (based on humoral immune response) one month after the last vaccine dose in the HZ/su – Pneumovax 23 co-administration (Co-Ad) group. To demonstrate non-inferiority of the humoral immune response to two doses of the HZ/su vaccine when Pneumovax 23 is co-administered with the first HZ/su vaccine dose compared to two doses of HZ/su vaccine (administered separately from Pneumovax 23), one month after the last vaccine dose. To demonstrate non-inferiority of the humoral immune response to Pneumovax 23 when co-administered with HZ/su vaccine at first vaccine dose compared to Pneumovax 23 (administered separately from HZ/su), for the following 12 serotypes included in Pneumovax 23, one month after the vaccine dose: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F.
    Protection of trial subjects
    All subjects were supervised after vaccination/product administration with appropriate medical treatment readily available. Vaccines were administered by qualified ad trained personnel. Vaccines were administered only to eligible subjects that had no contraindications to any components of the vaccines.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 May 2014
    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
    Estonia: 400
    Country: Number of subjects enrolled
    Canada: 299
    Country: Number of subjects enrolled
    United States: 166
    Worldwide total number of subjects
    865
    EEA total number of subjects
    400
    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)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    502
    From 65 to 84 years
    356
    85 years and over
    7

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    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
    		 Co-Ad group
    Arm description
    		 Subjects received one dose of the GSK1437173A study vaccine and one dose of the Pneumovax 23 vaccine at Day 0 and a second dose of GSK1437173A study vaccine at Month 2. GSK1437173A vaccine was administered intramuscularly, in the deltoid region of the non-dominant arm. Pneumovax 23 was administered intramuscularly, in the deltoid region of the dominant arm .
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK1437173A
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and suspension for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    One dose of the vaccine at Day 0 and a second dose at Month 2.

    Investigational medicinal product name
    Pneumovax 23
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    One dose of the vaccine at Day 0.

    Arm title
    		 Control group
    Arm description
    		 Subjects received one dose of the Pneumovax 23 vaccine at Day 0, one dose of the GSK1437173A study vaccine at Month 2 and a second dose of the GSK1437173A study vaccine at Month 4. GSK1437173A vaccine was administered intramuscularly, in the deltoid region of the non-dominant arm. Pneumovax 23 was administered intramuscularly, in the deltoid region of the dominant arm .
    Arm type
    		 Active comparator

    Investigational medicinal product name
    GSK1437173A
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and suspension for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    One dose of the vaccine at Day 0 and a second dose at Month 2.

    Investigational medicinal product name
    Pneumovax 23
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    One dose of the vaccine at Day 0.

    Number of subjects in period 1
    		Co-Ad group Control group
    Started
    432
    433
    Completed
    423
    419
    Not completed
    9
    14
         Consent withdrawn by subject
    1
    1
         Adverse event, non-fatal
    4
    4
         Lost to follow-up
    4
    9

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Co-Ad group
    Reporting group description
    		 Subjects received one dose of the GSK1437173A study vaccine and one dose of the Pneumovax 23 vaccine at Day 0 and a second dose of GSK1437173A study vaccine at Month 2. GSK1437173A vaccine was administered intramuscularly, in the deltoid region of the non-dominant arm. Pneumovax 23 was administered intramuscularly, in the deltoid region of the dominant arm .

    Reporting group title
    Control group
    Reporting group description
    		 Subjects received one dose of the Pneumovax 23 vaccine at Day 0, one dose of the GSK1437173A study vaccine at Month 2 and a second dose of the GSK1437173A study vaccine at Month 4. GSK1437173A vaccine was administered intramuscularly, in the deltoid region of the non-dominant arm. Pneumovax 23 was administered intramuscularly, in the deltoid region of the dominant arm .

    Reporting group values
    		 Co-Ad group Control group Total
    Number of subjects
    		 432 433 865
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 63.2 ± 8.4 63.2 ± 8.4 -
    Gender categorical
    Units: Subjects
        Female
    		 264 252 516
        Male
    		 168 181 349
    Race/Ethnicity, Customized
    Units: Subjects
        African Heritage / African American
    		 12 9 21
        American Indian or Alaskan Native
    		 1 3 4
        Asian - East Asian Heritage
    		 3 7 10
        Asian - Japanese Heritage
    		 0 1 1
        Asian - South East Asian Heritage
    		 4 2 6
        Other
    		 2 5 7
        White - Arabic / North African Heritage
    		 2 0 2
        White - Caucasian / European Heritage
    		 408 406 814

    End points

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    End points reporting groups
    Reporting group title
    Co-Ad group
    Reporting group description
    		 Subjects received one dose of the GSK1437173A study vaccine and one dose of the Pneumovax 23 vaccine at Day 0 and a second dose of GSK1437173A study vaccine at Month 2. GSK1437173A vaccine was administered intramuscularly, in the deltoid region of the non-dominant arm. Pneumovax 23 was administered intramuscularly, in the deltoid region of the dominant arm .

    Reporting group title
    Control group
    Reporting group description
    		 Subjects received one dose of the Pneumovax 23 vaccine at Day 0, one dose of the GSK1437173A study vaccine at Month 2 and a second dose of the GSK1437173A study vaccine at Month 4. GSK1437173A vaccine was administered intramuscularly, in the deltoid region of the non-dominant arm. Pneumovax 23 was administered intramuscularly, in the deltoid region of the dominant arm .

    Primary: Number of subjects with a vaccine response for anti-gE antibodies

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    End point title
    		 Number of subjects with a vaccine response for anti-gE antibodies [1] [2]
    End point description
    Vaccine response rate for anti-gE antibody concentrations, as determined by enzyme-linked immunosorbent assay (ELISA), in subjects from the Co-Ad group. Vaccine response defined as: For initially seronegative subjects, antibody concentration at post-vaccination ≥ 4 fold the cut-off for Anti-gE (4x 97 mIU/mL). For initially seropositive subjects, antibody concentration at post-vaccination ≥ 4 fold the pre-vaccination antibody concentration.
    End point type
    Primary
    End point timeframe
    At Month 3
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary end point was descriptive, no statistical hypothesis test was performed.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As only the Co-ad Group received vaccination containing gE antigen, only this group had results.
    End point values
    		 Co-Ad group
    Number of subjects analysed
    401
    Units: Subjects
        Subjects
    394
    No statistical analyses for this end point

    Primary: Anti-glicoprotein E (gE) antibody concentrations

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    End point title
    		 Anti-glicoprotein E (gE) antibody concentrations [3]
    End point description
    Antibody concentrations were determined by ELISA, presented as geometric mean concentrations and expressed as milli international units per milliliter (mIU/mL).
    End point type
    Primary
    End point timeframe
    At one month post-dose 2 (Month 3 for the Co-Ad Group and Month 5 for the Control Group)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary end point was descriptive, no statistical hypothesis test was performed.
    End point values
    		 Co-Ad group Control group
    Number of subjects analysed
    407
    402
    Units: mIU/mL
    geometric mean (confidence interval 95%)
        mIU/mL
    49918 (47143 to 52856.3)
    50327.9 (47200.4 to 53662.7)
    No statistical analyses for this end point

    Primary: Anti-pneumococcal antibody titers

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    End point title
    		 Anti-pneumococcal antibody titers [4]
    End point description
    Anti-pneumococcal antibody titers were presented as geometric mean titers (GMTs) for the 12 following serotypes as determined by Opsonophagocytic Assay (OPA): 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F.
    End point type
    Primary
    End point timeframe
    At one month post-dose (Month 1)
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary end point was descriptive, no statistical hypothesis test was performed.
    End point values
    		 Co-Ad group Control group
    Number of subjects analysed
    410
    413
    Units: Titers
    geometric mean (confidence interval 95%)
        MOPA-1 [N=410, 413]
    65.1 (54.2 to 78.1)
    68.6 (56.9 to 82.7)
        MOPA-9V [N=410, 413]
    1898.4 (1618.1 to 2227.2)
    1991.3 (1716 to 2310.8)
        MOPA-14 [N=410, 413]
    2629.4 (2297.4 to 3009.3)
    2612.8 (2230.7 to 3060.3)
        MOPA-3 [N=410, 413]
    106.7 (92.6 to 122.9)
    107.4 (92.7 to 124.4)
        MOPA-4 [N=410, 412]
    1079.4 (924 to 1260.9)
    1328.8 (1141 to 1547.6)
        MOPA-5 [N=410, 413]
    161.4 (134.6 to 193.6)
    149.5 (123.5 to 181)
        MOPA-6B [N=410, 413]
    1619 (1354.5 to 1935)
    1564.4 (1303.5 to 1877.6)
        MOPA-7F [N=410, 413]
    2352.5 (2049.5 to 2700.3)
    2460.4 (2128.7 to 2843.8)
        MOPA-18C [N=410, 413]
    1077.4 (921.1 to 1260.2)
    1076 (918.2 to 1260.9)
        MOPA-19A [N=410, 413]
    1349.6 (1152.1 to 1580.8)
    1573.1 (1350.7 to 1832.2)
        MOPA-19F [N=409, 413]
    904.3 (779.6 to 1049)
    953 (814.8 to 1114.6)
        MOPA-23F [N=409, 413]
    431.4 (356.1 to 522.7)
    367.3 (300.8 to 448.5)
    No statistical analyses for this end point

    Primary: Adjusted ratios of Geometric Mean Titers (GMTs) between groups

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    End point title
    		 Adjusted ratios of Geometric Mean Titers (GMTs) between groups
    End point description
    The Adjusted ratios of GMTs between groups (Control group and Co-Ad group) were presented for each individual pneumococcal conjugate serotype Opsonophagocytic Activity (OPA).
    End point type
    Primary
    End point timeframe
    At 1 month after vaccination
    End point values
    		 Co-Ad group Control group
    Number of subjects analysed
    411
    408
    Units: Titers
    geometric mean (confidence interval 95%)
        MOPA-1 [N=411, 408]
    67.6 (56.9 to 80.2)
    65.6 (55.2 to 119.5)
        MOPA-3 [N=411, 408]
    105 (92.2 to 119.5)
    108.9 (95.7 to 124.1)
        MOPA-4 [N=409, 408]
    1264.1 (1089.9 to 1466.2)
    1117.2 (963.1 to 1296.1)
        MOPA-5 [N=411, 408]
    152.6 (129.1 to 180.3)
    159.8 (135.1 to 188.9)
        MOPA-6B [N=409, 408]
    1536.8 (1307.9 to 1805.7)
    1666.6 (1418 to 1958.6)
        MOPA-7F [N=409, 407]
    2491.3 (2179.8 to 2847.5)
    2324.7 (2033.3 to 2657.9)
        MOPA-9V [N=410, 406]
    1911.8 (1651.6 to 2212.9)
    1970.3 (1700.9 to 2282.3)
        MOPA-14 [N=411, 407]
    2610.1 (2281.6 to 2986)
    2678.1 (2339.4 to 3065.8)
        MOPA-18C [N=411, 405]
    1040.9 (902.7 to 1200.4)
    1099.8 (952.8 to 1269.6)
        MOPA-19A [N=406, 406]
    1558.6 (1361.8 to 1783.8)
    1350.5 (1180 to 1545.7)
        MOPA-19F [N=409, 407]
    938.2 (814.6 to 1080.7)
    914.1 (793.4 to 1053.3)
        MOPA-23F [N=410, 405]
    372.8 (316 to 439.8)
    419.1 (354.9 to 494.9)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Adjusted ratios of GMTs between groups (Control group and Co-Ad group) for MOPA-1.
    Comparison groups
    Control group v Co-Ad group
    Number of subjects included in analysis
    819
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMT
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 1.31
    Notes
    [5] - Non Inferiority criterion used: Upper Limit (UL) of the 95% CI for each individual pneumococcal conjugate serotype Opsonophagocytic Assay (OPA) GMT ratio of the Control group over the Co-Ad group had to be below 2.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Adjusted ratios of GMTs between groups (Control group and Co-Ad group) for MOPA-3
    Comparison groups
    Control group v Co-Ad group
    Number of subjects included in analysis
    819
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMT
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 1.16
    Notes
    [6] - Non Inferiority criterion used: Upper Limit (UL) of the 95% CI for each individual pneumococcal conjugate serotype Opsonophagocytic Assay (OPA) GMT ratio of the Control group over the Co-Ad group had to be below 2.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Adjusted ratios of GMTs between groups (Control group and Co-Ad group) for MOPA-4
    Comparison groups
    Co-Ad group v Control group
    Number of subjects included in analysis
    819
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [7]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMT
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 1.4
    Notes
    [7] - Non Inferiority criterion used: Upper Limit (UL) of the 95% CI for each individual pneumococcal conjugate serotype Opsonophagocytic Assay (OPA) GMT ratio of the Control group over the Co-Ad group had to be below 2.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    Adjusted ratios of GMTs between groups (Control group and Co-Ad group) for MOPA-5
    Comparison groups
    Co-Ad group v Control group
    Number of subjects included in analysis
    819
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [8]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMT
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.21
    Notes
    [8] - Non Inferiority criterion used: Upper Limit (UL) of the 95% CI for each individual pneumococcal conjugate serotype Opsonophagocytic Assay (OPA) GMT ratio of the Control group over the Co-Ad group had to be below 2.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    Adjusted ratios of GMTs between groups (Control group and Co-Ad group) for MOPA-6B
    Comparison groups
    Co-Ad group v Control group
    Number of subjects included in analysis
    819
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMT
    Point estimate
    0.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.16
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    Adjusted ratios of GMTs between groups (Control group and Co-Ad group) for MOPA-7F
    Comparison groups
    Co-Ad group v Control group
    Number of subjects included in analysis
    819
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [9]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMT
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 1.29
    Notes
    [9] - Non Inferiority criterion used: Upper Limit (UL) of the 95% CI for each individual pneumococcal conjugate serotype Opsonophagocytic Assay (OPA) GMT ratio of the Control group over the Co-Ad group had to be below 2.
    Statistical analysis title
    		 Statistical analysis 7
    Statistical analysis description
    Adjusted ratios of GMTs between groups (Control group and Co-Ad group) for MOPA-9V
    Comparison groups
    Co-Ad group v Control group
    Number of subjects included in analysis
    819
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [10]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMT
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.19
    Notes
    [10] - Non Inferiority criterion used: Upper Limit (UL) of the 95% CI for each individual pneumococcal conjugate serotype Opsonophagocytic Assay (OPA) GMT ratio of the Control group over the Co-Ad group had to be below 2.
    Statistical analysis title
    		 Statistical analysis 8
    Statistical analysis description
    Adjusted ratios of GMTs between groups (Control group and Co-Ad group) for MOPA-14
    Comparison groups
    Co-Ad group v Control group
    Number of subjects included in analysis
    819
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [11]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMT
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 1.18
    Notes
    [11] - Non Inferiority criterion used: Upper Limit (UL) of the 95% CI for each individual pneumococcal conjugate serotype Opsonophagocytic Assay (OPA) GMT ratio of the Control group over the Co-Ad group had to be below 2.
    Statistical analysis title
    		 Statistical analysis 9
    Statistical analysis description
    Adjusted ratios of GMTs between groups (Control group and Co-Ad group) for MOPA-18C
    Comparison groups
    Co-Ad group v Control group
    Number of subjects included in analysis
    819
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [12]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMT
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.16
    Notes
    [12] - Non Inferiority criterion used: Upper Limit (UL) of the 95% CI for each individual pneumococcal conjugate serotype Opsonophagocytic Assay (OPA) GMT ratio of the Control group over the Co-Ad group had to be below 2.
    Statistical analysis title
    		 Statistical analysis 10
    Statistical analysis description
    Adjusted ratios of GMTs between groups (Control group and Co-Ad group) for MOPA-19A
    Comparison groups
    Co-Ad group v Control group
    Number of subjects included in analysis
    819
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [13]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMT
    Point estimate
    1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1.4
    Notes
    [13] - Non Inferiority criterion used: Upper Limit (UL) of the 95% CI for each individual pneumococcal conjugate serotype Opsonophagocytic Assay (OPA) GMT ratio of the Control group over the Co-Ad group had to be below 2.
    Statistical analysis title
    		 Statistical analysis 11
    Statistical analysis description
    Adjusted ratios of GMTs between groups (Control group and Co-Ad group) for MOPA-19F
    Comparison groups
    Co-Ad group v Control group
    Number of subjects included in analysis
    819
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [14]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMT
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.25
    Notes
    [14] - Non Inferiority criterion used: Upper Limit (UL) of the 95% CI for each individual pneumococcal conjugate serotype Opsonophagocytic Assay (OPA) GMT ratio of the Control group over the Co-Ad group had to be below 2.
    Statistical analysis title
    		 Statistical analysis 12
    Statistical analysis description
    Adjusted ratios of GMTs between groups (Control group and Co-Ad group) for MOPA-23F
    Comparison groups
    Co-Ad group v Control group
    Number of subjects included in analysis
    819
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [15]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMT
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1.12
    Notes
    [15] - Non Inferiority criterion used: Upper Limit (UL) of the 95% CI for each individual pneumococcal conjugate serotype Opsonophagocytic Assay (OPA) GMT ratio of the Control group over the Co-Ad group had to be below 2.

    Primary: Adjusted GMCs between groups

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    End point title
    		 Adjusted GMCs between groups
    End point description
    The Adjusted ratios of GMCs between groups (Control group and Co-Ad group) was presented for anti-gE antibody ELISA concentrations
    End point type
    Primary
    End point timeframe
    At 1 month after last vaccine dose
    End point values
    		 Co-Ad group Control group
    Number of subjects analysed
    401
    402
    Units: mIU/mL
    geometric mean (confidence interval 95%)
        mIU/mL
    49569 (46641.4 to 52680.4)
    50474.5 (47497.4 to 53638.2)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Adjusted ratios of GMCs between groups (Control group and Co-Ad group) for anti-gE antibody ELISA concentrations
    Comparison groups
    Co-Ad group v Control group
    Number of subjects included in analysis
    803
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [16]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMT
    Point estimate
    1.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.93
         upper limit
    		 1.11
    Notes
    [16] - Non Inferiority criterion used: UL of the 95% CI for the anti-gE antibodies GMC ratio between the Control group and the Co-Ad group had to be below 1.5

    Secondary: Number of subjects with any and Grade 3 solicited local symptoms, by dose

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    End point title
    		 Number of subjects with any and Grade 3 solicited local symptoms, by dose
    End point description
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. The Co-Ad Group received only 2 vaccine doses.
    End point type
    Secondary
    End point timeframe
    Within 7 days (Days 0 - 6) after each vaccination
    End point values
    		 Co-Ad group Control group
    Number of subjects analysed
    429
    431
    Units: Subjects
        Any Pain, Dose 1 [N=428, 431]
    344
    168
        Grade 3 Pain, Dose 1 [N=428, 431]
    46
    5
        Any Redness, Dose 1 [N=428, 431]
    182
    30
        Grade 3 Redness, Dose 1 [N=428, 431]
    15
    2
        Any Swelling, Dose 1 [N=428, 431]
    99
    18
        Grade 3 Swelling, Dose 1 [N=428, 431]
    4
    1
        Any Pain, Dose 2 [N=416, 422]
    298
    289
        Grade 3 Pain, Dose 2 [N=416, 422]
    35
    28
        Any Redness, Dose 2 [N=416, 422]
    144
    128
        Grade 3 Redness, Dose 2 [N=416, 422]
    15
    4
        Any Swelling, Dose 2 [N=416, 422]
    77
    64
        Grade 3 Swelling, Dose 2 [N=416, 422]
    4
    2
        Any Pain, Dose 3 [N=0, 419]
    0
    293
        Grade 3 Pain, Dose 3 [N=0, 419]
    0
    32
        Any Redness, Dose 3 [N=0, 419]
    0
    136
        Grade 3 Redness, Dose 3 [N=0, 419]
    0
    8
        Any Swelling, Dose 3 [N=0, 419]
    0
    74
        Grade 3 Swelling, Dose 3 [N=0, 419]
    0
    3
        Any Pain, Across Doses [N=429, 431]
    372
    356
        Grade 3 Pain, Across Doses [N=429, 431]
    68
    49
        Any Redness, Across Doses [N=429, 431]
    232
    192
        Grade 3 Redness, Across Doses [N=429, 431]
    27
    12
        Any Swelling, Across Doses [N=429, 431]
    135
    111
        Grade 3 Swelling, Across Doses [N=429, 431]
    7
    6
    No statistical analyses for this end point

    Secondary: Number of subjects with solicited local symptoms, across doses, by vaccine

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    End point title
    		 Number of subjects with solicited local symptoms, across doses, by vaccine
    End point description
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.
    End point type
    Secondary
    End point timeframe
    Within 7 days (Days 0 - 6) after vaccination
    End point values
    		 Co-Ad group Control group
    Number of subjects analysed
    429
    431
    Units: Subjects
        Any Pain, GSK1437173A, Across Doses [N=429, 426]
    369
    343
        Any Pain, Pneumovax 23, Across Doses [N=428, 431]
    223
    169
        Any Redness, GSK1437173A, Across Doses [N=429,431]
    223
    186
        Any Redness,Pneumovax 23,Across Doses [N=428,431]
    69
    31
        Any Swelling,GSK1437173A,Across Doses [N=429,426]
    129
    108
        Any Swelling,Pneumovax 23,Across Doses [N=428,431]
    36
    21
    No statistical analyses for this end point

    Secondary: Number of days with any solicited local and general symptoms

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    End point title
    		 Number of days with any solicited local and general symptoms
    End point description
    The Co-Ad Group received only 2 vaccine doses. Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain.
    End point type
    Secondary
    End point timeframe
    Within 7 days (Days 0 - 6) after each vaccination
    End point values
    		 Co-Ad group Control group
    Number of subjects analysed
    344
    293
    Units: days
    median (inter-quartile range (Q1-Q3))
        Any Pain, Dose 1 [N=344, 169]
    3 (2 to 4)
    2 (1 to 3)
        Any Pain, Dose 2 [N=298, 290]
    3 (2 to 4)
    3 (2 to 4)
        Any Pain, Dose 3 [N=0, 293]
    0 (0 to 0)
    3 (2 to 4)
        Any Redness, Dose 1 [N=182, 31]
    3 (2 to 5)
    2 (1 to 3)
        Any Redness, Dose 2 [N=146, 129]
    3 (2 to 4)
    3 (2 to 5)
        Any Redness, Dose 3 [N=0, 136]
    0 (0 to 0)
    3 (2 to 4)
        Any Swelling, Dose 1 [N=99, 21]
    3 (2 to 5)
    2 (1 to 3)
        Any Swelling, Dose 2 [N=79, 67]
    3 (2 to 4)
    4 (2 to 5)
        Any Swelling, Dose 3 [N=0, 74]
    0 (0 to 0)
    3 (2 to 5)
        Any Fatigue, Dose 1 [N=194, 87]
    2 (1 to 4)
    2 (1 to 4)
        Any Fatigue, Dose 2 [N=191, 124]
    2 (1 to 3)
    2 (1 to 3)
        Any Fatigue, Dose 3 [N=0, 174]
    0 (0 to 0)
    2 (1 to 3)
        Any Gastrointestinal, Dose 1 [N=76, 31]
    2 (1 to 2.5)
    2 (1 to 3)
        Any Gastrointestinal, Dose 2 [N=61, 38]
    2 (1 to 3)
    2 (1 to 3)
        Any Gastrointestinal, Dose 3 [N=0, 47]
    0 (0 to 0)
    1 (1 to 2)
        Any Headache, Dose 1 [N=156, 72]
    2 (1 to 3)
    2 (1 to 2)
        Any Headache, Dose 2 [N=141, 104]
    2 (1 to 3)
    2 (1 to 2.5)
        Any Headache, Dose 3 [N=0, 144]
    0 (0 to 0)
    2 (1 to 2)
        Any Myalgia, Dose 1 [N=187, 87]
    2 (2 to 4)
    2 (1 to 3)
        Any Myalgia, Dose 2 [N=182, 124]
    2 (1 to 3)
    2 (1 to 3.5)
        Any Myalgia, Dose 3 [N=0, 162]
    0 (0 to 0)
    2 (2 to 3)
        Any Shivering, Dose 1 [N=91, 27]
    1 (1 to 2)
    2 (1 to 2)
        Any Shivering, Dose 2 [N=83, 30]
    1 (1 to 2)
    1 (1 to 2)
        Any Shivering, Dose 3 [N=0, 72]
    0 (0 to 0)
    1 (1 to 2)
        Any Temperature (Oral), Dose 1 [N=69, 12]
    1 (1 to 2)
    1 (1 to 2)
        Any Temperature (Oral), Dose 2 [N=67, 30]
    1 (1 to 2)
    1 (1 to 2)
        Any Temperature (Oral), Dose 3 [N=0, 67]
    0 (0 to 0)
    1 (1 to 2)
    No statistical analyses for this end point

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

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    End point title
    		 Number of subjects with unsolicited adverse events (AEs)
    End point description
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.
    End point type
    Secondary
    End point timeframe
    From the first dose up to 30 days post last vaccination period
    End point values
    		 Co-Ad group Control group
    Number of subjects analysed
    432
    433
    Units: Subjects
        Subjects with any AE(s)
    132
    140
        Subjects with grade 3 AE(s)
    16
    28
        Subjects with related AE(s)
    34
    28
    No statistical analyses for this end point

    Secondary: Number of subjects with serious adverse events (SAEs) [from the first dose up to 30 days post last vaccination period]

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    End point title
    		 Number of subjects with serious adverse events (SAEs) [from the first dose up to 30 days post last vaccination period]
    End point description
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
    End point type
    Secondary
    End point timeframe
    From the first dose up to 30 days post last vaccination period
    End point values
    		 Co-Ad group Control group
    Number of subjects analysed
    432
    433
    Units: Subjects
        Subjects with any SAE(s)
    7
    9
        Fatal SAEs
    0
    0
        Related SAEs
    0
    0
    No statistical analyses for this end point

    Secondary: Number of subjects with potential Immune Mediated Diseases (pIMDs) [from first vaccination up to 30 days post last vaccination]

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    End point title
    		 Number of subjects with potential Immune Mediated Diseases (pIMDs) [from first vaccination up to 30 days post last vaccination]
    End point description
    Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
    End point type
    Secondary
    End point timeframe
    From first vaccination up to 30 days post last vaccination (Month 0 – Month 3 for the Co-Ad Group; Month 0 – Month 5 for the Control Group)
    End point values
    		 Co-Ad group Control group
    Number of subjects analysed
    432
    433
    Units: Subjects
        Any pIMDs
    0
    1
        Related pIMDs
    0
    0
    No statistical analyses for this end point

    Secondary: Number of subjects with potential Immune Mediated Diseases (pIMDs) [during the period starting after 30 days post last vaccination up to study end]

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    End point title
    		 Number of subjects with potential Immune Mediated Diseases (pIMDs) [during the period starting after 30 days post last vaccination up to study end]
    End point description
    Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
    End point type
    Secondary
    End point timeframe
    During the period starting after 30 days post last vaccination up to study end (Month 3 – Month 14 for the Co-Ad Group; Month 5 – Month 16 for the Control Group)
    End point values
    		 Co-Ad group Control group
    Number of subjects analysed
    432
    433
    Units: Subjects
        Subjects
    1
    0
    No statistical analyses for this end point

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

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    End point title
    		 Number of subjects with any, Grade 3 and related solicited general symptoms
    End point description
    Assessed solicited general symptoms were arthralgia, fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], headache, myalgia, shivering and sweating. Any = occurrence of the symptom regardless of intensity grade. Grade 3 (G3) symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related (Rel) = symptom assessed by the investigator as related to the vaccination.
    End point type
    Secondary
    End point timeframe
    During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
    End point values
    		 Co-Ad group Control group
    Number of subjects analysed
    429
    431
    Units: Subjects
        Any Fatigue, Dose 1 (N=427,430)
    194
    87
        G3 Fatigue, Dose 1 (N=427,430)
    27
    3
        Rel Fatigue, Dose 1 (N=427,430)
    175
    81
        Any Gastrointestinal symptoms, Dose 1 (N=427,430)
    76
    31
        G3 Gastrointestinal symptoms, Dose 1 (N=427,430)
    6
    1
        Rel Gastrointestinal symptoms, Dose 1 (N=427,430)
    67
    28
        Any Headache, Dose 1 (N=427,430)
    156
    72
        G3 Headache, Dose 1 (N=427,430)
    15
    3
        Rel Headache, Dose 1 (N=427,430)
    141
    64
        Any Myalgia, Dose 1 (N=427,430)
    187
    87
        G3 Myalgia, Dose 1 (N=427,430)
    29
    5
        Rel Myalgia, Dose 1 (N=427,430)
    177
    82
        Any Shivering, Dose 1 (N=427,430)
    91
    27
        G3 Shivering, Dose 1 (N=427,430)
    27
    1
        Rel Shivering, Dose 1 (N=427,430)
    86
    26
        Any Temperature, Dose 1 (N=427,430)
    69
    12
        G3 Temperature, Dose 1 (N=427,430)
    1
    1
        Rel Temperature, Dose 1 (N=427,430)
    67
    11
        Any Fatigue, Dose 2 (N=415,421)
    191
    124
        G3 Fatigue, Dose 2 (N=415,421)
    29
    11
        Rel Fatigue, Dose 2 (N=415,421)
    174
    109
        Any Gastrointestinal symptoms, Dose 2 (N=415,421)
    61
    38
        G3 Gastrointestinal symptoms, Dose 2 (N=415,421)
    6
    4
        Rel Gastrointestinal symptoms, Dose 2 (N=415,421)
    52
    29
        Any Headache, Dose 2 (N=415,421)
    141
    104
        G3 Headache, Dose 2 (N=415,421)
    19
    9
        Rel Headache, Dose 2 (N=415,421)
    124
    85
        Any Myalgia, Dose 2 (N=415,421)
    182
    124
        G3 Myalgia, Dose 2 (N=415,421)
    25
    11
        Rel Myalgia, Dose 2 (N=415,421)
    171
    119
        Any Shivering, Dose 2 (N=415,421)
    83
    30
        G3 Shivering, Dose 2 (N=415,421)
    14
    3
        Rel Shivering, Dose 2 (N=415,421)
    78
    25
        Any Temperature, Dose 2 (N=415,421)
    67
    30
        G3 Temperature, Dose 2 (N=415,421)
    0
    0
        Rel Temperature, Dose 2 (N=415,421)
    63
    26
        Any Fatigue, Dose 3 (N=0, 419)
    0
    174
        G3 Fatigue, Dose 3 (N=0, 419)
    0
    22
        Rel Fatigue, Dose 3 (N=0, 419)
    0
    166
        Any Gastrointestinal symptoms, Dose 3 (N=0, 419)
    0
    47
        G3 Gastrointestinal symptoms, Dose 3 (N=0, 419)
    0
    3
        Rel Gastrointestinal symptoms, Dose 3 (N=0, 419)
    0
    46
        Any Headache, Dose 3 (N=0, 419)
    0
    144
        G3 Headache, Dose 3 (N=0, 419)
    0
    13
        Rel Headache, Dose 3 (N=0, 419)
    0
    135
        Any Myalgia, Dose 3 (N=0, 419)
    0
    162
        G3 Myalgia, Dose 3 (N=0, 419)
    0
    26
        Rel Myalgia, Dose 3 (N=0, 419)
    0
    157
        Any Shivering, Dose 3 (N=0, 419)
    0
    72
        G3 Shivering, Dose 3 (N=0, 419)
    0
    11
        Rel Shivering, Dose 3 (N=0, 419)
    0
    69
        Any Temperature, Dose 3 (N=0, 419)
    0
    67
        G3 Temperature, Dose 3 (N=0, 419)
    0
    2
        Rel Temperature, Dose 3 (N=0, 419)
    0
    66
        Any Fatigue, Across doses (N=429,431)
    253
    228
        G3 Fatigue, Across doses (N=429,431)
    47
    31
        Rel Fatigue, Across doses (N=429,431)
    236
    216
        Any Gastrointestinal sympt,Across doses(N=429,431)
    114
    84
        G3 Gastrointestinal sympt, Across doses(N=429,431)
    12
    7
        Rel Gastrointestinal sympt,Across doses(N=429,431)
    100
    77
        Any Headache, Across doses (N=429,431)
    209
    208
        G3 Headache, Across doses (N=429,431)
    29
    24
        Rel Headache, Across doses (N=429,431)
    195
    193
        Any Myalgia, Across doses (N=429,431)
    257
    225
        G3 Myalgia, Across doses (N=429,431)
    46
    37
        Rel Myalgia, Across doses (N=429,431)
    245
    218
        Any Shivering, Across doses (N=429,431)
    137
    99
        G3 Shivering, Across doses (N=429,431)
    25
    15
        Rel Shivering, Across doses (N=429,431)
    131
    95
        Any Temperature, Across doses (N=429,431)
    112
    96
        G3 Temperature, Across doses (N=429,431)
    1
    3
        Rel Temperature, Across doses (N=429,431)
    108
    91
    No statistical analyses for this end point

    Secondary: Number of subjects with serious adverse events (SAEs) [from 30 days post last vaccination up to study end]

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    End point title
    		 Number of subjects with serious adverse events (SAEs) [from 30 days post last vaccination up to study end]
    End point description
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
    End point type
    Secondary
    End point timeframe
    From 30 days post last vaccination up to study end
    End point values
    		 Co-Ad group Control group
    Number of subjects analysed
    432
    433
    Units: Subjects
        Subjects with any SAE(s)
    10
    10
        Fatal SAE(s)
    2
    2
        Related SAE(s)
    2
    2
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Solicited symptoms during the 7-day post-vaccination period, Unsolicited AEs during the 30-day post-vaccination period. SAE(s) were collected during the entire study period (Month 0 to Month 16)
    Adverse event reporting additional description
    Individual SAEs remain blinded as long as the study is ongoing.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Control Group
    Reporting group description
    		 Subjects received one dose of the Pneumovax™ 23 vaccine at Day 0, one dose of the GSK1437173A study vaccine at Month 2 and a second dose of the GSK1437173A study vaccine at Month 4. GSK1437173A vaccine was administered intramuscularly, in the deltoid region of the non-dominant arm. Pneumovax™ 23 was administered intramuscularly, in the deltoid region of the dominant arm.

    Reporting group title
    Co-Ad Group
    Reporting group description
    		 Subjects received one dose of the GSK1437173A study vaccine and one dose of the Pneumovax™ 23 vaccine at Day 0 and a second dose of GSK1437173A study vaccine at Month 2. GSK1437173A vaccine was administered intramuscularly, in the deltoid region of the non-dominant arm. Pneumovax™ 23 was administered intramuscularly, in the deltoid region of the dominant arm.

    Serious adverse events
    		 Control Group Co-Ad Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    19 / 433 (4.39%)
    17 / 432 (3.94%)
         number of deaths (all causes)
    2
    2
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Angiomyolipoma
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma stage iv
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glioblastoma multiforme
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aortic dissection
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Arteriosclerosis
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    2 / 433 (0.46%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Sarcoidosis
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         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
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Limb traumatic amputation
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 433 (0.23%)
    3 / 432 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 433 (0.23%)
    2 / 432 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    2 / 433 (0.46%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (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
    Carotid artery stenosis
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    2 / 433 (0.46%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolic stroke
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbosacral radiculopathy
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebral artery dissection
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Leukocytosis
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis ulcerative
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Calculus urinary
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic abscess
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 433 (0.69%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metabolism and nutrition disorders
    Gout
         subjects affected / exposed
    0 / 433 (0.00%)
    1 / 432 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperlipidaemia
         subjects affected / exposed
    1 / 433 (0.23%)
    0 / 432 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Control Group Co-Ad Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    393 / 433 (90.76%)
    400 / 432 (92.59%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    209 / 433 (48.27%)
    210 / 432 (48.61%)
         occurrences all number
    331
    306
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    228 / 433 (52.66%)
    253 / 432 (58.56%)
         occurrences all number
    385
    385
    Pain
         subjects affected / exposed
    357 / 433 (82.45%)
    372 / 432 (86.11%)
         occurrences all number
    754
    642
    Pyrexia
         subjects affected / exposed
    97 / 433 (22.40%)
    112 / 432 (25.93%)
         occurrences all number
    110
    138
    Swelling
         subjects affected / exposed
    115 / 433 (26.56%)
    137 / 432 (31.71%)
         occurrences all number
    162
    178
    Erythema
         subjects affected / exposed
    194 / 433 (44.80%)
    234 / 432 (54.17%)
         occurrences all number
    297
    330
    Gastrointestinal disorders
    Gastrointestinal disorder
         subjects affected / exposed
    84 / 433 (19.40%)
    114 / 432 (26.39%)
         occurrences all number
    116
    137
    Chills
         subjects affected / exposed
    99 / 433 (22.86%)
    137 / 432 (31.71%)
         occurrences all number
    130
    176
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    227 / 433 (52.42%)
    257 / 432 (59.49%)
         occurrences all number
    376
    370

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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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    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.

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